Pharmaceutical compositions comprising an HIV integrase inhibitor

Abstract

The present disclosure relates generally to pharmaceutical compositions (e.g., solid oral dosage forms) of a compound of Formula I: Also disclosed are methods of treating or preventing a human immunodeficiency virus (HIV) infection in a human, comprising orally administering to the human a solid oral dosage form or pharmaceutical composition disclosed herein.

Description

Cross-references to related applications

[0001] This application claims priority to U.S. Provisional Application No. 63 / 560,226, filed March 1, 2024, and U.S. Provisional Application No. 63 / 673,408, filed July 19, 2024. The entire contents of these applications are hereby incorporated by reference. Technical Field

[0002] The present invention provides a pharmaceutical composition comprising an HIV integrase inhibitor (1S,2R,5S)-8-hydroxy-2,5-dimethyl-7,9-dioxo-N-(2,4,6-trifluorobenzyl)-2,5,7,9-tetrahydro-1,6-bridged methylenepyrido[1,2-b][1,2,5]triazacyclononane-10-carboxamide or a pharmaceutically acceptable salt thereof, and a method of treating or preventing HIV in a subject, the method comprising orally administering a therapeutically effective amount of the pharmaceutical composition to the subject, optionally in combination with one or more other therapeutic agents. Background Technology

[0003] There is a persistent need for antiviral agents and methods for treating HIV infection. There is also a ongoing need to develop methods for preparing and purifying antiviral agents, as well as improved pharmaceutical formulations for preparing these antiviral agents. The pharmaceutical compositions disclosed herein help to meet these and other needs. Summary of the Invention

[0004] This disclosure provides pharmaceutical compositions (e.g., solid oral dosage forms) comprising: compounds of formula I. I (1S,2R,5S)-8-hydroxy-2,5-dimethyl-7,9-dioxo-N-(2,4,6-trifluorobenzyl)-2,5,7,9-tetrahydro-1,6-bridged methylenepyrido[1,2-b][1,2,5]triazacyclononane-10-carboxamide Or a pharmaceutically acceptable salt thereof, and one or more excipients.

[0005] This disclosure also provides methods for treating or preventing HIV in a subject, including, optionally, administering orally to the subject a therapeutically effective amount of the dosage form in combination with one or more other therapeutic agents.

[0006] In one aspect, this article provides a solid oral dosage form comprising an amount of about 5 mg to about 1400 mg of a compound of formula I or a pharmaceutically acceptable salt thereof, wherein the amount is based on the free acid form.

[0007] In one aspect, this article provides a solid oral dosage form comprising an amount of about 5 mg to about 1400 mg of a compound of formula I or a pharmaceutically acceptable salt thereof, wherein the amount is based on the free acid form; a filler; a disintegrant; a binder; and a lubricant.

[0008] In one aspect, this article provides a pharmaceutical composition comprising about 5% to about 35% by weight of a compound of formula I or a pharmaceutically acceptable salt thereof; about 50% to about 90% by weight of a filler; about 1% to about 10% by weight of a disintegrant; about 1% to about 10% by weight of a binder; and about 0.1% to about 5% by weight of a lubricant.

[0009] In one aspect, this article provides a method for treating or preventing HIV infection in a person, the method comprising orally administering to a person a solid oral dosage form or pharmaceutical composition disclosed herein. Attached Figure Description

[0010] Figure 1 The image shows the XRPD pattern of compound form I of formula I.

[0011] Figure 2 The DSC curves for compound form I of formula I are shown. Figure 3 The TGA curves for compound form I of formula I are shown.

[0012] Figure 4 The DVS curves for compound form I of formula I are shown.

[0013] Figure 5 The diagram shows a ball-and-stick representation of compound form I of formula I.

[0014] Figure 6 The XRPD pattern of compound form II of formula I is shown.

[0015] Figure 7 The DSC curves for compound form II of formula I are shown.

[0016] Figure 8 The TGA curves for compound form II of formula I are shown.

[0017] Figure 9 The image shows an XRPD pattern of the sodium salt form of compound I.

[0018] Figure 10 The DSC curve of the sodium salt form I of compound I is shown.

[0019] Figure 11 The TGA curves for the sodium salt form I of compound I are shown.

[0020] Figure 12 The DVS curve of the sodium salt form I of compound I is shown.

[0021] Figure 13 The XRPD pattern of sodium salt form II of compound I is shown.

[0022] Figure 14 The DSC curve of sodium salt form II of compound I is shown.

[0023] Figure 15 The TGA curves for the sodium salt form II of compound I are shown.

[0024] Figure 16 The XRPD pattern of sodium salt form III of compound I is shown.

[0025] Figure 17 The image shows an XRPD pattern of the sodium salt form IV of compound I.

[0026] Figure 18 The image shows an XRPD pattern of the potassium salt form of compound I.

[0027] Figure 19 The DSC curve of the potassium salt form I of compound I is shown.

[0028] Figure 20 The TGA curves for the potassium salt form I of compound I are shown.

[0029] Figure 21 The DVS curve of compound potassium salt form I is shown.

[0030] Figure 22 The atomic shift ellipsoid diagram of the potassium salt form I of compound I is shown.

[0031] Figure 23 The image shows an XRPD pattern of potassium salt form II of compound I.

[0032] Figure 24 The TGA curves for potassium salt form II of compound I are shown.

[0033] Figure 25 The image shows an XRPD pattern of potassium salt form III of compound I.

[0034] Figure 26 The image shows an XRPD pattern of the diethylamine salt form I of compound I.

[0035] Figure 27 The DSC curve of compound I, diethylamine salt form I, is shown.

[0036] Figure 28 The TGA curves of compound II, the diethylamine salt of formula I, are shown.

[0037] Figure 29 The DVS curve of compound II, the diethylamine salt of formula I, is shown.

[0038] Figure 30 The image shows the XRPD pattern of the ammonium salt of compound I.

[0039] Figure 31 The DSC curve of the ammonium salt of compound I is shown.

[0040] Figure 32 The TGA curves of the ammonium salt of compound I are shown.

[0041] Figure 33 The DVS curve of the ammonium salt of compound I is shown.

[0042] Figure 34 The image shows an XRPD pattern of the calcium salt form of compound I.

[0043] Figure 35 The DSC curve of the calcium salt form I of compound I is shown.

[0044] Figure 36 The XRPD pattern of compound II, calcium salt form of Formula I, is shown.

[0045] Figure 37 The XRPD pattern of calcium salt form III of compound I is shown.

[0046] Figure 38 The image shows the XRPD pattern of the magnesium salt form of compound I.

[0047] Figure 39 The DSC curve of the magnesium salt form I of compound I is shown.

[0048] Figure 40 The XRPD pattern of magnesium salt form II of compound I is shown.

[0049] Figure 41 The compound of formula I is shown. N XRPD pattern of butylamine salt.

[0050] Figure 42 The compound of formula I is shown. N DSC curve of 1-butanamine salt.

[0051] Figure 43 The compound of formula I is shown.N TGA curve of 1-butanamine salt.

[0052] Figure 44 The compound of formula I is shown. N DVS curve of 1-butanamine salt.

[0053] Figure 45 The XRPD pattern of the diethanolamine salt of compound I is shown.

[0054] Figure 46 The XRPD pattern of the ethylenediamine salt of compound I is shown.

[0055] Figure 47 The XRPD pattern of the morpholine salt of Formula I is shown.

[0056] Figure 48 The image shows an XRPD pattern of the L-arginine salt form of compound I.

[0057] Figure 49 The XRPD pattern of compound I, L-arginine salt form II, is shown.

[0058] Figure 50 The XRPD pattern of L-arginine salt form III of compound I is shown.

[0059] Figure 51 The XRPD pattern of the trans-ferulic acid eutectic form I of compound I is shown.

[0060] Figure 52 The DSC curve of the trans-ferulic acid eutectic form I of compound I is shown.

[0061] Figure 53 The TGA curve of the trans-ferulic acid eutectic form I of compound I is shown.

[0062] Figure 54 The DVS curve of the trans-ferulic acid eutectic form I of compound I is shown.

[0063] Figure 55 The XRPD pattern of the trans-ferulic acid eutectic form II of compound I is shown.

[0064] Figure 56 The DSC curve of the trans-ferulic acid eutectic form II of compound I is shown.

[0065] Figure 57 The TGA curves of the trans-ferulic acid eutectic form II of compound I are shown.

[0066] Figure 58The XRPD pattern of the aminobutanetriol cocrystal of Formula I is shown.

[0067] Figure 59 The DSC curve of the aminobutanetriol eutectic of Formula I is shown.

[0068] Figure 60 The TGA curve of the aminobutanetriol cocrystal of Formula I is shown.

[0069] Figure 61 A flowchart illustrating the exemplary preparation of a solid oral dosage form (e.g., tablet) disclosed herein is shown.

[0070] Figure 62 A flowchart illustrating an exemplary preparation of the spray-dried dispersion (SDD) disclosed herein is shown.

[0071] Figure 63 The results show the fold change in potency (relative to wild type) of compounds of Formula I when testing antiviral activity against HIV-1 mutants resistant to NRTI, NNRTI, PI, and CAI.

[0072] Figure 64 The results show the fold change in potency (relative to wild type) of compounds of Formula I, bictegravir, and raltegravir when tested for antiviral activity against HIV-1 mutants resistant to INSTI. Detailed Implementation

[0073] This disclosure relates to pharmaceutical compositions comprising an HIV integrase inhibitor (1S,2R,5S)-8-hydroxy-2,5-dimethyl-7,9-dioxo-N-(2,4,6-trifluorobenzyl)-2,5,7,9-tetrahydro-1,6-bridged methylenepyrido[1,2-b][1,2,5]triazacyclononane-10-carboxamide (a compound of formula I, see below), which is disclosed in WO 2022 / 159387.

[0074] Compounds of Formula I The pharmaceutical compositions disclosed herein can be used to treat or prevent HIV infection (e.g., HIV-1 and / or HIV-2) in a subject (e.g., a human) by administering a therapeutically effective amount of a compound of Formula I or a pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula I or a pharmaceutically acceptable salt thereof is administered as a monotherapy (i.e., in the absence of an additional therapeutic agent). In some embodiments, the compound of Formula I or a pharmaceutically acceptable salt thereof is administered in combination with one or more other therapeutic agents (such as anti-HIV agents). In some embodiments, the compound of Formula I or a pharmaceutically acceptable salt thereof is administered orally.

[0075] I. definition Unless the context otherwise requires, throughout this specification and claims, the word “comprising” and its variations such as “including” and “containing” shall be interpreted in an open, inclusive sense, that is, as “including but not limited to”.

[0076] Throughout this specification, the phrase "an embodiment" or "an embodiment" means that a particular feature, structure, or characteristic described in connection with that embodiment is included in at least one embodiment described herein. Therefore, the phrases "in an embodiment" or "in an embodiment" appearing in various places throughout this specification do not necessarily refer to the same embodiment. Furthermore, in one or more embodiments, a particular feature, structure, or characteristic may be combined in any suitable manner.

[0077] As used herein, “crystalline form” means a particular lattice configuration of a crystalline substance (e.g., a salt or eutectic). Different crystalline forms of the same substance typically have different lattices (e.g., unit cells) due to different physical properties characteristic of each crystalline form. In some cases, different lattice configurations have different water or solvent contents, resulting in solvated or hydrated crystalline forms. As used herein, the term “solvated” means a crystalline form in which solvent molecules are contained in the lattice. As used herein, the term “hydrated” means a solvated crystalline form in which the solvent is water and water molecules are contained in the lattice. Examples of “hydrated” crystalline forms include hemihydrates, monohydrates, dihydrates, etc. Other hydrated forms (such as channel hydrates, etc.) are also included within the meaning of this term. The term “fully hydrated” means that the water content of the hydrate is present in the expected stoichiometric amount. The term “partially hydrated” means that the water content of the hydrate is present in a less than expected stoichiometric amount (e.g., in which some water of the monohydrate has been removed). Similarly, the terms "solvent-free" or "anhydrous" refer to a crystalline form that is essentially free of solvent or water, but some residual solvent or water may be present, for example, solvent or water left over from the process used to prepare the crystalline form.

[0078] Different crystalline forms can be identified using solid-state characterization methods, such as X-ray powder diffraction (XRPD). Other characterization methods, such as differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and dynamic vapor adsorption (DVS), can help further identify the forms and determine stability and solvent / water content.

[0079] XRPD patterns of reflection (peaks) are generally considered fingerprints of a specific crystalline form. Unless otherwise stated, all XRPD patterns mentioned herein were obtained using copper radiation (Cu Kα, λ = 1.5418 Å) on a diffractometer (PANanalytical XPERT-PRO, PANanalytical BV, Almelo, Netherlands). Samples for analysis were prepared by depositing powder samples at the center of an aluminum support equipped with a zero-background plate. The generator was operated at a voltage of 45 kV and a current intensity of 40 mA. The slits used were a Soler slit of 0.02 rad, an anti-scattering slit of 1.0°, and a diverging slit. The sample rotation speed was 2 seconds. Scans were performed from 2° to 40° 2θ in steps of 0.0167° 2θ over 15 minutes. Data analysis was performed using X'PertHighscore version 2.2c (PANalytical BV, Almelo, Netherlands) and X'Pert Data Viewer version 1.2d (PANalytical BV, Almelo, Netherlands).

[0080] As is well known, the relative intensities of XRPD peaks can vary extensively, particularly depending on sample preparation techniques, crystal size distribution, the various filters used, sample setup procedures, and the specific instrument employed. In some cases, depending on the type or setup of the instrument, new peaks may be observed, or existing peaks may disappear. As used herein, the term "peak" refers to a reflection with a relative height / intensity of at least about 5% of the maximum peak height / intensity. Furthermore, instrument variations and other factors can affect the 2θ values. Therefore, peak assignments (such as those reported herein) can vary by about 0.2° (2θ) positive or negative, and the terms "substantially" and "about" as used herein in the context of XRPD are intended to encompass the aforementioned variations.

[0081] Similarly, temperature readings associated with DSC can vary by approximately ±3°C depending on the instrument, specific settings, sample preparation, etc. Therefore, the crystalline form or the term "approximately" used in this report, which describes DSC thermograms as "substantially" as shown in any figure, should be understood to accommodate such variations.

[0082] The d mentioned in this article 90The value describes the fact that 90% of the particles in the sample have a higher density than the specified d. 90 Granularity values ​​that are even smaller. For example, d = approximately 4 μm. 90 This means that 90% of the particles in the sample are smaller than 4μm.

[0083] "Excipients" include, but are not limited to, any pharmaceutically acceptable adjuvant, carrier, excipient, gliding agent, sweetener, diluent, preservative, dye / coloring agent, flavor enhancer, surfactant, wetting agent, dispersant, suspending agent, stabilizer, isotonic agent, solvent, emulsifier, alkalizing agent, solubilizer, gliding agent, filler, binder, lubricant, disintegrant, pH adjuster, or coating agent that has been approved by the U.S. Food and Drug Administration for acceptable use in humans or domesticated animals. In some embodiments, such components are present as an admixture in a solid oral dosage form (e.g., tablet).

[0084] "Pharmaceutical acceptable" refers to compounds, salts, compositions, dosage forms, and other substances that can be used to prepare pharmaceutical compositions suitable for veterinary or human use.

[0085] A "pharmaceutically acceptable salt" is a salt of a compound that is pharmaceutically acceptable and has (or can be converted to have) the desired pharmacological activity of the parent compound. Such salts include acid addition salts formed with inorganic acids, and salts formed when an acidic proton present in the parent compound is replaced by a metal ion (e.g., an alkali metal ion, an alkaline earth ion, or an aluminum ion); or salts formed when coordinated with an organic base (such as diethanolamine, triethanolamine, N-methylglucosamine, etc.). This definition also includes ammonium and substituted or quaternized ammonium salts. A representative, non-restrictive list of pharmaceutically acceptable salts can be found in the following literature: SMBerge et al., J. Pharma Sci., 66(1), 1-19 (1977), and Remington: The Science and Practice of Pharmacy, R. Hendrickson, ed., 21st ed., Lippincott, Williams & Wilkins, Philadelphia, PA, (2005), p. 732, Tables 38-5, which are incorporated herein by reference.

[0086] "Treatment" is a method used to achieve a beneficial or desired outcome, including clinical outcomes. Beneficial or desired clinical outcomes include one or more of the following: a) suppressing a disease or condition (e.g., reducing one or more symptoms caused by the disease or condition, and / or reducing the severity of the disease or condition); b) slowing or halting the development of one or more clinical symptoms associated with the disease or condition (e.g., stabilizing the disease or condition, preventing or delaying the worsening or progression of the disease or condition, and / or preventing or delaying its spread (e.g., metastasis of the disease or condition); and / or c) alleviating the disease, i.e., leading to the resolution of clinical symptoms (e.g., improving the disease state, providing partial or overall relief from the disease or condition, enhancing the effect of another medication, delaying the progression of the disease, increasing quality of life, and / or prolonging survival).

[0087] As used herein, the term "prevention" refers to the administration of a compound, composition, or pharmaceutically acceptable salt according to this disclosure before or after exposure to a virus, but before the onset of symptoms of illness and / or before the virus is detected in the blood. The term also refers to prevention of the onset of symptoms of illness and / or prevention of the virus reaching detectable levels in the blood. This term includes pre-exposure prophylaxis (PrEP), post-exposure prophylaxis (PEP), and event-driven or "on-demand" prophylaxis. The term also refers to prevention of perinatal transmission of HIV from mother to infant by administration to the mother before delivery and to the infant during the first few days of life. The term also refers to prevention of HIV transmission via blood transfusion.

[0088] "Subject" refers to an animal, such as a mammal (e.g., a human), that is or will be the subject of treatment, observation, or experimentation. The methods described herein can be used for human therapeutics and / or veterinary applications. In some embodiments, the subject is a mammal. In one embodiment, the subject is a human.

[0089] The term "therapeutic effective amount" or "effective amount" as used in the description of a composition or compound or its pharmaceutically acceptable salts, isomers, or mixtures herein means an amount sufficient, when administered to a subject, to achieve a therapeutic effect to provide a beneficial therapeutic effect, such as improvement of symptoms or slowing of disease progression. For example, a therapeutic effective amount may be an amount sufficient to reduce symptoms of a disease or condition in response to HIV activity. Therapeutic effective amounts can vary depending on the subject, the disease or condition being treated, the subject's weight and age, the severity of the disease or condition, and the route of administration, which can be readily determined by those skilled in the art.

[0090] The term "about" as used herein includes (and describes) embodiments relating to that value or parameter itself. In some embodiments, the term "about" includes an indication of ±10%. In other embodiments, the term "about" includes an indication of ±5%. In some still embodiments, the term "about" includes an indication of ±1%. Furthermore, the term "about X" includes a description of "X".

[0091] The invention herein is also intended to cover all pharmaceutically acceptable salts and / or cocrystals of Formula I, which are isotopically labeled by having one or more atoms replaced by atoms of different atomic masses or mass numbers. Examples of isotopes that can be incorporated into the described compounds include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, fluorine, chlorine, and iodine, such as... 2 H, 3 H, 11 C 13 C 14 C 13 N、 15 N、 15 O、 17 O、 18 O、 31 P, 32 P, 35 S, 18 F, 36 Cl、 123 I and 125 I. These radiolabeled compounds can be used to help determine or measure the efficacy of compounds by characterizing, for example, the site or pattern of action or the binding affinity to pharmacologically important sites of action. Certain isotope-labeled salts and / or cocrystals of tenofovir alarfenamide, such as those doped with radioisotopes, can be used for drug and / or substrate tissue distribution studies. Radioisotope tritium (i.e....) 3 H) and carbon-14 (i.e. 14 (C) They are particularly useful for this purpose because they are easy to incorporate and readily available detection methods.

[0092] Using heavier isotopes (such as deuterium, i.e.) 2 H) substitution can offer certain therapeutic advantages due to its greater metabolic stability. For example, it can increase the half-life in vivo or reduce the dosage requirement. Therefore, in some cases, heavier isotopes may be preferred.

[0093] Using positron emission isotopes such as 11 C 18 F, 15 O and 13Substitution of N can be used in positron emission tomography (PET) studies to examine substrate acceptor occupancy. Isotope-labeled salts and / or cocrystals of compounds of Formula I can typically be prepared using conventional techniques known to those skilled in the art.

[0094] II. Mode I compounds The methods and pharmaceutical compositions described herein utilize compounds of Formula I, wherein the compounds of Formula I are in the form of free acids and / or pharmaceutically acceptable salts thereof. In some embodiments, the pharmaceutical composition comprises a compound of Formula I. In some embodiments, the pharmaceutical composition comprises a pharmaceutically acceptable salt of a compound of Formula I. The compounds of Formula I or their pharmaceutically acceptable salts may be crystalline, amorphous, or a combination thereof. In some embodiments, the compounds of Formula I or their pharmaceutically acceptable salts are crystalline. In some embodiments, the compounds of Formula I or their pharmaceutically acceptable salts are amorphous.

[0095] Formula I, Form I In some embodiments, the compound of Formula I is crystalline. In some embodiments, the compound of Formula I is crystalline form I (Form I of Formula I), wherein the crystal structure exhibits essentially as follows: Figure 1 The X-ray powder diffraction (XRPD) pattern shown is shown. Formula I, Form I, can exhibit essentially the same characteristics. Figure 2 The differential scanning calorimetry (DSC) thermogram shown is given. Equation I, Form I, can essentially represent... Figure 3 The thermogravimetric analysis (TGA) diagram is shown. Equation I, Form I, can essentially represent the following... Figure 4 The dynamic vapor adsorption (DVS) curve is shown.

[0096] When referring to, for example, XRPD plots, DSC thermograms, or TGA charts, the term “substantially as shown” includes plots, thermograms, or charts that are not necessarily the same as those described herein, but which, when considered by a person of ordinary skill in the art, fall within the limits of experimental error or bias.

[0097] In some embodiments, Form I has at least two, at least three, at least four, at least five, or at least six elements substantially as shown. Figure 1 The XRPD pattern shown is an XRPD pattern with maximum intensity 2θ angle reflection.

[0098] In some embodiments, Form I of Formula I has an XRPD pattern including 2θ reflections (+ / -0.2 degrees 2θ) at 7.0°, 13.9°, and 27.9°. In some embodiments, Form I of Formula I has an XRPD pattern including one, two, or three of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 7.0°, 13.9°, and 27.9°; and 2θ reflections (+ / -0.2 degrees 2θ) at 12.3°, 17.4°, and 24.6°. In some embodiments, Form I of Formula I has an XRPD pattern including one or two of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 7.0°, 13.9°, and 27.9°; and 2θ reflections (+ / -0.2 degrees 2θ) at 12.3°, 17.4°, and 24.6°. In some embodiments, Form I of Formula I has an XRPD pattern including one of 2θ reflections (+ / -0.2 degrees 2θ) at 7.0°, 13.9°, and 27.9° and 2θ reflections (+ / -0.2 degrees 2θ) at 12.3°, 17.4°, and 24.6°. In some embodiments, Form I of Formula I has an XRPD pattern including two of 2θ reflections (+ / -0.2 degrees 2θ) at 7.0°, 13.9°, and 27.9° and 2θ reflections (+ / -0.2 degrees 2θ) at 12.3°, 17.4°, and 24.6°. In some embodiments, Form I of Formula I has an XRPD pattern including 2θ reflections (+ / -0.2 degrees 2θ) at 7.0°, 12.3°, 13.9°, 17.4°, and 24.6° and 27.9°. In some embodiments, Form I has an XRPD pattern comprising any three 2θ reflections (+ / -0.2 degrees 2θ) selected from 7.0°, 12.3°, 13.9°, 17.4°, 24.6° and 27.9°.

[0099] In some embodiments, Form I has an XRPD pattern comprising one, two, or three of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 7.0°, 12.3°, 13.9°, 17.4°, 24.6°, and 27.9°; and 2θ reflections (+ / -0.2 degrees 2θ) at 21.4°, 23.2°, and 29.2°. In some embodiments, Form I has an XRPD pattern comprising one or two of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 7.0°, 12.3°, 13.9°, 17.4°, 24.6°, and 27.9°; and 2θ reflections (+ / -0.2 degrees 2θ) at 21.4°, 23.2°, and 29.2°. In some embodiments, Form I has an XRPD pattern comprising one of 2θ reflections (+ / -0.2 degrees 2θ) at 7.0°, 12.3°, 13.9°, 17.4°, 24.6°, and 27.9°, and 2θ reflections (+ / -0.2 degrees 2θ) at 21.4°, 23.2°, and 29.2°. In some embodiments, Form I has an XRPD pattern comprising both of 2θ reflections (+ / -0.2 degrees 2θ) at 7.0°, 12.3°, 13.9°, 17.4°, 24.6°, and 27.9°, and 2θ reflections (+ / -0.2 degrees 2θ) at 21.4°, 23.2°, and 29.2°. In some embodiments, Form I of Formula I has an XRPD pattern comprising 2θ reflections (+ / -0.2 degrees 2θ) at 7.0°, 12.3°, 13.9°, 17.4°, 21.4°, 23.2°, 24.6°, 27.9°, and 29.2°. In some embodiments, Form I of Formula I has an XRPD pattern comprising three of the 2θ reflections (+ / -0.2 degrees 2θ) at 7.0°, 12.3°, 13.9°, 17.4°, 21.4°, 23.2°, 24.6°, 27.9°, and 29.2°. In some embodiments, Form I of Formula I has an XRPD pattern comprising at least three of the 2θ reflections (+ / -0.2 degrees 2θ) at 7.0°, 12.3°, 13.9°, 17.4°, 21.4°, 23.2°, 24.6°, 27.9°, and 29.2°. In some embodiments, Form I of Formula I has an XRPD pattern comprising at least four of the 2θ reflections (+ / -0.2 degrees 2θ) at 7.0°, 12.3°, 13.9°, 17.4°, 21.4°, 23.2°, 24.6°, 27.9°, and 29.2°. In some embodiments, Form I has an XRPD pattern comprising at least five of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 7.0°, 12.3°, 13.9°, 17.4°, 21.4°, 23.2°, 24.6°, 27.9°, and 29.2°.

[0100] In some embodiments, Form I of Formula I has an XRPD pattern comprising at least three of the 2θ reflections (+ / -0.2 degrees 2θ) at 7.0°, 12.3°, 13.9°, 17.1°, 17.4°, 21.4°, 23.2°, 24.6°, 27.8°, 27.9°, and 29.2°. In some embodiments, Form I of Formula I has an XRPD pattern comprising at least four of the 2θ reflections (+ / -0.2 degrees 2θ) at 7.0°, 12.3°, 13.9°, 17.1°, 17.4°, 21.4°, 23.2°, 24.6°, 27.8°, 27.9°, and 29.2°. In some embodiments, Form I of Formula I has an XRPD pattern including at least five of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 7.0°, 12.3°, 13.9°, 17.1°, 17.4°, 21.4°, 23.2°, 24.6°, 27.8°, 27.9°, and 29.2°. In some embodiments, Form I of Formula I has an XRPD pattern including 2θ reflections (+ / -0.2 degrees 2θ) at 7.0°, 12.3°, 13.9°, 17.1°, 17.4°, 21.4°, 23.2°, 24.6°, 27.8°, 27.9°, and 29.2°.

[0101] In some implementations, Form I has an XRPD pattern including peaks at the following locations: In some embodiments, Formula I, Form I, is characterized by including a DSC curve of an endothermic transition initiating at approximately 192°C. In some embodiments, Formula I, Form I, is characterized by essentially as follows: Figure 2 The DSC curve shown.

[0102] In some embodiments, Formula I, Form I is non-solventized. In some embodiments, Formula I, Form I is characterized by being substantially as follows: Figure 3 The TGA curve shown.

[0103] In some implementation schemes, Form I is characterized by being essentially as follows: Figure 4 The DVS curve is shown. In some embodiments, Formula I absorbs approximately 0.15% water at 25°C and up to 95% RH.

[0104] The single-crystal data collected for Form I are summarized in Table 1 below, and additionally... Figure 5 As shown in the figure. The crystal system of Formula I is monoclinic, and the space group is P2 1. The unit cell parameters and calculated volume are as follows: a = 8.9146(2) Å,b =8.6717(2) Å, c = 12.7101(3) Å, α = 90°, β = 93.3170(10)°, γ = 90°, V = 980.95(4) Å 3 The molecular weight is 448.40 g mol. -1 ,in Z = 2, the calculated density is 1.518 g cm⁻¹ -3 .

[0105] Table 1. Crystal data and data collection parameters for Formula I, Form I

[0106] Form I Form II In some embodiments, the compound of Formula I is in crystalline form II (Form II of Formula I), wherein the crystal structure exhibits essentially as follows: Figure 6 The X-ray powder diffraction (XRPD) pattern shown.

[0107] In some embodiments, Formula I and Form II have at least two, at least three, at least four, at least five, or at least six elements substantially as shown. Figure 6 The XRPD pattern shown is an XRPD pattern with maximum intensity 2θ angle reflection.

[0108] In some embodiments, Form II of Formula I has an XRPD pattern including 2θ reflections (+ / -0.2 degrees 2θ) at 5.7°, 19.9°, and 26.8°. In some embodiments, Form II of Crystallized Formula I has an XRPD pattern including one, two, or three of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 5.7°, 19.9°, and 26.8° and θ reflections (+ / -0.2 degrees 2θ) at 11.4°, 17.6°, and 28.6°. In some embodiments, Form II of Crystallized Formula I has an XRPD pattern including one or two of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 5.7°, 19.9°, and 26.8° and 2θ reflections (+ / -0.2 degrees 2θ) at 11.4°, 17.6°, and 28.6°. In some embodiments, Crystalline Form I II has an XRPD pattern including one of 2θ reflections (+ / -0.2 degrees 2θ) at 5.7°, 19.9°, and 26.8° and 2θ reflections (+ / -0.2 degrees 2θ) at 11.4°, 17.6°, and 28.6°. In some embodiments, Crystalline Form I II has an XRPD pattern including two of 2θ reflections (+ / -0.2 degrees 2θ) at 5.7°, 19.9°, and 26.8° and 2θ reflections (+ / -0.2 degrees 2θ) at 11.4°, 17.6°, and 28.6°. In some embodiments, Crystalline Form I II has an XRPD pattern including 2θ reflections (+ / -0.2 degrees 2θ) at 5.7°, 11.4°, 17.6°, 19.9°, 26.8°, and 28.6°. In some embodiments, Crystalline Form II has an XRPD pattern comprising any three 2θ reflections (+ / -0.2 degrees 2θ) selected from 5.7°, 11.4°, 17.6°, 19.9°, 26.8° and 28.6°.

[0109] In some embodiments, Crystalline Form I II has an XRPD pattern comprising one, two, or three of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 5.7°, 11.4°, 17.6°, 19.9°, 26.8°, and 28.6°; and 2θ reflections (+ / -0.2 degrees 2θ) at 10.7°, 22.3°, and 25.1°. In some embodiments, Crystalline Form I II has an XRPD pattern comprising one or two of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 5.7°, 11.4°, 17.6°, 19.9°, 26.8°, and 28.6°; and 2θ reflections (+ / -0.2 degrees 2θ) at 10.7°, 22.3°, and 25.1°. In some embodiments, Crystalline Form II has an XRPD pattern comprising one of 2θ reflections (+ / -0.2 degrees 2θ) at 5.7°, 11.4°, 17.6°, 19.9°, 26.8°, and 28.6° and 2θ reflections (+ / -0.2 degrees 2θ) at 10.7°, 22.3°, and 25.1°. In some embodiments, Crystalline Form II has an XRPD pattern comprising two of 2θ reflections (+ / -0.2 degrees 2θ) at 5.7°, 11.4°, 17.6°, 19.9°, 26.8°, and 28.6° and 2θ reflections (+ / -0.2 degrees 2θ) at 10.7°, 22.3°, and 25.1°. In some embodiments, Crystalline Form I II has an XRPD pattern comprising any three 2θ reflections (+ / -0.2 degrees 2θ) selected from 5.7°, 10.7°, 11.4°, 17.6°, 19.9°, 22.3°, 25.1°, 26.8°, and 28.6°. In some embodiments, Crystalline Form I II has an XRPD pattern comprising 2θ reflections (+ / -0.2 degrees 2θ) at 5.7°, 10.7°, 11.4°, 17.6°, 19.9°, 22.3°, 25.1°, 26.8°, and 28.6°.

[0110] In some embodiments, crystalline form II has an XRPD pattern comprising at least three of the following 2θ reflectances (+ / -0.2 degrees 2θ) selected from 5.7°, 10.7°, 11.4°, 17.6°, 19.9°, 22.3°, 25.1°, 26.8°, and 28.6°. In some embodiments, crystalline form II has an XRPD pattern comprising at least four of the following 2θ reflectances (+ / -0.2 degrees 2θ): 5.7°, 10.7°, 11.4°, 17.6°, 19.9°, 22.3°, 25.1°, 26.8°, and 28.6°. In some embodiments, the crystalline form II has an XRPD pattern comprising at least five of the following 2θ reflections (+ / -0.2 degrees 2θ) selected from 5.7°, 10.7°, 11.4°, 17.6°, 19.9°, 22.3°, 25.1°, 26.8°, and 28.6°.

[0111] In some embodiments, crystalline form I II has an XRPD pattern comprising at least three of the following 2θ reflectances (+ / -0.2 degrees 2θ): 5.7°, 10.7°, 11.4°, 11.7°, 17.6°, 19.9°, 22.3°, 25.1°, 26.8°, and 28.6°. In some embodiments, crystalline form I II has an XRPD pattern comprising at least four of the following 2θ reflectances (+ / -0.2 degrees 2θ): 5.7°, 10.7°, 11.4°, 11.7°, 17.6°, 19.9°, 22.3°, 25.1°, 26.8°, and 28.6°. In some embodiments, the crystalline form II has an XRPD pattern comprising at least five of the following 2θ reflections (+ / -0.2 degrees 2θ) selected from 5.7°, 10.7°, 11.4°, 11.7°, 17.6°, 19.9°, 22.3°, 25.1°, 26.8°, and 28.6°.

[0112] In some embodiments, Formula I and Form II have an XRPD pattern including peaks at the following locations: In some embodiments, Formula I, Form II is characterized by including a DSC curve of an endothermic transition initiating at approximately 194°C. In some embodiments, Formula I, Form II is characterized by essentially as follows: Figure 7 The DSC curve shown.

[0113] In some embodiments, Formula I, Form II is non-solventized. In some embodiments, Formula I, Form II is characterized by being substantially as follows: Figure 8 The TGA curve shown.

[0114] Sodium salts of compounds of formula I In some embodiments, the pharmaceutical composition comprises a sodium salt of a compound of formula I, which may be amorphous or crystalline. In some embodiments, the sodium salt of the compound of formula I is crystalline.

[0115] In some embodiments, the crystalline sodium salt of the compound of formula I has essentially the following characteristics: Figure 9 The XRPD features shown are in form I ("sodium salt form I of formula I" or "sodium salt form I of formula I"). Sodium salt form I of formula I can exhibit essentially the following characteristics: Figure 10 The DSC thermogram shown. The sodium salt form I of compound I can exhibit essentially the following... Figure 11 The TGA diagram shown. The sodium salt form I of compound I can exhibit essentially the same characteristics as... Figure 12 The DVS curve shown.

[0116] In some embodiments, sodium salt form I of formula I has at least two, at least three, at least four, at least five, or at least six salts substantially as shown in the figure. Figure 9 The XRPD pattern shown is an XRPD pattern with maximum intensity 2θ angle reflection.

[0117] In some embodiments, the sodium salt form I of Formula I has an XRPD pattern including 2θ reflections (+ / -0.2 degrees 2θ) at 13.1°, 14.8°, and 26.8°. In some embodiments, the sodium salt form I of Formula I has an XRPD pattern including one, two, or three of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 13.1°, 14.8°, and 26.8°; and 2θ reflections (+ / -0.2 degrees 2θ) at 17.8°, 20.7°, and 28.2°. In some embodiments, the sodium salt form I of Formula I has an XRPD pattern including one or two of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 13.1°, 14.8°, and 26.8°; and 2θ reflections (+ / -0.2 degrees 2θ) at 17.8°, 20.7°, and 28.2°. In some embodiments, the sodium salt form I of Formula I has an XRPD pattern including one of 2θ reflections (+ / -0.2 degrees 2θ) at 13.1°, 14.8°, and 26.8° and 2θ reflections (+ / -0.2 degrees 2θ) at 17.8°, 20.7°, and 28.2°. In some embodiments, the sodium salt form I of Formula I has an XRPD pattern including two of 2θ reflections (+ / -0.2 degrees 2θ) at 13.1°, 14.8°, and 26.8° and 2θ reflections (+ / -0.2 degrees 2θ) at 17.8°, 20.7°, and 28.2°. In some embodiments, the sodium salt form I of Formula I has an XRPD pattern including 2θ reflections (+ / -0.2 degrees 2θ) at 13.1°, 14.8°, 17.8°, 20.7°, 26.8°, and 28.2°. In some embodiments, the sodium salt form I of Formula I has an XRPD pattern comprising any three of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 13.1°, 14.8°, 17.8°, 20.7°, 26.8°, and 28.2°.

[0118] In some embodiments, the sodium salt form I of Formula I has an XRPD pattern comprising one, two, or three of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 13.1°, 14.8°, 17.8°, 20.7°, 26.8°, and 28.2°; and 2θ reflections (+ / -0.2 degrees 2θ) at 6.2°, 21.2°, and 23.3°. In some embodiments, the sodium salt form I of Formula I has an XRPD pattern comprising one or two of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 13.1°, 14.8°, 17.8°, 20.7°, 26.8°, and 28.2°; and 2θ reflections (+ / -0.2 degrees 2θ) at 6.2°, 21.2°, and 23.3°. In some embodiments, the sodium salt form I of Formula I has an XRPD pattern comprising one of 2θ reflections (+ / -0.2 degrees 2θ) at 13.1°, 14.8°, 17.8°, 20.7°, 26.8°, and 28.2° and 2θ reflections (+ / -0.2 degrees 2θ) at 6.2°, 21.2°, and 23.3°. In some embodiments, the sodium salt form I of Formula I has an XRPD pattern comprising both of 2θ reflections (+ / -0.2 degrees 2θ) at 13.1°, 14.8°, 17.8°, 20.7°, 26.8°, and 28.2° and 2θ reflections (+ / -0.2 degrees 2θ) at 6.2°, 21.2°, and 23.3°. In some embodiments, the sodium salt form I of Formula I has an XRPD pattern including 2θ reflections (+ / -0.2 degrees 2θ) at 6.2°, 13.1°, 14.8°, 17.8°, 20.7°, 21.2°, 23.3°, 26.8°, and 28.2°. In some embodiments, the sodium salt form I of Formula I has an XRPD pattern including any three of the 2θ reflections (+ / -0.2 degrees 2θ) at 6.2°, 13.1°, 14.8°, 17.8°, 20.7°, 21.2°, 23.3°, 26.8°, and 28.2°.

[0119] In some embodiments, the sodium salt form I of Formula I has an XRPD pattern comprising at least three of the 2θ reflections (+ / -0.2 degrees 2θ) at 6.2°, 13.1°, 14.8°, 17.8°, 20.7°, 21.2°, 23.3°, 26.8°, and 28.2°. In some embodiments, the sodium salt form I of Formula I has an XRPD pattern comprising at least four of the 2θ reflections (+ / -0.2 degrees 2θ) at 6.2°, 13.1°, 14.8°, 17.8°, 20.7°, 21.2°, 23.3°, 26.8°, and 28.2°. In some embodiments, the sodium salt form I of Formula I has an XRPD pattern comprising at least five of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 6.2°, 13.1°, 14.8°, 17.8°, 20.7°, 21.2°, 23.3°, 26.8°, and 28.2°.

[0120] In some embodiments, the sodium salt form I of Formula I has an XRPD pattern comprising at least three of the 2θ reflections (+ / -0.2 degrees 2θ) at 6.2°, 12.4°, 13.1°, 14.8°, 16.6°, 17.8°, 20.7°, 21.2°, 21.9°, 23.3°, 25.2°, 26.8°, and 28.2°. In some embodiments, the sodium salt form I of Formula I has an XRPD pattern comprising at least four of the 2θ reflections (+ / -0.2 degrees 2θ) at 6.2°, 12.4°, 13.1°, 14.8°, 16.6°, 17.8°, 20.7°, 21.2°, 21.9°, 23.3°, 25.2°, 26.8°, and 28.2°. In some embodiments, the sodium salt form I of Formula I has an XRPD pattern comprising at least five of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 6.2°, 12.4°, 13.1°, 14.8°, 16.6°, 17.8°, 20.7°, 21.2°, 21.9°, 23.3°, 25.2°, 26.8°, and 28.2°.

[0121] In some embodiments, the sodium salt form I of formula I has an XRPD pattern including peaks at the following locations: In some implementations, sodium salt form I of formula I is characterized by essentially as follows: Figure 10 The DSC thermogram shown.

[0122] In some embodiments, sodium salt form I of formula I is characterized by having one or more of the following DSC thermograms: (i) an endothermic transition at 25°C, (ii) an endothermic transition at 81°C, (iii) an endothermic transition at 124°C, and (iv) an exothermic transition at 151°C. In some embodiments, sodium salt form I of formula I is characterized by having the following DSC thermograms: (i) an endothermic transition at 25°C, (ii) an endothermic transition at 81°C, (iii) an endothermic transition at 124°C, and (iv) an exothermic transition at 151°C.

[0123] In some implementations, sodium salt form I of formula I is characterized by essentially as follows: Figure 11 The TGA curve shown.

[0124] In some implementations, sodium salt form I of formula I is characterized by essentially as follows: Figure 12 The DVS curve shown.

[0125] In some implementations, the sodium salt form of Formula I absorbs approximately 4% water at 25°C and up to 95% RH.

[0126] In some embodiments, the crystalline sodium salt of the compound of formula I has essentially the following characteristics: Figure 13 The XRPD features shown are in form II (“sodium salt form II of formula I” or “sodium salt form II of formula I”). Sodium salt form II of formula I can exhibit essentially the following characteristics: Figure 14 The DSC thermogram shown. The sodium salt form II of compound I can exhibit essentially the same characteristics. Figure 15 The TGA diagram shown.

[0127] In some embodiments, the sodium salt form II of Formula I has an XRPD pattern comprising 2θ reflections (+ / -0.2 degrees 2θ) at 5.3°, 7.1°, and 13.4°. In some embodiments, the sodium salt form II of Formula I has an XRPD pattern comprising 2θ reflections (+ / -0.2 degrees 2θ) at 5.3°, 7.1°, 10.7°, and 13.4°.

[0128] In some embodiments, the sodium salt form II of formula I has an XRPD pattern including peaks at the following locations: In some embodiments, sodium salt form II of formula I is characterized by essentially the following: Figure 14 The DSC thermogram shown.

[0129] In some embodiments, sodium salt form II of formula I is characterized by having a DSC thermogram of one or both of the following: (i) an endothermic transition at about 32°C and (ii) an endothermic transition at about 122°C. In some embodiments, sodium salt form I of formula I is characterized by having a DSC thermogram of the following: (i) an endothermic transition at about 32°C and (ii) an endothermic transition at about 122°C.

[0130] In some embodiments, sodium salt form II of formula I is characterized by essentially the following: Figure 15 The TGA curve shown.

[0131] In some implementations, sodium salt of formula I, form II, begins to experience mass loss at approximately ambient temperature.

[0132] In some embodiments, the crystalline sodium salt of the compound of formula I is form III ("sodium salt form III of formula I" or "sodium salt form III of formula I"). In some embodiments, the sodium salt form III of formula I has essentially the following characteristics: Figure 16 The XRPD spectrum shown.

[0133] In some embodiments, sodium salt form III of formula I has at least two, at least three, at least four, at least five, or at least six salts substantially as shown in the figure. Figure 16 The XRPD pattern shown is an XRPD pattern with maximum intensity 2θ angle reflection.

[0134] In some embodiments, the sodium salt form III of Formula I has an XRPD pattern including 2θ reflections (+ / -0.2 degrees 2θ) at 7.9°, 8.8°, and 23.1°. In some embodiments, the sodium salt form III of Formula I has an XRPD pattern including one, two, or three of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 7.9°, 8.8°, and 23.1° and 2θ reflections (+ / -0.2 degrees 2θ) at 26.2°, 26.6°, and 30.3°. In some embodiments, the sodium salt form III of Formula I has an XRPD pattern including one or two of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 7.9°, 8.8°, and 23.1° and 2θ reflections (+ / -0.2 degrees 2θ) at 26.2°, 26.6°, and 30.3°. In some embodiments, the sodium salt form III of Formula I has an XRPD pattern including one of 2θ reflections (+ / -0.2 degrees 2θ) at 7.9°, 8.8°, and 23.1° and 2θ reflections (+ / -0.2 degrees 2θ) at 26.2°, 26.6°, and 30.3°. In some embodiments, the sodium salt form III of Formula I has an XRPD pattern including two of 2θ reflections (+ / -0.2 degrees 2θ) at 7.9°, 8.8°, and 23.1° and 2θ reflections (+ / -0.2 degrees 2θ) at 26.2°, 26.6°, and 30.3°. In some embodiments, the sodium salt form III of Formula I has an XRPD pattern including 2θ reflections (+ / -0.2 degrees 2θ) at 7.9°, 8.8°, 23.1°, 26.2°, 26.6°, and 30.3°. In some embodiments, the sodium salt form I of Formula I has an XRPD pattern comprising any three of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 7.9°, 8.8°, 23.1°, 26.2°, 26.6°, and 30.3°.

[0135] In some embodiments, the sodium salt form III of Formula I has an XRPD pattern comprising at least three of the 2θ reflections (+ / -0.2 degrees 2θ) at 7.9°, 8.8°, 23.1°, 26.2°, 26.6°, and 30.3°. In some embodiments, the sodium salt form III of Formula I has an XRPD pattern comprising at least four of the 2θ reflections (+ / -0.2 degrees 2θ) at 7.9°, 8.8°, 23.1°, 26.2°, 26.6°, and 30.3°. In some embodiments, the sodium salt form III of Formula I has an XRPD pattern comprising at least five of the 2θ reflections (+ / -0.2 degrees 2θ) at 7.9°, 8.8°, 23.1°, 26.2°, 26.6°, and 30.3°.

[0136] In some embodiments, the sodium salt form III of formula I has an XRPD pattern including peaks at the following locations: In some embodiments, the crystalline sodium salt of the compound of formula I is form IV ("sodium salt form IV of formula I" or "sodium salt form IV of formula I"). In some embodiments, the sodium salt form IV of formula I has essentially the following characteristics: Figure 17 The XRPD spectrum shown.

[0137] In some embodiments, sodium salt form IV of formula I has at least two, at least three, at least four, at least five, or at least six salts substantially as shown in the figure. Figure 17 The XRPD pattern shown is an XRPD pattern with maximum intensity 2θ angle reflection.

[0138] In some embodiments, the sodium salt form IV of Formula I has an XRPD pattern including 2θ reflections (+ / -0.2 degrees 2θ) at 5.3°, 6.4°, and 12.8°. In some embodiments, the sodium salt form IV of Formula I has an XRPD pattern including one, two, or three of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 5.3°, 6.4°, and 12.8° and 2θ reflections (+ / -0.2 degrees 2θ) at 14.1°, 24.5°, and 26.4°. In some embodiments, the sodium salt form IV of Formula I has an XRPD pattern including one or two of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 5.3°, 6.4°, and 12.8° and 2θ reflections (+ / -0.2 degrees 2θ) at 14.1°, 24.5°, and 26.4°. In some embodiments, the sodium salt form IV of Formula I has an XRPD pattern including one of 2θ reflections (+ / -0.2 degrees 2θ) at 5.3°, 6.4°, and 12.8° and 2θ reflections (+ / -0.2 degrees 2θ) at 14.1°, 24.5°, and 26.4°. In some embodiments, the sodium salt form IV of Formula I has an XRPD pattern including two of 2θ reflections (+ / -0.2 degrees 2θ) at 5.3°, 6.4°, and 12.8° and 2θ reflections (+ / -0.2 degrees 2θ) at 14.1°, 24.5°, and 26.4°. In some embodiments, the sodium salt form IV of Formula I has an XRPD pattern including 2θ reflections (+ / -0.2 degrees 2θ) at 5.3°, 6.4°, 12.8°, 14.1°, 24.5°, and 26.4°. In some embodiments, the sodium salt form IV of Formula I has an XRPD pattern comprising any three of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 5.3°, 6.4°, 12.8°, 14.1°, 24.5°, and 26.4°.

[0139] In some embodiments, the sodium salt form IV of Formula I has an XRPD pattern comprising one, two, or three of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 5.3°, 6.4°, 12.8°, 14.1°, 24.5°, and 26.4°; and 2θ reflections (+ / -0.2 degrees 2θ) at 8.4°, 15.8°, and 20.7°. In some embodiments, the sodium salt form IV of Formula I has an XRPD pattern comprising one or two of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 5.3°, 6.4°, 12.8°, 14.1°, 24.5°, and 26.4°; and 2θ reflections (+ / -0.2 degrees 2θ) at 8.4°, 15.8°, and 20.7°. In some embodiments, the sodium salt form IV of Formula I has an XRPD pattern comprising one of 2θ reflections (+ / -0.2 degrees 2θ) at 5.3°, 6.4°, 12.8°, 14.1°, 24.5°, and 26.4° and 2θ reflections (+ / -0.2 degrees 2θ) at 8.4°, 15.8°, and 20.7°. In some embodiments, the sodium salt form IV of Formula I has an XRPD pattern comprising both of 2θ reflections (+ / -0.2 degrees 2θ) at 5.3°, 6.4°, 12.8°, 14.1°, 24.5°, and 26.4° and 2θ reflections (+ / -0.2 degrees 2θ) at 8.4°, 15.8°, and 20.7°. In some embodiments, the sodium salt form IV of Formula I has an XRPD pattern including 2θ reflections (+ / -0.2 degrees 2θ) at 5.3°, 6.4°, 8.4°, 12.8°, 14.1°, 15.8°, 20.7°, 24.5°, and 26.4°. In some embodiments, the sodium salt form IV of Formula I has an XRPD pattern including any three of the 2θ reflections (+ / -0.2 degrees 2θ) at 5.3°, 6.4°, 8.4°, 12.8°, 14.1°, 15.8°, 20.7°, 24.5°, and 26.4°.

[0140] In some embodiments, the sodium salt form IV of Formula I has an XRPD pattern comprising at least three of the 2θ reflections (+ / -0.2 degrees 2θ) at 5.3°, 6.4°, 8.4°, 12.8°, 14.1°, 15.8°, 20.7°, 24.5°, and 26.4°. In some embodiments, the sodium salt form IV of Formula I has an XRPD pattern comprising at least four of the 2θ reflections (+ / -0.2 degrees 2θ) at 5.3°, 6.4°, 8.4°, 12.8°, 14.1°, 15.8°, 20.7°, 24.5°, and 26.4°. In some embodiments, the sodium salt form IV of Formula I has an XRPD pattern comprising at least five of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 5.3°, 6.4°, 8.4°, 12.8°, 14.1°, 15.8°, 20.7°, 24.5°, and 26.4°.

[0141] In some embodiments, the sodium salt form IV of Formula I has an XRPD pattern comprising at least three of the 2θ reflections (+ / -0.2 degrees 2θ) at 5.3°, 6.4°, 8.4°, 12.8°, 14.1°, 15.8°, 20.7°, 21.7°, 22.8°, 23.2°, 24.5°, and 26.4°. In some embodiments, the sodium salt form IV of Formula I has an XRPD pattern comprising at least four of the 2θ reflections (+ / -0.2 degrees 2θ) at 5.3°, 6.4°, 8.4°, 12.8°, 14.1°, 15.8°, 20.7°, 21.7°, 22.8°, 23.2°, 24.5°, and 26.4°. In some embodiments, the sodium salt form IV of Formula I has an XRPD pattern comprising at least five of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 5.3°, 6.4°, 8.4°, 12.8°, 14.1°, 15.8°, 20.7°, 21.7°, 22.8°, 23.2°, 24.5°, and 26.4°.

[0142] In some embodiments, the sodium salt form IV of formula I has an XRPD pattern including peaks at the following locations: Potassium salts of compounds of formula I In some embodiments, the composition comprises a potassium salt of a compound of formula I, which may be amorphous or crystalline. In some embodiments, the potassium salt of the compound of formula I is crystalline.

[0143] In some embodiments, the crystalline potassium salt of the compound of formula I is form I ("potassium salt form I of formula I" or "potassium salt form I of formula I"). In some embodiments, potassium salt form I of formula I has essentially the following characteristics: Figure 18 The XRPD spectrum shown. Formula I, potassium salt form I, can exhibit essentially the same characteristics as... Figure 19 The DSC thermogram shown. Potassium salt form I of formula I can exhibit essentially the following... Figure 20 The TGA diagram shown. Formula I, potassium salt form I, can exhibit essentially the same characteristics as... Figure 21 The DVS curve shown.

[0144] In some embodiments, the potassium salt form of Formula I has at least two, at least three, at least four, at least five, or at least six [symbols] substantially as shown in the diagram. Figure 18 The XRPD pattern shown is an XRPD pattern with maximum intensity 2θ angle reflection.

[0145] In some embodiments, the potassium salt form I of Formula I has an XRPD pattern including 2θ reflections (+ / -0.2 degrees 2θ) at 7.1°, 20.1°, and 25.8°. In some embodiments, the potassium salt form I of Formula I has an XRPD pattern including one, two, or three of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 7.1°, 20.1°, and 25.8° and 2θ reflections (+ / -0.2 degrees 2θ) at 6.2°, 13.0°, and 19.2°. In some embodiments, the potassium salt form I of Formula I has an XRPD pattern including one or two of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 7.1°, 20.1°, and 25.8° and 2θ reflections (+ / -0.2 degrees 2θ) at 6.2°, 13.0°, and 19.2°. In some embodiments, the potassium salt form I of Formula I has an XRPD pattern including one of 2θ reflections (+ / -0.2 degrees 2θ) at 7.1°, 20.1°, and 25.8° and 2θ reflections (+ / -0.2 degrees 2θ) at 6.2°, 13.0°, and 19.2°. In some embodiments, the potassium salt form I of Formula I has an XRPD pattern including two of 2θ reflections (+ / -0.2 degrees 2θ) at 7.1°, 20.1°, and 25.8° and 2θ reflections (+ / -0.2 degrees 2θ) at 6.2°, 13.0°, and 19.2°. In some embodiments, the potassium salt form I of Formula I has an XRPD pattern including 2θ reflections (+ / -0.2 degrees 2θ) at 6.2°, 7.1°, 13.0°, 19.2°, 20.1°, and 25.8°. In some embodiments, the potassium salt form I of Formula I has an XRPD pattern comprising any three of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 6.2°, 7.1°, 13.0°, 19.2°, 20.1°, and 25.8°.

[0146] In some embodiments, the potassium salt form I of Formula I has an XRPD pattern comprising one, two, or three of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 6.2°, 7.1°, 13.0°, 19.2°, 20.1°, and 25.8°; and 2θ reflections (+ / -0.2 degrees 2θ) at 14.2°, 15.5°, and 22.9°. In some embodiments, the potassium salt form I of Formula I has an XRPD pattern comprising one or two of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 6.2°, 7.1°, 13.0°, 19.2°, 20.1°, and 25.8°; and 2θ reflections (+ / -0.2 degrees 2θ) at 14.2°, 15.5°, and 22.9°. In some embodiments, the potassium salt form I of Formula I has an XRPD pattern comprising one of 2θ reflections (+ / -0.2 degrees 2θ) at 6.2°, 7.1°, 13.0°, 19.2°, 20.1°, and 25.8° and 2θ reflections (+ / -0.2 degrees 2θ) at 14.2°, 15.5°, and 22.9°. In some embodiments, the potassium salt form I of Formula I has an XRPD pattern comprising both of 2θ reflections (+ / -0.2 degrees 2θ) at 6.2°, 7.1°, 13.0°, 19.2°, 20.1°, and 25.8° and 2θ reflections (+ / -0.2 degrees 2θ) at 14.2°, 15.5°, and 22.9°. In some embodiments, the potassium salt form I of Formula I has an XRPD pattern including 2θ reflections (+ / -0.2 degrees 2θ) at 6.2°, 7.1°, 13.0°, 14.2°, 15.5°, 19.2°, 20.1°, 22.9°, and 25.8°. In some embodiments, the potassium salt form I of Formula I has an XRPD pattern including any three of the 2θ reflections (+ / -0.2 degrees 2θ) at 6.2°, 7.1°, 13.0°, 14.2°, 15.5°, 19.2°, 20.1°, 22.9°, and 25.8°.

[0147] In some embodiments, the potassium salt form I of Formula I has an XRPD pattern comprising at least three of the 2θ reflections (+ / -0.2 degrees 2θ) at 6.2°, 7.1°, 13.0°, 14.2°, 15.5°, 16.4°, 18.1°, 19.2°, 20.1°, 21.9°, 22.9°, and 25.8°. In some embodiments, the potassium salt form I of Formula I has an XRPD pattern comprising at least four of the 2θ reflections (+ / -0.2 degrees 2θ) at 6.2°, 7.1°, 13.0°, 14.2°, 15.5°, 16.4°, 18.1°, 19.2°, 20.1°, 21.9°, 22.9°, and 25.8°. In some embodiments, the potassium salt form I of Formula I has an XRPD pattern comprising at least five of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 6.2°, 7.1°, 13.0°, 14.2°, 15.5°, 16.4°, 18.1°, 19.2°, 20.1°, 21.9°, 22.9°, and 25.8°.

[0148] In some embodiments, the potassium salt form I of formula I has an XRPD pattern including peaks at the following locations: In some implementations, the potassium salt form of formula I is characterized by essentially the following: Figure 19 The DSC thermogram shown.

[0149] In some embodiments, the potassium salt form I of Formula I is characterized by having a DSC thermogram of one or both of the following: (i) an endothermic transition at about 17°C and (ii) an endothermic transition at about 230°C. In some embodiments, the potassium salt form I of Formula I is characterized by having a DSC thermogram of the following: (i) an endothermic transition at about 17°C and (ii) an endothermic transition at about 230°C.

[0150] In some implementations, the potassium salt form of formula I is characterized by essentially the following: Figure 20 The TGA curve is shown. In some embodiments, the potassium salt form I of Formula I experiences mass loss in multiple stages, one of which begins at approximately ambient temperature, and the next stage begins at approximately 100°C.

[0151] In some implementations, the potassium salt form of formula I is characterized by essentially the following: Figure 21 The DVS curve is shown. In some embodiments, the potassium salt form I of formula I absorbs more than about 18% of water at 25°C and up to 95% RH.

[0152] The single-crystal data collected for potassium salt form I of formula I are summarized in Table 2 below, and additionally... Figure 22As shown in the diagram. The crystal system is trigonal, and the space group is [space group number missing]. P3 2 21 The unit cell parameters and calculated volume are as follows: a = 28.6496(4) Å, b =28.6496(4) Å, c = 6.89340(10) Å, α = 90°, β =90°, γ = 120°, V = 4900.06(15) Å 3 The molecular weight is 494.49 g mol. -1 ,in Z = 6, the calculated density is 1.005 g cm³. -3 .

[0153] Table 2. Crystal data and data collection parameters for potassium salt of formula I, form I.

[0154] In some embodiments, the crystalline potassium salt of the compound of formula I is form II ("potassium salt form II of formula I" or "potassium salt form II of formula I"). In some embodiments, potassium salt form II of formula I has essentially the following characteristics: Figure 23 The XRPD spectrum is shown. Compound II, the potassium salt of Formula I, can exhibit essentially the same characteristics. Figure 24 The TGA curve shown.

[0155] In some embodiments, the potassium salt form II of formula I has at least two, at least three, at least four, at least five, or at least six salts substantially as shown in the figure. Figure 23 The XRPD pattern shown is an XRPD pattern with maximum intensity 2θ angle reflection.

[0156] In some embodiments, the potassium salt form II of Formula I has an XRPD pattern including 2θ reflections (+ / -0.2 degrees 2θ) at 6.8°, 30.7°, and 31.4°. In some embodiments, the potassium salt form II of Formula I has an XRPD pattern including one, two, or three of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 6.8°, 30.7°, and 31.4° and 2θ reflections (+ / -0.2 degrees 2θ) at 12.5°, 28.0°, and 32.6°. In some embodiments, the potassium salt form II of Formula I has an XRPD pattern including one or two of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 6.8°, 30.7°, and 31.4° and 2θ reflections (+ / -0.2 degrees 2θ) at 12.5°, 28.0°, and 32.6°. In some embodiments, the potassium salt form II of Formula I has an XRPD pattern including one of 2θ reflections (+ / -0.2 degrees 2θ) at 6.8°, 30.7°, and 31.4° and 2θ angular reflections (+ / -0.2 degrees 2θ) at 12.5°, 28.0°, and 32.6°. In some embodiments, the potassium salt form II of Formula I has an XRPD pattern including both of 2θ reflections (+ / -0.2 degrees 2θ) at 6.8°, 30.7°, and 31.4° and 2θ angular reflections (+ / -0.2 degrees 2θ) at 12.5°, 28.0°, and 32.6°. In some embodiments, the potassium salt form II of Formula I has an XRPD pattern including 2θ reflections (+ / -0.2 degrees 2θ) at 6.8°, 12.5°, 28.0°, 30.7°, 31.4°, and 32.6°. In some embodiments, the potassium salt form II of Formula I has an XRPD pattern comprising any three of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 6.8°, 12.5°, 28.0°, 30.7°, 31.4°, and 32.6°.

[0157] In some embodiments, the potassium salt form II of Formula I has an XRPD pattern comprising one, two, or three of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 6.8°, 12.5°, 28.0°, 30.7°, 31.4°, and 32.6°; and 2θ reflections (+ / -0.2 degrees 2θ) at 14.3°, 24.2°, and 25.7°. In some embodiments, the potassium salt form II of Formula I has an XRPD pattern comprising one or two of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 6.8°, 12.5°, 28.0°, 30.7°, 31.4°, and 32.6°; and 2θ reflections (+ / -0.2 degrees 2θ) at 14.3°, 24.2°, and 25.7°. In some embodiments, the potassium salt form II of Formula I has an XRPD pattern comprising one of 2θ reflections (+ / -0.2 degrees 2θ) at 6.8°, 12.5°, 28.0°, 30.7°, 31.4°, and 32.6° and 2θ reflections (+ / -0.2 degrees 2θ) at 14.3°, 24.2°, and 25.7°. In some embodiments, the potassium salt form II of Formula I has an XRPD pattern comprising two of 2θ reflections (+ / -0.2 degrees 2θ) at 6.8°, 12.5°, 28.0°, 30.7°, 31.4°, and 32.6° and 2θ reflections (+ / -0.2 degrees 2θ) at 14.3°, 24.2°, and 25.7°. In some embodiments, the potassium salt form II of Formula I has an XRPD pattern including 2θ reflections (+ / -0.2 degrees 2θ) at 6.8°, 12.5°, 14.3°, 24.2°, 25.7°, 28.0°, 30.7°, 31.4°, and 32.6°. In some embodiments, the potassium salt form II of Formula I has an XRPD pattern including any three of the 2θ reflections (+ / -0.2 degrees 2θ) at 6.8°, 12.5°, 14.3°, 24.2°, 25.7°, 28.0°, 30.7°, 31.4°, and 32.6°.

[0158] In some embodiments, the potassium salt form II of Formula I has an XRPD pattern comprising at least three of the 2θ reflections (+ / -0.2 degrees 2θ) at 6.8°, 12.5°, 14.3°, 24.2°, 25.7°, 28.0°, 29.7°, 30.7°, 31.4°, 32.3°, and 32.6°. In some embodiments, the potassium salt form II of Formula I has an XRPD pattern comprising at least four of the 2θ reflections (+ / -0.2 degrees 2θ) at 6.8°, 12.5°, 14.3°, 24.2°, 25.7°, 28.0°, 29.7°, 30.7°, 31.4°, 32.3°, and 32.6°. In some embodiments, the potassium salt form II of Formula I has an XRPD pattern comprising at least five of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 6.8°, 12.5°, 14.3°, 24.2°, 25.7°, 28.0°, 29.7°, 30.7°, 31.4°, 32.3°, and 32.6°.

[0159] In some embodiments, the potassium salt form II of formula I has an XRPD pattern including peaks at the following locations: In some implementations, the potassium salt form II of formula I is characterized by essentially the following: Figure 24 The TGA curve is shown. In some embodiments, the mass loss of potassium salt form II of Formula I occurs in multiple stages, one of which begins at approximately ambient temperature, and the next stage begins at approximately 100°C.

[0160] In some embodiments, the crystalline potassium salt of the compound of formula I is form III ("potassium salt form III of formula I" or "potassium salt form III of formula I"). In some embodiments, potassium salt form III of formula I has essentially the following characteristics: Figure 25 The XRPD spectrum shown.

[0161] In some embodiments, the potassium salt form III of formula I has at least two, at least three, at least four, at least five, or at least six salts substantially as shown in the figure. Figure 25 The XRPD pattern shown is an XRPD pattern with maximum intensity 2θ angle reflection.

[0162] In some embodiments, the potassium salt form III of Formula I has an XRPD pattern including 2θ reflections (+ / -0.2 degrees 2θ) at 5.2°, 13.2°, and 13.7°. In some embodiments, the potassium salt form III of Formula I has an XRPD pattern including one, two, or three of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 5.2°, 13.2°, and 13.7° and 2θ reflections (+ / -0.2 degrees 2θ) at 11.2°, 12.4°, and 18.7°. In some embodiments, the potassium salt form III of Formula I has an XRPD pattern including one or two of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 5.2°, 13.2°, and 13.7° and 2θ reflections (+ / -0.2 degrees 2θ) at 11.2°, 12.4°, and 18.7°. In some embodiments, the potassium salt form III of Formula I has an XRPD pattern including one of 2θ reflections (+ / -0.2 degrees 2θ) at 5.2°, 13.2°, and 13.7° and 2θ angular reflections (+ / -0.2 degrees 2θ) at 11.2°, 12.4°, and 18.7°. In some embodiments, the potassium salt form III of Formula I has an XRPD pattern including both of 2θ reflections (+ / -0.2 degrees 2θ) at 5.2°, 13.2°, and 13.7° and 2θ angular reflections (+ / -0.2 degrees 2θ) at 11.2°, 12.4°, and 18.7°. In some embodiments, the potassium salt form III of Formula I has an XRPD pattern including 2θ reflections (+ / -0.2 degrees 2θ) at 5.2°, 11.2°, 12.4°, 13.2°, 13.7°, and 18.7°. In some embodiments, the potassium salt form III of Formula I has an XRPD pattern comprising any three of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 5.2°, 11.2°, 12.4°, 13.2°, 13.7°, and 18.7°.

[0163] In some embodiments, the potassium salt form III of Formula I has an XRPD pattern including one or both of 2θ reflections (+ / -0.2 degrees 2θ) at 5.2°, 11.2°, 12.4°, 13.2°, 13.7°, and 18.7° and 2θ reflections (+ / -0.2 degrees 2θ) at 6.5° and 15.0°. In some embodiments, the potassium salt form III of Formula I has an XRPD pattern including 2θ reflections (+ / -0.2 degrees 2θ) at 5.2°, 6.5°, 11.2°, 12.4°, 13.2°, 13.7°, 15.0°, and 18.7°. In some embodiments, the potassium salt form III of Formula I has an XRPD pattern including any three of the 2θ reflections (+ / -0.2 degrees 2θ) at 5.2°, 6.5°, 11.2°, 12.4°, 13.2°, 13.7°, 15.0°, and 18.7°.

[0164] In some embodiments, the potassium salt form III of Formula I has an XRPD pattern comprising at least three of the 2θ reflections (+ / -0.2 degrees 2θ) at 5.2°, 6.5°, 11.2°, 12.4°, 13.2°, 13.7°, 15.0°, and 18.7°. In some embodiments, the potassium salt form III of Formula I has an XRPD pattern comprising at least four of the 2θ reflections (+ / -0.2 degrees 2θ) at 5.2°, 6.5°, 11.2°, 12.4°, 13.2°, 13.7°, 15.0°, and 18.7°. In some embodiments, the potassium salt form III of Formula I has an XRPD pattern comprising at least five of the 2θ reflections (+ / -0.2 degrees 2θ) at 5.2°, 6.5°, 11.2°, 12.4°, 13.2°, 13.7°, 15.0°, and 18.7°.

[0165] In some embodiments, the potassium salt form III of formula I has an XRPD pattern including peaks at the following locations: diethylamine salt of compound I In some embodiments, the composition comprises a diethylamine salt of a compound of formula I, which may be amorphous or crystalline. In some embodiments, the diethylamine salt of the compound of formula I is crystalline.

[0166] In some embodiments, the crystalline diethylamine salt of the compound of formula I has essentially the following characteristics: Figure 26 The XRPD spectrum is shown. The crystalline diethylamine salt of the compound of formula I can exhibit essentially the following characteristics. Figure 27 The DSC thermogram shown. The crystalline diethylamine salt of the compound of formula I can exhibit essentially the following... Figure 28 The TGA diagram shown. The crystalline diethylamine salt of the compound of formula I can exhibit essentially the following... Figure 29 The DVS curve shown.

[0167] In some embodiments, the crystalline diethylamine salt of the compound of formula I has at least two, at least three, at least four, at least five, or at least six [symbols] substantially as shown in the figure. Figure 26 The XRPD pattern shown is an XRPD pattern with maximum intensity 2θ angle reflection.

[0168] In some embodiments, the crystalline diethylamine salt of the compound of Formula I has an XRPD pattern including 2θ reflections (+ / -0.2 degrees 2θ) at 9.7°, 19.5°, and 20.5°. In some embodiments, the crystalline diethylamine salt of the compound of Formula I has an XRPD pattern including one, two, or three of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 9.7°, 19.5°, and 20.5° and 2θ reflections (+ / -0.2 degrees 2θ) at 21.9°, 26.5°, and 27.2°. In some embodiments, the crystalline diethylamine salt of the compound of Formula I has an XRPD pattern including one or two of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 9.7°, 19.5°, and 20.5° and 2θ reflections (+ / -0.2 degrees 2θ) at 21.9°, 26.5°, and 27.2°. In some embodiments, the crystalline diethylamine salt of the compound of Formula I has an XRPD pattern comprising one of 2θ reflections (+ / -0.2 degrees 2θ) at 9.7°, 19.5°, and 20.5° and 2θ reflections (+ / -0.2 degrees 2θ) at 21.9°, 26.5°, and 27.2°. In some embodiments, the crystalline diethylamine salt of the compound of Formula I has an XRPD pattern comprising both of 2θ reflections (+ / -0.2 degrees 2θ) at 9.7°, 19.5°, and 20.5° and 2θ reflections (+ / -0.2 degrees 2θ) at 21.9°, 26.5°, and 27.2°. In some embodiments, the crystalline diethylamine salt of the compound of Formula I has an XRPD pattern comprising 2θ reflections (+ / -0.2 degrees 2θ) at 9.7°, 19.5°, 20.5°, 21.9°, 26.5°, and 27.2°. In some embodiments, the crystalline diethylamine salt of the compound of Formula I has an XRPD pattern comprising any three of the 2θ reflections (+ / -0.2 degrees 2θ) at 9.7°, 19.5°, 20.5°, 21.9°, 26.5°, and 27.2°.

[0169] In some embodiments, the crystalline diethylamine salt of the compound of Formula I has an XRPD pattern comprising one, two, or three of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 9.7°, 19.5°, 20.5°, 21.9°, 26.5°, and 27.2°, and 2θ reflections (+ / -0.2 degrees 2θ) at 6.2°, 10.7°, and 17.1°. In some embodiments, the crystalline diethylamine salt of the compound of Formula I has an XRPD pattern comprising one or two of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 9.7°, 19.5°, 20.5°, 21.9°, 26.5°, and 27.2°, and 2θ reflections (+ / -0.2 degrees 2θ) at 6.2°, 10.7°, and 17.1°. In some embodiments, the crystalline diethylamine salt of the compound of Formula I has an XRPD pattern comprising one of 2θ reflections (+ / -0.2 degrees 2θ) at 9.7°, 19.5°, 20.5°, 21.9°, 26.5°, and 27.2° and 2θ angular reflections (+ / -0.2 degrees 2θ) at 6.2°, 10.7°, and 17.1°. In some embodiments, the crystalline diethylamine salt of the compound of Formula I has an XRPD pattern comprising both of 2θ reflections (+ / -0.2 degrees 2θ) at 9.7°, 19.5°, 20.5°, 21.9°, 26.5°, and 27.2° and 2θ angular reflections (+ / -0.2 degrees 2θ) at 6.2°, 10.7°, and 17.1°. In some embodiments, the crystalline diethylamine salt of the compound of Formula I has an XRPD pattern comprising 2θ reflections (+ / -0.2 degrees 2θ) at 6.2°, 9.7°, 10.7°, 17.1°, 19.5°, 20.5°, 21.9°, 26.5°, and 27.2°. In some embodiments, the crystalline diethylamine salt of the compound of Formula I has an XRPD pattern comprising any three of the 2θ reflections (+ / -0.2 degrees 2θ) at 6.2°, 9.7°, 10.7°, 17.1°, 19.5°, 20.5°, 21.9°, 26.5°, and 27.2°.

[0170] In some embodiments, the crystalline diethylamine salt of the compound of Formula I has an XRPD pattern comprising at least three of the 2θ reflections (+ / -0.2 degrees 2θ) at 6.2°, 9.0°, 9.7°, 10.7°, 17.1°, 17.8°, 18.6°, 19.5°, 20.5°, 21.5°, 21.9°, 26.5°, 27.2°, and 30.7°. In some embodiments, the crystalline diethylamine salt of the compound of Formula I has an XRPD pattern comprising at least four of the 2θ reflections (+ / -0.2 degrees 2θ) at 6.2°, 9.0°, 9.7°, 10.7°, 17.1°, 17.8°, 18.6°, 19.5°, 20.5°, 21.5°, 21.9°, 26.5°, 27.2°, and 30.7°. In some embodiments, the crystalline diethylamine salt of the compound of formula I has an XRPD pattern comprising at least five of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 6.2°, 9.0°, 9.7°, 10.7°, 17.1°, 17.8°, 18.6°, 19.5°, 20.5°, 21.5°, 21.9°, 26.5°, 27.2°, and 30.7°.

[0171] In some embodiments, the crystalline diethylamine salt of the compound of formula I has an XRPD pattern including peaks at the following locations: In some embodiments, the crystalline diethylamine salt of the compound of formula I is characterized by essentially as follows: Figure 27 The DSC thermogram shown. In some embodiments, the crystalline diethylamine salt of the compound of formula I is characterized by having a DSC thermogram showing an endothermic transition at about 140°C.

[0172] In some embodiments, the crystalline diethylamine salt of the compound of formula I is characterized by essentially as follows: Figure 28 The TGA curve is shown. In some embodiments, the crystalline diethylamine salt of the compound of formula I undergoes mass loss in multiple stages, one of which begins at about 100°C and the next at about 175°C.

[0173] In some embodiments, the crystalline diethylamine salt of the compound of formula I is characterized by essentially as follows: Figure 29 The DVS curve is shown. In some embodiments, the crystalline diethylamine salt of the compound of formula I absorbs less than about 1% water at 25°C and up to 95% RH.

[0174] ammonium salts of compounds of formula I In some embodiments, the pharmaceutical composition comprises an ammonium salt of a compound of formula I, which may be amorphous or crystalline. In some embodiments, the ammonium salt of the compound of formula I is crystalline.

[0175] In some embodiments, the crystalline ammonium salt of the compound of formula I has essentially the following characteristics: Figure 30 The XRPD spectrum is shown. The crystalline ammonium salts of compounds of formula I can exhibit essentially the following characteristics. Figure 31 The DSC thermogram shown. The crystalline ammonium salts of compounds of formula I can exhibit essentially the following... Figure 32 The TGA diagram shown. Crystalline ammonium salts of compounds of formula I can exhibit essentially the following... Figure 33 The DVS curve shown.

[0176] In some embodiments, the crystalline ammonium salts of the compounds of formula I have at least two, at least three, at least four, at least five, or at least six [symbols] substantially as shown in the diagram. Figure 30 The XRPD pattern shown is an XRPD pattern with maximum intensity 2θ angle reflection.

[0177] In some embodiments, the crystalline ammonium salt of the compound of Formula I has an XRPD pattern including 2θ reflections (+ / -0.2 degrees 2θ) at 6.9°, 12.1°, and 12.5°. In some embodiments, the crystalline ammonium salt of the compound of Formula I has an XRPD pattern including one, two, or three of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 6.9°, 12.1°, and 12.5° and 2θ reflections (+ / -0.2 degrees 2θ) at 18.4°, 21.0°, and 25.4°. In some embodiments, the crystalline ammonium salt of the compound of Formula I has an XRPD pattern including one or two of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 6.9°, 12.1°, and 12.5° and 2θ reflections (+ / -0.2 degrees 2θ) at 18.4°, 21.0°, and 25.4°. In some embodiments, the crystalline ammonium salt of the compound of Formula I has an XRPD pattern including one of 2θ reflection (+ / -0.2 degrees 2θ) at 6.9°, 12.1°, and 12.5° and 2θ reflection (+ / -0.2 degrees 2θ) at 18.4°, 21.0°, and 25.4°. In some embodiments, the crystalline ammonium salt of the compound of Formula I has an XRPD pattern including two of 2θ reflection (+ / -0.2 degrees 2θ) at 6.9°, 12.1°, and 12.5° and 2θ reflection (+ / -0.2 degrees 2θ) at 18.4°, 21.0°, and 25.4°. In some embodiments, the crystalline ammonium salt of the compound of Formula I has an XRPD pattern including 2θ reflection (+ / -0.2 degrees 2θ) at 6.9°, 12.1°, 12.5°, 18.4°, 21.0°, and 25.4°. In some embodiments, the crystalline ammonium salt of the compound of formula I has an XRPD pattern comprising any three of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 6.9°, 12.1°, 12.5°, 18.4°, 21.0°, and 25.4°.

[0178] In some embodiments, the crystalline ammonium salt of the compound of Formula I has an XRPD pattern comprising one, two, or three of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 6.9°, 12.1°, 12.5°, 18.4°, 21.0°, and 25.4°; and 2θ reflections (+ / -0.2 degrees 2θ) at 9.2°, 23.1°, and 30.6°. In some embodiments, the crystalline ammonium salt of the compound of Formula I has an XRPD pattern comprising one or two of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 6.9°, 12.1°, 12.5°, 18.4°, 21.0°, and 25.4°; and 2θ reflections (+ / -0.2 degrees 2θ) at 9.2°, 23.1°, and 30.6°. In some embodiments, the crystalline ammonium salt of the compound of Formula I has an XRPD pattern comprising one of 2θ reflections (+ / -0.2 degrees 2θ) at 6.9°, 12.1°, 12.5°, 18.4°, 21.0°, and 25.4° and 2θ reflections (+ / -0.2 degrees 2θ) at 9.2°, 23.1°, and 30.6°. In some embodiments, the crystalline ammonium salt of the compound of Formula I has an XRPD pattern comprising two of 2θ reflections (+ / -0.2 degrees 2θ) at 6.9°, 12.1°, 12.5°, 18.4°, 21.0°, and 25.4° and 2θ reflections (+ / -0.2 degrees 2θ) at 9.2°, 23.1°, and 30.6°. In some embodiments, the crystalline ammonium salt of the compound of Formula I has an XRPD pattern comprising 2θ reflections (+ / -0.2 degrees 2θ) at 6.9°, 9.2°, 12.1°, 12.5°, 18.4°, 21.0°, 23.1°, 25.4°, and 30.6°. In some embodiments, the crystalline ammonium salt of the compound of Formula I has an XRPD pattern comprising any three of the 2θ reflections (+ / -0.2 degrees 2θ) at 6.9°, 9.2°, 12.1°, 12.5°, 18.4°, 21.0°, 23.1°, 25.4°, and 30.6°.

[0179] In some embodiments, the crystalline ammonium salt of the compound of Formula I has an XRPD pattern comprising at least three of the 2θ reflections (+ / -0.2 degrees 2θ) at 6.9°, 9.2°, 12.1°, 12.5°, 15.6°, 17.1°, 18.4°, 21.0°, 23.1°, 25.4°, 26.4°, and 30.6°. In some embodiments, the crystalline ammonium salt of the compound of Formula I has an XRPD pattern comprising at least four of the 2θ reflections (+ / -0.2 degrees 2θ) at 6.9°, 9.2°, 12.1°, 12.5°, 15.6°, 17.1°, 18.4°, 21.0°, 23.1°, 25.4°, 26.4°, and 30.6°. In some embodiments, the crystalline ammonium salt of the compound of formula I has an XRPD pattern comprising at least five of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 6.9°, 9.2°, 12.1°, 12.5°, 15.6°, 17.1°, 18.4°, 21.0°, 23.1°, 25.4°, 26.4°, and 30.6°.

[0180] In some embodiments, the crystalline ammonium salt of the compound of formula I has an XRPD pattern including peaks at the following locations: In some embodiments, the crystalline ammonium salt of the compound of formula I is characterized by essentially as follows: Figure 31 The DSC thermogram is shown. In some embodiments, the crystalline ammonium salt of the compound of formula I is characterized by having one or both of the following DSC thermograms: (i) an endothermic transition at about 121°C and (ii) an endothermic transition at about 194°C. In some embodiments, the crystalline ammonium salt of the compound of formula I is characterized by having the following DSC thermograms: (i) an endothermic transition at about 121°C and (ii) an endothermic transition at about 194°C.

[0181] In some embodiments, the crystalline ammonium salt of the compound of formula I is characterized by essentially as follows: Figure 32 The TGA curve is shown. In some embodiments, the crystalline ammonium salt of the compound of formula I begins to experience mass loss from about 80°C.

[0182] In some embodiments, the crystalline ammonium salt of the compound of formula I is characterized by essentially as follows: Figure 33 The DVS curve is shown. In some embodiments, the crystalline ammonium salt of the compound of formula I absorbs less than about 1% water at 25°C and up to 95% RH.

[0183] Calcium salts of compounds of formula I In some embodiments, the pharmaceutical composition comprises a calcium salt of a compound of formula I, which may be in any form, for example, crystalline or amorphous. In some embodiments, the calcium salt of the compound of formula I is crystalline.

[0184] In some embodiments, the crystalline calcium salt of the compound of formula I has essentially the following characteristics: Figure 34 The XRPD features shown are in form I (“Calcium salt form I of Formula I” or “Calcium salt form I of Formula I”). Calcium salt form I of Formula I can exhibit essentially the following characteristics: Figure 35 The DSC thermogram shown.

[0185] In some embodiments, the calcium salt form of compound I is characterized by essentially as follows: Figure 35 The DSC thermogram is shown. In some embodiments, the calcium salt form I of compound I is characterized by a DSC thermogram showing a glass transition at about 130°C.

[0186] In some embodiments, the crystalline calcium salt of the compound of formula I is form II ("calcium salt form II of formula I" or "calcium salt form II of formula I"). In some embodiments, the calcium salt form II of formula I has essentially the following characteristics: Figure 36 The XRPD spectrum shown.

[0187] In some embodiments, the calcium salt form II of formula I has at least two, at least three, at least four, at least five, or at least six salts substantially as shown in the figure. Figure 36 The XRPD pattern shown is an XRPD pattern with maximum intensity 2θ angle reflection.

[0188] In some embodiments, the calcium salt form II of Formula I has an XRPD pattern including 2θ reflections (+ / -0.2 degrees 2θ) at 7.1°, 8.5°, and 11.7°. In some embodiments, the calcium salt form II of Formula I has an XRPD pattern including one, two, or three of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 7.1°, 8.5°, and 11.7° and 2θ reflections (+ / -0.2 degrees 2θ) at 14.1°, 16.5°, and 20.1°. In some embodiments, the calcium salt form II of Formula I has an XRPD pattern including one or two of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 7.1°, 8.5°, and 11.7° and 2θ reflections (+ / -0.2 degrees 2θ) at 14.1°, 16.5°, and 20.1°. In some embodiments, the calcium salt form II of Formula I has an XRPD pattern including one of 2θ reflections (+ / -0.2 degrees 2θ) at 7.1°, 8.5°, and 11.7° and 2θ reflections (+ / -0.2 degrees 2θ) at 14.1°, 16.5°, and 20.1°. In some embodiments, the calcium salt form II of Formula I has an XRPD pattern including two of 2θ reflections (+ / -0.2 degrees 2θ) at 7.1°, 8.5°, and 11.7° and 2θ reflections (+ / -0.2 degrees 2θ) at 14.1°, 16.5°, and 20.1°. In some embodiments, the calcium salt form II of Formula I has an XRPD pattern including 2θ reflections (+ / -0.2 degrees 2θ) at 7.1°, 8.5°, 11.7°, 14.1°, 16.5°, and 20.1°. In some embodiments, the calcium salt form II of Formula I has an XRPD pattern comprising any three of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 7.1°, 8.5°, 11.7°, 14.1°, 16.5°, and 20.1°.

[0189] In some embodiments, the calcium salt form II of Formula I has an XRPD pattern comprising at least three of the 2θ reflections (+ / -0.2 degrees 2θ) at 7.1°, 8.5°, 11.7°, 14.1°, 16.5°, and 20.1°. In some embodiments, the calcium salt form II of Formula I has an XRPD pattern comprising at least four of the 2θ reflections (+ / -0.2 degrees 2θ) at 7.1°, 8.5°, 11.7°, 14.1°, 16.5°, and 20.1°. In some embodiments, the calcium salt form II of Formula I has an XRPD pattern comprising at least five of the 2θ reflections (+ / -0.2 degrees 2θ) at 7.1°, 8.5°, 11.7°, 14.1°, 16.5°, and 20.1°.

[0190] In some embodiments, the calcium salt form II of formula I has an XRPD pattern including peaks at the following locations: In some embodiments, the crystalline calcium salt of the compound of formula I is form III ("calcium salt form III of formula I" or "calcium salt form III of formula I"). In some embodiments, the calcium salt form III of formula I has essentially the following characteristics: Figure 37 The XRPD spectrum shown.

[0191] In some embodiments, the calcium salt form III of formula I has at least two, at least three, at least four, at least five, or at least six salts substantially as shown in the figure. Figure 37 The XRPD pattern shown is an XRPD pattern with maximum intensity 2θ angle reflection.

[0192] In some embodiments, the calcium salt form III of Formula I has an XRPD pattern including 2θ reflections (+ / -0.2 degrees 2θ) at 6.3°, 7.2°, and 25.5°. In some embodiments, the calcium salt form III of Formula I has an XRPD pattern including one, two, or three of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 6.3°, 7.2°, and 25.5° and 2θ reflections (+ / -0.2 degrees 2θ) at 21.2°, 28.4°, and 31.4°. In some embodiments, the calcium salt form III of Formula I has an XRPD pattern including one or two of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 6.3°, 7.2°, and 25.5° and 2θ reflections (+ / -0.2 degrees 2θ) at 21.2°, 28.4°, and 31.4°. In some embodiments, the calcium salt form III of Formula I has an XRPD pattern including one of 2θ reflections (+ / -0.2 degrees 2θ) at 6.3°, 7.2°, and 25.5° and 2θ reflections (+ / -0.2 degrees 2θ) at 21.2°, 28.4°, and 31.4°. In some embodiments, the calcium salt form III of Formula I has an XRPD pattern including two of 2θ reflections (+ / -0.2 degrees 2θ) at 6.3°, 7.2°, and 25.5° and 2θ reflections (+ / -0.2 degrees 2θ) at 21.2°, 28.4°, and 31.4°. In some embodiments, the calcium salt form III of Formula I has an XRPD pattern including 2θ reflections (+ / -0.2 degrees 2θ) at 6.3°, 7.2°, 21.2°, 25.5°, 28.4°, and 31.4°. In some embodiments, the calcium salt form III of Formula I has an XRPD pattern comprising any three of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 6.3°, 7.2°, 21.2°, 25.5°, 28.4°, and 31.4°.

[0193] In some embodiments, the calcium salt form III of Formula I has an XRPD pattern comprising at least three of the 2θ reflections (+ / -0.2 degrees 2θ) at 6.3°, 7.2°, 21.2°, 25.5°, 28.4°, and 31.4°. In some embodiments, the calcium salt form III of Formula I has an XRPD pattern comprising at least four of the 2θ reflections (+ / -0.2 degrees 2θ) at 6.3°, 7.2°, 21.2°, 25.5°, 28.4°, and 31.4°. In some embodiments, the calcium salt form III of Formula I has an XRPD pattern comprising at least five of the 2θ reflections (+ / -0.2 degrees 2θ) at 6.3°, 7.2°, 21.2°, 25.5°, 28.4°, and 31.4°.

[0194] In some embodiments, the calcium salt form III of formula I has an XRPD pattern including peaks at the following locations: Magnesium salts of compounds of formula I In some embodiments, the pharmaceutical composition comprises a magnesium salt of a compound of formula I, the calcium salt of which can be in any form, for example, crystalline or amorphous. In some embodiments, the magnesium salt of the compound of formula I is crystalline.

[0195] In some embodiments, the crystalline magnesium salt of the compound of formula I is form I ("magnesium salt of formula I form I" or "magnesium salt of formula I form I"). In some embodiments, the magnesium salt of the compound of formula I has essentially the following characteristics: Figure 38 The XRPD spectrum shown. Formula I magnesium salt form I can exhibit essentially the same characteristics as... Figure 39 The DSC thermogram shown.

[0196] In some implementations, the magnesium salt form of Formula I is characterized by essentially the following: Figure 39 The DSC thermogram shown. In some embodiments, the magnesium salt form I of formula I is characterized by a DSC thermogram showing a glass transition at about 155°C.

[0197] In some embodiments, the crystalline magnesium salt of the compound of Formula I is form II ("magnesium salt form II of Formula I" or "magnesium salt form II of Formula I"). In some embodiments, the magnesium salt form II of Formula I has essentially the following characteristics: Figure 40 The XRPD spectrum shown.

[0198] In some embodiments, the magnesium salt form II of formula I has at least two, at least three, at least four, at least five, or at least six salts substantially as shown in the figure. Figure 40 The XRPD pattern shown is an XRPD pattern with maximum intensity 2θ angle reflection.

[0199] In some embodiments, Formula I magnesium salt form II has an XRPD pattern including 2θ reflections (+ / -0.2 degrees 2θ) at 7.0°, 19.8°, and 24.3°. In some embodiments, Formula I magnesium salt form II has an XRPD pattern including one, two, or three of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 7.0°, 19.8°, and 24.3° and 2θ reflections (+ / -0.2 degrees 2θ) at 6.5°, 13.0°, and 21.2°. In some embodiments, Formula I magnesium salt form II has an XRPD pattern including one or two of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 7.0°, 19.8°, and 24.3° and 2θ reflections (+ / -0.2 degrees 2θ) at 6.5°, 13.0°, and 21.2°. In some embodiments, Formula I magnesium salt form II has an XRPD pattern including one of 2θ reflections (+ / -0.2 degrees 2θ) at 7.0°, 19.8°, and 24.3° and 2θ reflections (+ / -0.2 degrees 2θ) at 6.5°, 13.0°, and 21.2°. In some embodiments, Formula I magnesium salt form II has an XRPD pattern including two of 2θ reflections (+ / -0.2 degrees 2θ) at 7.0°, 19.8°, and 24.3° and 2θ reflections (+ / -0.2 degrees 2θ) at 6.5°, 13.0°, and 21.2°. In some embodiments, Formula I magnesium salt form II has an XRPD pattern including 2θ reflections (+ / -0.2 degrees 2θ) at 6.5°, 7.0°, 13.0°, 19.8°, 21.2°, and 24.3°. In some embodiments, Formula I magnesium salt form II has an XRPD pattern comprising any three of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 6.5°, 7.0°, 13.0°, 19.8°, 21.2°, and 24.3°.

[0200] In some embodiments, Formula I magnesium salt form II has an XRPD pattern comprising at least three of the 2θ reflections (+ / -0.2 degrees 2θ) at 6.5°, 7.0°, 13.0°, 19.8°, 21.2°, and 24.3°. In some embodiments, Formula I magnesium salt form II has an XRPD pattern comprising at least four of the 2θ reflections (+ / -0.2 degrees 2θ) at 6.5°, 7.0°, 13.0°, 19.8°, 21.2°, and 24.3°. In some embodiments, Formula I magnesium salt form II has an XRPD pattern comprising at least five of the 2θ reflections (+ / -0.2 degrees 2θ) at 6.5°, 7.0°, 13.0°, 19.8°, 21.2°, and 24.3°.

[0201] In some embodiments, the magnesium salt form II of Formula I has an XRPD pattern including peaks at the following locations: Compounds of Formula I N -Butamine salt In some embodiments, the pharmaceutical composition comprises a compound of formula I. N -Butylamine salt, the compound of formula I N -Butylamine salts can be amorphous or crystalline. In some embodiments, the compounds of formula I... N -Butylamine salts are crystalline.

[0202] In some embodiments, the crystallization of the compound of formula I N -Butylamine salts have essentially the same properties as Figure 41 The XRPD spectrum is shown. Crystallization of the compound of formula I. N -Butylamine salts can exhibit essentially the following characteristics: Figure 42 The DSC thermogram shown. Crystallization of the compound of formula I. N -Butylamine salts can exhibit essentially the following characteristics: Figure 43 The TGA diagram shown. Crystallization of the compound of formula I. N -Butylamine salts can exhibit essentially the following characteristics: Figure 44 The DVS curve shown.

[0203] In some embodiments, the crystallization of the compound of formula I N The -butylamine salt has an XRPD pattern including 2θ reflections (+ / -0.2 degrees 2θ) at 5.8°, 8.0°, and 10.7°. In some embodiments, the compound of formula I is crystallized. N The 2-butanamine salt has an XRPD pattern comprising one, two, or three of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 5.8°, 8.0°, and 10.7°, and 2θ reflections (+ / -0.2 degrees 2θ) at 9.7°, 11.6°, and 19.2°. In some embodiments, the compound of formula I is crystallized... N The 2-butanamine salt has an XRPD pattern comprising one or both of 2θ reflections (+ / -0.2 degrees 2θ) at 5.8°, 8.0°, and 10.7° and 2θ reflections (+ / -0.2 degrees 2θ) at 9.7°, 11.6°, and 19.2°. In some embodiments, the compound of formula I is crystallized... N The 2-butanamine salt has an XRPD pattern comprising one of 2θ reflections (+ / -0.2 degrees 2θ) at 5.8°, 8.0°, and 10.7° and 2θ reflections (+ / -0.2 degrees 2θ) at 9.7°, 11.6°, and 19.2°. In some embodiments, the compound of formula I is crystallized. NThe 2-butamine salt has an XRPD pattern comprising both 2θ reflections (+ / -0.2 degrees 2θ) at 5.8°, 8.0°, and 10.7° and 2θ reflections (+ / -0.2 degrees 2θ) at 9.7°, 11.6°, and 19.2°. In some embodiments, the compound of formula I is crystallized... N The -butylamine salt has an XRPD pattern including 2θ reflections (+ / -0.2 degrees 2θ) at 5.8°, 8.0°, 9.7°, 10.7°, 11.6°, and 19.2°. In some embodiments, the compound of formula I is crystallized. N 1-Butylamine salts have XRPD patterns comprising any three of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 5.8°, 8.0°, 9.7°, 10.7°, 11.6°, and 19.2°.

[0204] In some embodiments, the crystallization of the compound of formula I N The 2-butamine salt has an XRPD pattern comprising one, two, or three of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 5.8°, 8.0°, 9.7°, 10.7°, 11.6°, and 19.2°, and 2θ reflections (+ / -0.2 degrees 2θ) at 18.7°, 22.3°, and 26.5°. In some embodiments, the compound of Formula I is crystallized... N The 2-butamine salt has an XRPD pattern comprising one or both of 2θ reflections (+ / -0.2 degrees 2θ) at 5.8°, 8.0°, 9.7°, 10.7°, 11.6°, and 19.2° and 2θ reflections (+ / -0.2 degrees 2θ) at 18.7°, 22.3°, and 26.5°. In some embodiments, the compound of formula I is crystallized. N The 2-butanamine salt has an XRPD pattern comprising one of two reflections (+ / -0.2 degrees θ2θ) at 5.8°, 8.0°, 9.7°, 10.7°, 11.6°, and 19.2° and two reflections (+ / -0.2 degrees θ2θ) at 18.7°, 22.3°, and 26.5°. In some embodiments, the compound of formula I is crystallized... N The 2-butamine salt has an XRPD pattern comprising two of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 5.8°, 8.0°, 9.7°, 10.7°, 11.6°, and 19.2°; and 2θ reflections (+ / -0.2 degrees 2θ) at 18.7°, 22.3°, and 26.5°. In some embodiments, the compound of Formula I is crystallized. NThe 2-butanamine salt has an XRPD pattern including 2θ reflection (+ / -0.2 degrees 2θ) at 5.8°, 8.0°, 9.7°, 10.7°, 11.6°, 18.7°, 19.2°, 22.3°, and 26.5°. In some embodiments, the compound of formula I is crystallized. N 1-Butylamine salts have XRPD patterns comprising any three of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 5.8°, 8.0°, 9.7°, 10.7°, 11.6°, 18.7°, 19.2°, 22.3°, and 26.5°.

[0205] In some embodiments, the crystallization of the compound of formula I N The -butylamine salt has an XRPD pattern comprising at least three of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 5.8°, 8.0°, 9.7°, 10.2°, 10.7°, 11.6°, 16.7°, 18.7°, 19.2°, 20.3°, 22.3°, 23.7°, 25.3°, 26.1°, and 26.5°. In some embodiments, the compound of formula I is crystallized. N The -butylamine salt has an XRPD pattern comprising at least four of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 5.8°, 8.0°, 9.7°, 10.2°, 10.7°, 11.6°, 16.7°, 18.7°, 19.2°, 20.3°, 22.3°, 23.7°, 25.3°, 26.1°, and 26.5°. In some embodiments, the compound of formula I is crystallized. N The -butylamine salt has an XRPD pattern comprising at least five of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 5.8°, 8.0°, 9.7°, 10.2°, 10.7°, 11.6°, 16.7°, 18.7°, 19.2°, 20.3°, 22.3°, 23.7°, 25.3°, 26.1°, and 26.5°. In some embodiments, the compound of formula I is crystallized. N -Butylamine salts have an XRPD pattern including peaks at the following locations: In some embodiments, the crystallization of the compound of formula I N -Butylamine salts are characterized by essentially the following Figure 42 The DSC thermogram shown.

[0206] In some embodiments, the crystallization of the compound of formula I N -Butylamine salts are characterized by a DSC thermogram showing an endothermic transition that begins at approximately 166 °C.

[0207] In some embodiments, the crystallization of the compound of formula IN -Butylamine salts are characterized by essentially the following Figure 43 The TGA curves are shown. In some embodiments, the crystallization of the compound of formula I... N 1-Butylamine salts experience mass loss in several stages starting from about 80°C and in another stage starting from about 175°C.

[0208] In some embodiments, the crystallization of the compound of formula I N -Butylamine salts are characterized by essentially the following Figure 44 The DVS curve is shown. In some embodiments, the crystallization of the compound of formula I... N 1-Butylamine salt absorbs less than about 0.2% water at 25°C and up to 95% RH.

[0209] diethanolamine salts of compounds of formula I In some embodiments, the pharmaceutical composition comprises a diethanolamine salt of a compound of formula I, which may be amorphous or crystalline. In some embodiments, the diethanolamine salt of the compound of formula I is crystalline.

[0210] In some embodiments, the crystalline diethanolamine salt of the compound of formula I has essentially the following characteristics: Figure 45 The XRPD spectrum is shown. In some embodiments, the crystalline diethanolamine salt of the compound of formula I has at least two, at least three, at least four, at least five, or at least six [symbols] substantially as shown. Figure 45 The XRPD pattern shown is an XRPD pattern with maximum intensity 2θ angle reflection.

[0211] In some embodiments, the crystalline diethanolamine salt of the compound of Formula I has an XRPD pattern including 2θ reflections (+ / -0.2 degrees 2θ) at 6.1°, 18.4°, and 19.5°. In some embodiments, the crystalline diethanolamine salt of the compound of Formula I has an XRPD pattern including one, two, or three of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 6.1°, 18.4°, and 19.5° and 2θ reflections (+ / -0.2 degrees 2θ) at 9.9°, 20.4°, and 21.8°. In some embodiments, the crystalline diethanolamine salt of the compound of Formula I has an XRPD pattern including one or two of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 6.1°, 18.4°, and 19.5° and 2θ reflections (+ / -0.2 degrees 2θ) at 9.9°, 20.4°, and 21.8°. In some embodiments, the crystalline diethanolamine salt of the compound of Formula I has an XRPD pattern including one of 2θ reflections (+ / -0.2 degrees 2θ) at 6.1°, 18.4°, and 19.5° and 2θ reflections (+ / -0.2 degrees 2θ) at 9.9°, 20.4°, and 21.8°. In some embodiments, the crystalline diethanolamine salt of the compound of Formula I has an XRPD pattern including two of 2θ reflections (+ / -0.2 degrees 2θ) at 6.1°, 18.4°, and 19.5° and 2θ reflections (+ / -0.2 degrees 2θ) at 9.9°, 20.4°, and 21.8°. In some embodiments, the crystalline diethanolamine salt of the compound of Formula I has an XRPD pattern including 2θ reflections (+ / -0.2 degrees 2θ) at 6.1°, 9.9°, 18.4°, 19.5°, 20.4°, and 21.8°. In some embodiments, the crystalline diethanolamine salt of the compound of formula I has an XRPD pattern comprising any three of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 6.1°, 9.9°, 18.4°, 19.5°, 20.4°, and 21.8°.

[0212] In some embodiments, the crystalline diethanolamine salt of the compound of Formula I has an XRPD pattern comprising one, two, or three of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 6.1°, 9.9°, 18.4°, 19.5°, 20.4°, and 21.8°; and 2θ reflections (+ / -0.2 degrees 2θ) at 16.9°, 18.9°, and 26.5°. In some embodiments, the crystalline diethanolamine salt of the compound of Formula I has an XRPD pattern comprising one or two of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 6.1°, 9.9°, 18.4°, 19.5°, 20.4°, and 21.8°; and 2θ reflections (+ / -0.2 degrees 2θ) at 16.9°, 18.9°, and 26.5°. In some embodiments, the crystalline diethanolamine salt of the compound of Formula I has an XRPD pattern comprising one of 2θ reflections (+ / -0.2 degrees 2θ) at 6.1°, 9.9°, 18.4°, 19.5°, 20.4°, and 21.8° and 2θ reflections (+ / -0.2 degrees 2θ) at 16.9°, 18.9°, and 26.5°. In some embodiments, the crystalline diethanolamine salt of the compound of Formula I has an XRPD pattern comprising two of 2θ reflections (+ / -0.2 degrees 2θ) at 6.1°, 9.9°, 18.4°, 19.5°, 20.4°, and 21.8° and 2θ reflections (+ / -0.2 degrees 2θ) at 16.9°, 18.9°, and 26.5°. In some embodiments, the crystalline diethanolamine salt of the compound of Formula I has an XRPD pattern comprising 2θ reflections (+ / -0.2 degrees 2θ) at 6.1°, 9.9°, 16.9°, 18.4°, 18.9°, 19.5°, 20.4°, 21.8°, and 26.5°. In some embodiments, the crystalline diethanolamine salt of the compound of Formula I has an XRPD pattern comprising any three of the 2θ reflections (+ / -0.2 degrees 2θ) at 6.1°, 9.9°, 16.9°, 18.4°, 18.9°, 19.5°, 20.4°, 21.8°, and 26.5°.

[0213] In some embodiments, the crystalline diethanolamine salt of the compound of Formula I has an XRPD pattern comprising at least three of the 2θ reflections (+ / -0.2 degrees 2θ) at 6.1°, 9.9°, 16.9°, 18.4°, 18.9°, 19.5°, 20.4°, 21.8°, and 26.5°. In some embodiments, the crystalline diethanolamine salt of the compound of Formula I has an XRPD pattern comprising at least four of the 2θ reflections (+ / -0.2 degrees 2θ) at 6.1°, 9.9°, 16.9°, 18.4°, 18.9°, 19.5°, 20.4°, 21.8°, and 26.5°. In some embodiments, the crystalline diethanolamine salt of the compound of formula I has an XRPD pattern comprising at least five of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 6.1°, 9.9°, 16.9°, 18.4°, 18.9°, 19.5°, 20.4°, 21.8°, and 26.5°.

[0214] In some embodiments, the crystalline diethanolamine salt of the compound of formula I has an XRPD pattern including peaks at the following locations: Ethylenediamine salts of compounds of formula I In some embodiments, the pharmaceutical composition comprises an ethylenediamine salt of a compound of formula I, which may be amorphous or crystalline. In some embodiments, the ethylenediamine salt of the compound of formula I is crystalline.

[0215] In some embodiments, the crystalline ethylenediamine salt of the compound of formula I has essentially the following characteristics: Figure 46 The XRPD spectrum is shown. In some embodiments, the crystalline ethylenediamine salt of the compound of formula I has at least two, at least three, at least four, at least five, or at least six [symbols] substantially as shown. Figure 46 The XRPD pattern shown is an XRPD pattern with maximum intensity 2θ angle reflection.

[0216] In some embodiments, the crystalline ethylenediamine salt of the compound of Formula I has an XRPD pattern including 2θ reflections (+ / -0.2 degrees 2θ) at 3.5°, 6.9°, and 12.0°. In some embodiments, the crystalline ethylenediamine salt of the compound of Formula I has an XRPD pattern including one, two, or three of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 3.5°, 6.9°, and 12.0° and 2θ reflections (+ / -0.2 degrees 2θ) at 9.2°, 12.5°, and 20.2°. In some embodiments, the crystalline ethylenediamine salt of the compound of Formula I has an XRPD pattern including one or two of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 3.5°, 6.9°, and 12.0° and 2θ reflections (+ / -0.2 degrees 2θ) at 9.2°, 12.5°, and 20.2°. In some embodiments, the crystalline ethylenediamine salt of the compound of Formula I has an XRPD pattern including one of 2θ reflection (+ / -0.2 degrees 2θ) at 3.5°, 6.9°, and 12.0° and 2θ reflection (+ / -0.2 degrees 2θ) at 9.2°, 12.5°, and 20.2°. In some embodiments, the crystalline ethylenediamine salt of the compound of Formula I has an XRPD pattern including two of 2θ reflection (+ / -0.2 degrees 2θ) at 3.5°, 6.9°, and 12.0° and 2θ reflection (+ / -0.2 degrees 2θ) at 9.2°, 12.5°, and 20.2°. In some embodiments, the crystalline ethylenediamine salt of the compound of Formula I has an XRPD pattern including 2θ reflection (+ / -0.2 degrees 2θ) at 3.5°, 6.9°, 9.2°, 12.0°, 12.5°, and 20.2°. In some embodiments, the crystalline ethylenediamine salt of the compound of formula I has an XRPD pattern comprising any three of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 3.5°, 6.9°, 9.2°, 12.0°, 12.5°, and 20.2°.

[0217] In some embodiments, the crystalline ethylenediamine salt of the compound of Formula I has an XRPD pattern comprising at least three of the 2θ reflections (+ / -0.2 degrees 2θ) at 3.5°, 6.9°, 9.2°, 12.0°, 12.5°, and 20.2°. In some embodiments, the crystalline ethylenediamine salt of the compound of Formula I has an XRPD pattern comprising at least four of the 2θ reflections (+ / -0.2 degrees 2θ) at 3.5°, 6.9°, 9.2°, 12.0°, 12.5°, and 20.2°. In some embodiments, the crystalline ethylenediamine salt of the compound of Formula I has an XRPD pattern comprising at least five of the 2θ reflections (+ / -0.2 degrees 2θ) at 3.5°, 6.9°, 9.2°, 12.0°, 12.5°, and 20.2°.

[0218] In some embodiments, the crystalline ethylenediamine salt of the compound of formula I has an XRPD pattern including peaks at the following locations: Morpholine salts of compounds of formula I In some embodiments, the pharmaceutical composition comprises a morpholine salt of a compound of formula I, which may be amorphous or crystalline. In some embodiments, the morpholine salt of a compound of formula I is crystalline.

[0219] In some embodiments, the crystalline morpholine salt of the compound of formula I has essentially the following properties: Figure 47 The XRPD spectrum is shown. In some embodiments, the crystalline morpholine salt of the compound of formula I has at least two, at least three, at least four, at least five, or at least six [symbols] substantially as shown. Figure 47 The XRPD pattern shown is an XRPD pattern with maximum intensity 2θ angle reflection.

[0220] In some embodiments, the crystalline morpholine salt of the compound of Formula I has an XRPD pattern including 2θ reflections (+ / -0.2 degrees 2θ) at 14.3°, 19.0°, and 22.7°. In some embodiments, the crystalline morpholine salt of the compound of Formula I has an XRPD pattern including one, two, or three of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 14.3°, 19.0°, and 22.7° and 2θ reflections (+ / -0.2 degrees 2θ) at 9.0°, 14.5°, and 22.3°. In some embodiments, the crystalline morpholine salt of the compound of Formula I has an XRPD pattern including one or two of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 14.3°, 19.0°, and 22.7° and 2θ reflections (+ / -0.2 degrees 2θ) at 9.0°, 14.5°, and 22.3°. In some embodiments, the crystalline morpholine salt of the compound of Formula I has an XRPD pattern including one of 2θ reflection (+ / -0.2 degrees 2θ) at 14.3°, 19.0°, and 22.7° and 2θ reflection (+ / -0.2 degrees 2θ) at 9.0°, 14.5°, and 22.3°. In some embodiments, the crystalline morpholine salt of the compound of Formula I has an XRPD pattern including two of 2θ reflection (+ / -0.2 degrees 2θ) at 14.3°, 19.0°, and 22.7° and 2θ reflection (+ / -0.2 degrees 2θ) at 9.0°, 14.5°, and 22.3°. In some embodiments, the crystalline morpholine salt of the compound of Formula I has an XRPD pattern including 2θ reflection (+ / -0.2 degrees 2θ) at 9.0°, 14.3°, 14.5°, 19.0°, 22.3°, and 22.7°. In some embodiments, the crystalline morpholine salt of the compound of formula I has an XRPD pattern comprising any three of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 9.0°, 14.3°, 14.5°, 19.0°, 22.3°, and 22.7°.

[0221] In some embodiments, the crystalline morpholine salt of the compound of Formula I has an XRPD pattern comprising one, two, or three of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 9.0°, 14.3°, 14.5°, 19.0°, 22.3°, and 22.7°; and 2θ reflections (+ / -0.2 degrees 2θ) at 4.7°, 17.2°, and 26.0°. In some embodiments, the crystalline morpholine salt of the compound of Formula I has an XRPD pattern comprising one or two of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 9.0°, 14.3°, 14.5°, 19.0°, 22.3°, and 22.7°; and 2θ reflections (+ / -0.2 degrees 2θ) at 4.7°, 17.2°, and 26.0°. In some embodiments, the crystalline morpholine salt of the compound of Formula I has an XRPD pattern comprising one of 2θ reflections (+ / -0.2 degrees 2θ) at 9.0°, 14.3°, 14.5°, 19.0°, 22.3°, and 22.7° and 2θ reflections (+ / -0.2 degrees 2θ) at 4.7°, 17.2°, and 26.0°. In some embodiments, the crystalline morpholine salt of the compound of Formula I has an XRPD pattern comprising both of 2θ reflections (+ / -0.2 degrees 2θ) at 9.0°, 14.3°, 14.5°, 19.0°, 22.3°, and 22.7° and 2θ reflections (+ / -0.2 degrees 2θ) at 4.7°, 17.2°, and 26.0°. In some embodiments, the crystalline morpholine salt of the compound of Formula I has an XRPD pattern comprising 2θ reflections (+ / -0.2 degrees 2θ) at 4.7°, 9.0°, 14.3°, 14.5°, 17.2°, 19.0°, 22.3°, 22.7°, and 26.0°. In some embodiments, the crystalline morpholine salt of the compound of Formula I has an XRPD pattern comprising any three of the 2θ reflections (+ / -0.2 degrees 2θ) at 4.7°, 9.0°, 14.3°, 14.5°, 17.2°, 19.0°, 22.3°, 22.7°, and 26.0°.

[0222] In some embodiments, the crystalline morpholine salt of the compound of Formula I has an XRPD pattern comprising at least three of the 2θ reflections (+ / -0.2 degrees 2θ) at 4.7°, 9.0°, 14.3°, 14.5°, 17.2°, 19.0°, 22.3°, 22.7°, and 26.0°. In some embodiments, the crystalline morpholine salt of the compound of Formula I has an XRPD pattern comprising at least four of the 2θ reflections (+ / -0.2 degrees 2θ) at 4.7°, 9.0°, 14.3°, 14.5°, 17.2°, 19.0°, 22.3°, 22.7°, and 26.0°. In some embodiments, the crystalline morpholine salt of the compound of formula I has an XRPD pattern comprising at least five of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 4.7°, 9.0°, 14.3°, 14.5°, 17.2°, 19.0°, 22.3°, 22.7°, and 26.0°.

[0223] In some embodiments, the crystalline morpholine salt of the compound of formula I has an XRPD pattern including peaks at the following locations: L-arginine salts of compounds of formula I In some embodiments, the pharmaceutical composition comprises an L-arginine salt, which may be amorphous or crystalline. In some embodiments, the L-arginine salt of the compound of formula I is crystalline.

[0224] In some embodiments, the crystalline L-arginine salt of the compound of formula I is form I ("form I of L-arginine salt of formula I" or "form I L-arginine form I").

[0225] In some embodiments, form I of formula I L-arginine salt has essentially the same properties as... Figure 48 The XRPD spectrum is shown. In some embodiments, Formula I L-arginine salt form I has at least two, at least three, at least four, at least five, or at least six [symbols] substantially as shown. Figure 48 The XRPD pattern shown is an XRPD pattern with maximum intensity 2θ angle reflection.

[0226] In some embodiments, Formula I L-arginine salt form I has an XRPD pattern including 2θ reflections (+ / -0.2 degrees 2θ) at 15.0°, 23.3°, and 27.7°. In some embodiments, Formula I L-arginine salt form I has an XRPD pattern including one, two, or three of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 15.0°, 23.3°, and 27.7° and 2θ reflections (+ / -0.2 degrees 2θ) at 19.4°, 24.6°, and 29.9°. In some embodiments, Formula I L-arginine salt form I has an XRPD pattern including one or two of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 15.0°, 23.3°, and 27.7° and 2θ reflections (+ / -0.2 degrees 2θ) at 19.4°, 24.6°, and 29.9°. In some embodiments, Formula I L-arginine salt form I has an XRPD pattern comprising one of 2θ reflections (+ / -0.2 degrees 2θ) at 15.0°, 23.3°, and 27.7° and 2θ reflections (+ / -0.2 degrees 2θ) at 19.4°, 24.6°, and 29.9°. In some embodiments, Formula I L-arginine salt form I has an XRPD pattern comprising both of 2θ reflections (+ / -0.2 degrees 2θ) at 15.0°, 23.3°, and 27.7° and 2θ reflections (+ / -0.2 degrees 2θ) at 19.4°, 24.6°, and 29.9°. In some embodiments, Formula I L-arginine salt form I has an XRPD pattern including 2θ reflections (+ / -0.2 degrees 2θ) at 15.0°, 19.4°, 23.3°, 24.6°, 27.7°, and 29.9°. In some embodiments, Formula I L-arginine salt form I has an XRPD pattern including any three of the 2θ reflections (+ / -0.2 degrees 2θ) at 15.0°, 19.4°, 23.3°, 24.6°, 27.7°, and 29.9°.

[0227] In some embodiments, Formula I L-arginine salt form I has an XRPD pattern comprising one, two, or three of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 15.0°, 19.4°, 23.3°, 24.6°, 27.7°, and 29.9°, and 2θ reflections (+ / -0.2 degrees 2θ) at 11.3°, 16.7°, and 22.7°. In some embodiments, Formula I L-arginine salt form I has an XRPD pattern comprising one or two of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 15.0°, 19.4°, 23.3°, 24.6°, 27.7°, and 29.9°, and 2θ reflections (+ / -0.2 degrees 2θ) at 11.3°, 16.7°, and 22.7°. In some embodiments, Formula I L-arginine salt form I has an XRPD pattern comprising one of 2θ reflections (+ / -0.2 degrees 2θ) at 15.0°, 19.4°, 23.3°, 24.6°, 27.7°, and 29.9° and 2θ reflections (+ / -0.2 degrees 2θ) at 11.3°, 16.7°, and 22.7°. In some embodiments, Formula I L-arginine salt form I has an XRPD pattern comprising both of 2θ reflections (+ / -0.2 degrees 2θ) at 15.0°, 19.4°, 23.3°, 24.6°, 27.7°, and 29.9° and 2θ reflections (+ / -0.2 degrees 2θ) at 11.3°, 16.7°, and 22.7°. In some embodiments, Formula I L-arginine salt form I has an XRPD pattern including 2θ reflections (+ / -0.2 degrees 2θ) at 11.3°, 15.0°, 16.7°, 19.4°, 22.7°, 23.3°, 24.6°, 27.7°, and 29.9°. In some embodiments, Formula I L-arginine salt form I has an XRPD pattern including any three of the 2θ reflections (+ / -0.2 degrees 2θ) at 11.3°, 15.0°, 16.7°, 19.4°, 22.7°, 23.3°, 24.6°, 27.7°, and 29.9°.

[0228] In some embodiments, Formula I L-arginine salt form I has an XRPD pattern comprising at least three of the 2θ reflections (+ / -0.2 degrees 2θ) at 11.3°, 15.0°, 16.7°, 19.4°, 22.7°, 23.3°, 24.6°, 27.7°, and 29.9°. In some embodiments, Formula I L-arginine salt form I has an XRPD pattern comprising at least four of the 2θ reflections (+ / -0.2 degrees 2θ) at 11.3°, 15.0°, 16.7°, 19.4°, 22.7°, 23.3°, 24.6°, 27.7°, and 29.9°. In some embodiments, Formula I L-arginine salt form I has an XRPD pattern comprising at least five of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 11.3°, 15.0°, 16.7°, 19.4°, 22.7°, 23.3°, 24.6°, 27.7°, and 29.9°.

[0229] In some embodiments, Formula I L-arginine salt form I has an XRPD pattern including peaks at the following locations: In some embodiments, the crystalline L-arginine salt of the compound of formula I is form II ("form II of L-arginine salt of formula I" or "form II of L-arginine of formula I").

[0230] In some embodiments, Formula I L-arginine salt form II has essentially the same properties as Figure 49 The XRPD spectrum is shown. In some embodiments, Formula I L-arginine salt form II has at least two, at least three, at least four, at least five, or at least six [symbols] substantially as shown. Figure 49 The XRPD pattern shown is an XRPD pattern with maximum intensity 2θ angle reflection.

[0231] In some embodiments, Formula I L-arginine form II has an XRPD pattern including 2θ reflections (+ / -0.2 degrees 2θ) at 6.8°, 14.5°, and 20.5°. In some embodiments, Formula I L-arginine form II has an XRPD pattern including one, two, or three of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 6.8°, 14.5°, and 20.5° and 2θ reflections (+ / -0.2 degrees 2θ) at 8.9°, 11.8°, and 17.2°. In some embodiments, Formula I L-arginine form II has an XRPD pattern including one or two of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 6.8°, 14.5°, and 20.5° and 2θ reflections (+ / -0.2 degrees 2θ) at 8.9°, 11.8°, and 17.2°. In some embodiments, Formula I L-arginine salt form II has an XRPD pattern including one of 2θ reflections (+ / -0.2 degrees 2θ) at 6.8°, 14.5°, and 20.5° and 2θ reflections (+ / -0.2 degrees 2θ) at 8.9°, 11.8°, and 17.2°. In some embodiments, Formula I L-arginine salt form II has an XRPD pattern including two of 2θ reflections (+ / -0.2 degrees 2θ) at 6.8°, 14.5°, and 20.5°. In some embodiments, Formula IL-arginine salt form II has an XRPD pattern including 2θ reflections (+ / -0.2 degrees 2θ) at 6.8°, 8.9°, 11.8°, 14.5°, 17.2°, and 20.5°. In some embodiments, Formula I L-arginine salt form II has an XRPD pattern comprising any three of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 6.8°, 8.9°, 11.8°, 14.5°, 17.2°, and 20.5°.

[0232] In some embodiments, Formula I L-arginine form II has an XRPD pattern comprising at least three of the 2θ reflections (+ / -0.2 degrees 2θ) at 6.8°, 8.9°, 11.8°, 14.5°, 17.2°, and 20.5°. In some embodiments, Formula I L-arginine form II has an XRPD pattern comprising at least four of the 2θ reflections (+ / -0.2 degrees 2θ) at 6.8°, 8.9°, 11.8°, 14.5°, 17.2°, and 20.5°. In some embodiments, Formula I L-arginine form II has an XRPD pattern comprising at least five of the 2θ reflections (+ / -0.2 degrees 2θ) at 6.8°, 8.9°, 11.8°, 14.5°, 17.2°, and 20.5°.

[0233] In some embodiments, Formula I L-arginine salt form II has an XRPD pattern including peaks at the following locations: In some embodiments, the crystalline L-arginine salt of the compound of Formula I is form III ("Form III of L-arginine salt of Formula I" or "Form III of L-arginine of Formula I").

[0234] In some embodiments, Formula I L-arginine salt form III has essentially the same properties as... Figure 50 The XRPD spectrum is shown. In some embodiments, Formula I L-arginine salt form III has at least two, at least three, at least four, at least five, or at least six [symbols] substantially as shown. Figure 50 The XRPD pattern shown is an XRPD pattern with maximum intensity 2θ angle reflection.

[0235] In some embodiments, Formula I L-arginine salt form III has an XRPD pattern including 2θ reflection (+ / -0.2 degrees 2θ) at 7.3°. In some embodiments, Formula I L-arginine salt form III has an XRPD pattern including 2θ reflection (+ / -0.2 degrees 2θ) at 7.3° and 9.6°.

[0236] In some embodiments, Formula I L-arginine salt form II has an XRPD pattern including peaks at the following locations: trans-feruloate of compound I In some embodiments, the pharmaceutical composition comprises a trans-feruloate of Formula I. In some embodiments, the pharmaceutical composition comprises a cocrystal of a compound of Formula I. In some embodiments, the trans-feruloate of a compound of Formula I is a trans-ferulic acid cocrystal (“trans-ferulic acid cocrystal of Formula I” or “trans-ferulic acid cocrystal of Formula I”).

[0237] In some embodiments, the trans-ferulic acid cocrystal of Formula I is crystalline.

[0238] In some embodiments, the crystalline trans-ferulic acid cocrystal of Formula I is form I ("trans-ferulic acid cocrystal of Formula I, form I" or "trans-ferulic acid cocrystal of Formula I, form I"). In some embodiments, trans-ferulic acid cocrystal of Formula I has substantially the following characteristics: Figure 51 The XRPD spectrum is shown. Formula I, trans-ferulic acid eutectic form I, can exhibit essentially the following characteristics. Figure 52 The DSC thermogram shown. Formula I trans-ferulic acid eutectic form I can exhibit essentially the following... Figure 53 The TGA diagram shown. Formula I, trans-ferulic acid eutectic form I, can exhibit essentially the following characteristics. Figure 54 The DVS curve shown.

[0239] In some embodiments, the trans-ferulic acid eutectic form I of formula I has at least two, at least three, at least four, at least five, or at least six [symbols] substantially as shown in the figure. Figure 51 The XRPD pattern shown is an XRPD pattern with maximum intensity 2θ angle reflection.

[0240] In some embodiments, Formula I trans-ferulic acid eutectic form I has an XRPD pattern including 2θ reflections (+ / -0.2 degrees 2θ) at 6.4°, 16.3°, and 25.0°. In some embodiments, Formula I trans-ferulic acid eutectic form I has an XRPD pattern including one, two, or three of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 6.4°, 16.3°, and 25.0° and 2θ reflections (+ / -0.2 degrees 2θ) at 8.7°, 24.2°, and 28.8°. In some embodiments, Formula I trans-ferulic acid eutectic form I has an XRPD pattern including one or two of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 6.4°, 16.3°, and 25.0° and 2θ reflections (+ / -0.2 degrees 2θ) at 8.7°, 24.2°, and 28.8°. In some embodiments, the trans-ferulic acid eutectic form I of Formula I has an XRPD pattern comprising one of 2θ reflections (+ / -0.2 degrees 2θ) at 6.4°, 16.3°, and 25.0° and 2θ reflections (+ / -0.2 degrees 2θ) at 8.7°, 24.2°, and 28.8°. In some embodiments, the trans-ferulic acid eutectic form I of Formula I has an XRPD pattern comprising both of 2θ reflections (+ / -0.2 degrees 2θ) at 6.4°, 16.3°, and 25.0° and 2θ reflections (+ / -0.2 degrees 2θ) at 8.7°, 24.2°, and 28.8°. In some embodiments, Formula I trans-ferulic acid eutectic form I has an XRPD pattern including 2θ reflections (+ / -0.2 degrees 2θ) at 6.4°, 8.7°, 16.3°, 24.2°, 25.0°, and 28.8°. In some embodiments, Formula I trans-ferulic acid eutectic form I has an XRPD pattern including any three of the 2θ reflections (+ / -0.2 degrees 2θ) at 6.4°, 8.7°, 16.3°, 24.2°, 25.0°, and 28.8°.

[0241] In some embodiments, the trans-ferulic acid eutectic form I of Formula I has an XRPD pattern comprising one, two, or three of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 6.4°, 8.7°, 16.3°, 24.2°, 25.0°, and 28.8°; and 2θ reflections (+ / -0.2 degrees 2θ) at 21.3°, 22.7°, and 26.9°. In some embodiments, the trans-ferulic acid eutectic form I of Formula I has an XRPD pattern comprising one or two of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 6.4°, 8.7°, 16.3°, 24.2°, 25.0°, and 28.8°; and 2θ reflections (+ / -0.2 degrees 2θ) at 21.3°, 22.7°, and 26.9°. In some embodiments, Formula I trans-ferulic acid eutectic form I has an XRPD pattern comprising one of 2θ reflections (+ / -0.2 degrees 2θ) at 6.4°, 8.7°, 16.3°, 24.2°, 25.0°, and 28.8° and 2θ reflections (+ / -0.2 degrees 2θ) at 21.3°, 22.7°, and 26.9°. In some embodiments, Formula I trans-ferulic acid eutectic form I has an XRPD pattern comprising both of 2θ reflections (+ / -0.2 degrees 2θ) at 6.4°, 8.7°, 16.3°, 24.2°, 25.0°, and 28.8° and 2θ reflections (+ / -0.2 degrees 2θ) at 21.3°, 22.7°, and 26.9°. In some embodiments, Formula I trans-ferulic acid eutectic form I has an XRPD pattern including 2θ reflections (+ / -0.2 degrees 2θ) at 6.4°, 8.7°, 16.3°, 21.3°, 22.7°, 24.2°, 25.0°, 26.9°, and 28.8°. In some embodiments, Formula I trans-ferulic acid eutectic form I has an XRPD pattern including any three of the 2θ reflections (+ / -0.2 degrees 2θ) at 6.4°, 8.7°, 16.3°, 21.3°, 22.7°, 24.2°, 25.0°, 26.9°, and 28.8°.

[0242] In some embodiments, the trans-ferulic acid eutectic form I of Formula I has an XRPD pattern comprising at least three of the following 2θ reflections (+ / -0.2 degrees 2θ) at 6.4°, 8.7°, 10.7°, 14.2°, 15.1°, 16.3°, 18.9°, 21.3°, 22.7°, 24.2°, 25.0°, 26.9°, and 28.8°. In some embodiments, the trans-ferulic acid eutectic form I of Formula I has an XRPD pattern comprising at least four of the following 2θ reflections (+ / -0.2 degrees 2θ) at 6.4°, 8.7°, 10.7°, 14.2°, 15.1°, 16.3°, 18.9°, 21.3°, 22.7°, 24.2°, 25.0°, 26.9°, and 28.8°. In some embodiments, Formula I trans-ferulic acid eutectic form I has an XRPD pattern comprising at least five of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 6.4°, 8.7°, 10.7°, 14.2°, 15.1°, 16.3°, 18.9°, 21.3°, 22.7°, 24.2°, 25.0°, 26.9°, and 28.8°.

[0243] In some embodiments, Formula I trans-ferulic acid eutectic form I has an XRPD pattern including peaks at the following locations: In some embodiments, the trans-ferulic acid eutectic form I of formula I is characterized by being substantially as follows: Figure 52 The DSC thermogram shown.

[0244] In some embodiments, the trans-ferulic acid eutectic form I of Formula I is characterized by having a DSC thermogram of one or both of the following: (i) an endothermic transition at about 139 °C and (ii) an endothermic transition at about 180 °C.

[0245] In some embodiments, the trans-ferulic acid eutectic form I of formula I is characterized by being substantially as follows: Figure 53 The TGA curve is shown. In some embodiments, the eutectic form I of formula I trans-ferulic acid begins to experience mass loss from about 115°C.

[0246] In some embodiments, the trans-ferulic acid eutectic form I of formula I is characterized by being substantially as follows: Figure 54 The DVS curve is shown. In some embodiments, the eutectic form of Formula I trans-ferulic acid absorbs less than about 0.35% water at 25°C and up to 90% RH.

[0247] In some embodiments, the crystalline trans-ferulic acid cocrystal of Formula I is form II ("trans-ferulic acid cocrystal of Formula I form II" or "trans-ferulic acid cocrystal of Formula I form II"). In some embodiments, the trans-ferulic acid cocrystal of Formula I form II has essentially the following characteristics: Figure 55 The XRPD spectrum shown. Formula I trans-ferulic acid eutectic form II can exhibit essentially the same characteristics as... Figure 56 The DSC thermogram shown. Formula I trans-ferulic acid eutectic form II can exhibit essentially the same characteristics as... Figure 57 The TGA diagram shown.

[0248] In some embodiments, the eutectic form II of formula I trans-ferulic acid has at least two, at least three, at least four, at least five, or at least six [symbols] substantially as shown in the figure. Figure 55 The XRPD pattern shown is an XRPD pattern with maximum intensity 2θ angle reflection.

[0249] In some embodiments, Formula I trans-ferulic acid eutectic form II has an XRPD pattern including 2θ reflections (+ / -0.2 degrees 2θ) at 4.7°, 5.9°, and 25.9°. In some embodiments, Formula I trans-ferulic acid eutectic form II has an XRPD pattern including one, two, or three of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 4.7°, 5.9°, and 25.9° and 2θ reflections (+ / -0.2 degrees 2θ) at 15.7°, 18.9°, and 24.4°. In some embodiments, Formula I trans-ferulic acid eutectic form II has an XRPD pattern including one or two of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 4.7°, 5.9°, and 25.9° and 2θ reflections (+ / -0.2 degrees 2θ) at 15.7°, 18.9°, and 24.4°. In some embodiments, the eutectic form II of Formula I trans-ferulic acid has an XRPD pattern comprising one of 2θ reflections (+ / -0.2 degrees 2θ) at 4.7°, 5.9°, and 25.9° and 2θ reflections (+ / -0.2 degrees 2θ) at 15.7°, 18.9°, and 24.4°. In some embodiments, the eutectic form II of Formula I trans-ferulic acid has an XRPD pattern comprising two of 2θ reflections (+ / -0.2 degrees 2θ) at 4.7°, 5.9°, and 25.9° and 2θ reflections (+ / -0.2 degrees 2θ) at 15.7°, 18.9°, and 24.4°. In some embodiments, Formula I trans-ferulic acid eutectic form II has an XRPD pattern including 2θ reflections (+ / -0.2 degrees 2θ) at 4.7°, 5.9°, 15.7°, 18.9°, 24.4°, and 25.9°. In some embodiments, Formula I trans-ferulic acid eutectic form II has an XRPD pattern including any three of the 2θ reflections (+ / -0.2 degrees 2θ) at 4.7°, 5.9°, 15.7°, 18.9°, 24.4°, and 25.9°.

[0250] In some embodiments, the Formula I trans-ferulic acid eutectic form II has an XRPD pattern comprising one, two, or three of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 4.7°, 5.9°, 15.7°, 18.9°, 24.4°, and 25.9°; and 2θ reflections (+ / -0.2 degrees 2θ) at 4.3°, 9.3°, and 14.4°. In some embodiments, the Formula I trans-ferulic acid eutectic form II has an XRPD pattern comprising one or two of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 4.7°, 5.9°, 15.7°, 18.9°, 24.4°, and 25.9°; and 2θ reflections (+ / -0.2 degrees 2θ) at 4.3°, 9.3°, and 14.4°. In some embodiments, the Formula I trans-ferulic acid eutectic form II has an XRPD pattern comprising one of 2θ reflections (+ / -0.2 degrees 2θ) at 4.7°, 5.9°, 15.7°, 18.9°, 24.4°, and 25.9° and 2θ reflections (+ / -0.2 degrees 2θ) at 4.3°, 9.3°, and 14.4°. In some embodiments, the Formula I trans-ferulic acid eutectic form II has an XRPD pattern comprising both 2θ reflections (+ / -0.2 degrees 2θ) at 4.7°, 5.9°, 15.7°, 18.9°, 24.4°, and 25.9° and 22θ reflections (+ / -0.2 degrees 2θ) at 4.3°, 9.3°, and 14.4°. In some embodiments, the Formula I trans-ferulic acid eutectic form II has an XRPD pattern including 2θ reflections (+ / -0.2 degrees 2θ) at 4.3°, 4.7°, 5.9°, 9.3°, 14.4°, 15.7°, 18.9°, 24.4°, and 25.9°. In some embodiments, the Formula I trans-ferulic acid eutectic form II has an XRPD pattern including any three of the 2θ reflections (+ / -0.2 degrees 2θ) at 4.3°, 4.7°, 5.9°, 9.3°, 14.4°, 15.7°, 18.9°, 24.4°, and 25.9°.

[0251] In some embodiments, the Formula I trans-ferulic acid eutectic form II has an XRPD pattern comprising at least three of the 2θ reflections (+ / -0.2 degrees 2θ) at 4.3°, 4.7°, 5.9°, 9.3°, 14.4°, 15.7°, 18.9°, 24.4°, and 25.9°. In some embodiments, the Formula I trans-ferulic acid eutectic form II has an XRPD pattern comprising at least four of the 2θ reflections (+ / -0.2 degrees 2θ) at 4.3°, 4.7°, 5.9°, 9.3°, 14.4°, 15.7°, 18.9°, 24.4°, and 25.9°. In some embodiments, Formula I trans-ferulic acid eutectic form II has an XRPD pattern comprising at least five of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 4.3°, 4.7°, 5.9°, 9.3°, 14.4°, 15.7°, 18.9°, 24.4°, and 25.9°.

[0252] In some embodiments, the eutectic form II of Formula I trans-ferulic acid has an XRPD pattern including peaks at the following locations: In some embodiments, the eutectic form II of formula I trans-ferulic acid is characterized by being substantially as follows: Figure 56 The DSC thermogram shown.

[0253] In some embodiments, the trans-ferulic acid eutectic form II of Formula I is characterized by having a DSC thermogram of at least one of the following: (i) an endothermic transition at about 136 °C, (ii) an endothermic transition at about 153 °C, (iii) an endothermic transition at about 222 °C, and (iv) an exothermic transition at about 290 °C. In some embodiments, the trans-ferulic acid eutectic form II of Formula I is characterized by having a DSC thermogram of the following: (i) an endothermic transition at about 136 °C, (ii) an endothermic transition at about 153 °C, (iii) an endothermic transition at about 222 °C, and (iv) an exothermic transition at about 290 °C.

[0254] In some embodiments, the eutectic form II of formula I trans-ferulic acid is characterized by being substantially as follows: Figure 57 The TGA curve is shown. In some embodiments, the eutectic form II of formula I trans-ferulic acid is characterized by being non-solventized.

[0255] aminobutanetriol salts of compounds of formula I In some embodiments, the pharmaceutical composition comprises an aminobutanetriol salt of Formula I. In some embodiments, the aminobutanetriol salt of the Formula I compound is an aminobutanetriol cocrystal (“aminobutanetriol cocrystal of Formula I” or “aminobutanetriol cocrystal of Formula I”).

[0256] In some embodiments, the aminobutanetriol cocrystal of Formula I is crystalline.

[0257] In some embodiments, the crystalline aminobutanetriol cocrystal of Formula I has essentially the following characteristics: Figure 58 The XRPD spectrum is shown. The crystalline form of the aminobutanetriol cocrystal of formula I can exhibit essentially the following characteristics. Figure 59 The DSC thermogram shown. The crystalline aminobutanetriol cocrystal of Formula I can exhibit essentially the following characteristics. Figure 60 The TGA diagram shown.

[0258] In some embodiments, the crystalline aminobutanetriol cocrystal of Formula I has an XRPD pattern including 2θ reflections (+ / -0.2 degrees 2θ) at 6.8°, 20.4°, and 27.3°. In some embodiments, the crystalline aminobutanetriol cocrystal of Formula I has an XRPD pattern including one, two, or three of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 6.8°, 20.4°, and 27.3° and 2θ reflections (+ / -0.2 degrees 2θ) at 16.4°, 17.3°, and 25.5°. In some embodiments, the crystalline aminobutanetriol cocrystal of Formula I has an XRPD pattern including one or two of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 6.8°, 20.4°, and 27.3° and 2θ reflections (+ / -0.2 degrees 2θ) at 16.4°, 17.3°, and 25.5°. In some embodiments, the crystalline aminobutanetriol cocrystal of Formula I has an XRPD pattern comprising one of 2θ reflections (+ / -0.2 degrees 2θ) at 6.8°, 20.4°, and 27.3° and 2θ reflections (+ / -0.2 degrees 2θ) at 16.4°, 17.3°, and 25.5°. In some embodiments, the crystalline aminobutanetriol cocrystal of Formula I has an XRPD pattern comprising both of 2θ reflections (+ / -0.2 degrees 2θ) at 6.8°, 20.4°, and 27.3° and 2θ reflections (+ / -0.2 degrees 2θ) at 16.4°, 17.3°, and 25.5°. In some embodiments, the crystalline aminobutanetriol cocrystal of Formula I has an XRPD pattern including 2θ reflections (+ / -0.2 degrees 2θ) at 6.8°, 16.4°, 17.3°, 20.4°, 25.5°, and 27.3°. In some embodiments, the crystalline aminobutanetriol cocrystal of Formula I has an XRPD pattern including any three of the 2θ reflections (+ / -0.2 degrees 2θ) at 6.8°, 16.4°, 17.3°, 20.4°, 25.5°, and 27.3°.

[0259] In some embodiments, the crystalline aminobutanetriol cocrystal of Formula I has an XRPD pattern comprising one, two, or three of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 6.8°, 16.4°, 17.3°, 20.4°, 25.5°, and 27.3°, and 2θ reflections (+ / -0.2 degrees 2θ) at 12.6°, 21.6°, and 23.7°. In some embodiments, the crystalline aminobutanetriol cocrystal of Formula I has an XRPD pattern comprising one or two of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 6.8°, 16.4°, 17.3°, 20.4°, 25.5°, and 27.3°, and 2θ reflections (+ / -0.2 degrees 2θ) at 12.6°, 21.6°, and 23.7°. In some embodiments, the crystalline aminobutanetriol cocrystal of Formula I has an XRPD pattern comprising one of 2θ reflections (+ / -0.2 degrees 2θ) at 6.8°, 16.4°, 17.3°, 20.4°, 25.5°, and 27.3° and 2θ reflections (+ / -0.2 degrees 2θ) at 12.6°, 21.6°, and 23.7°. In some embodiments, the crystalline aminobutanetriol cocrystal of Formula I has an XRPD pattern comprising two of 2θ reflections (+ / -0.2 degrees 2θ) at 6.8°, 16.4°, 17.3°, 20.4°, 25.5°, and 27.3° and 2θ reflections (+ / -0.2 degrees 2θ) at 12.6°, 21.6°, and 23.7°. In some embodiments, the crystalline aminobutanetriol cocrystal of Formula I has an XRPD pattern including 2θ reflections (+ / -0.2 degrees 2θ) at 6.8°, 12.6°, 16.4°, 17.3°, 20.4°, 21.6°, 23.7°, 25.5°, and 27.3°. In some embodiments, the crystalline aminobutanetriol cocrystal of Formula I has an XRPD pattern including any three of the 2θ reflections (+ / -0.2 degrees 2θ) at 6.8°, 12.6°, 16.4°, 17.3°, 20.4°, 21.6°, 23.7°, 25.5°, and 27.3°.

[0260] In some embodiments, the crystalline aminobutanetriol cocrystal of Formula I has an XRPD pattern comprising at least three of the following 2θ reflections (+ / -0.2 degrees 2θ) at 6.2°, 6.8°, 12.6°, 14.3°, 16.4°, 17.3°, 20.4°, 21.6°, 23.7°, 25.5°, 26.8°, 27.3°, 32.9°, and 37.3°. In some embodiments, the crystalline aminobutanetriol cocrystal of Formula I has an XRPD pattern comprising at least four of the following 2θ reflections (+ / -0.2 degrees 2θ) at 6.2°, 6.8°, 12.6°, 14.3°, 16.4°, 17.3°, 20.4°, 21.6°, 23.7°, 25.5°, 26.8°, 27.3°, 32.9°, and 37.3°. In some embodiments, the crystalline compound of formula I, aminobutanetriol cocrystal, has an XRPD pattern comprising at least five of the following: 2θ reflections (+ / -0.2 degrees 2θ) at 6.2°, 6.8°, 12.6°, 14.3°, 16.4°, 17.3°, 20.4°, 21.6°, 23.7°, 25.5°, 26.8°, 27.3°, 32.9°, and 37.3°.

[0261] In some embodiments, the crystalline aminobutanetriol cocrystal of Formula I has an XRPD pattern including peaks at the following locations: In some embodiments, the crystalline aminobutanetriol cocrystal of Formula I is characterized by essentially as follows: Figure 59 The DSC thermogram shown.

[0262] In some embodiments, the crystalline aminobutanetriol cocrystal of Formula I is characterized by having a DSC thermogram showing an endothermic transition that begins at about 63°C.

[0263] In some embodiments, the crystalline aminobutanetriol cocrystal of Formula I is characterized by essentially as follows: Figure 60 The TGA curve is shown. In some embodiments, the crystalline aminobutanetriol cocrystal of Formula I undergoes mass loss in multiple stages starting from about 50°C and in another stage starting from about 140°C.

[0264] Compounds of Formula I may be present in the pharmaceutical compositions described herein in solvated and / or non-solvated forms, and references to “compounds of Formula I” or “compounds of Formula I or a pharmaceutically acceptable salt thereof” include solvated and non-solvated forms and mixtures thereof. As used herein, and in the absence of a specific pharmaceutically acceptable salt and / or solvate of a compound of Formula I, any dose (whether expressed in milligrams or % by weight, for example) shall be considered to refer to the amount of a compound of Formula I, i.e., the amount of the following compounds: I.

[0265] Therefore, for example, mentioning "500 mg of a compound of formula I or a pharmaceutically acceptable salt thereof" means the amount of a compound of formula I or a pharmaceutically acceptable salt thereof, which provides the same amount as 500 mg of the free acid of a compound of formula I.

[0266] Compounds of Formula I or pharmaceutically acceptable salts thereof may have any suitable purity. For example, compounds of Formula I or pharmaceutically acceptable salts thereof may have a purity of at least about 90%, or at least about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, or at least about 99.1%, about 99.2%, about 99.3%, about 99.4%, about 99.5%, about 99.6%, about 99.7%, about 99.8%, or at least about 99.9%. In some embodiments, compounds of Formula I or pharmaceutically acceptable salts thereof have a purity of at least about 99.1%. In some embodiments, compounds of Formula I or pharmaceutically acceptable salts thereof have a purity of at least about 99.3%. In some embodiments, compounds of Formula I or pharmaceutically acceptable salts thereof have a purity of at least about 99.5%. In some embodiments, compounds of Formula I or pharmaceutically acceptable salts thereof have a purity of at least about 99.7%. In some embodiments, the compound of Formula I or a pharmaceutically acceptable salt thereof has a purity of at least about 99.5%. In some embodiments, the compound of Formula I or a pharmaceutically acceptable salt thereof has a purity of at least about 99.9%.

[0267] In some embodiments, the compound of formula I or a pharmaceutically acceptable salt thereof is micronized. Micronization is a process of reducing the particle size of bulk solid materials (e.g., pharmaceutical raw materials) to the micron or submicron level. Micronization of bulk pharmaceutical solids can be achieved by methods including, for example, grinding or milling.

[0268] In some embodiments, the particle size of the compound of Formula I or a pharmaceutically acceptable salt thereof is controlled by milling, such as jet milling (fluid energy milling), bead milling, dry milling, helical milling, or high-shear wet milling (HSWM). In one embodiment, the particle size of the compound of Formula I or a pharmaceutically acceptable salt thereof is controlled by high-shear wet milling. High-shear wet milling may be integrated into the crystallization process or performed after crystallization. In some embodiments, HSWM is performed at a single speed of about 3,000 rpm to about 20,000 rpm; about 3,000 rpm, about 4,000 rpm, about 5,000 rpm, about 6,000 rpm, about 7,000 rpm, about 8,000 rpm, about 9,000 rpm, about 10,000 rpm, about 11,000 rpm, about 12,000 rpm, about 13,000 rpm, about 14,000 rpm, about 15,000 rpm, or about 16,000 rpm. In one embodiment, HSWM is performed at a single speed of 4,200 rpm. In one embodiment, HSWM is performed at a single speed of 5,500 rpm. In one embodiment, HSWM is performed at a single speed of 8,000 rpm. In one embodiment, HSWM is performed at a single speed of 12,000 rpm. In one embodiment, HSWM is performed at a single speed of 16,000 rpm. In some embodiments, the wet abrasive particles are passed through a comul after drying. In some embodiments, the comul screen size is from about 0.032 inches to about 0.250 inches. In one embodiment, the comul screen size is about 0.032 inches. In one embodiment, the comul screen size is about 0.250 inches. In some embodiments, the wet abrasive particles are dried in a drum dryer. In some embodiments, the wet abrasive particles are dried in a stirred filter / dryer. In some embodiments, the wet abrasive particles are dried in a vacuum oven dryer.

[0269] In one embodiment, the particle size of the compound of Formula I or a pharmaceutically acceptable salt thereof is controlled by jet milling. In one embodiment, the particle size of the compound of Formula I or a pharmaceutically acceptable salt thereof is controlled by annular jet milling. In one embodiment, the particle size of the compound of Formula I or a pharmaceutically acceptable salt thereof is controlled by a 0202 Jet-O-Mizer (JOM) annular jet milling system. In one embodiment, the particle size of the compound of Formula I or a pharmaceutically acceptable salt thereof is controlled by helical jet milling.

[0270] The particle size distribution of solid materials can be measured using a variety of analytical characterization methods known to those skilled in the art, including, for example, sieving, laser diffraction, quasi-elastic light scattering, centrifugation-optical, resistivity sensing, microelectrophoresis, optical microscopy, and scanning electron microscopy. In some embodiments, the particle size distribution of compounds of Formula I or their pharmaceutically acceptable salts is measured using optical microscopy. In some embodiments, the particle size distribution of compounds of Formula I or their pharmaceutically acceptable salts is measured using laser diffraction. The particle size distribution of solid materials can be measured using d as defined herein. 90 Value representation.

[0271] In some embodiments, the compound of formula I or a pharmaceutically acceptable salt thereof has a dm of less than about 800 μm, less than about 300 μm, or less than about 100 μm. 90 Value. In some embodiments, the compound of formula I or a pharmaceutically acceptable salt thereof has a d value. 90 Particle size distribution with a value less than approximately 200 μm. For example, compounds of formula I or their pharmaceutically acceptable salts have a d... 90 Particle size distributions with values ​​less than about 150 μm, about 125 μm, about 100 μm, about 95 μm, about 90 μm, about 85 μm, about 80 μm, about 70 μm, about 65 μm, about 60 μm, about 55 μm, about 50 μm, about 45 μm, about 40 μm, about 35 μm, about 30 μm, about 25 μm, about 20 μm, about 15 μm, about 10 μm, about 9 μm, about 8 μm, about 7 μm, about 6 μm, about 5 μm, about 4 μm, about 3 μm, about 2 μm, or about 1 μm. In some embodiments, the compound of formula I or a pharmaceutically acceptable salt thereof has a d 90 Values ​​range from approximately 1 μm to approximately 150 μm (e.g., approximately 1 μm to approximately 125 μm, approximately 1 μm to approximately 100 μm, approximately 1 μm to approximately 95 μm, approximately 1 μm to approximately 90 μm, approximately 1 μm to approximately 85 μm, approximately 1 μm to approximately 80 μm, approximately 1 μm to approximately 75 μm, approximately 1 μm to approximately 70 μm, approximately 1 μm to approximately 15 μm, approximately 5 μm to approximately 60 μm, approximately 1 μm to approximately 55 μm, approximately 1 μm to approximately 50 μm, approximately 1 μm to approximately 4 μm). Particle size distributions of 5 μm, about 1 μm to about 40 μm, about 1 μm to about 35 μm, about 1 μm to about 30 μm, about 1 μm to about 25 μm, about 1 μm to about 20 μm, about 1 μm to about 15 μm, about 1 μm to about 10 μm, 1 μm to about 9 μm, 1 μm to about 8 μm, 1 μm to about 7 μm, 1 μm to about 6 μm, 1 μm to about 5 μm, 1 μm to about 4 μm, 1 μm to about 3 μm, or 1 μm to 2 μm. In some embodiments, the compound of formula I or a pharmaceutically acceptable salt thereof has a d 90The particle size distribution is approximately 55 μm. In some embodiments, the compound of formula I or a pharmaceutically acceptable salt thereof has a d... 90 The particle size distribution is approximately 53 μm. In some embodiments, the compound of formula I or a pharmaceutically acceptable salt thereof has a d... 90 The particle size distribution is approximately 52 μm. In some embodiments, the compound of formula I or a pharmaceutically acceptable salt thereof has a d... 90 The particle size distribution is approximately 25 μm. In some embodiments, the compound of formula I or a pharmaceutically acceptable salt thereof has a d... 90 The particle size distribution is approximately 24 μm. In some embodiments, the compound of formula I or a pharmaceutically acceptable salt thereof has a d... 90 The particle size distribution is approximately 14 μm. In some embodiments, the compound of formula I or a pharmaceutically acceptable salt thereof has a d... 90 The particle size distribution has a value of approximately 11 μm. In some embodiments, the compound of formula I or a pharmaceutically acceptable salt thereof has a d 90 The particle size distribution has a value of approximately 9 μm.

[0272] In some embodiments, the compound of formula I or a pharmaceutically acceptable salt thereof has d 90 A particle size distribution with a value ≤ approximately 30 μm. In some embodiments, the compound of formula I or a pharmaceutically acceptable salt thereof has a d... 90 A particle size distribution with a value ≤ approximately 20 μm. In some embodiments, the compound of formula I or a pharmaceutically acceptable salt thereof has a d... 90 A particle size distribution with a value ≤ approximately 15 μm. In some embodiments, the compound of formula I or a pharmaceutically acceptable salt thereof has a d 90 Particle size distribution with a value ≤ approximately 10 μm.

[0273] In some embodiments, the compound of formula I or a pharmaceutically acceptable salt thereof has d 90 The particle size distribution is from about 1 μm to about 150 μm. In some embodiments, the compound of formula I or a pharmaceutically acceptable salt thereof has a d 90 The particle size distribution is from approximately 5 μm to approximately 125 μm. In some embodiments, the compound of formula I or a pharmaceutically acceptable salt thereof has a d 90 The particle size distribution is from approximately 14 μm to approximately 113 μm. In some embodiments, the compound of formula I or a pharmaceutically acceptable salt thereof has a d 90 The particle size distribution is from approximately 5 μm to approximately 60 μm. In some embodiments, the compound of formula I or a pharmaceutically acceptable salt thereof has a d 90 The value is a particle size distribution of approximately 5 μm to approximately 15 μm.

[0274] In some embodiments, the compound of Formula I or a pharmaceutically acceptable salt thereof is processed by solvent evaporation methods (e.g., spray drying, lyophilization, supercritical fluid, coprecipitation, electrospinning). In some embodiments, the compound of Formula I or a pharmaceutically acceptable salt thereof is spray-dried.

[0275] III. pharmaceutical preparations The pharmaceutical formulations described herein comprise a compound of formula I or a pharmaceutically acceptable salt thereof, and one or more excipients. These excipients may be, for example, inert diluents, fillers, granulators, disintegrants, binders, lubricants, surfactants, pH adjusters, and / or flow aids. In some embodiments, one or more excipients include fillers, disintegrants, lubricants, surfactants, pH adjusters, binders, or combinations thereof. In some embodiments, the pharmaceutical formulations disclosed herein comprise a compound of formula I or a pharmaceutically acceptable salt thereof, and one or more excipients selected from fillers, disintegrants, lubricants, surfactants, pH adjusters, and binders. In some embodiments, the pharmaceutical formulations disclosed herein comprise a compound of formula I or a pharmaceutically acceptable salt thereof, fillers, disintegrants, binders, and lubricants.

[0276] The pharmaceutical compositions disclosed herein can exist as discrete units (unit dosage forms), including but not limited to capsules, pouches, or tablets each containing a predetermined amount of the active ingredient. For example, when intended for oral use, they can be prepared as tablets, sugar lozenges, tablets, aqueous or oily suspensions, dispersible powders or granules, emulsions, hard or soft capsules, syrups, or elixirs. Compositions intended for oral use can be prepared according to any method known in the art for manufacturing pharmaceutical compositions, and such compositions may contain one or more pharmaceutical agents (including sweeteners, flavoring agents, coloring agents, and preservatives) to provide a palatable preparation.

[0277] In some embodiments, the pharmaceutical formulations disclosed herein are solid dosage forms. The solid dosage forms disclosed herein contain one or more excipients. The excipients should be compatible with the other components of the formulation and physiologically harmless to the recipient. Examples of suitable excipients can be found, for example, in Handbook of Pharmaceutical Excipients (edited by Rowe, Sheskey, and Quinn), 6th edition, 2009.

[0278] The pharmaceutical formulations disclosed herein are intended for oral administration to subjects (e.g., humans). Therefore, this document provides solid dosage forms (“solid oral dosage forms”) of compounds of formula I for oral administration.

[0279] In some embodiments, this document discloses solid oral dosage forms comprising a compound of formula I or a pharmaceutically acceptable salt thereof, and one or more excipients. Solid oral dosage forms (e.g., tablets) can be prepared by hot melt extrusion or spray-dried dispersion (SDD) technology. In some embodiments, the oral dosage form is prepared by spray drying a dispersion having one or more polymers (e.g., copovidone, povidone, hydroxypropyl methylcellulose, hydroxypropyl methylcellulose phthalate, hydroxypropyl methylcellulose acetate succinate, cellulose acetate, methacrylate-ethyl acrylate copolymer, or combinations thereof).

[0280] In some embodiments, a compound of formula I or a pharmaceutically acceptable salt thereof is spray-dried in a dispersion comprising one or more polymers. In some embodiments, the one or more polymers comprise neutral or charged polymers. In some embodiments, the one or more polymers are selected from copovidone, povidone, hydroxypropyl methylcellulose, hydroxypropyl methylcellulose phthalate, hydroxypropyl methylcellulose acetate succinate, cellulose acetate, (meth)acrylate polymers, or combinations thereof. In some embodiments, the (meth)acrylate polymer comprises a methacrylate-methyl methacrylate copolymer, a methacrylate-ethyl acrylate copolymer, or combinations thereof. In some embodiments, the one or more polymers comprise copovidone.

[0281] In some embodiments, a compound of formula I or a pharmaceutically acceptable salt thereof is spray-dried in a dispersion comprising one or more polymers, wherein the dispersion comprises about 40% to about 60% by weight of a compound of formula I or a pharmaceutically acceptable salt thereof and about 40% to about 60% by weight of one or more polymers. In some embodiments, the dispersion comprises about 50% by weight of a compound of formula I or a pharmaceutically acceptable salt thereof and about 50% by weight of one or more polymers.

[0282] In some embodiments, the solid oral dosage form is a tablet or capsule. In some embodiments, the solid oral dosage form is a tablet. In some embodiments, this document discloses a tablet containing an active ingredient blended with one or more excipients suitable for manufacturing the tablet. The tablet may be uncoated or may be coated using known techniques including microencapsulation to delay disintegration and adsorption in the gastrointestinal tract, thereby providing sustained action over a longer period. For example, delaying materials such as glyceryl monostearate or glyceryl distearate may be used alone or in combination with waxes.

[0283] In some embodiments, the solid oral dosage form is a capsule. In some embodiments, this document discloses hard capsules filled with powder, beads, or granules containing an active ingredient blended with one or more excipients suitable for manufacturing hard or soft capsules.

[0284] In some embodiments, the pharmaceutical compositions disclosed herein (e.g., solid oral dosage forms) comprise one or more excipients selected from fillers, disintegrants, binders, and lubricants. In some embodiments, one or more excipients include fillers, disintegrants, and lubricants. In some embodiments, one or more excipients include fillers, disintegrants, lubricants, and binders.

[0285] The pharmaceutical compositions disclosed herein may have desired properties for medical or pharmaceutical use. Such properties may include manufacturability (e.g., compressibility, ease of handling, ability to consistently produce doses of the same strength), physical stability (e.g., thermal stability, shelf life), chemical stability, drug loading, dissolution rate (e.g., bioavailability), and process control. Therefore, the pharmaceutical compositions (e.g., tablets) may offer advantages such as improved manufacturing processes of the compound, improved stability or storability of the compound in its pharmaceutical product form, or improved drug loading.

[0286] Compounds of Formula I The pharmaceutical compositions described herein (e.g., solid oral dosage forms) utilize compounds of Formula I, wherein the compounds of Formula I are in the form of free acids and / or pharmaceutically acceptable salts thereof.

[0287] The compound of Formula I or a pharmaceutically acceptable salt thereof may be in any suitable form (e.g., amorphous or crystalline). In some embodiments of the oral dosage forms disclosed herein, the dosage form comprises a compound of Formula I. In some embodiments of the oral dosage forms disclosed herein, the compound of Formula I is crystalline. In some embodiments of the oral dosage forms disclosed herein, the compound of Formula I is in crystalline form I. In some embodiments of the oral dosage forms disclosed herein, the compound of Formula I is amorphous.

[0288] In some embodiments of the oral dosage forms disclosed herein, the dosage form comprises a pharmaceutically acceptable salt of a compound of formula I. In some embodiments of the oral dosage forms disclosed herein, the dosage form comprises a sodium salt of a compound of formula I. In some embodiments of the oral dosage forms disclosed herein, the dosage form comprises an n-butylamine salt of a compound of formula I. In some embodiments of the oral dosage forms disclosed herein, the dosage form comprises an ammonium salt of a compound of formula I. In some embodiments of the oral dosage forms disclosed herein, the dosage form comprises an aminobutanetriol salt of a compound of formula I. In some embodiments of the oral dosage forms disclosed herein, the dosage form comprises a potassium salt of a compound of formula I. In some embodiments of the oral dosage forms disclosed herein, the dosage form comprises a diethylamine salt of a compound of formula I. In some embodiments of the oral dosage forms disclosed herein, the dosage form comprises a calcium salt of a compound of formula I. In some embodiments of the oral dosage forms disclosed herein, the dosage form comprises a magnesium salt of a compound of formula I. In some embodiments of the oral dosage forms disclosed herein, the dosage form comprises a diethanolamine salt of a compound of formula I. In some embodiments of the oral dosage forms disclosed herein, the dosage form comprises an ethylenediamine salt of a compound of formula I. In some embodiments of the oral dosage forms disclosed herein, the dosage form comprises a morpholine salt of a compound of formula I. In some embodiments of the oral dosage forms disclosed herein, the dosage form comprises an L-arginine salt of a compound of formula I. In some embodiments of the oral dosage forms disclosed herein, the dosage form comprises a trans-feruloate of a compound of formula I. In some embodiments of the oral dosage forms disclosed herein, the salt of a compound of formula I is crystalline. In some embodiments of the oral dosage forms disclosed herein, the salt of a compound of formula I is amorphous.

[0289] The pharmaceutical compositions disclosed herein (e.g., solid oral dosage forms) may comprise any suitable amount of a compound of Formula I or a pharmaceutically acceptable salt thereof, such as about 0.1 mg to about 2000 mg of a compound of Formula I or a pharmaceutically acceptable salt thereof, wherein the amount is based on the free acid form. In some embodiments, the compound of Formula I or a pharmaceutically acceptable salt thereof is expressed in amounts of about 1 mg to about 1500 mg, about 5 mg to about 1400 mg, about 5 mg to about 750 mg, about 5 mg to about 300 mg, about 5 mg to about 100 mg, about 10 mg to about 500 mg, about 10 mg to about 400 mg, about 10 mg to about 200 mg, about 10 mg to about 100 mg, about 10 mg to about 50 mg, about 10 mg to about 30 mg, about 50 mg to about 1000 mg, about 50 mg to about 800 mg, about 50 mg to about 600 mg, about 50 mg to about 400 mg, about 50 mg to about 50 mg. mg to about 300 mg, about 50 mg to about 100 mg, about 100 mg to about 1000 mg, about 100 mg to about 800 mg, about 100 mg to about 600 mg, about 100 mg to about 400 mg, about 100 mg to about 200 mg, about 200 mg to about 1000 mg, about 200 mg to about 800 mg, about 200 mg to about 700 mg, about 200 mg to about 600 mg, about 200 mg to about 400 mg, about 200 mg to about 300 mg, about 300 mg to about 1000 mg, about 300 mg to about 800 mg, about 300 mg to about 600 mg Approximately 300mg to approximately 500mg, approximately 300mg to approximately 400mg, approximately 400mg to approximately 1000mg, approximately 400mg to approximately 800mg, approximately 400mg to approximately 700mg, approximately 400mg to approximately 600mg, approximately 400mg to approximately 500mg, approximately 500mg to approximately 1000mg, approximately 500mg to approximately 800mg, approximately 500mg to approximately 600mg, approximately 600mg to approximately 1000mg, approximately 600mg to approximately 900mg, approximately 600mg to approximately 800mg, approximately 600mg to approximately 700mg, approximately 700mg to approximately 1000mg, approximately 700mg The substance is present in amounts of about 900 mg, about 700 mg to about 800 mg, about 800 mg to about 1000 mg, about 800 mg to about 900 mg, about 900 mg to about 1000 mg, about 200 mg to about 1500 mg, about 200 mg to about 1400 mg, about 400 mg to about 1300 mg, about 600 mg to about 1350 mg, about 800 mg to about 1200 mg, about 800 mg to about 1000 mg, about 1000 mg to about 1500 mg, about 1000 mg to about 1200 mg, or about 1200 mg to about 1400 mg, wherein the amount is based on the free acid form.In some embodiments, the compound of formula I or a pharmaceutically acceptable salt thereof is present in an amount of about 5 mg to about 1400 mg, wherein the amount is based on the free acid form.

[0290] In some embodiments, this document provides a solid dosage form comprising a compound of Formula I or a pharmaceutically acceptable salt thereof, and one or more excipients; wherein the compound of Formula I or a pharmaceutically acceptable salt thereof is present in an amount of about 5 mg to about 1400 mg, wherein this amount is based on a free acid form. In some embodiments, the compound of Formula I or a pharmaceutically acceptable salt thereof is present in an amount of about 5 mg to about 1350 mg, wherein this amount is based on a free acid form. In some embodiments, the compound of Formula I or a pharmaceutically acceptable salt thereof is present in an amount of about 5 mg to about 750 mg, wherein this amount is based on a free acid form. In some embodiments, the compound of Formula I or a pharmaceutically acceptable salt thereof is present in an amount of about 5 mg to about 300 mg, wherein this amount is based on a free acid form. In some embodiments, the compound of Formula I or a pharmaceutically acceptable salt thereof is present in an amount of about 5 mg to about 100 mg, wherein this amount is based on a free acid form. In some embodiments, the compound of Formula I or a pharmaceutically acceptable salt thereof is present in an amount of about 10 mg to about 250 mg, wherein this amount is based on the free acid form. In some embodiments, the compound of Formula I or a pharmaceutically acceptable salt thereof is present in an amount of about 100 mg to about 200 mg, wherein this amount is based on the free acid form. In some embodiments, the compound of Formula I or a pharmaceutically acceptable salt thereof is present in an amount of about 200 mg to about 300 mg, wherein this amount is based on the free acid form. In some embodiments, the compound of Formula I or a pharmaceutically acceptable salt thereof is present in an amount of about 300 mg to about 500 mg, wherein this amount is based on the free acid form. In some embodiments, the compound of Formula I or a pharmaceutically acceptable salt thereof is present in an amount of about 300 mg to about 400 mg, wherein this amount is based on the free acid form. In some embodiments, the compound of Formula I or a pharmaceutically acceptable salt thereof is present in an amount of about 400 mg to about 700 mg, wherein this amount is based on the free acid form. In some embodiments, the compound of Formula I or a pharmaceutically acceptable salt thereof is present in an amount of about 400 mg to about 500 mg, wherein this amount is based on the free acid form. In some embodiments, the compound of Formula I or a pharmaceutically acceptable salt thereof is present in an amount of about 600 mg to about 700 mg, wherein this amount is based on the free acid form.

[0291] In some embodiments, the compound of Formula I or a pharmaceutically acceptable salt thereof is present in an amount of about 5 mg to about 500 mg, wherein the amount is based on the free acid form. In some embodiments, the compound of Formula I or a pharmaceutically acceptable salt thereof is present in an amount of about 10 mg to about 450 mg, wherein the amount is based on the free acid form.

[0292] In some embodiments, the oral dosage form comprises a compound of formula I in an amount of about 5 mg to about 500 mg. In some embodiments, the oral dosage form comprises a compound of formula I in an amount of about 5 mg to about 500 mg, wherein the compound of formula I is in crystalline form I.

[0293] In some embodiments, the oral dosage form comprises a compound of formula I in an amount of about 10 mg to about 450 mg. In some embodiments, the oral dosage form comprises a compound of formula I in an amount of about 10 mg to about 450 mg, wherein the compound of formula I is in crystalline form I.

[0294] In some embodiments, the oral dosage form comprises a compound of formula I in an amount of about 10 mg to about 250 mg. In some embodiments, the oral dosage form comprises a compound of formula I in an amount of about 10 mg to about 250 mg, wherein the compound of formula I is in crystalline form I.

[0295] In some embodiments, the compound of Formula I or a pharmaceutically acceptable salt thereof is present in an amount of about 10 mg, wherein this amount is based on the free acid form. In some embodiments, the compound of Formula I or a pharmaceutically acceptable salt thereof is present in an amount of about 40 mg, wherein this amount is based on the free acid form. In some embodiments, the compound of Formula I or a pharmaceutically acceptable salt thereof is present in an amount of about 50 mg, wherein this amount is based on the free acid form. In some embodiments, the compound of Formula I or a pharmaceutically acceptable salt thereof is present in an amount of about 62.5 mg, wherein this amount is based on the free acid form. In some embodiments, the compound of Formula I or a pharmaceutically acceptable salt thereof is present in an amount of about 250 mg, wherein this amount is based on the free acid form. In some embodiments, the compound of Formula I or a pharmaceutically acceptable salt thereof is present in an amount of about 325 mg, wherein this amount is based on the free acid form. In some embodiments, the compound of Formula I or a pharmaceutically acceptable salt thereof is present in an amount of about 450 mg, wherein this amount is based on the free acid form. In some embodiments, the compound of formula I or a pharmaceutically acceptable salt thereof is present in an amount of about 650 mg, wherein the amount is based on the free acid form.

[0296] In some embodiments, the oral dosage form comprises about 10 mg of the compound of formula I. In some embodiments, the oral dosage form comprises about 10 mg of the compound of formula I, wherein the compound of formula I is in crystalline form I.

[0297] In some embodiments, the oral dosage form comprises about 50 mg of the compound of formula I. In some embodiments, the oral dosage form comprises about 50 mg of the compound of formula I, wherein the compound of formula I is in crystalline form I.

[0298] In some embodiments, the oral dosage form comprises about 250 mg of the compound of formula I. In some embodiments, the oral dosage form comprises about 250 mg of the compound of formula I, wherein the compound of formula I is in crystalline form I.

[0299] In some embodiments, the oral dosage form comprises about 325 mg of the compound of formula I. In some embodiments, the oral dosage form comprises about 325 mg of the compound of formula I, wherein the compound of formula I is in crystalline form I.

[0300] In some embodiments, the oral dosage form comprises about 450 mg of the compound of formula I. In some embodiments, the oral dosage form comprises about 450 mg of the compound of formula I, wherein the compound of formula I is in crystalline form I.

[0301] In some embodiments of the pharmaceutical compositions disclosed herein, the pharmaceutical composition comprises about 1% to about 50% by weight of a compound of formula I or a pharmaceutically acceptable salt thereof. For example, the pharmaceutical composition comprises about 5% to about 45%, about 1% to about 30%, about 30% to about 50%, about 1% to about 20%, about 5% to about 10%, about 10% to about 30%, about 20% to about 40%, about 5% to about 25%, about 15% to about 35%, or about 25% to about 35% of a compound of formula I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 5% to about 35% by weight of a compound of formula I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 5% to about 35% by weight of a compound of formula I. In some embodiments, the pharmaceutical composition comprises about 5% to about 10% by weight of a compound of formula I. In some embodiments, the pharmaceutical composition comprises about 7.4% by weight of a compound of formula I. In some embodiments, the pharmaceutical composition comprises about 28% to about 32% by weight of a compound of formula I. In some embodiments, the pharmaceutical composition comprises about 30% by weight of a compound of formula I.

[0302] In some embodiments of the solid oral dosage forms disclosed herein, the compound of Formula I or a pharmaceutically acceptable salt thereof is present in an amount of about 1% to about 50% (i.e., by weight) of the total weight of the dosage form. For example, the compound of Formula I or a pharmaceutically acceptable salt thereof is present in an amount of about 5% to about 45%, about 1% to about 30%, about 30% to about 50%, about 1% to about 20%, about 5% to about 10%, about 10% to about 30%, about 20% to about 40%, about 5% to about 25%, about 15% to about 35%, or about 25% to about 35% of the total weight of the dosage form. In some embodiments, the compound of Formula I or a pharmaceutically acceptable salt thereof is present in an amount of about 5% to about 45% of the total weight of the dosage form.

[0303] In some embodiments, the compound of Formula I or a pharmaceutically acceptable salt thereof is present in an amount of about 20% to about 40% of the total weight of the dosage form. In some embodiments, the compound of Formula I or a pharmaceutically acceptable salt thereof is present in an amount of about 20% of the total weight of the dosage form.

[0304] In some embodiments, the compound of Formula I or a pharmaceutically acceptable salt thereof is present in an amount of about 25% to about 35% of the total weight of the dosage form. In some embodiments, the compound of Formula I or a pharmaceutically acceptable salt thereof is present in an amount of about 30% of the total weight of the dosage form.

[0305] In some embodiments, the compound of Formula I or a pharmaceutically acceptable salt thereof is present in an amount of about 5% to about 10% of the total weight of the dosage form. In some embodiments, the compound of Formula I or a pharmaceutically acceptable salt thereof is present in an amount of about 7% of the total weight of the dosage form.

[0306] In some embodiments, the oral dosage form comprises about 5% to about 35% by weight of a compound of formula I or a pharmaceutically acceptable salt thereof. In some embodiments, the oral dosage form comprises about 5% to about 35% by weight of a compound of formula I. In some embodiments, the oral dosage form comprises about 5% to about 35% by weight of a compound of formula I, wherein the compound of formula I is in crystalline form I.

[0307] In some embodiments, the oral dosage form comprises about 5% to about 10% by weight of a compound of formula I or a pharmaceutically acceptable salt thereof. In some embodiments, the oral dosage form comprises about 5% to about 10% by weight of a compound of formula I. In some embodiments, the oral dosage form comprises about 5% to about 10% by weight of a compound of formula I, wherein the compound of formula I is in crystalline form I.

[0308] In some embodiments, the oral dosage form comprises about 7.4% by weight of a compound of formula I or a pharmaceutically acceptable salt thereof. In some embodiments, the oral dosage form comprises about 7.4% by weight of a compound of formula I. In some embodiments, the oral dosage form comprises about 7.4% by weight of a compound of formula I, wherein the compound of formula I is in crystalline form I.

[0309] In some embodiments, the oral dosage form comprises about 28% to about 32% by weight of a compound of formula I or a pharmaceutically acceptable salt thereof. In some embodiments, the oral dosage form comprises about 28% to about 32% by weight of a compound of formula I. In some embodiments, the oral dosage form comprises about 28% to about 32% by weight of a compound of formula I, wherein the compound of formula I is in crystalline form I.

[0310] In some embodiments, the oral dosage form comprises about 30% by weight of a compound of formula I or a pharmaceutically acceptable salt thereof. In some embodiments, the oral dosage form comprises about 30% by weight of a compound of formula I. In some embodiments, the oral dosage form comprises about 30% by weight of a compound of formula I, wherein the compound of formula I is in crystalline form I.

[0311] filler In some embodiments of the pharmaceutical compositions disclosed herein (e.g., solid oral dosage forms), one or more excipients include fillers (i.e., expanding agents or diluents). Examples of fillers that may be used in the pharmaceutical compositions disclosed herein (e.g., solid oral dosage forms) include, but are not limited to, starch, maltodextrin, polyols (such as lactose), cellulose, carbonates (such as calcium carbonate or sodium carbonate), phosphates (such as calcium phosphate or sodium phosphate), and povidone. In some embodiments, the filler includes microcrystalline cellulose, lactose, mannitol, calcium phosphate, or combinations thereof. In some embodiments, the filler includes lactose. In some embodiments, lactose is lactose monohydrate. In some embodiments, the filler includes microcrystalline cellulose. In some embodiments, the filler includes both lactose and microcrystalline cellulose.

[0312] In some embodiments of the pharmaceutical compositions disclosed herein, the pharmaceutical composition comprises about 1% to about 95% by weight of a filler. In some embodiments, the pharmaceutical composition comprises about 20% to about 90% by weight, about 30% to about 90% by weight, about 40% to about 90% by weight, about 50% to about 90% by weight, about 60% to about 90% by weight, about 70% to about 90% by weight, about 80% to about 90% by weight, about 45% to about 95% by weight, about 55% to about 95% by weight, about 65% to about 95% by weight, about 75% to about 95% by weight, about 85% to about 95% by weight, about 50% to about 80% by weight, about 50% to about 70% by weight, about... The pharmaceutical composition comprises 50% to about 60% by weight, about 60% to about 80% by weight, about 60% to about 70% by weight, about 70% to about 80% by weight, about 45% to about 85% by weight, about 45% to about 75% by weight, about 45% to about 65% by weight, about 55% to about 85% by weight, about 55% to about 75% by weight, about 55% to about 65% by weight, about 55% to about 60% by weight, about 65% to about 85% by weight, about 65% to about 75% by weight, about 75% to about 85% by weight, or about 80% to about 85% by weight of filler. In some embodiments, the pharmaceutical composition comprises about 50% to about 90% by weight of filler.

[0313] In some embodiments of the solid oral dosage forms disclosed herein, the filler is present in an amount of about 1% to about 95% (i.e., by weight) of the total weight of the dosage form. In some embodiments, the filler is present in amounts of about 20% to about 90%, about 30% to about 90%, about 40% to about 90%, about 50% to about 90%, about 60% to about 90%, about 60% to about 82%, about 70% to about 90%, about 80% to about 90%, about 45% to about 95%, about 55% to about 95%, about 65% to about 95%, about 75% to about 95%, about 85% to about 95%, about 50% to about 80%, about 5% to about 90% of the total weight of the dosage form. The filler is present in amounts ranging from 0% to 70%, from about 50% to 60%, from about 60% to 80%, from about 60% to 70%, from about 70% to 80%, from about 45% to 85%, from about 45% to 75%, from about 45% to 65%, from about 55% to 85%, from about 55% to 75%, from about 55% to 65%, from about 55% to 60%, from about 65% to 85%, from about 65% to 75%, from about 75% to 85%, or from about 80% to 85% of the total weight of the dosage form. In some embodiments of the solid oral dosage form disclosed herein, the filler is present in amounts ranging from about 1% to about 95% or from about 50% to about 90% of the total weight of the dosage form. In some embodiments of the solid oral dosage form disclosed herein, the filler is present in amounts ranging from about 50% to about 90% of the total weight of the dosage form. In some embodiments, the filler is present in amounts ranging from about 55% to about 85% of the total weight of the dosage form.

[0314] In some embodiments of the solid oral dosage forms disclosed herein, the filler is present in an amount of about 81% to about 83% of the total weight of the dosage form. In some embodiments of the solid oral dosage forms disclosed herein, the filler is present in an amount of about 82% of the total weight of the dosage form.

[0315] In some embodiments of the solid oral dosage forms disclosed herein, the filler is present in an amount of about 58% to about 60% of the total weight of the dosage form. In some embodiments of the solid oral dosage forms disclosed herein, the filler is present in an amount of about 59% of the total weight of the dosage form.

[0316] In some embodiments, the solid oral dosage form comprises a filler in an amount of about 50 mg to about 1000 mg. In some embodiments, the solid oral dosage form comprises about 50 mg to about 950 mg, about 50 mg to about 900 mg, about 50 mg to about 850 mg, about 50 mg to about 800 mg, about 50 mg to about 750 mg, about 50 mg to about 700 mg, about 50 mg to about 650 mg, about 50 mg to about 600 mg, about 50 mg to about 550 mg, about 50 mg to about 500 mg, about 50 mg to about 450 mg, about 50 mg to about 400 mg, about 50 mg to about 350 mg, about 5... 0 mg to about 300 mg, about 50 mg to about 250 mg, about 50 mg to about 200 mg, about 50 mg to about 150 mg, about 50 mg to about 100 mg, about 90 mg to about 500 mg, about 90 mg to about 450 mg, about 90 mg to about 400 mg, about 90 mg to about 350 mg, about 90 mg to about 300 mg, about 90 mg to about 250 mg, about 90 mg to about 200 mg, about 90 mg to about 150 mg, about 150 mg to about 500 mg, about 150 mg to Approximately 450 mg, approximately 150 mg to approximately 400 mg, approximately 150 mg to approximately 350 mg, approximately 150 mg to approximately 300 mg, approximately 150 mg to approximately 250 mg, approximately 150 mg to approximately 200 mg, approximately 200 mg to approximately 500 mg, approximately 200 mg to approximately 450 mg, approximately 200 mg to approximately 400 mg, approximately 200 mg to approximately 350 mg, approximately 200 mg to approximately 300 mg, approximately 200 mg to approximately 250 mg, approximately 250 mg to approximately 500 mg, approximately 250 mg to approximately 450 mg A filler in amounts of about 250 mg to about 400 mg, about 250 mg to about 350 mg, about 250 mg to about 300 mg, about 300 mg to about 500 mg, about 300 mg to about 450 mg, about 300 mg to about 400 mg, about 300 mg to about 350 mg, about 350 mg to about 500 mg, about 350 mg to about 450 mg, about 350 mg to about 400 mg, about 400 mg to about 500 mg, about 400 mg to about 450 mg, or about 450 mg to about 500 mg.

[0317] In some embodiments, the solid oral dosage form contains a filler amount of about 60 mg to about 1000 mg. In some embodiments, the solid oral dosage form contains a filler amount of about 90 mg to about 900 mg. In some embodiments, the solid oral dosage form contains a filler amount of about 90 mg to about 500 mg. In some embodiments, the solid oral dosage form contains a filler amount of about 111 mg. In some embodiments, the solid oral dosage form contains a filler amount of about 99 mg. In some embodiments, the solid oral dosage form contains a filler amount of about 493 mg. In some embodiments, the solid oral dosage form contains a filler amount of about 641 mg. In some embodiments, the solid oral dosage form contains a filler amount of about 887 mg.

[0318] In some embodiments of the pharmaceutical compositions disclosed herein, the pharmaceutical compositions comprise lactose (e.g., lactose monohydrate). In some embodiments, the pharmaceutical compositions comprise about 20% to about 50% by weight or about 25% to about 45% by weight of lactose. In some embodiments, the pharmaceutical compositions comprise about 20% to about 50% by weight of lactose. In some embodiments, the pharmaceutical compositions comprise about 25% to about 45% by weight of lactose. In some embodiments, the pharmaceutical compositions comprise about 35% to about 45% by weight of lactose. In some embodiments, the pharmaceutical compositions comprise about 41% by weight of lactose. In some embodiments, the pharmaceutical compositions comprise about 25% to about 35% by weight of lactose. In some embodiments, the pharmaceutical compositions comprise about 30% by weight of lactose.

[0319] In some embodiments of the solid oral dosage forms disclosed herein, the filler includes lactose (e.g., lactose monohydrate). In some embodiments, lactose is present in an amount of about 20% to about 50% or about 25% to about 45% of the total weight of the dosage form. In some embodiments, lactose is present in an amount of about 20% to about 50% of the total weight of the dosage form. In some embodiments, lactose is present in an amount of about 25% to about 45% of the total weight of the dosage form.

[0320] In some embodiments, the oral dosage form contains about 20% to about 50% by weight of lactose, wherein the lactose is lactose monohydrate. In some embodiments, the oral dosage form contains about 25% to about 45% by weight of lactose, wherein the lactose is lactose monohydrate.

[0321] In some embodiments, lactose is present in an amount of about 25% to about 35% of the total weight of the dosage form. In some embodiments, lactose is present in an amount of about 29% to about 31% of the total weight of the dosage form. In some embodiments, lactose is present in an amount of about 30% of the total weight of the dosage form.

[0322] In some embodiments, the oral dosage form contains about 25% to about 35% by weight of lactose, wherein the lactose is lactose monohydrate. In some embodiments, the oral dosage form contains about 30% by weight of lactose, wherein the lactose is lactose monohydrate.

[0323] In some embodiments, lactose is present in an amount of about 35% to about 45% of the total weight of the dosage form. In some embodiments, lactose is present in an amount of about 40% to about 42% of the total weight of the dosage form. In some embodiments, lactose is present in an amount of about 41% of the total weight of the dosage form.

[0324] In some embodiments, the oral dosage form contains about 35% to about 45% by weight of lactose, wherein the lactose is lactose monohydrate. In some embodiments, the oral dosage form contains about 41% by weight of lactose, wherein the lactose is lactose monohydrate.

[0325] In some embodiments, the solid oral dosage form contains an amount of lactose (e.g., lactose monohydrate) of about 1 mg to about 1000 mg. In some embodiments, the solid oral dosage form contains about 10 mg to about 900 mg, about 10 mg to about 800 mg, about 10 mg to about 700 mg, about 10 mg to about 600 mg, about 10 mg to about 500 mg, about 10 mg to about 400 mg, about 10 mg to about 300 mg, about 10 mg to about 250 mg, about 10 mg to about 200 mg, about 10 mg to about 150 mg, about 10 mg to about 100 mg, about 10 mg to about 60 mg, about 50 mg to about 500 mg, about 50 mg to about 300 mg, about... Lactose monohydrate in amounts of 50 mg to about 250 mg, about 45 mg to about 250 mg, about 50 mg to about 200 mg, about 50 mg to about 150 mg, about 100 mg to about 500 mg, about 100 mg to about 300 mg, about 100 mg to about 250 mg, about 100 mg to about 200 mg, about 200 mg to about 500 mg, about 200 mg to about 450 mg, about 200 mg to about 400 mg, about 200 mg to about 350 mg, about 200 mg to about 300 mg, or about 200 mg to about 250 mg.

[0326] In some embodiments, the solid oral dosage form contains about 10 mg to about 500 mg of lactose. In some embodiments, the solid oral dosage form contains about 30 mg to about 500 mg of lactose. In some embodiments, the solid oral dosage form contains about 10 mg to about 450 mg of lactose. In some embodiments, the solid oral dosage form contains about 10 mg to about 250 mg of lactose. In some embodiments, the solid oral dosage form contains about 40 mg to about 250 mg of lactose. In some embodiments, the solid oral dosage form contains about 45 mg to about 450 mg of lactose. In some embodiments, the solid oral dosage form contains about 45 mg to about 250 mg of lactose. In some embodiments, the solid oral dosage form contains about 55 mg of lactose. In some embodiments, the solid oral dosage form contains about 49 mg of lactose. In some embodiments, the solid oral dosage form contains about 246 mg of lactose. In some embodiments, the solid oral dosage form contains about 320 mg of lactose. In some implementations, the solid oral dosage form contains approximately 444 mg of lactose.

[0327] In some embodiments of the pharmaceutical compositions disclosed herein, the pharmaceutical compositions comprise microcrystalline cellulose. In some embodiments, the pharmaceutical compositions comprise about 20% to about 50% by weight or about 25% to about 45% by weight of microcrystalline cellulose. In some embodiments, the pharmaceutical compositions comprise about 20% to about 50% by weight of microcrystalline cellulose. In some embodiments, the pharmaceutical compositions comprise about 25% to about 45% by weight of microcrystalline cellulose. In some embodiments, the pharmaceutical compositions comprise about 35% to about 45% by weight of microcrystalline cellulose. In some embodiments, the pharmaceutical compositions comprise about 41% by weight of microcrystalline cellulose. In some embodiments, the pharmaceutical compositions comprise about 25% to about 35% by weight of microcrystalline cellulose. In some embodiments, the pharmaceutical compositions comprise about 30% by weight of microcrystalline cellulose.

[0328] In some embodiments of the solid oral dosage forms disclosed herein, the filler includes microcrystalline cellulose. In some embodiments, microcrystalline cellulose is present in an amount of about 20% to about 50% or about 25% to about 45% of the total weight of the dosage form. In some embodiments, microcrystalline cellulose is present in an amount of about 20% to about 50% of the total weight of the dosage form. In some embodiments, microcrystalline cellulose is present in an amount of about 25% to about 45% of the total weight of the dosage form.

[0329] In some embodiments, microcrystalline cellulose is present in an amount of about 25% to about 35% of the total weight of the dosage form. In some embodiments, microcrystalline cellulose is present in an amount of about 29% to about 31% of the total weight of the dosage form. In some embodiments, microcrystalline cellulose is present in an amount of about 30% of the total weight of the dosage form.

[0330] In some embodiments, microcrystalline cellulose is present in an amount of about 35% to about 45% of the total weight of the dosage form. In some embodiments, microcrystalline cellulose is present in an amount of about 40% to about 42% of the total weight of the dosage form. In some embodiments, microcrystalline cellulose is present in an amount of about 41% of the total weight of the dosage form.

[0331] In some embodiments, the solid oral dosage form comprises microcrystalline cellulose in an amount of about 1 mg to about 1000 mg. In some embodiments, the solid oral dosage form comprises about 10 mg to about 900 mg, about 10 mg to about 800 mg, about 10 mg to about 700 mg, about 10 mg to about 600 mg, about 10 mg to about 500 mg, about 10 mg to about 400 mg, about 10 mg to about 300 mg, about 10 mg to about 250 mg, about 10 mg to about 200 mg, about 10 mg to about 150 mg, about 10 mg to about 100 mg, about 10 mg to about 60 mg, about 50 mg to about 500 mg, about 50 mg to about 300 mg, about... Microcrystalline cellulose in amounts of 50 mg to about 250 mg, about 45 mg to about 250 mg, about 50 mg to about 200 mg, about 50 mg to about 150 mg, about 100 mg to about 500 mg, about 100 mg to about 300 mg, about 100 mg to about 250 mg, about 100 mg to about 200 mg, about 200 mg to about 500 mg, about 200 mg to about 450 mg, about 200 mg to about 400 mg, about 200 mg to about 350 mg, about 200 mg to about 300 mg, or about 200 mg to about 250 mg. In some embodiments, the solid oral dosage form contains about 10 mg to about 250 mg of microcrystalline cellulose.

[0332] In some embodiments, the solid oral dosage form contains about 10 mg to about 500 mg of microcrystalline cellulose. In some embodiments, the solid oral dosage form contains about 30 mg to about 500 mg of microcrystalline cellulose. In some embodiments, the solid oral dosage form contains about 45 mg to about 450 mg of microcrystalline cellulose. In some embodiments, the solid oral dosage form contains about 45 mg to about 250 mg of microcrystalline cellulose. In some embodiments, the solid oral dosage form contains about 55 mg of microcrystalline cellulose. In some embodiments, the solid oral dosage form contains about 49 mg of microcrystalline cellulose. In some embodiments, the solid oral dosage form contains about 246 mg of microcrystalline cellulose. In some embodiments, the solid oral dosage form contains about 320 mg of microcrystalline cellulose. In some embodiments, the solid oral dosage form contains about 444 mg of microcrystalline cellulose.

[0333] In some embodiments, the filler comprises a mixture of lactose and microcrystalline cellulose, wherein the weight ratio of lactose to microcrystalline cellulose is about 1:4 to about 4:1, about 1:3 to about 3:1, about 2:3 to about 3:2, or about 1:1. In some embodiments, the filler comprises a mixture of lactose and microcrystalline cellulose, wherein the weight ratio of lactose to microcrystalline cellulose is about 2:3 to about 3:2. In some embodiments, the filler comprises a mixture of lactose and microcrystalline cellulose, wherein the weight ratio of lactose to microcrystalline cellulose is about 1:4, about 4:1, about 1:3, 3:1, about 2:3, about 3:2, or about 1:1. In some embodiments, the filler comprises a mixture of lactose and microcrystalline cellulose, wherein the weight ratio of lactose to microcrystalline cellulose is about 1:1.

[0334] In some embodiments, the oral dosage form comprises about 5 mg to about 500 mg of the compound of formula I and about 60 mg to about 1000 mg of a filler. In some embodiments, the oral dosage form comprises about 10 mg to about 450 mg of the compound of formula I and about 90 mg to about 900 mg of a filler. In some embodiments, the oral dosage form comprises about 10 mg to about 250 mg of the compound of formula I and about 90 mg to about 500 mg of a filler. In some embodiments, the oral dosage form comprises about 10 mg of the compound of formula I and about 111 mg of a filler. In some embodiments, the oral dosage form comprises about 50 mg of the compound of formula I and about 99 mg of a filler. In some embodiments, the oral dosage form comprises about 250 mg of the compound of formula I and about 493 mg of a filler. In some embodiments, the oral dosage form comprises about 325 mg of the compound of formula I and about 641 mg of a filler. In some embodiments, the oral dosage form comprises about 450 mg of the compound of formula I and about 887 mg of a filler. In some embodiments, the solid dosage form is a tablet.

[0335] In some embodiments, the oral dosage form comprises about 5 mg to about 500 mg of the compound of formula I, about 30 mg to about 500 mg of lactose, and about 30 mg to about 500 mg of microcrystalline cellulose. In some embodiments, the oral dosage form comprises about 10 mg to about 450 mg of the compound of formula I, about 45 mg to about 450 mg of lactose, and about 45 mg to about 450 mg of microcrystalline cellulose. In some embodiments, the oral dosage form comprises about 10 mg to about 250 mg of the compound of formula I, about 45 mg to about 250 mg of lactose, and about 45 mg to about 250 mg of microcrystalline cellulose. In some embodiments, the oral dosage form comprises about 10 mg of the compound of formula I, about 55 mg of lactose, and about 55 mg of microcrystalline cellulose. In some embodiments, the oral dosage form comprises about 50 mg of the compound of formula I, about 49 mg of lactose, and about 49 mg of microcrystalline cellulose. In some embodiments, the oral dosage form comprises about 250 mg of the compound of formula I, about 246 mg of lactose, and about 246 mg of microcrystalline cellulose. In some embodiments, the oral dosage form comprises about 325 mg of the compound of formula I, about 320 mg of lactose, and about 320 mg of microcrystalline cellulose. In some embodiments, the oral dosage form comprises about 450 mg of the compound of formula I, about 444 mg of lactose, and about 444 mg of microcrystalline cellulose. In some embodiments, the solid dosage form is a tablet.

[0336] Disintegrant In some embodiments of the pharmaceutical compositions disclosed herein (e.g., solid oral dosage forms), one or more excipients include disintegrants (i.e., cleavage agents). Examples of cleavage agents that may be used in the pharmaceutical compositions described herein (e.g., solid oral dosage forms) include, but are not limited to, starch (e.g., corn starch), pregelatinized starch, hydroxypropyl starch, cellulose (e.g., microcrystalline cellulose and low-substituted hydroxypropyl cellulose), cross-linked PVP (crosspovidone), sodium carboxymethyl starch, sodium cross-linked carboxymethyl cellulose, and alginate. In some embodiments, the disintegrant includes starch, pregelatinized starch, hydroxypropyl starch, cellulose, crosspovidone, sodium carboxymethyl starch, sodium cross-linked carboxymethyl cellulose, or combinations thereof. In some embodiments, the disintegrant includes pregelatinized starch. In some embodiments, the disintegrant includes sodium cross-linked carboxymethyl cellulose. In some embodiments, the disintegrant includes crosspovidone.

[0337] In some implementations, the filler includes lactose and microcrystalline cellulose, and the disintegrant includes croscarmellose sodium.

[0338] In some embodiments of the pharmaceutical compositions disclosed herein, the pharmaceutical compositions comprise about 1% to about 50% by weight, about 1% to about 20% by weight, about 1% to about 15% by weight, about 1% to about 10% by weight, about 5% to about 15% by weight, or about 5% to about 8% by weight of a disintegrant. In some embodiments, the pharmaceutical compositions comprise about 1% to about 10% by weight of a disintegrant.

[0339] In some embodiments of the solid oral dosage forms disclosed herein, the disintegrant is present in an amount of about 1% to about 50%, about 1% to about 20%, about 1% to about 15%, about 1% to about 10%, about 5% to about 15%, or about 5% to about 8% (i.e., by weight%) of the total weight of the dosage form. In some embodiments, the disintegrant is present in an amount of about 1% to about 9%, about 1% to about 8%, about 1% to about 7%, about 1% to about 6%, about 1% to about 5%, about 1% to about 4%, about 1% to about 3%, about 1% to about 2%, about 2% to about 10%, 2% to about 9%, about 2% to about 8%, about 2% to about 7%, about 2% to about 6%, about 2% to about 5%, about 2% to about 4%, about 2% to about 3%, about 3% to about 10%, about 3% to about 9%, about 3% to about 8%, about 3% to about 7%, about 3% to about 6 ... The amounts are present in quantities of approximately 5%, approximately 3% to approximately 4%, approximately 4% to approximately 10%, approximately 4% to approximately 9%, approximately 4% to approximately 8%, approximately 4% to approximately 7%, approximately 4% to approximately 6%, approximately 4% to approximately 5%, approximately 5% to approximately 10%, approximately 5% to approximately 9%, approximately 5% to approximately 8%, approximately 5% to approximately 7%, approximately 5% to approximately 6%, approximately 6% to approximately 10%, approximately 6% to approximately 9%, approximately 6% to approximately 8%, approximately 6% to approximately 7%, approximately 7% to approximately 10%, approximately 7% to approximately 9%, approximately 7% to approximately 8%, approximately 8% to approximately 10%, approximately 8% to approximately 9%, or approximately 9% to approximately 10%.

[0340] In some embodiments of the solid oral dosage forms disclosed herein, the disintegrant is present in an amount of about 1% to about 10% of the total weight of the dosage form. In some embodiments, the disintegrant is present in an amount of about 3% to about 7% of the total weight of the dosage form. In some embodiments, the disintegrant is present in an amount of about 5% of the total weight of the dosage form.

[0341] In some embodiments, the solid oral dosage form contains a disintegrant in an amount of about 1 mg to about 200 mg. In some embodiments, the solid oral dosage form contains a disintegrant in an amount of about 5 mg to about 150 mg, 5 mg to about 140 mg, 5 mg to about 130 mg, 5 mg to about 120 mg, 5 mg to about 111 mg, 5 mg to about 100 mg, 5 mg to about 90 mg, 5 mg to about 80 mg, 5 mg to about 70 mg, 5 mg to about 60 mg, 5 mg to about 50 mg, 5 mg to about 45 mg, 5 mg to about 40 mg, about 5 mg to about 30 mg, about 5 mg to about 20 mg, about 5 mg to about 10 mg, about 10 mg to about 50 mg, about 10 mg to about 40 mg, about 10 mg to about 30 mg, about 10 mg to about 20 mg, about 20 mg to about 50 mg, about 30 mg to about 50 mg, about 20 mg to about 30 mg, about 30 mg to about 40 mg, or about 40 mg to about 50 mg.

[0342] In some embodiments, the solid oral dosage form contains about 1 mg to about 100 mg of disintegrant. In some embodiments, the solid oral dosage form contains about 5 mg to about 80 mg of disintegrant. In some embodiments, the solid oral dosage form contains about 5 mg to about 45 mg of disintegrant. In some embodiments, the solid oral dosage form contains about 7 mg of disintegrant. In some embodiments, the solid oral dosage form contains about 8 mg of disintegrant. In some embodiments, the solid oral dosage form contains about 42 mg of disintegrant. In some embodiments, the solid oral dosage form contains about 54 mg of disintegrant. In some embodiments, the solid oral dosage form contains about 75 mg of disintegrant.

[0343] In some embodiments of the pharmaceutical compositions disclosed herein, the disintegrant includes croscarmellose sodium. In some embodiments, the pharmaceutical composition comprises about 1% to about 50% by weight, about 1% to about 20% by weight, about 1% to about 15% by weight, about 1% to about 10% by weight, about 5% to about 15% by weight, or about 5% to about 8% by weight of croscarmellose sodium. In some embodiments, the pharmaceutical composition comprises about 1% to about 10% by weight of croscarmellose sodium. In some embodiments, the pharmaceutical composition comprises about 3% to about 7% by weight of croscarmellose sodium. In some embodiments, the pharmaceutical composition comprises about 5% by weight of croscarmellose sodium.

[0344] In some embodiments of the solid oral dosage forms disclosed herein, the disintegrant includes croscarmellose sodium. In some embodiments, the solid oral dosage form comprises about 1% to about 50% by weight, about 1% to about 20% by weight, about 1% to about 15% by weight, about 1% to about 10% by weight, about 5% to about 15% by weight, or about 5% to about 8% by weight of croscarmellose sodium. In some embodiments, the solid oral dosage form comprises about 1% to about 10% by weight of croscarmellose sodium. In some embodiments, the solid oral dosage form comprises about 3% to about 7% by weight of croscarmellose sodium. In some embodiments, the solid oral dosage form comprises about 5% by weight of croscarmellose sodium.

[0345] In some embodiments, the solid oral dosage form contains about 1 mg to about 200 mg of croscarmellose sodium. In some embodiments, the solid oral dosage form contains about 1 mg to about 100 mg of croscarmellose sodium. In some embodiments, the solid oral dosage form contains about 5 mg to about 80 mg of croscarmellose sodium. In some embodiments, the solid oral dosage form contains about 5 mg to about 45 mg of croscarmellose sodium. In some embodiments, the solid oral dosage form contains about 7 mg of croscarmellose sodium. In some embodiments, the solid oral dosage form contains about 8 mg of croscarmellose sodium. In some embodiments, the solid oral dosage form contains about 42 mg of croscarmellose sodium. In some embodiments, the solid oral dosage form contains about 54 mg of croscarmellose sodium. In some embodiments, the solid oral dosage form contains about 75 mg of croscarmellose sodium.

[0346] In some embodiments, the solid oral dosage form comprises about 5 mg to about 500 mg of the compound of formula I and about 1 mg to about 100 mg of a disintegrant. In some embodiments, the solid oral dosage form comprises about 10 mg to about 450 mg of the compound of formula I and about 5 mg to about 80 mg of a disintegrant. In some embodiments, the solid oral dosage form comprises about 10 mg to about 250 mg of the compound of formula I and about 5 mg to about 45 mg of a disintegrant. In some embodiments, the solid oral dosage form comprises about 10 mg of the compound of formula I and about 7 mg of a disintegrant. In some embodiments, the solid oral dosage form comprises about 50 mg of the compound of formula I and about 8 mg of a disintegrant. In some embodiments, the solid oral dosage form comprises about 250 mg of the compound of formula I and about 42 mg of a disintegrant. In some embodiments, the solid oral dosage form comprises about 325 mg of the compound of formula I and about 54 mg of a disintegrant. In some embodiments, the solid oral dosage form comprises about 450 mg of the compound of formula I and about 75 mg of a disintegrant. In some embodiments, the solid oral dosage form is a tablet.

[0347] lubricant In some embodiments of the pharmaceutical compositions disclosed herein (e.g., solid oral dosage forms), one or more excipients include a lubricant. Examples of lubricants that may be used in the pharmaceutical compositions disclosed herein (e.g., solid oral dosage forms) include, but are not limited to, magnesium stearate, calcium stearate, stearic acid, hydrogenated vegetable oil, glyceryl palmitate, glyceryl betaine, sodium stearoyl fumarate, colloidal silica, carnauba wax, polyethylene glycol, and talc. In some embodiments, the lubricant includes stearic acid, sodium stearoyl fumarate, magnesium stearate, or combinations thereof. In some embodiments, the lubricant includes magnesium stearate.

[0348] In some embodiments, the filler includes lactose and microcrystalline cellulose, the disintegrant includes croscarmellose sodium, and the lubricant includes magnesium stearate.

[0349] In some embodiments of the pharmaceutical compositions disclosed herein, the pharmaceutical compositions comprise about 0.01% to about 10% by weight, about 0.1% to about 5% by weight, or about 0.1% to about 2% by weight of a lubricant. In some embodiments, the pharmaceutical compositions comprise about 0.1% to about 5% by weight of a lubricant.

[0350] In some embodiments of the solid oral dosage forms disclosed herein, the lubricant is present in an amount of about 0.01% to about 10%, about 0.1% to about 5%, or about 0.1% to about 2% (i.e., by weight) of the total weight of the dosage form. In some embodiments, the lubricant is present in an amount of about 0.01% to about 10% of the total weight of the dosage form. In some embodiments, the lubricant is present in an amount of about 0.1% to about 5% of the total weight of the dosage form. In some embodiments, the lubricant is present in an amount of about 0.1% to about 2% of the total weight of the dosage form. In some embodiments, the lubricant is present in an amount of about 1% to about 2% of the total weight of the dosage form. In some embodiments, the lubricant is present in an amount of about 1.5% of the total weight of the dosage form.

[0351] In some embodiments, the solid oral dosage form contains less than about 100 mg of lubricant. For example, the solid oral dosage form contains less than about 90 mg, less than about 80 mg, less than about 70 mg, less than about 60 mg, less than about 50 mg, less than about 40 mg, less than about 30 mg, less than about 20 mg, less than about 15 mg, or less than about 10 mg of lubricant. In some embodiments, the solid oral dosage form contains lubricant in amounts of about 0.1 mg to about 100 mg, about 0.5 mg to about 50 mg, about 0.5 mg to about 40 mg, about 0.5 mg to about 30 mg, about 0.5 mg to about 20 mg, about 0.5 mg to about 15 mg, about 0.5 mg to about 10 mg, about 1 mg to about 15 mg, about 1.5 mg to about 12.5 mg, or about 2 mg to about 12 mg.

[0352] In some embodiments, the solid oral dosage form contains about 0.5 mg to about 30 mg of lubricant. In some embodiments, the solid oral dosage form contains about 0.5 mg to about 25 mg of lubricant. In some embodiments, the solid oral dosage form contains about 0.5 mg to about 20 mg of lubricant. In some embodiments, the solid oral dosage form contains about 0.5 mg to about 10 mg of lubricant. In some embodiments, the solid oral dosage form contains about 2 mg to about 23 mg of lubricant. In some embodiments, the solid oral dosage form contains about 2 mg to about 12 mg of lubricant. In some embodiments, the solid oral dosage form contains about 2 mg of lubricant. In some embodiments, the solid oral dosage form contains about 2.5 mg of lubricant. In some embodiments, the solid oral dosage form contains about 12 mg of lubricant. In some embodiments, the solid oral dosage form contains about 16 mg of lubricant. In some embodiments, the solid oral dosage form contains about 22 mg of lubricant.

[0353] In some embodiments, the pharmaceutical compositions disclosed herein comprise magnesium stearate. In some embodiments, the pharmaceutical composition comprises about 0.1% to about 2% by weight of magnesium stearate. In some embodiments, the pharmaceutical composition comprises about 1% to about 2% by weight of magnesium stearate. In some embodiments, the pharmaceutical composition comprises about 1.5% by weight of magnesium stearate.

[0354] In some embodiments, the solid oral dosage forms disclosed herein comprise magnesium stearate. In some embodiments, the oral dosage form comprises about 0.1% by weight to about 2% by weight of magnesium stearate. In some embodiments, the oral dosage form comprises about 1% by weight to about 2% by weight of magnesium stearate. In some embodiments, the solid oral dosage form comprises about 1.5% by weight of magnesium stearate. In some embodiments, the solid oral dosage form comprises magnesium stearate in amounts of about 0.1 mg to about 100 mg, about 0.5 mg to about 50 mg, about 0.5 mg to about 40 mg, about 0.5 mg to about 30 mg, about 0.5 mg to about 20 mg, about 0.5 mg to about 15 mg, about 0.5 mg to about 10 mg, about 1 mg to about 15 mg, about 1.5 mg to about 12.5 mg, or about 2 mg to about 12 mg.

[0355] In some embodiments, the solid oral dosage form contains magnesium stearate in an amount of about 0.5 mg to about 30 mg. In some embodiments, the solid oral dosage form contains magnesium stearate in an amount of about 0.5 mg to about 25 mg. In some embodiments, the solid oral dosage form contains magnesium stearate in an amount of about 0.5 mg to about 20 mg. In some embodiments, the solid oral dosage form contains magnesium stearate in an amount of about 0.5 mg to about 10 mg. In some embodiments, the solid oral dosage form contains magnesium stearate in an amount of about 2 mg to about 23 mg. In some embodiments, the solid oral dosage form contains magnesium stearate in an amount of about 2 mg to about 12 mg. In some embodiments, the solid oral dosage form contains magnesium stearate in an amount of about 2 mg. In some embodiments, the solid oral dosage form contains magnesium stearate in an amount of about 2.5 mg. In some embodiments, the solid oral dosage form contains magnesium stearate in an amount of about 12 mg. In some embodiments, the solid oral dosage form contains magnesium stearate in an amount of about 16 mg. In some implementations, the solid oral dosage form contains approximately 22 mg of magnesium stearate.

[0356] In some embodiments, the solid oral dosage form comprises about 5 mg to about 500 mg of the compound of formula I and about 0.5 mg to about 30 mg of a lubricant. In some embodiments, the solid oral dosage form comprises about 10 mg to about 450 mg of the compound of formula I and about 0.5 mg to about 25 mg of a lubricant. In some embodiments, the solid oral dosage form comprises about 10 mg to about 250 mg of the compound of formula I and about 0.5 mg to about 10 mg of a lubricant. In some embodiments, the solid oral dosage form comprises about 10 mg of the compound of formula I and about 2 mg of a lubricant. In some embodiments, the solid oral dosage form comprises about 50 mg of the compound of formula I and about 2.5 mg of a lubricant. In some embodiments, the solid oral dosage form comprises about 250 mg of the compound of formula I and about 12 mg of a lubricant. In some embodiments, the solid oral dosage form comprises about 325 mg of the compound of formula I and about 16 mg of a lubricant. In some embodiments, the solid oral dosage form comprises about 450 mg of the compound of formula I and about 22 mg of a lubricant. In some embodiments, the solid oral dosage form is a tablet.

[0357] In some embodiments, the pharmaceutical compositions disclosed herein (e.g., solid oral dosage forms) comprise an in-particle lubricant and an out-of-particle lubricant. In some embodiments, the pharmaceutical composition comprises about 0.05% by weight to about 1% by weight of an in-particle lubricant and about 0.05% by weight to about 1% by weight of an out-of-particle lubricant. In some embodiments, the pharmaceutical composition comprises about 0.75% by weight of an in-particle lubricant and about 0.75% by weight of an out-of-particle lubricant.

[0358] adhesives In some embodiments of the pharmaceutical compositions disclosed herein (e.g., solid oral dosage forms), one or more excipients include a binder. Examples of binders that may be used in the pharmaceutical compositions disclosed herein (e.g., solid oral dosage forms) include, but are not limited to, cellulose (e.g., microcrystalline cellulose, hydroxypropyl cellulose), starch, gelatin, and gum arabic. In some embodiments, the binder includes cellulose, starch, gelatin, gum arabic, or combinations thereof. In some embodiments, the binder includes microcrystalline cellulose, hydroxypropyl cellulose, starch, gelatin, gum arabic, or combinations thereof. In some embodiments, the binder includes cellulose. In some embodiments, the binder includes hydroxypropyl cellulose.

[0359] In some embodiments, the filler includes lactose and microcrystalline cellulose, the disintegrant includes croscarmellose sodium, the lubricant includes magnesium stearate, and the binder includes hydroxypropyl cellulose.

[0360] In some embodiments of the pharmaceutical compositions disclosed herein, the pharmaceutical compositions comprise about 1% to about 10% by weight of a binder. In some embodiments of the pharmaceutical compositions disclosed herein, the pharmaceutical compositions comprise about 2% to about 6% by weight of a binder.

[0361] In some embodiments of the solid oral dosage forms disclosed herein, the binder is present in an amount of about 1% to about 10% (i.e., weight %) of the total weight of the dosage form. In some embodiments, the binder is present in an amount of about 1% to about 9%, about 1% to about 8%, about 1% to about 7%, about 1% to about 6%, about 1% to about 5%, about 2% to about 9%, about 2% to about 8%, about 2% to about 6%, about 2% to about 5%, about 3% to about 9%, about 3% to about 8%, about 3% to about 7%, about 3% to about 6%, about 3% to about 5%, or about 4% to about 6% of the total weight of the dosage form. In some embodiments, the binder is present in an amount of about 2% to about 6% of the total weight of the dosage form. In some embodiments, the binder is present in an amount of about 4% of the total weight of the dosage form.

[0362] In some embodiments, the solid oral dosage form comprises a binder in an amount of about 0.1 mg to about 100 mg. In some embodiments, the solid oral dosage form comprises a binder in an amount of about 1 mg to about 50 mg, about 1 mg to about 40 mg, about 1 mg to about 30 mg, about 1 mg to about 20 mg, about 1 mg to about 15 mg, about 1 mg to about 10 mg, about 5 mg to about 10 mg, about 10 mg to about 50 mg, about 10 mg to about 40 mg, about 20 mg to about 50 mg, about 20 mg to about 40 mg, about 20 mg to about 30 mg, about 30 mg to about 50 mg, about 30 mg to about 40 mg, or about 30 mg to about 35 mg.

[0363] In some embodiments, the solid oral dosage form contains a binder in an amount of about 1 mg to about 80 mg. In some embodiments, the solid oral dosage form contains a binder in an amount of about 5 mg to about 60 mg. In some embodiments, the solid oral dosage form contains a binder in an amount of about 5 mg to about 35 mg. In some embodiments, the solid oral dosage form contains a binder in an amount of about 5 mg. In some embodiments, the solid oral dosage form contains a binder in an amount of about 7 mg. In some embodiments, the solid oral dosage form contains a binder in an amount of about 33 mg. In some embodiments, the solid oral dosage form contains a binder in an amount of about 43 mg. In some embodiments, the solid oral dosage form contains a binder in an amount of about 60 mg.

[0364] In some embodiments, the pharmaceutical compositions disclosed herein comprise hydroxypropyl cellulose. In some embodiments, the pharmaceutical composition comprises about 1% to about 10% by weight of hydroxypropyl cellulose. In some embodiments, the pharmaceutical composition comprises about 2% to about 6% by weight of hydroxypropyl cellulose. In some embodiments, the pharmaceutical composition comprises about 4% by weight of hydroxypropyl cellulose.

[0365] In some embodiments, the solid oral dosage forms disclosed herein comprise hydroxypropyl cellulose. In some embodiments, the oral dosage form comprises about 1% to about 10% by weight of hydroxypropyl cellulose. In some embodiments, the oral dosage form comprises about 2% to about 6% by weight of hydroxypropyl cellulose. In some embodiments, the oral dosage form comprises about 4% by weight of hydroxypropyl cellulose.

[0366] In some embodiments, the solid oral dosage form contains about 0.1 mg to about 100 mg of hydroxypropyl cellulose. In some embodiments, the solid oral dosage form contains about 1 mg to about 80 mg of hydroxypropyl cellulose. In some embodiments, the solid oral dosage form contains about 1 mg to about 60 mg of hydroxypropyl cellulose. In some embodiments, the solid oral dosage form contains about 1 mg to about 50 mg of hydroxypropyl cellulose. In some embodiments, the solid oral dosage form contains about 5 mg to about 60 mg of hydroxypropyl cellulose. In some embodiments, the solid oral dosage form contains about 5 mg to about 35 mg of hydroxypropyl cellulose. In some embodiments, the solid oral dosage form contains about 5 mg of hydroxypropyl cellulose. In some embodiments, the solid oral dosage form contains about 7 mg of hydroxypropyl cellulose. In some embodiments, the solid oral dosage form contains about 33 mg of hydroxypropyl cellulose. In some embodiments, the solid oral dosage form contains about 43 mg of hydroxypropyl cellulose. In some embodiments, the solid oral dosage form contains about 60 mg of hydroxypropyl cellulose.

[0367] In some embodiments, the solid oral dosage form comprises about 5 mg to about 500 mg of a compound of formula I and about 1 mg to about 80 mg of a binder. In some embodiments, the solid oral dosage form comprises about 10 mg to about 450 mg of a compound of formula I and about 5 mg to about 60 mg of a binder. In some embodiments, the solid oral dosage form comprises about 10 mg to about 250 mg of a compound of formula I and about 5 mg to about 35 mg of a binder. In some embodiments, the solid oral dosage form comprises about 10 mg of a compound of formula I and about 5 mg of a binder. In some embodiments, the solid oral dosage form comprises about 50 mg of a compound of formula I and about 7 mg of a binder. In some embodiments, the solid oral dosage form comprises about 250 mg of a compound of formula I and about 33 mg of a binder. In some embodiments, the solid oral dosage form comprises about 325 mg of a compound of formula I and about 43 mg of a binder. In some embodiments, the solid oral dosage form comprises about 450 mg of the compound of formula I and about 60 mg of a binder. In some embodiments, the solid oral dosage form is a tablet.

[0368] In some embodiments, this document provides a pharmaceutical composition comprising a compound of formula I or a pharmaceutically acceptable salt thereof; a filler; a disintegrant; a binder; and a lubricant. In some embodiments, this document provides a pharmaceutical composition comprising a compound of formula I or a pharmaceutically acceptable salt thereof; a filler; a disintegrant; a binder; and a lubricant; wherein the compound of formula I has a crystalline form I.

[0369] In some embodiments, the pharmaceutical composition comprises: About 5% by weight to about 35% by weight of a compound of formula I or a pharmaceutically acceptable salt thereof; Approximately 50% to approximately 90% by weight of fillers; From about 1% to about 10% by weight of disintegrant; Adhesives of about 1% to about 10% by weight; and Lubricant of about 0.1% to about 5% by weight.

[0370] In some embodiments, this document provides a pharmaceutical composition comprising a compound of formula I or a pharmaceutically acceptable salt thereof; lactose, microcrystalline cellulose, croscarmellose sodium, hydroxypropyl cellulose, and magnesium stearate. In some embodiments, this document provides a pharmaceutical composition comprising a compound of formula I or a pharmaceutically acceptable salt thereof; lactose, microcrystalline cellulose, croscarmellose sodium, hydroxypropyl cellulose, and magnesium stearate, wherein the compound of formula I has a crystalline form I. In some embodiments, this document provides a pharmaceutical composition comprising a compound of formula I or a pharmaceutically acceptable salt thereof; lactose, microcrystalline cellulose, croscarmellose sodium, hydroxypropyl cellulose, and magnesium stearate; wherein the lactose is lactose monohydrate. In some embodiments, this document provides a pharmaceutical composition comprising a compound of formula I or a pharmaceutically acceptable salt thereof; lactose, microcrystalline cellulose, croscarmellose sodium, hydroxypropyl cellulose, and magnesium stearate, wherein the weight ratio of lactose to microcrystalline cellulose is about 1:1.

[0371] In some embodiments, the pharmaceutical composition comprises: About 5% by weight to about 35% by weight of a compound of formula I or a pharmaceutically acceptable salt thereof; Approximately 20% by weight to approximately 50% by weight of lactose; Approximately 20% to approximately 50% by weight of microcrystalline cellulose; From about 1% to about 10% by weight of croscarmellose sodium; Hydroxypropyl cellulose, about 1% by weight to about 10% by weight; and Magnesium stearate, approximately 0.1% to approximately 2% by weight.

[0372] In some embodiments, the pharmaceutical composition comprises: About 5% by weight to about 35% by weight of compounds of formula I; Approximately 25% by weight to approximately 45% by weight of lactose; Approximately 25% to approximately 45% by weight of microcrystalline cellulose; From about 3% to about 7% by weight of croscarmellose sodium; About 2% by weight to about 6% by weight of hydroxypropyl cellulose; and Magnesium stearate, approximately 0.1% to approximately 2% by weight.

[0373] In some embodiments, the pharmaceutical composition comprises: About 5% by weight to about 10% by weight of compounds of formula I; Approximately 35% to approximately 45% by weight of lactose; Approximately 35% to approximately 45% by weight of microcrystalline cellulose; From about 3% to about 7% by weight of croscarmellose sodium; About 2% by weight to about 6% by weight of hydroxypropyl cellulose; and Magnesium stearate, approximately 0.1% to approximately 2% by weight.

[0374] In some embodiments, the pharmaceutical composition comprises: Approximately 7.4% by weight of a compound of formula I; Approximately 41% by weight of lactose; Approximately 41% by weight of microcrystalline cellulose; Approximately 5% by weight of cross-linked sodium carboxymethyl cellulose; Approximately 4% by weight of hydroxypropyl cellulose; and Approximately 1.5% by weight of magnesium stearate.

[0375] In some embodiments, the pharmaceutical composition comprises: About 28% by weight to about 32% by weight of compounds of formula I; Approximately 25% by weight to approximately 35% by weight of lactose; Approximately 25% to approximately 35% by weight of microcrystalline cellulose; From about 3% to about 7% by weight of croscarmellose sodium; About 2% by weight to about 6% by weight of hydroxypropyl cellulose; and Magnesium stearate, approximately 0.1% to approximately 2% by weight.

[0376] In some embodiments, the pharmaceutical composition comprises: Approximately 30% by weight of a compound of formula I; Approximately 30% by weight of lactose; Approximately 30% by weight of microcrystalline cellulose; Approximately 5% by weight of cross-linked sodium carboxymethyl cellulose; Approximately 4% by weight of hydroxypropyl cellulose; and Approximately 1.5% by weight of magnesium stearate.

[0377] In some embodiments, this document provides a solid oral dosage form (e.g., tablet) comprising about 5 mg to about 1400 mg of a compound of formula I or a pharmaceutically acceptable salt thereof, wherein the amount is based on the free acid form; a filler; a disintegrant; a binder; and a lubricant; wherein the compound of formula I has a crystalline form I.

[0378] In some implementations, the oral dosage form includes: About 5% by weight to about 35% by weight of a compound of formula I or a pharmaceutically acceptable salt thereof; Approximately 50% to approximately 90% by weight of fillers; From about 1% to about 10% by weight of disintegrant; Adhesives of about 1% to about 10% by weight; and Lubricant of about 0.1% to about 5% by weight.

[0379] In some embodiments, this document provides a solid oral dosage form (e.g., tablet) comprising about 5 mg to about 1400 mg of a compound of formula I or a pharmaceutically acceptable salt thereof, wherein the amount is based on a free acid form; lactose, microcrystalline cellulose, croscarmellose sodium, hydroxypropyl cellulose, and magnesium stearate. In some embodiments, this document provides a solid oral dosage form (e.g., tablet) comprising about 5 mg to about 1400 mg of a compound of formula I or a pharmaceutically acceptable salt thereof, wherein the amount is based on a free acid form; lactose, microcrystalline cellulose, croscarmellose sodium, hydroxypropyl cellulose, and magnesium stearate; wherein the compound of formula I has a crystalline form I. In some embodiments, this document provides a solid oral dosage form (e.g., tablet) comprising about 5 mg to about 1400 mg of a compound of formula I or a pharmaceutically acceptable salt thereof, wherein the amount is based on a free acid form; lactose, microcrystalline cellulose, croscarmellose sodium, hydroxypropyl cellulose, and magnesium stearate; wherein the lactose is lactose monohydrate. In some embodiments, this document provides a solid oral dosage form (e.g., tablets) comprising an amount of about 5 mg to about 1400 mg of a compound of formula I or a pharmaceutically acceptable salt thereof, wherein the amount is based on the free acid form; lactose, microcrystalline cellulose, croscarmellose sodium, hydroxypropyl cellulose, and magnesium stearate; wherein the weight ratio of lactose to microcrystalline cellulose is about 1:1.

[0380] In some implementations, the oral dosage form includes: About 5% by weight to about 35% by weight of a compound of formula I or a pharmaceutically acceptable salt thereof; Approximately 20% by weight to approximately 50% by weight of lactose; Approximately 20% to approximately 50% by weight of microcrystalline cellulose; From about 1% to about 10% by weight of croscarmellose sodium; Hydroxypropyl cellulose, about 1% by weight to about 10% by weight; and Magnesium stearate, approximately 0.1% to approximately 2% by weight.

[0381] In some implementations, the oral dosage form includes: About 5% by weight to about 35% by weight of compounds of formula I; Approximately 25% by weight to approximately 45% by weight of lactose; Approximately 25% to approximately 45% by weight of microcrystalline cellulose; From about 3% to about 7% by weight of croscarmellose sodium; About 2% by weight to about 6% by weight of hydroxypropyl cellulose; and Magnesium stearate, approximately 0.1% to approximately 2% by weight.

[0382] In some implementations, the oral dosage form includes: About 5% by weight to about 10% by weight of compounds of formula I; Approximately 35% to approximately 45% by weight of lactose; Approximately 35% to approximately 45% by weight of microcrystalline cellulose; From about 3% to about 7% by weight of croscarmellose sodium; About 2% by weight to about 6% by weight of hydroxypropyl cellulose; and Magnesium stearate, approximately 0.1% to approximately 2% by weight.

[0383] In some implementations, the oral dosage form includes: Approximately 7.4% by weight of a compound of formula I; Approximately 41% by weight of lactose; Approximately 41% by weight of microcrystalline cellulose; Approximately 5% by weight of cross-linked sodium carboxymethyl cellulose; Approximately 4% by weight of hydroxypropyl cellulose; and Approximately 1.5% by weight of magnesium stearate.

[0384] In some implementations, the oral dosage form includes: About 28% by weight to about 32% by weight of compounds of formula I; Approximately 25% by weight to approximately 35% by weight of lactose; Approximately 25% to approximately 35% by weight of microcrystalline cellulose; From about 3% to about 7% by weight of croscarmellose sodium; About 2% by weight to about 6% by weight of hydroxypropyl cellulose; and Magnesium stearate, approximately 0.1% to approximately 2% by weight.

[0385] In some implementations, the oral dosage form includes: Approximately 30% by weight of a compound of formula I; Approximately 30% by weight of lactose; Approximately 30% by weight of microcrystalline cellulose; Approximately 5% by weight of cross-linked sodium carboxymethyl cellulose; Approximately 4% by weight of hydroxypropyl cellulose; and Approximately 1.5% by weight of magnesium stearate.

[0386] In some implementations, the oral dosage form includes: A compound of formula I in amounts from about 5 mg to about 500 mg; A filler in amounts from approximately 60 mg to approximately 1000 mg; Disintegrant in amounts of approximately 1 mg to approximately 100 mg; The adhesive in amounts from about 1 mg to about 80 mg; and Lubricant in amounts ranging from approximately 0.5 mg to approximately 30 mg.

[0387] In some implementations, the oral dosage form includes: A compound of formula I in amounts from about 5 mg to about 500 mg; Lactose in amounts ranging from approximately 30 mg to approximately 500 mg; Microcrystalline cellulose in amounts ranging from approximately 30 mg to approximately 500 mg; Sodium croscarmellose in amounts ranging from approximately 1 mg to approximately 100 mg; Hydroxypropyl cellulose in amounts from about 1 mg to about 80 mg; and magnesium stearate in amounts from about 0.5 mg to about 30 mg.

[0388] In some implementations, the oral dosage form includes: A compound of formula I in amounts from about 10 mg to about 450 mg; A filler in amounts from approximately 90 mg to approximately 900 mg; Disintegrant in amounts of approximately 5 mg to approximately 80 mg; The adhesive in amounts of approximately 5 mg to approximately 60 mg; and Lubricant in amounts from approximately 0.5 mg to approximately 25 mg.

[0389] In some implementations, the oral dosage form includes: A compound of formula I in amounts from about 10 mg to about 450 mg; Approximately 45 mg to approximately 450 mg of lactose; Microcrystalline cellulose in amounts of approximately 45 mg to approximately 450 mg; Approximately 5 mg to approximately 80 mg of croscarmellose sodium; Hydroxypropyl cellulose in amounts from about 5 mg to about 60 mg; and Magnesium stearate in amounts from about 0.5 mg to about 25 mg.

[0390] In some implementations, the oral dosage form includes: A compound of formula I in amounts of about 10 mg to about 250 mg; A filler in amounts ranging from approximately 90 mg to approximately 500 mg; Disintegrant in amounts of approximately 5 mg to approximately 45 mg; The adhesive in amounts of approximately 5 mg to approximately 35 mg; and Lubricant in amounts from approximately 0.5 mg to approximately 20 mg.

[0391] In some implementations, the oral dosage form includes: A compound of formula I in amounts of about 10 mg to about 250 mg; Approximately 45 mg to approximately 250 mg of lactose; Microcrystalline cellulose in amounts of approximately 45 mg to approximately 250 mg; Sodium croscarmellose, in amounts ranging from approximately 5 mg to approximately 45 mg; Hydroxypropyl cellulose in an amount of about 5 mg to about 35 mg; and magnesium stearate in an amount of about 0.5 mg to about 20 mg.

[0392] In some implementations, the oral dosage form includes: Approximately 10 mg of a compound of formula I; Approximately 55 mg of lactose; Approximately 55 mg of microcrystalline cellulose; Approximately 7 mg of croscarmellose sodium; Approximately 5 mg of hydroxypropyl cellulose; and Approximately 2 mg of magnesium stearate.

[0393] In some implementations, the oral dosage form includes: Approximately 50 mg of a compound of formula I; Approximately 49 mg of lactose; Approximately 49 mg of microcrystalline cellulose; Approximately 8 mg of croscarmellose sodium; Approximately 7 mg of hydroxypropyl cellulose; and approximately 2.5 mg of magnesium stearate.

[0394] In some implementations, the oral dosage form includes: Approximately 250 mg of a compound of formula I; Approximately 246 mg of lactose; Approximately 246 mg of microcrystalline cellulose; Approximately 42 mg of croscarmellose sodium; Approximately 33 mg of hydroxypropyl cellulose; and Approximately 12 mg of magnesium stearate.

[0395] In some implementations, the oral dosage form includes: Approximately 325 mg of a compound of formula I; Approximately 320 mg of lactose; Approximately 320 mg of microcrystalline cellulose; Approximately 54 mg of croscarmellose sodium; Approximately 43 mg of hydroxypropyl cellulose; and Approximately 16 mg of magnesium stearate.

[0396] In some implementations, the oral dosage form includes: Approximately 450 mg of a compound of formula I; Approximately 444 mg of lactose; Approximately 444 mg of microcrystalline cellulose; Approximately 75 mg of croscarmellose sodium; Approximately 60 mg of hydroxypropyl cellulose; and Approximately 22 mg of magnesium stearate.

[0397] Other excipients Any other suitable excipient may be used with the pharmaceutical compositions disclosed herein. In some embodiments, the pharmaceutical compositions described herein (e.g., solid oral dosage forms) comprise a surfactant. In some embodiments, the surfactant comprises sodium lauryl sulfate, D-α-tocopherol polyethylene glycol 1000 succinate (TPGS), or combinations thereof.

[0398] In some embodiments, the pharmaceutical compositions described herein (e.g., solid oral dosage forms) comprise a pH adjuster. In some embodiments, the pH adjuster is a basic excipient. In some embodiments, the pH adjuster is sodium carbonate, sodium bicarbonate, or a combination thereof. In some embodiments, the pH adjuster is sodium bicarbonate.

[0399] In some embodiments, the pharmaceutical compositions described herein (e.g., solid oral dosage forms) contain a flow aid. In some embodiments, the flow aid is colloidal silica.

[0400] Film coating In some embodiments, the solid oral dosage forms (e.g., tablets) provided herein are uncoated. In some embodiments, the solid dosage forms (e.g., tablets) provided herein are coated (e.g., they comprise a film coating). In some embodiments, the coated solid dosage forms (e.g., tablets) comprise a non-enteric coating. Examples of film coatings may consist of hydrophilic polymeric materials, but are not limited to polysaccharide materials, such as hydroxypropyl methylcellulose (HPMC), methylcellulose, hydroxyethyl cellulose (HEC), hydroxypropyl cellulose (HPC), poly(vinyl alcohol-co-ethylene glycol), and other water-soluble polymers. While the water-soluble material included in the film coatings of the embodiments disclosed herein in some embodiments comprises a single polymeric material, in some other embodiments it may be formed using a mixture of more than one polymer.

[0401] Suitable film coatings include, but are not limited to, polymer film coatings, such as those containing polyvinyl alcohol, for example, 'Opadry'. ® II' (which contains partially hydrolyzed PVA, titanium dioxide, polyethylene glycol 3350 (PEG) and talc, and optional colorants such as iron oxide (e.g., iron oxide red or iron oxide black) or indigo carmine or iron oxide yellow or FD&C yellow #6) and Opadry ® II (which comprises polyethylene glycol / polyvinyl alcohol graft copolymer, talc, titanium dioxide, caprylic / capric acid mono- and diglycerides (caprylic / capric acid mono- and diglycerides type I), polyvinyl alcohol, and optional colorants such as iron oxide (e.g., iron oxide red or iron oxide black) or indigo carmine or iron oxide yellow or FD&C yellow #6). In some embodiments, the film coating includes Opadry. ® II. In some embodiments, the film coating is beige. In some embodiments, the film coating includes opaquery. ® IIBeige. In some embodiments, the film coating is beige. In some embodiments, the film coating includes opaque. ® II beige 85F570135. In some embodiments, the oral solid dosage form comprises about 1% to about 5% film coating (based on tablet core weight). In some embodiments, the oral solid dosage form comprises about 2% to about 4% film coating (based on tablet core weight). In some embodiments, the amount of film coating is about 3% by weight (based on tablet core weight).

[0402] Unless otherwise specified, when the dosage form is coated, it should be understood that the weight percentage mentioned is calculated relative to the tablet core weight.

[0403] The “core weight” calculated herein is the total weight of the compound of Formula I or a pharmaceutically acceptable salt thereof, and one or more excipients in the core. In some embodiments, the core weight is the total weight of the compound of Formula I or a pharmaceutically acceptable salt thereof, filler, disintegrant, binder, and lubricant. The core weight does not include the weight of the film coating.

[0404] The “core weight” calculated herein is (i) the total weight of the compound of Formula I or a pharmaceutically acceptable salt thereof, plus one or more excipients, and (ii) the total weight of the film coating. In some embodiments, the tablet weight is the total weight of the compound of Formula I or a pharmaceutically acceptable salt thereof, filler, disintegrant, binder, lubricant, and film coating.

[0405] In some embodiments of the solid oral dosage forms disclosed herein, the dosage form is a tablet comprising a core and a film coating. A “core” refers to a compound of Formula I or a pharmaceutically acceptable salt thereof, and one or more excipients blended with a compound of Formula I, and does not contain a film coating. In some embodiments, the core comprises in-particle and out-of-particle excipients. In some embodiments, the core comprises a compound of Formula I or a pharmaceutically acceptable salt thereof, a filler, a disintegrant, a binder, and a lubricant.

[0406] In some embodiments of the solid oral dosage forms disclosed herein, the dosage form is a tablet comprising a core and a film coating, wherein the core comprises a compound of formula I or a pharmaceutically acceptable salt thereof, a filler, a disintegrant, a binder, and a lubricant.

[0407] In some implementations, the solid dosage form includes: In some implementations, the solid dosage form comprises tablets containing the following: In some implementations, the solid dosage form comprises tablets containing the following: In some implementations, the solid dosage form comprises tablets containing the following: In some implementations, the solid dosage form comprises tablets containing the following: In some implementations, the solid dosage form comprises tablets containing the following: In some implementations, the solid dosage form comprises tablets containing the following: In some implementations, the solid dosage form comprises tablets containing the following: In some implementations, the solid dosage form comprises tablets containing the following: In some implementations, the solid dosage form includes: In some implementations, the solid dosage form includes: In some implementations, the solid dosage form includes: In some implementations, the solid dosage form includes: In some embodiments, the solid dosage form comprises 10 mg of a compound of formula I, lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, hydroxypropyl cellulose, magnesium stearate, and a film coating. In some embodiments, the solid dosage form comprises 10 mg of a compound of formula I, lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, hydroxypropyl cellulose, magnesium stearate, and opadryl. ® II Beige.

[0408] In some embodiments, the solid dosage form comprises 50 mg of a compound of formula I, lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, hydroxypropyl cellulose, magnesium stearate, and a film coating. In some embodiments, the solid dosage form comprises 50 mg of a compound of formula I, lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, hydroxypropyl cellulose, magnesium stearate, and opadryl. ® II Beige.

[0409] In some embodiments, the solid dosage form comprises 250 mg of a compound of formula I, lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, hydroxypropyl cellulose, magnesium stearate, and a film coating. In some embodiments, the solid dosage form comprises 250 mg of a compound of formula I, lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, hydroxypropyl cellulose, magnesium stearate, and opadryl. ® II Beige.

[0410] In some embodiments, the solid dosage form comprises 325 mg of a compound of formula I, lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, hydroxypropyl cellulose, magnesium stearate, and a film coating. In some embodiments, the solid dosage form comprises 325 mg of a compound of formula I, lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, hydroxypropyl cellulose, magnesium stearate, and opadryl. ® II Beige.

[0411] In some embodiments, the solid dosage form comprises 450 mg of a compound of formula I, lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, hydroxypropyl cellulose, magnesium stearate, and a film coating. In some embodiments, the solid dosage form comprises 450 mg of a compound of formula I, lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, hydroxypropyl cellulose, magnesium stearate, and opadryl. ® II Beige.

[0412] In some embodiments of the solid oral dosage forms disclosed herein, the dosage forms are prepared by wet granulation. In some embodiments of the solid oral dosage forms disclosed herein, the dosage forms are prepared by dry granulation.

[0413] IV. How to use This document provides methods for treating or preventing HIV infection in humans, including oral administration of a therapeutically effective amount of a compound of formula I or a pharmaceutically acceptable salt thereof. Compounds of formula I or pharmaceutically acceptable salts thereof may be formulated into pharmaceutical compositions as described herein.

[0414] Therefore, this document provides a method for treating or preventing HIV infection in a person, the method comprising orally administering to a person a therapeutically effective amount of any of the pharmaceutical compositions provided herein. In some embodiments, this document provides a method for treating or preventing HIV infection in a person, the method comprising orally administering to a person a solid oral dosage form or pharmaceutical composition provided herein. In some embodiments, the method comprises orally administering to a person a solid oral dosage form provided herein. In some embodiments, the method comprises orally administering to a person a tablet provided herein.

[0415] This article also provides for the use of any of the pharmaceutical compositions provided herein for the treatment or prevention of HIV infection.

[0416] In some embodiments of the methods provided herein, the pharmaceutical composition (e.g., a solid oral dosage form) is administered hourly, daily, weekly, or monthly. For example, a single dose may be administered every 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 16 hours, or every 24 hours. A single dose may also be administered every 1 day, every 2 days, every 3 days, every 4 days, every 5 days, every 6 days, every 7 days, every 8 days, every 9 days, or every 10 days. A single dose may also be administered every 1 week, 2 weeks, 3 weeks, or every 4 weeks. In some embodiments, a single dose may be administered weekly.

[0417] In some embodiments, the pharmaceutical compositions or solid oral dosage forms disclosed herein are administered once every 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 days. In some embodiments, the pharmaceutical compositions or solid oral dosage forms disclosed herein are administered once daily (QD). In some embodiments, the pharmaceutical compositions or solid oral dosage forms disclosed herein are administered once every two days. In some embodiments, the pharmaceutical compositions or solid oral dosage forms disclosed herein are administered once every three days. In some embodiments, the pharmaceutical compositions or solid oral dosage forms disclosed herein are administered once every four days. In some embodiments, the pharmaceutical compositions or solid oral dosage forms disclosed herein are administered once every five days. In some embodiments, the pharmaceutical compositions or solid oral dosage forms disclosed herein are administered once every six days. In some embodiments, the pharmaceutical compositions or solid oral dosage forms disclosed herein are administered once every seven days. In some embodiments, the pharmaceutical compositions or solid oral dosage forms disclosed herein are administered once every eight days. In some embodiments, the pharmaceutical compositions or solid oral dosage forms disclosed herein are administered once every seven days. In some embodiments, the pharmaceutical compositions or solid oral dosage forms disclosed herein are administered once every nine days. In some embodiments, the pharmaceutical compositions or solid oral dosage forms disclosed herein are administered once every seven days. In some embodiments, the pharmaceutical compositions or solid oral dosage forms disclosed herein are administered once every ten days.

[0418] In some embodiments, the pharmaceutical compositions or solid oral dosage forms disclosed herein are administered once weekly (QW). In some embodiments, the pharmaceutical compositions or solid oral dosage forms disclosed herein are administered twice weekly. In some embodiments, the pharmaceutical compositions or solid oral dosage forms disclosed herein are administered every two weeks (Q2W). In some embodiments, the pharmaceutical compositions or solid oral dosage forms disclosed herein are administered every three weeks (Q3W).

[0419] In some embodiments, the method comprises administering a dose of about 1 mg to about 2500 mg of a compound of formula I or a pharmaceutically acceptable salt thereof, wherein the dose is based on the free acid form. In some embodiments, the method comprises administering a dose of about 10 mg to about 1500 mg of a compound of formula I or a pharmaceutically acceptable salt thereof, wherein the dose is based on the free acid form.In some embodiments, the method includes administering about 10 mg to about 1450 mg, about 10 mg to about 1400 mg, about 10 mg to about 1350 mg, about 10 mg to about 750 mg, about 10 mg to about 500 mg, about 10 mg to about 400 mg, about 10 mg to about 300 mg, about 10 mg to about 200 mg, about 10 mg to about 100 mg, about 10 mg to about 50 mg, about 10 mg to about 30 mg, about 50 mg to about 1000 mg, about 50 mg to about 800 mg, about 50 mg to about 600 mg, about 50 mg to about 400 mg, or about 50 mg to about 300 mg. mg, about 50 mg to about 100 mg, about 100 mg to about 1000 mg, about 100 mg to about 800 mg, about 100 mg to about 600 mg, about 100 mg to about 400 mg, about 100 mg to about 200 mg, about 200 mg to about 1000 mg, about 200 mg to about 800 mg, about 200 mg to about 700 mg, about 200 mg to about 600 mg, about 200 mg to about 400 mg, about 200 mg to about 300 mg, about 300 mg to about 1000 mg, about 300 mg to about 800 mg, about 300 mg to about 600 mg, about 300 mg to about 500 mg 00mg, about 300mg to about 400mg, about 400mg to about 1000mg, about 400mg to about 800mg, about 400mg to about 700mg, about 400mg to about 600mg, about 400mg to about 500mg, about 500mg to about 1000mg, about 500mg to about 800mg, about 500mg to about 600mg, about 600mg to about 1000mg, about 600mg to about 900mg, about 600mg to about 800mg, about 600mg to about 700mg, about 700mg to about 1000mg, about 700mg to about 900mg, about 700mg to about 900mg, about 700mg to about 10 ... A compound of formula I or a pharmaceutically acceptable salt thereof in doses of about 800 mg, about 800 mg to about 1000 mg, about 800 mg to about 900 mg, about 900 mg to about 1000 mg, about 200 mg to about 1500 mg, about 200 mg to about 1400 mg, about 400 mg to about 1300 mg, about 600 mg to about 1350 mg, about 800 mg to about 1200 mg, about 800 mg to about 1000 mg, about 1000 mg to about 1500 mg, about 1000 mg to about 1200 mg, or about 1200 mg to about 1400 mg, wherein the dose is based on the free acid form.

[0420] In some embodiments, the method comprises administering a dose of about 5 mg to about 1350 mg of a compound of formula I or a pharmaceutically acceptable salt thereof, wherein the dose is based on the free acid form. In some embodiments, the method comprises administering a dose of about 10 mg to about 1350 mg of a compound of formula I or a pharmaceutically acceptable salt thereof, wherein the dose is based on the free acid form. In some embodiments, the method comprises administering a dose of about 50 mg to about 500 mg of a compound of formula I or a pharmaceutically acceptable salt thereof, wherein the dose is based on the free acid form. In some embodiments, the method comprises administering a dose of about 10 mg to about 250 mg of a compound of formula I or a pharmaceutically acceptable salt thereof, wherein the dose is based on the free acid form. In some embodiments, the method comprises administering a dose of about 200 mg to about 300 mg of a compound of formula I or a pharmaceutically acceptable salt thereof, wherein the dose is based on the free acid form. In some embodiments, the method comprises administering a dose of about 500 mg to about 1000 mg of a compound of formula I or a pharmaceutically acceptable salt thereof, wherein the dose is based on the free acid form. In some embodiments, the method comprises administering a dose of about 400 mg to about 700 mg of a compound of formula I or a pharmaceutically acceptable salt thereof, wherein the dose is based on the free acid form. In some embodiments, the method comprises administering a dose of about 600 mg to about 700 mg of a compound of formula I or a pharmaceutically acceptable salt thereof, wherein the dose is based on the free acid form. In some embodiments, the method comprises administering a dose of about 400 mg to about 500 mg of a compound of formula I or a pharmaceutically acceptable salt thereof, wherein the dose is based on the free acid form.

[0421] In some embodiments, the method comprises administering a dose of about 5 mg to about 1000 mg of a compound of formula I or a pharmaceutically acceptable salt thereof, wherein the dose is based on the free acid form. In some embodiments, the method comprises administering a dose of about 5 mg to about 750 mg of a compound of formula I or a pharmaceutically acceptable salt thereof, wherein the dose is based on the free acid form. In some embodiments, the method comprises administering a dose of about 5 mg to about 650 mg of a compound of formula I or a pharmaceutically acceptable salt thereof, wherein the dose is based on the free acid form. In some embodiments, the method comprises administering a dose of about 5 mg to about 500 mg of a compound of formula I or a pharmaceutically acceptable salt thereof, wherein the dose is based on the free acid form. In some embodiments, the method comprises administering a dose of about 10 mg to about 450 mg of a compound of formula I or a pharmaceutically acceptable salt thereof, wherein the dose is based on the free acid form. In some embodiments, the method comprises administering a dose of about 10 mg to about 250 mg of a compound of formula I or a pharmaceutically acceptable salt thereof, wherein the dose is based on the free acid form.

[0422] In some embodiments, the method includes administering about 10 mg, about 40 mg, about 50 mg, about 62.5 mg, about 100 mg, about 125 mg, about 150 mg, about 175 mg, about 200 mg, about 225 mg, about 250 mg, about 275 mg, about 300 mg, about 325 mg, about 350 mg, about 375 mg, about 400 mg, about 425 mg, about 450 mg, about 475 mg, about 500 mg, about 525 mg, about 550 mg, about 575 mg, about 600 mg, about 625 mg, about 650 mg, etc. Approximately 675mg, approximately 700mg, approximately 725mg, approximately 750mg, approximately 775mg, approximately 800mg, approximately 825mg, approximately 850mg, approximately 875mg, approximately 900mg, approximately 925mg, approximately 950mg, approximately 975mg, approximately 1000mg, approximately 1025mg, approximately 1050mg, approximately 1075mg, approximately 1100mg, approximately 1125mg, approximately 1150mg, approximately 1175mg, approximately 1200mg, approximately 1225mg, approximately 1250mg, approximately 1275mg, approximately 1300mg, approximately 1325mg. Approximately 1350mg, approximately 1375mg, approximately 1400mg, approximately 1425mg, approximately 1450mg, approximately 1475mg, approximately 1500mg, approximately 1525mg, approximately 1550mg, approximately 1575mg, approximately 1600mg, approximately 1625mg, approximately 1650mg, approximately 1675mg, approximately 1700mg, approximately 1725mg, approximately 1750mg, approximately 1775mg, approximately 1800mg, approximately 1825mg, approximately 1850mg, approximately 1875mg, approximately 1900mg, approximately 1925mg, approximately 1950mg, approximately 19 A compound of formula I or a pharmaceutically acceptable salt thereof in doses of 75 mg, about 2000 mg, about 2025 mg, about 2050 mg, about 2075 mg, about 2100 mg, about 2125 mg, about 2150 mg, about 2175 mg, about 2200 mg, about 2225 mg, about 2250 mg, about 2275 mg, about 2300 mg, about 2325 mg, about 2350 mg, about 2375 mg, about 2400 mg, about 2425 mg, about 2450 mg, about 2475 mg, or about 2500 mg, wherein the dose is based on the free acid form.

[0423] In some embodiments, the method comprises administering a compound of formula I or a pharmaceutically acceptable salt thereof in a dose of about 10 mg, about 30 mg, about 50 mg, about 150 mg, about 250 mg, about 325 mg, about 450 mg, about 900 mg, about 1300 mg, or about 1350 mg, wherein the dose is based on the free acid form. In some embodiments, the method comprises administering a compound of formula I or a pharmaceutically acceptable salt thereof in a dose of about 30 mg, about 150 mg, about 450 mg, about 900 mg, or about 1350 mg, wherein the dose is based on the free acid form.

[0424] In some embodiments, the method comprises administering about 10 mg of a compound of formula I or a pharmaceutically acceptable salt thereof, wherein the dose is based on the free acid form. In some embodiments, the method comprises administering about 30 mg of a compound of formula I or a pharmaceutically acceptable salt thereof, wherein the dose is based on the free acid form. In some embodiments, the method comprises administering about 50 mg of a compound of formula I or a pharmaceutically acceptable salt thereof, wherein the dose is based on the free acid form. In some embodiments, the method comprises administering about 150 mg of a compound of formula I or a pharmaceutically acceptable salt thereof, wherein the dose is based on the free acid form. In some embodiments, the method comprises administering about 250 mg of a compound of formula I or a pharmaceutically acceptable salt thereof, wherein the dose is based on the free acid form. In some embodiments, the method comprises administering about 325 mg of a compound of formula I or a pharmaceutically acceptable salt thereof, wherein the dose is based on the free acid form. In some embodiments, the method comprises administering about 450 mg of a compound of formula I or a pharmaceutically acceptable salt thereof, wherein the dose is based on the free acid form. In some embodiments, the method comprises administering about 650 mg of a compound of formula I or a pharmaceutically acceptable salt thereof, wherein the dose is based on the free acid form. In some embodiments, the method comprises administering about 900 mg of a compound of formula I or a pharmaceutically acceptable salt thereof, wherein the dose is based on the free acid form. In some embodiments, the method comprises administering about 1300 mg of a compound of formula I or a pharmaceutically acceptable salt thereof, wherein the dose is based on the free acid form. In some embodiments, the method comprises administering about 1350 mg of a compound of formula I or a pharmaceutically acceptable salt thereof, wherein the dose is based on the free acid form.

[0425] In some embodiments, the dose is administered in a single solid dosage form (e.g., one tablet). In some embodiments, the dose is administered in one or more solid dosage forms (e.g., two or more tablets).

[0426] In some embodiments, the pharmaceutical formulations described herein, such as solid dosage forms (e.g., tablets), contain 10 mg of a compound of formula I and are administered once weekly. In some embodiments, the pharmaceutical formulations described herein, such as solid dosage forms (e.g., tablets), contain 50 mg of a compound of formula I and are administered once weekly (QW). In some embodiments, the pharmaceutical formulations described herein, such as solid dosage forms (e.g., tablets), contain 150 mg of a compound of formula I and are administered once weekly (QW). In some embodiments, the pharmaceutical formulations described herein, such as solid dosage forms (e.g., tablets), contain 250 mg of a compound of formula I and are administered once weekly (QW). In some embodiments, the pharmaceutical formulations described herein, such as solid dosage forms (e.g., tablets), contain 325 mg of a compound of formula I and are administered once weekly (QW). In some embodiments, the pharmaceutical formulations described herein, such as solid dosage forms (e.g., tablets), contain 450 mg of a compound of formula I and are administered once weekly (QW). In some embodiments, the pharmaceutical formulations described herein, such as solid dosage forms (e.g., tablets), contain 650 mg of the compound of formula I and are administered once weekly (QW). In some embodiments, the 650 mg of the compound of formula I is administered once weekly in two solid dosage forms, wherein each solid dosage form (e.g., tablets) contains 325 mg of the compound of formula I.

[0427] In some embodiments of the methods provided herein, the person is already infected with HIV. In some embodiments of the methods provided herein, the person has an HIV-1 RNA copy number of less than about 50 copies / mL (i.e., virologically suppressed). In some embodiments of the methods provided herein, the person is infected with HIV but has not yet developed AIDS. In some embodiments of the methods provided herein, the person is infected with HIV and has developed AIDS. In some embodiments of the methods provided herein, the person has an HIV-1 RNA copy number of from about 5000 copies / mL to about 400,000 copies / mL.

[0428] In some implementations, the person is treatment-experienced, meaning the patient has previously taken one or more forms of HIV medication. In some implementations, the person is not treatment-experienced. In some implementations, the person is treatment-experienced and has not received treatment with an integrase strand transfer inhibitor (INSTI). In some implementations, the person is treatment-experienced and has discontinued antiretroviral therapy for at least twelve weeks.

[0429] In some embodiments, HIV infection is characterized by resistance to one or more antiretroviral drugs in an HIV-1 mutant. In some embodiments, HIV infection is characterized by resistance to two or more antiretroviral drugs in an HIV-1 mutant. In some embodiments, HIV infection is characterized by resistance to three or more antiretroviral drugs in an HIV-1 mutant.

[0430] In some embodiments, the HIV-1 mutant is resistant to a protease inhibitor (PI), a capsid assembly inhibitor (CAI), a nucleoside or nucleotide reverse transcriptase inhibitor (NRTI), a non-nucleoside or non-nucleotide reverse transcriptase inhibitor (NNRTI), or an integrase strand transfer inhibitor (INSTI). In some embodiments, the HIV-1 mutant is resistant to a protease inhibitor (PI), a nucleoside or nucleotide reverse transcriptase inhibitor (NRTI), a non-nucleoside or non-nucleotide reverse transcriptase inhibitor (NNRTI), or an integrase strand transfer inhibitor (INSTI). In some embodiments, the HIV-1 mutant resistant to a protease inhibitor is selected from I50V, I84V / L90M, G48V / V82A / L90M, and G48V / V82S. In some embodiments, the HIV-1 mutant resistant to a nucleoside or nucleotide reverse transcriptase inhibitor is selected from K65R, M184V, and 6TAM. In some embodiments, HIV-1 mutants resistant to nucleoside or nucleotide reverse transcriptase inhibitors are selected from K65R, M184V, M41L / T215Y, and 6TAM. In some embodiments, HIV-1 mutants resistant to non-nucleoside or non-nucleotide reverse transcriptase inhibitors are selected from K103N, Y181C, Y188L, L100I / K103N, and K103N / Y181C. In some embodiments, HIV-1 mutants resistant to capsid assembly inhibitors are selected from L56I, N57H, M66I, K70N, Q67H / N74D, and Q67H / N74D.

[0431] In some embodiments, HIV-1 mutants resistant to integrase strand transfer inhibitors contain one or more integrase substitutions associated with INSTI-class resistance. In some embodiments, HIV-1 mutants resistant to integrase strand transfer inhibitors contain one or two integrase substitutions associated with INSTI-class resistance. In some embodiments, HIV-1 mutants resistant to integrase strand transfer inhibitors are selected from Y143R, E138K / Q148K, G140S / Q148R, E92Q / N155H, N155H / Q148R, and R263K / M50I. In some embodiments, the HIV-1 mutant resistant to integrase strand transfer inhibitors is selected from E92Q, Y143R, Q148R, N155H, R263K, E138K / Q148K, G140S / Q148R, E92Q / N155H, N155H / Q148R, and R263K / M50I. In some embodiments, the HIV-1 mutant resistant to integrase strand transfer inhibitors is selected from G140A / S, Q148H / K, L741, T97A, E138A / K, S153F, S153Y, and combinations thereof. In some embodiments, the HIV-1 mutant resistant to integrase strand transfer inhibitors is the S153 variant.

[0432] In some embodiments, the person (or “patient”) is infected with HIV-1 that is resistant to at least one antiretroviral drug. In some embodiments, the patient is infected with multidrug-resistant HIV-1 that is resistant to at least one antiretroviral drug from each of two different classes of antiretroviral drugs. In some embodiments, the patient is infected with multidrug-resistant HIV-1 that is resistant to at least one antiretroviral drug from each of three different classes of antiretroviral drugs. In some embodiments, the different classes of antiretroviral drugs are selected from nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs), non-nucleoside or non-nucleotide reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), capsid assembly inhibitors (CAIs), and integrase strand transfer inhibitors (INSTIs). In some embodiments, the different classes of antiretroviral drugs are selected from nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs), non-nucleoside or non-nucleotide reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), and integrase strand transfer inhibitors (INSTIs).

[0433] In some implementations, the NRTI is selected from emtricitabine, lamivudine (3TC), zidovudine (azidothymidine (AZT)), didanosine (ddI), dideoxyinosine, tenofovir, tenofovir alafenamide, tenofovir alafenamide hemifumarate, tenofovir disoproxil fumarate, stavudine (d4T), zalcitabine (dideoxycytidine (ddC), and abacavir.

[0434] In some implementation schemes, NNRTI is selected from efavirenz, etravirine, rilpivirine, nevirapine, and delavirdine.

[0435] In some implementation schemes, the PI is selected from amprenavir, atazanavir, darunavir, fosamprenavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, and tipranavir.

[0436] In some implementations, CAI stands for lenacapavir.

[0437] In some implementations, INSTI is selected from raltegravir, elvitegravir, and dolutegravir.

[0438] In some implementations of this method, the patient has previously been treated with at least one antiretroviral drug for at least 3 months, at least 6 months, at least 9 months, or at least 12 months.

[0439] In some embodiments, a prior HIV treatment regimen including the administration of at least one antiretroviral drug has failed for the patient. In some embodiments, the prior treatment regimen includes the administration of at least one antiretroviral drug from each of two different classes of antiretroviral drugs. In some embodiments, the prior treatment regimen includes the administration of at least one antiretroviral drug from each of three different classes of antiretroviral drugs. In some embodiments, the different classes of antiretroviral drugs are selected from nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), and integrase strand transfer inhibitors (INSTIs).

[0440] In some embodiments of the methods provided herein, a compound of formula I or a pharmaceutically acceptable salt thereof is administered in combination with one or more additional therapeutic agents (e.g., one, two, three, or four additional therapeutic agents). In some embodiments of the methods provided herein, the method includes administering one, two, three, or four additional therapeutic agents to a person.

[0441] In some embodiments, this specification provides a method for treating HIV infection, the method comprising administering to a patient in need a therapeutically effective amount of the pharmaceutical composition described herein (e.g., a solid oral dosage form) in combination with one or more additional therapeutic agents.

[0442] The combination or co-administration of a compound of Formula I or a pharmaceutically acceptable salt thereof with one or more additional therapeutic agents generally refers to the simultaneous or sequential administration of a compound of Formula I or a pharmaceutically acceptable salt thereof with one or more additional therapeutic agents, such that a therapeutically effective amount of the compound of Formula I or a pharmaceutically acceptable salt thereof with one or more additional therapeutic agents is present in the patient. When administered sequentially, the combination may be administered in two or more doses.

[0443] Co-administration includes administering a unit dose of the disclosed compound before or after administering a unit dose of one or more additional therapeutic agents. For example, the disclosed compound may be administered within seconds, minutes, or hours after administering one or more additional therapeutic agents. In some embodiments, a unit dose of the disclosed compound is administered first, followed by a unit dose of one or more additional therapeutic agents within seconds or minutes. Alternatively, a unit dose of one or more additional therapeutic agents is administered first, followed by a unit dose of the disclosed compound within seconds or minutes. In other embodiments, a unit dose of the disclosed compound is administered first, followed by a unit dose of one or more additional therapeutic agents several hours later (e.g., 1 hour to 12 hours). In yet another embodiment, a unit dose of one or more additional therapeutic agents is administered first, followed by a unit dose of the disclosed compound several hours later (e.g., 1 hour to 12 hours).

[0444] In some implementations, the adjunctive therapeutic agent may be an anti-HIV agent. In some cases, the adjunctive therapeutic agent may be an HIV protease inhibitor, a non-nucleoside or non-nucleotide inhibitor of HIV reverse transcriptase, a nucleoside or nucleotide inhibitor of HIV reverse transcriptase, an HIV integrase inhibitor, an HIV non-catalytic site (or allosteric) integrase inhibitor, an HIV entry inhibitor, an HIV maturation inhibitor, an HIV capsid inhibitor, an HIV Tat or Rev inhibitor, an immunomodulator, an immunotherapeutic agent, an antibody-drug conjugate, a gene modifier, gene editing materials (such as CRISPR / Cas9, zinc finger nucleases, homing nucleases, synthetic nucleases, TALEN), cell therapies (such as chimeric antigen receptor T cells, CAR-T and engineered T cell receptors, TCR-T, autologous T cell therapy, engineered B cells), a latency reversal agent, an immunotherapy, a phosphatidylinositol 3-kinase (PI3K) inhibitor, an HIV antibody, a bispecific antibody, and an "antibody-like" therapeutic protein. p17 matrix protein inhibitors, IL-13 antagonists, peptidyl prolyl cis-trans isomerase A modulators, protein disulfide isomerase inhibitors, complement C5a receptor antagonists, DNA methyltransferase inhibitors, fatty acid synthase inhibitors, HIV vif gene modulators, Vif dimerization antagonists, HIV-1 viral infectivity factor inhibitors, HIV-1 Nef modulators, TNFα ligand inhibitors, HIV Nef inhibitors, Hck tyrosine kinase modulators, mixed lineage kinase-3 (MLK-3) inhibitors, HIV-1 splicing inhibitors, integrin antagonists, nucleoprotein inhibitors, splicing factor modulators, COMM domain-containing protein 1 modulators, HIV ribonuclease H inhibitors, IFN antagonists, retrocycline modulators, CDK-4 inhibitors, CDK-6 inhibitors, CDK-9 inhibitors, dendritic cell ICAM-3 non-integrin 1 inhibitors, HIV GAG protein inhibitors, HIV POL protein inhibitors, complement factor H regulators, ubiquitin ligase inhibitors, deoxycytidine kinase inhibitors, cyclin-dependent kinase inhibitors, proprotein convertase PC9 stimulators, ATP-dependent RNA helicase DDX3X inhibitors, reverse transcriptase initiation complex inhibitors, G6PD and NADH oxidase inhibitors, mTOR complex 1 inhibitors, mTOR complex 2 inhibitors, P-glycoprotein regulators, TAT protein inhibitors, prolyl endopeptidase inhibitors, phospholipase A2 inhibitors, pharmacokinetic enhancers, HIV gene therapy, HIV vaccines, and combinations thereof.

[0445] In some implementations, the adjunctive treatment agent is selected from the group consisting of: HIV protease inhibitors, non-nucleoside or non-nucleotide inhibitors of HIV reverse transcriptase, nucleoside or nucleotide inhibitors of HIV reverse transcriptase, HIV capsid inhibitors, gp41 inhibitors, CXCR4 inhibitors, gp120 inhibitors, CCR5 inhibitors, latency reversal agents, capsid polymerization inhibitors, HIV bNAb, TLR7 agonists, pharmacokinetic enhancers, other drugs for treating HIV, or combinations thereof.

[0446] In some implementations, the adjunctive therapeutic agent is selected from the group consisting of: combination drug products for HIV, other drugs for the treatment of HIV, HIV protease inhibitors, HIV reverse transcriptase inhibitors, HIV integrase inhibitors, HIV non-catalytic site (or allosteric) integrase inhibitors, HIV entry (fusion) inhibitors, HIV maturation inhibitors, latency reversal agents, capsid inhibitors, immune-based therapies, PI3K inhibitors, HIV antibodies and bispecific antibodies and "antibody-like" therapeutic proteins, and combinations thereof.

[0447] In some embodiments, the adjunctive therapeutic agent is independently selected from HIV capsid inhibitors, HIV protease inhibitors, non-nucleoside inhibitors of HIV reverse transcriptase, nucleoside inhibitors of HIV reverse transcriptase, nucleotide inhibitors of HIV reverse transcriptase, HIV integrase inhibitors, and CCR5 inhibitors. In some embodiments, the adjunctive therapeutic agent is independently selected from HIV reverse transcriptase nucleoside or nucleotide inhibitors and HIV capsid inhibitors or HIV capsid polymerization inhibitors.

[0448] In some embodiments of the methods disclosed herein, a compound of Formula I or a pharmaceutically acceptable salt thereof is administered in combination with a first adjunctive therapeutic agent and a second adjunctive therapeutic agent, the first adjunctive therapeutic agent being selected from the group consisting of tenofovir alafenamide fumarate, tenofovir alafenamide, and tenofovir alafenamide hemifumarate, wherein the second adjunctive therapeutic agent is emtricitabine. In some embodiments of the methods disclosed herein, a compound of Formula I or a pharmaceutically acceptable salt thereof is administered in combination with a first adjunctive therapeutic agent and a second adjunctive therapeutic agent, the first adjunctive therapeutic agent being selected from the group consisting of tenofovir disoproxil fumarate, tenofovir disoproxil fumarate, and tenofovir disoproxil fumarate, wherein the second adjunctive therapeutic agent is emtricitabine.

[0449] In some embodiments of the methods disclosed herein, a compound of formula I or a pharmaceutically acceptable salt thereof is administered in combination with at least one additional therapeutic agent selected from the group consisting of: (1) Nucleoside reverse transcriptase translocation inhibitors (“NRTTIs”), such as 4'-ethynyl-2-fluoro-2'-deoxyadenosine triphosphate (also known as MK-8591 and EFdA). (2) Nucleoside or nucleotide reverse transcriptase inhibitors (“NRTIs”), such as tenofovir alafenamide fumarate, tenofovir alafenamide, tenofovir alafenamide hemifumarate, GS-9131 and GS-9148. (3) Non-nucleoside or non-nucleotide reverse transcriptase inhibitors (“NNRTIs”), such as efavirenz, ectavirin, rilpivirine, nevirapine and delavudine; (4) Protease inhibitors (“PIs”), such as ampravir, atazanavir, becanavir, darenavir, fosanavir, fosanavir calcium, indinavir, indinavir sulfate, lopinavir, nelfinavir, nelfinavir mesylate, ritonavir, saquinavir, saquinavir mesylate, telanavir, DG-17, TMB-657 (PPL-100), T-169, BL-008, and TMC-31091; and (5) Integrase strand transfer inhibitors (“INSTIs”), such as bicteravir, cabotevir, retigvir and dulutevir.

[0450] HIV Combination drug products Examples of combination drug products include, but are not limited to, ATRIPLA ® (Efavirenz, Tenofovir disoproxil fumarate, and Emtricitabine); COMPLERA ® (EVIPLERA) ® Rilpivirine, tenofovir disoproxil fumarate, and emtricitabine); STRIBILD ® (Ertiravir, Cobistat, Tenofovir Disoproxil Fumarate, and Emtricitabine); TRUVADA ® (Tenofovir disoproxil fumarate and emtricitabine; TDF+FTC); DESCOVY ® (Tenofovir alafenamide and emtricitabine); ODESEY ® (Tenofovir alafenamide, emtricitabine, and rilpivirine); GENVOYA ®(Tenofovir alafenamide, emtricitabine, cobistat, and ertiravir); diravir, tenofovir alafenamide hemifumarate, emtricitabine, and cobistat; efavirenz, lamivudine, and tenofovir disoproxil fumarate; lamivudine and tenofovir disoproxil fumarate; tenofovir and lamivudine; tenofovir alafenamide and emtricitabine; tenofovir alafenamide hemifumarate and emtricitabine; tenofovir alafenamide hemifumarate, emtricitabine, and rilpivirine; tenofovir alafenamide hemifumarate, emtricitabine, cobistat, and ertiravir; tenofovir analogues; COMBIVIR ® (Zidovudine and Lamivudine; AZT+3TC); EPZICOM ® (KIVEXA) ® Abacavir sulfate and lamivudine; ABC+3TC); KALETRA ® (ALUVIA) ® (Lopinavir and ritonavir); TRIUMEQ ® (Durutvir, Abacavir, and Lamivudine); BIKTARVY ® (Bimetiravir + Emtricitabine + Tenofovir Alaminamide), DOVATO ® (Dolutegravir + Lamivudine), TRIZIVIR ® (Abacavir sulfate, zidovudine, and lamivudine; ABC+AZT+3TC); Atazanavir and cobistat; Atazanavir sulfate and cobistat; Atazanavir sulfate and ritonavir; Dermavir and cobistat; Duluthvir and rilpivirine; Duluthvir and rilpivirine hydrochloride; Duluthvir, abacavir sulfate, and lamivudine; Lamivudine, nevirapine, and zidovudine; Rettagvir and lamivudine; Doravirine, lamivudine, and tenofovir disoproxil fumarate; Doravirine, lamivudine, and tenofovir disoproxil fumarate; Duluthvir + lamivudine, Lamivudine + abacavir + zidovudine, Lamivudine + abacavir, Lamivudine + tenofovir disoproxil fumarate, lamivudine + lamivudine; lamivudine + abacavir, Lamivudine + tenofovir disoproxil fumarate, lamivudine + lamivudine; lamivudine + lamivudine, lamivudine + abacavir, Lamivudine + tenofovir disoproxil fumarate, lamivudine + zidovudine, Lam ... lamivudine, lamivudine + zidovudine, Lamivudine + abacavir, Lamivudine + tenofovir disoproxil fumarate, lamivudine + zidovudine, Lamivudine + zidovud Mivudine + Zidovudine + Nevirapine, Lopinavir + Ritonavir, Lopinavir + Ritonavir + Abacavir + Lamivudine, Lopinavir + Ritonavir + Zidovudine + Lamivudine, Tenofovir + Lamivudine, Tenofovir disoproxil fumarate + Emtricitabine + Rilpivirine Hydrochloride, Lopinavir, Ritonavir, Zidovudine, Lopinavir + Ritonavir + Abacavir + Lamivudine, Lamivudine, Cabotevir + Rilpivirine, 3-BNC117 + Ebovetine, Elpida (Isavirin, VM-1500) and VM-1500A, Lenapapvir + Islatrixvir (oral, injection) and dual-targeting HIV-1 reverse transcriptase / nucleocapsid protein 7 inhibitors.

[0451] other HIV drug Examples of other medications used to treat HIV include, but are not limited to, aspergillin C, acemannan, aliporivir, BanLec, deferiprone, gamimune, metenkefalin, naltrexone, prolastin, REP 9, RPI-MN, VSSP, H1viral, SB-728-T, and 1,5-Dicaffeoylquinic acid, rHIV7-shl-TAR-CCR5RZ, AAV-eCD4-Ig gene therapy, MazF gene therapy, BlockAide, bevirimat derivatives, ABBV-382, ABX-464, AG-1105, APH-0812, APH0202, bryozoin-1, bryozoin analogs, BIT-225, BRII-732, BRII-778, CYT-107, CS-TATI-1, fluoro-β-D-arabinose (FANA) modified antisense oligonucleotides, FX- 101. Griffithsin, GSK-3739937, GSK-3739937 (long-acting), HGTV-43, HPH-116, HS-10234, Hydroxychloroquine, IMB-10035, IMO-3100, IND-02, JL-18008, LADAVRU, MK-1376, MK-2048, MK-4250, MK-8507, MK-8558, MK-8591 (Isratravir), NOV-205, OB-002H, ODE-Bn-TFV, PA-1050040 (PA- 040), PC-707, PGN-007, QF-036, S-648414, SCY-635, SB-9200, SCB-719, TR-452, TEV-90110, TEV-90112, TEV-90111, TEV-90113, RN-18, DIACC-1010, Fasnall, Immuglo, 2-CLIPS peptide, HRF-4467, thrombospondin analogue, TBL-1004HI, VG-1177, XL-081, AVI-CO- 004, rfhSP-D, [18F]-MC-225, URMC-099-C, RES-529, Verdinexor, IMC-M113V, IML-106, antiviral fc conjugate (AVC), WP-1096, WP-1097, Gammora, ISR-CO48, ISR-48, ISR-49, MK-8527, cannabinoids, ENOB-HV-32, HiviCide-I, T-1144, VIR-576, nipamovir, Covimro, and ABBV-1882.

[0452] HIV protease inhibitors Examples of HIV protease inhibitors include, but are not limited to, ampravir, atazanavir, becanavir, deruravir, forosanavir, forosanavir calcium, indinavir, indinavir sulfate, lopinavir, nelfinavir, nelfinavir mesylate, ritonavir, saquinavir, saquinavir mesylate, telanavir, ASC-09+ritonavir, AEBL-2, DG-17, GS-1156, TMB-657 (PPL-100), T-169, BL-008, MK-8122, TMB-607, GRL-02031, and TMC-310911.

[0453] Additional examples of HIV protease inhibitors are described, for example, in U.S. Patent Nos. 10,294,234 and U.S. Patent Application Publications Nos. US2020030327 and US2019210978.

[0454] HIV Gag protein inhibitors Examples of HIV Gag protein inhibitors include, but are not limited to, HRF-10071.

[0455] HIV Ribonuclease H Inhibitors Examples of HIV ribonuclease H inhibitors include, but are not limited to, NSC-727447.

[0456] HIV Nef Inhibitors Examples of HIV Nef inhibitors include, but are not limited to, FP-1.

[0457] HIV Reverse transcriptase inhibitors Examples of non-nucleoside or non-nucleotide inhibitors of HIV reverse transcriptase include, but are not limited to, dapirine, delavudine, delavudine mesylate, doravirine, efavirenz, iletravirine, lentinan, nevirapine, rilpivirine, ACC-007, ACC-008, AIC-292, F-18, KM-023, PC-1005, M1-TFV, M2-TFV, VM-1500A-LAI, PF-3450074, isavirin (extended-release oral, for HIV infection), doravirine + isavirin (fixed-dose combination / oral tablet formulation, for HIV-1 infection), isavirin (long-acting injectable nanosuspension, for HIV infection), and isavirin (VM-1500).

[0458] Examples of nucleoside or nucleotide inhibitors of HIV reverse transcriptase include, but are not limited to, adefovir, adefovir dipivoxil, azavudine, emtricitabine, tenofovir, tenofovir alafenamide, tenofovir alafenamide fumarate, tenofovir alafenamide hemifumarate, tenofovir disoproxil fumarate, tenofovir alafenamide fumarate, tenofovir octadecyloxyethyl ester (AGX-1009), tenofovir disoproxil fumarate, and VIDEX. ® and VIDEX EC ® (Dysinosteroids, DDL), Abacavir, Abacavir sulfate, Alovudine, Alitabin, Cesarvudine, Dysinosteroids, Avtabin, Fertinavir, Fosalvudine Tidoxil, CMX-157, Dapirine, Doravirine, Etravirine, OCR-5753, Tenofovir Disoproxil Orotate, Fosalvudine Tidoxil, Lamivudine, Azide, Stavudine, Zacitabine, Zidovudine, Rovafovir Etalaflavinamide (GS-9131), GS-9148, MK-8504, Isratravir, MK-8583, VM-2500, and KP-1461.

[0459] Additional examples of nucleoside or nucleotide inhibitors of HIV reverse transcriptase include, but are not limited to, those described in patent publications US2007049754, US2016250215, US2016237062, US2016251347, US2002119443, US2013065856, US2013090473, US2014221356, and WO04096286.

[0460] HIV Integrase inhibitors Examples of HIV integrase inhibitors include, but are not limited to, erteiravir, erteiravir (extended-release microcapsules), curcumin, curcumin derivatives, chicoric acid, chicoric acid derivatives, 3,5-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid derivatives, ginsenoside tricarboxylic acid, ginsenoside tricarboxylic acid derivatives, caffeic acid phenethyl ester, caffeic acid phenethyl ester derivatives, tyrphostin, tyrphostin derivatives, quercetin, quercetin derivatives, retegvir, PEGylated retegvir, dulutegravir, and JTK-351. Bimetiravir, AVX-15567, Cabotevir (long-acting injectable), diketoquinoline-4-1 derivatives, integrase-LEDGF inhibitors, ledgins, M-522, M-532, MK-0536, NSC-310217, NSC-371056, NSC-48240, NSC-642710, NSC-699171, NSC-699172, NSC-699173, NSC-699174, stilbenedisulfonic acid, T169, STP-0404, VM-3500, XVIR-110, and ACC-017.

[0461] Examples of HIV noncatalytic site or allosteric integrase inhibitors (NCINIs) include, but are not limited to, CX-05045, CX-05168, and CX-14442.

[0462] Additional examples of HIV capsid inhibitors include, but are not limited to, those described in U.S. Patent Application Publication Nos. US2014221356 and US2016016973.

[0463] HIV Viral infectious agent inhibitors Examples of inhibitors of HIV infectious agents include, but are not limited to, 2-amino-N-(2-methoxyphenyl)-6-((4-nitrophenyl)thio)benzamide derivatives and Irino-L.

[0464] HIV Entry inhibitor Examples of HIV entry (fusion) inhibitors include, but are not limited to, AAR-501, LBT-5001, cineviro, CCR5 inhibitors, gp41 inhibitors, CD4 attachment inhibitors, gp120 inhibitors, gp160 inhibitors, and CXCR4 inhibitors.

[0465] Examples of CCR5 inhibitors include, but are not limited to, apravirone, vevicvirone, maravirone, maravirone (long-acting injectable nanoemulsion), suniverone, lerolimumab (PRO-140), adatavir (RAP-101), nifevirone (TD-0232), anti-GP120 / CD4 or CCR5 bispecific antibody, B-07, MB-66, peptide C25P, TD-0680, celavirone, and vMIP (Haimipu).

[0466] Examples of gp41 inhibitors include, but are not limited to, Abovetine, Enfuvirtide, Griffon (a gp41 / gp120 / gp160 inhibitor), BMS-986197, enfuvirtide biomodification, enfuvirtide biosimilar, HIV-1 fusion inhibitor (P26-Bapc), ITV-1, ITV-2, ITV-3, ITV-4, CPT-31, Cl3hmAb, lipuvirtide, PIE-12 trimer, and sifvirtide.

[0467] Examples of CD4 attachment inhibitors include, but are not limited to, ibalizumab and CADA analogues. Examples of gp120 inhibitors include, but are not limited to, anti-HIV microbial agents, Radha-108 (receptol) 3B3-PE38, BMS818251, BanLec, bentonite-based nanomedicines, fostemsavir (aminobutyric acid), IQP-0831, VVX-004, and BMS-663068.

[0468] Examples of gp160 inhibitors include, but are not limited to, tetrandrine.

[0469] Examples of CXCR4 inhibitors include, but are not limited to, praxavir, ALT-1188, N15 peptide, and vMIP (Haimipu).

[0470] HIV Maturation inhibitors Examples of HIV maturation inhibitors include, but are not limited to, BMS-955176, GSK-3640254, and GSK-2838232.

[0471] Latency reversal agent Examples of latency reversal agents include, but are not limited to, toll-like receptor (TLR) agonists (including TLR7 agonists, such as GS-9620, TLR8 agonists, and TLR9 agonists), histone deacetylase (HDAC) inhibitors, proteasome inhibitors such as velcade, protein kinase C (PKC) activators, Smyd2 inhibitors, BET-bromodomain 4 (BRD4) inhibitors (such as ZL-0580 and apabelon), ionomycin, and IAP antagonists (inhibitors of apoptosis proteins, such as APG-1387 and LBW-). 242) SMAC mimics (including TL32711, LCL161, GDC-0917, HGS1029, AT-406, Debio-1143), PMA, SAHA (aminosuccinate or succinyl, aniline and isohydroxamic acid), NIZ-985, IL-15 modulating antibodies (including IL-15, IL-15 fusion proteins and IL-15 receptor agonists), JQ1, disulfiram, amphotericin B and ubiquitin inhibitors (such as lagazole analogs, APH-0812 and GSK-343). Examples of PKC activators include, but are not limited to, indolactam, prostratin, ingenol B and DAG lactone.

[0472] Additional examples of TLR7 agonists include, but are not limited to, those described in U.S. Patent Application Publication No. US2010143301.

[0473] Additional examples of TLR8 agonists include, but are not limited to, those described in U.S. Patent Application Publication No. US2017071944.

[0474] Histone deacetylase ( HDAC Inhibitors In some embodiments, the agent as described herein is combined with an inhibitor of histone deacetylase, such as histone deacetylase 1, histone deacetylase 9 (HDAC9, HD7, HD7b, HD9, HDAC, HDAC7, HDAC7B, HDAC9B, HDAC9FL, HDRP, MITR; gene ID: 9734). Examples of HDAC inhibitors include, but are not limited to, abexinostat, ACY-241, AR-42, BEBT-908, belinostat, CKD-581, CS-055 (HBI-8000), CT-101, CUDC-907 (fimepinostat), entinostat, givinostat, mocetinostat, panobinostat, pracinostat, quisinostat (JNJ-26481585), remixitana, ricolinostat, romidesin, SHP-141, TMB-ADC, valproic acid (VAL-001), vorinostat, tinostamustine, remetinostat, and entinostat.

[0475] Capsid inhibitors Examples of capsid inhibitors include, but are not limited to, capsid polymerization inhibitors or capsid disruption compounds, HIV nucleocapsid p7 (NCp7) inhibitors (such as azodicarbonamide), HIV p24 capsid protein inhibitors, lenakapavir (GS-6207), GS-CA1, AVI-621, AVI-101, AVI-201, AVI-301 and the AVI-CAN1-15 series, PF-3450074, HIV-1 capsid inhibitors (HIV-1 infection, Shandong University) and compounds described in (GSK WO2019 / 087016).

[0476] Additional examples of capsid inhibitors include, but are not limited to, those described in U.S. Patent Application Publication Nos. US2018051005 and US2016108030.

[0477] Cytochrome P450 3 Inhibitors Examples of cytochrome P450 3 inhibitors include, but are not limited to, those described in U.S. Patent No. 7,939,553.

[0478] RNA Polymerase regulators Examples of RNA polymerase regulators include, but are not limited to, those described in U.S. Patent Nos. 10,065,958 and 8,008,264.

[0479] Immune checkpoint modulators In various embodiments, the agents described herein are combined with one or more blockers or inhibitors of inhibitory immune checkpoint proteins or receptors and / or with one or more stimulators, activators, or agonists of stimulating immune checkpoint proteins or receptors. Blockage or inhibition of inhibitory immune checkpoints can positively modulate T cell or NK cell activation and prevent immune escape by infected cells. Stimulation or activation of immune checkpoints can enhance the efficacy of immune checkpoint inhibitors in the treatment of infections. In various embodiments, immune checkpoint proteins or receptors regulate T cell responses (e.g., in Xu et al., J Exp Clin Cancer Research (Reviewed in (2018) 37:110). In various implementations, immune checkpoint proteins or receptors regulate NK cell responses (e.g., as reviewed in the following literature: Davis et al., Semin Immunol (2017) 31:64–75; and Chiossone et al., Nat Rev Immunol (Reviewed in .(2018) 18(11):671-688).

[0480] Examples of immune checkpoint proteins or receptors include, but are not limited to, CD27, CD70; CD40, CD40LG; CD47, CD48 (SLAMF2); transmembrane and immunoglobulin domain-containing receptors 2 (TMIGD2, CD28H); CD84 (LY9B, SLAMF5); CD96, CD160, MS4A1 (CD20); CD244 (SLAMF4); CD276 (B7H3); T cell activation inhibitors 1 containing V-set domains (VTCN1, B7H4); V-set immunomodulatory receptors (VSIR, B7H5, VISTA); immunoglobulin superfamily member 11 (IGSF11, VSIG3); natural killer cell cytotoxic receptor 3 ligand 1 (NCR3LG1, B7H6); HERV-H LTR-related 2 (HHLA2, B7H7); inducible T cell costimulatory factors (ICOS, CD278); inducible T cell costimulatory ligands (ICOSLG, B7H2); TNF receptor superfamily member 4 (TNFRSF4, OX40); TNF superfamily member 4 (TNFSF4, OX40L); TNFRSF8 (CD30), TNFSF8 (CD30L); TNFRSF10A (CD261, DR4, TRAILR1), TNFRSF9 (CD137) TNFSF9 (CD137L); TNFRSF10B (CD262, DR5, TRAILR2), TNFRSF10 (TRAIL); TNFRSF14 (HVEML, CD270), TNFSF14 (HVEML); CD272 (B and T lymphocyte-associated (BTLA)); TNFRSF17 (BCMA, CD269); TNFSF13B (BAFF); TNFRSF18 (GITR), TNFSF18 (GITRL); MHC MHC class I peptide-associated sequence A (MICA); MHC class I peptide-associated sequence B (MICB); CD274 (CD274, PDL1, PD-L1); programmed cell death 1 (PDCD1, PD1, PD-1); cytotoxic T-lymphocyte-associated protein 4 (CTLA4, CD152); CD80 (B7-1), CD28; nectin cell adhesion molecule 2 (NECTIN2, CD112); CD226 (DNAM-1); poliovirus receptor (PVR) cell adhesion molecule (PVR, CD155); containing PVR-associated immunoglobulin domains (PVRIG, CD112R); T-cell immune receptor with Ig and ITIM domains (TIGIT); containing T-cell immunoglobulin and mucin domains 4 (TIMD4; TIM4); hepatitis A virus cell receptor 2 (HAVCR2, TIMD3, TIM3); galactohemagglutinin 9 (LGALS9).Lymphocyte activation 3 (LAG3, CD223); Signal transduction lymphocyte activation molecule family member 1 (SLAMF1, SLAM, CD150); Lymphocyte antigen 9 (LY9, CD229, SLAMF3); SLAM family member 6 (SLAMF6, CD352); SLAM family member 7 (SLAMF7, CD319); UL16 binding protein 1 (ULBP1); UL16 binding protein 2 (ULBP2); UL16 binding protein 3 (ULBP3); Early retinoic acid transcript 1E (RAET1E; ULBP4); Early retinoic acid transcript 1G (RAET1G; ULBP5); Early retinoic acid transcript 1L (RAET1L; ULBP6); Lymphocyte activation 3 (CD223); Cytokine immunoglobulin-like receptor, three Ig domains and long cytoplasmic tail 1 (KIR, CD158E1); Cytokine lectin-like receptor C1 (KLRC1, NKG) 2A, CD159A); cytotoxic cell lectin-like receptor K1 (KLRK1, NKG2D, CD314); cytotoxic cell lectin-like receptor C2 (KLRC2, CD159c, NKG2C); cytotoxic cell lectin-like receptor C3 (KLRC3, NKG2E); cytotoxic cell lectin-like receptor C4 (KLRC4, NKG2F); cytotoxic cell immunoglobulin-like receptor, two Ig domains and long cytoplasmic tail 1 (KIR2DL1); cytotoxic cells Cellular immunoglobulin-like receptor, two Ig domains and long cytoplasmic tail 2 (KIR2DL2); cytotoxic cell immunoglobulin-like receptor, two Ig domains and long cytoplasmic tail 3 (KIR2DL3); cytotoxic cell immunoglobulin-like receptor, three Ig domains and long cytoplasmic tail 1 (KIR3DL1); cytotoxic cell lectin-like receptor D1 (KLRD1); SLAM family member 7 (SLAMF7); and hematopoietic progenitor cell kinase 1 (HPK1, MAP4K1).

[0481] In various embodiments, the agents described herein are combined with one or more blockers or inhibitors of one or more T-cell suppressor immune checkpoint proteins or receptors. Exemplary T-cell suppressor immune checkpoint proteins or receptors include, but are not limited to, CD274 (CD274, PDL1, PD-L1); programmed cell death 1 ligand 2 (PDCD1LG2, PD-L2, CD273); programmed cell death 1 (PDCD1, PD1, PD-1); cytotoxic T-lymphocyte-associated protein 4 (CTLA4, CD152); CD276 (B7H3); V-set domain-containing T-cell activation inhibitor 1 (VTCN1, B7H4); V-set immunomodulatory receptors (VSIR, B7H5, VISTA); immunoglobulin superfamily member 11 (IGSF11, VSIG3); TNFRSF14 (HVEM, CD270), TNFSF14 (HVEML); CD272 (B and T lymphocyte-associated (BTLA)); PVR-containing immunomodulatory receptors. Immunoglobulin domains (PVRIG, CD112R); T-cell immune receptors with Ig and ITIM domains (TIGIT); lymphocyte activation 3 (LAG3, CD223); hepatitis A virus cell receptor 2 (HAVCR2, TIMD3, TIM3); galactoglobulin 9 (LGALS9); cytotoxic cell immunoglobulin-like receptor with three Ig domains and a long cytoplasmic tail 1 (KIR, CD158E1); cytotoxic cell immunoglobulin-like receptor with two Ig domains and a long cytoplasmic tail 1 (KIR2DL1); cytotoxic cell immunoglobulin-like receptor with two Ig domains and a long cytoplasmic tail 2 (KIR2DL2); cytotoxic cell immunoglobulin-like receptor with two Ig domains and a long cytoplasmic tail 3 (KIR2DL3); and cytotoxic cell immunoglobulin-like receptor with three Ig domains and a long cytoplasmic tail 1 (KIR3DL1). In various embodiments, the reagents as described herein are combined with one or more agonists or activators of one or more T-cell stimulating immune checkpoint proteins or receptors.Exemplary T-cell stimulating immune checkpoint proteins or receptors include, but are not limited to, CD27, CD70; CD40, CD40LG; inducible T-cell costimulators (ICOS, CD278); inducible T-cell costimulator ligands (ICOSLG, B7H2); TNF receptor superfamily member 4 (TNFRSF4, OX40); TNF superfamily member 4 (TNFSF4, OX40L); TNFRSF9 (CD137), TNFSF9 (CD137L); TNFRSF18 (GITR), TNFSF18 (GITRL); CD80 (B7-1), CD28; nectin cell adhesion molecule 2 (NECTIN2, CD112); CD226 (DNAM-1); CD244 (2B4, SLAMF4); poliovirus receptor (PVR) cell adhesion molecule (PVR, CD155). See, for example, Xu et al. J Exp Clin Cancer Research .(2018) 37:110.

[0482] In various embodiments, the agent as described herein is combined with one or more blockers or inhibitors of one or more NK cell inhibitory immune checkpoint proteins or receptors. Exemplary NK cell inhibitory immune checkpoint proteins or receptors include, but are not limited to, cytotoxic cell immunoglobulin-like receptors with three Ig domains and a long cytoplasmic tail 1 (KIR, CD158E1); cytotoxic cell immunoglobulin-like receptors with two Ig domains and a long cytoplasmic tail 1 (KIR2DL1); cytotoxic cell immunoglobulin-like receptors with two Ig domains and a long cytoplasmic tail 2 (KIR2DL2); cytotoxic cell immunoglobulin-like receptors with two Ig domains and a long cytoplasmic tail 3 (KIR2DL3); cytotoxic cell immunoglobulin-like receptors with three Ig domains and a long cytoplasmic tail 1 (KIR3DL1); cytotoxic cell lectin-like receptor C1 (KLRC1, NKG2A, CD159A); and cytotoxic cell lectin-like receptor D1 (KLRD1, CD94). In various embodiments, the agent as described herein is combined with one or more agonists or activators of one or more NK cell-stimulating immune checkpoint proteins or receptors. Exemplary NK cell-stimulating immune checkpoint proteins or receptors include, but are not limited to, CD16, CD226 (DNAM-1); CD244 (2B4, SLAMF4); cytotoxic lectin-like receptor K1 (KLRK1, NKG2D, CD314); and SLAM family member 7 (SLAMF7). See, for example, Davis et al., Semin Immunol. (2017) 31:64–75; Fang et al., Semin Immunol. (2017) 31:37-54; and Chiossone et al., Nat Rev Immunol. (2018) 18(11):671-688.

[0483] In some embodiments, one or more immune checkpoint inhibitors include protein (e.g., antibody or fragment thereof or antibody mimic) inhibitors of PD-L1 (CD274), PD-1 (PDCD1), or CTLA4. In some embodiments, one or more immune checkpoint inhibitors include small organic molecule inhibitors of PD-L1 (CD274), PD-1 (PDCD1), or CTLA4. In some embodiments, the small molecule inhibitors of CD274 or PDCD1 are selected from the group consisting of GS-4224, GS-4416, INCB086550, and MAX10181. In some embodiments, the small molecule inhibitor of CTLA4 includes BPI-002.

[0484] Examples of CTLA4 inhibitors that can be co-administered include, but are not limited to, ipilimumab, trimemumab, BMS-986218, AGEN1181, AGEN1884, BMS-986249, MK-1308, REGN-4659, ADU-1604, CS-1002, BCD-145, APL-509, JS-007, BA-3071, ONC-392, AGEN-2041, JHL-1155, KN-044, CG-0161, ATOR-1144, PBI-5D3H5, BPI-002, and multispecific inhibitors FPT-155 (CTLA4 / PD-L1 / CD28) and PF-06936308 (PD-1 / CTLA4), MGD-019 (PD-1 / CTLA4), KN-046 (PD-1 / CTLA4), MEDI-5752 (CTLA4 / PD-1), XmAb-20717 (PD-1 / CTLA4) and AK-104 (CTLA4 / PD-1).

[0485] Examples of PD-L1 (CD274) or PD-1 (PDCD1) inhibitors that can be co-administered include, but are not limited to, pembrolizumab, nivolumab, cimetizumab, pildizumab, AMP-224, MEDI0680 (AMP-514), spartazumab, atezolizumab, avelumab, durvalumab, BMS-936559, CK-301, PF-06801591, BGB-A317 (tislelizumab), GLS-010 (WBP-3055), AK-103 (HX-008), AK-105, CS-1003, HLX-10, MGA-012, and BI-754091. AGEN-2034, JS-001 (Toripalimab), JNJ-63723283, Genomeamarab (CBT-501), LZM-009, BCD-100, LY-3300054, SHR-1201, SHR-1210 (Camrelizumab), Sym-021, ABBV-181 (Bug's maize), PD1-PIK, BAT-1306 (MSB0010718C), CX-072, CBT-502, TSR-042 (Dotalimab), MSB-2311, JTX-4014, BGB-A333, SHR-1316, CS-1001 (WBP- 3155, KN-035, IBI-308 (sintilimab), HLX-20, KL-A167, STI-A1014, STI-A1015 (IMC-001), BCD-135, FAZ-053, TQB-2450, MDX1105-01, GS-4224, GS-4416, INCB086550, MAX10181, and multispecific inhibitors FPT-155 (CTLA4 / PD-L1 / CD28), PF-06936308 (PD-1 / CTLA4), MGD-013 (PD-1 / LAG-3), FS-118 (LAG-3 / PD-L1), and PD-L1 / PD-L1 / PD-L1. -L1) MGD-019 (PD-1 / CTLA4), KN-046 (PD-1 / CTLA4), MEDI-5752 (CTLA4 / PD-1), RO-7121661 (PD-1 / TIM-3), XmAb-20717 (PD-1 / CTLA4), AK-104 (C TLA4 / PD-1), M7824 (PD-L1 / TGFβ-EC domain), CA-170 (PD-L1 / VISTA), CDX-527 (CD27 / PD-L1), LY-3415244 (TIM3 / PDL1), and INBRX-105 (4-1BB / PDL1).

[0486] In various implementation schemes, the agents described herein are combined with anti-TIGIT antibodies such as BMS-986207, RG-6058 and AGEN-1307.

[0487] TNF Receptor superfamily ( TNFRSF Member agonists or activators In various embodiments, the agent as described herein is combined with an agonist of one or more members of the TNF receptor superfamily (TNFRSF), such agonists being one or more of the following: TNFRSF1A (NCBI gene ID: 7132), TNFRSF1B (NCBI gene ID: 7133), TNFRSF4 (OX40, CD134; NCBI gene ID: 7293), TNFRSF5 (CD40; NCBI gene ID: 958), TNFRSF6 (FAS, NCBI gene ID: 35). 5) TNFRSF7 (CD27, NCBI gene ID: 939), TNFRSF8 (CD30, NCBI gene ID: 943), TNFRSF9 (4-1BB, CD137, NCBI gene ID: 3604), TNFRSF10A (CD261, DR4, TRAILR1, NCBI gene ID: 8797), TNFRSF10B (CD262, DR5, TRAILR2, NCBI gene ID: 8795), TNFRSF10C (CD263, TRAILR3, ... TNFRSF10D (CD264, TRAILR4, NCBI gene ID: 8793), TNFRSF11A (CD265, RANK, NCBI gene ID: 8792), TNFRSF11B (NCBI gene ID: 4982), TNFRSF12A (CD266, NCBI gene ID: 51330), TNFRSF13B (CD267, NCBI gene ID: 23495), TNFRSF13C (CD268, NCBI gene ID: 8794), ...CD268, NCBI gene ID: 4982), TNFRSF12A (CD266, NCBI gene ID: 51330), TNFRSF13B (CD267, NCBI gene ID: 23495), TNFRSF13C (CD268, NCBI gene ID: 8794), TNFRSF10D (CD264, TRAILR4, NCBI gene ID: 8793), TNFRSF11 D: 115650), TNFRSF16 (NGFR, CD271, NCBI gene ID: 4804), TNFRSF17 (BCMA, CD269, NCBI gene ID: 608), TNFRSF18 (GITR, CD357, NCBI gene ID: 8784), TNFRSF19 (NCBI gene ID: 55504), TNFRSF21 (CD358, DR6, NCBI gene ID: 27242) and TNFRSF25 (DR3, NCBI gene ID: 8718).

[0488] Examples of anti-TNFRSF4 (OX40) antibodies that can be co-administered include, but are not limited to, MEDI6469, MEDI6383, MEDI0562 (tavorizumab), MOXR0916, PF-04518600, RG-7888, GSK-3174998, INCAGN1949, BMS-986178, GBR-8383, ABBV-368, and those described in WO2016179517, WO2017096179, WO2017096182, WO2017096281, and WO2018089628.

[0489] Examples of anti-TNFRSF5 (CD40) antibodies that can be co-administered include, but are not limited to, RG7876, SEA-CD40, APX-005M, and ABBV-428.

[0490] In some implementations, the anti-TNFRSF7 (CD27) antibody varigramab (CDX-1127) is co-administered.

[0491] Examples of anti-TNFRSF9 (4-1BB, CD137) antibodies that can be co-administered include, but are not limited to, urinumab, urinumab (PF-05082566), AGEN2373, and ADG-106.

[0492] Examples of anti-TNFRSF18 (GITR) antibodies that can be co-administered include, but are n...

Claims

1. A solid oral dosage form comprising a compound of formula I: I Or a pharmaceutically acceptable salt thereof, and one or more excipients; wherein the compound of formula I or a pharmaceutically acceptable salt thereof is present in an amount of about 5 mg to about 1400 mg, wherein the amount is based on the free acid form.

2. The oral dosage form according to claim 1, wherein the compound of formula I or a pharmaceutically acceptable salt thereof is present in an amount of about 5 mg to about 750 mg, wherein the amount is based on the free acid form.

3. The oral dosage form according to claim 1 or 2, wherein the compound of formula I or a pharmaceutically acceptable salt thereof is present in an amount of about 5 mg to about 300 mg, wherein the amount is based on the free acid form.

4. The oral dosage form according to claim 1 or 2, wherein the compound of formula I or a pharmaceutically acceptable salt thereof is present in an amount of about 300 mg to about 500 mg, wherein the amount is based on the free acid form.

5. The oral dosage form according to claim 1 or 2, wherein the compound of formula I or a pharmaceutically acceptable salt thereof is present in an amount of about 400 mg to about 700 mg, wherein the amount is based on the free acid form.

6. The oral dosage form according to claim 1 or 2, wherein the compound of formula I or a pharmaceutically acceptable salt thereof is present in an amount of about 400 mg to about 500 mg, wherein the amount is based on the free acid form.

7. The oral dosage form according to claim 1 or 2, wherein the compound of formula I or a pharmaceutically acceptable salt thereof is present in an amount of about 450 mg, wherein the amount is based on the free acid form.

8. The oral dosage form according to claim 1 or 2, wherein the compound of formula I or a pharmaceutically acceptable salt thereof is present in an amount of about 600 mg to about 700 mg, wherein the amount is based on the free acid form.

9. The oral dosage form according to claim 1 or 2, wherein the compound of formula I or a pharmaceutically acceptable salt thereof is present in an amount of about 650 mg, wherein the amount is based on the free acid form.

10. The oral dosage form according to claim 1 or 2, wherein the compound of formula I or a pharmaceutically acceptable salt thereof is present in an amount of about 5 mg to about 500 mg, wherein the amount is based on the free acid form.

11. The oral dosage form according to claim 1 or 2, wherein the compound of formula I or a pharmaceutically acceptable salt thereof is present in an amount of about 10 mg to about 450 mg, wherein the amount is based on the free acid form.

12. The oral dosage form according to claim 1 or 2, wherein the compound of formula I or a pharmaceutically acceptable salt thereof is present in an amount of about 10 mg to about 250 mg, wherein the amount is based on the free acid form.

13. The oral dosage form according to claim 1 or 2, wherein the compound of formula I or a pharmaceutically acceptable salt thereof is present in an amount of about 10 mg, wherein the amount is based on the free acid form.

14. The oral dosage form according to claim 1 or 2, wherein the compound of formula I or a pharmaceutically acceptable salt thereof is present in an amount of about 40 mg, wherein the amount is based on the free acid form.

15. The oral dosage form according to claim 1 or 2, wherein the compound of formula I or a pharmaceutically acceptable salt thereof is present in an amount of about 50 mg, wherein the amount is based on the free acid form.

16. The oral dosage form according to claim 1 or 2, wherein the compound of formula I or a pharmaceutically acceptable salt thereof is present in an amount of about 62.5 mg, wherein the amount is based on the free acid form.

17. The oral dosage form according to claim 1 or 2, wherein the compound of formula I or a pharmaceutically acceptable salt thereof is present in an amount of about 250 mg, wherein the amount is based on the free acid form.

18. The oral dosage form according to claim 1 or 2, wherein the compound of formula I or a pharmaceutically acceptable salt thereof is present in an amount of about 325 mg, wherein the amount is based on the free acid form.

19. The oral dosage form according to any one of claims 1 to 18, wherein the compound of formula I or a pharmaceutically acceptable salt thereof is present in an amount of about 1% to about 50% of the total weight of the dosage form.

20. The oral dosage form according to any one of claims 1 to 19, wherein the compound of formula I or a pharmaceutically acceptable salt thereof is present in an amount of about 5% to about 45% of the total weight of the dosage form.

21. The oral dosage form according to any one of claims 1 to 20, wherein the compound of formula I or a pharmaceutically acceptable salt thereof is present in an amount of about 20% to about 40% of the total weight of the dosage form.

22. The oral dosage form according to any one of claims 1 to 21, wherein the compound of formula I or a pharmaceutically acceptable salt thereof is present in an amount of about 20% of the total weight of the dosage form.

23. The oral dosage form according to any one of claims 1 to 21, wherein the compound of formula I or a pharmaceutically acceptable salt thereof is present in an amount of about 25% to about 35% of the total weight of the dosage form.

24. The oral dosage form according to any one of claims 1 to 21 and 23, wherein the compound of formula I or a pharmaceutically acceptable salt thereof is present in an amount of about 30% of the total weight of the dosage form.

25. The oral dosage form according to any one of claims 1 to 20, wherein the compound of formula I or a pharmaceutically acceptable salt thereof is present in an amount of about 5% to about 10% of the total weight of the dosage form.

26. The oral dosage form according to any one of claims 1 to 20 and 25, wherein the compound of formula I or a pharmaceutically acceptable salt thereof is present in an amount of about 7% of the total weight of the dosage form.

27. The oral dosage form according to any one of claims 1 to 26, wherein the dosage form is a tablet or a capsule.

28. The oral dosage form according to any one of claims 1 to 27, wherein the dosage form is a tablet.

29. The oral dosage form according to any one of claims 1 to 28, wherein the dosage form is prepared by wet granulation.

30. The oral dosage form according to any one of claims 1 to 28, wherein the dosage form is prepared by dry granulation.

31. The oral dosage form according to any one of claims 1 to 30, wherein the one or more excipients comprise fillers, disintegrants, lubricants, surfactants, pH adjusters, binders, or combinations thereof.

32. The oral dosage form according to claim 31, wherein the filler comprises microcrystalline cellulose, lactose, mannitol, calcium phosphate, or a combination thereof.

33. The oral dosage form according to claim 31 or 32, wherein the filler comprises lactose.

34. The oral dosage form according to claim 32 or 33, wherein the lactose is lactose monohydrate.

35. The oral dosage form according to any one of claims 31 to 34, wherein the filler comprises microcrystalline cellulose.

36. The oral dosage form according to any one of claims 31 to 35, wherein the filler comprises lactose and microcrystalline cellulose.

37. The oral dosage form according to any one of claims 31 to 36, wherein the filler is present in an amount of about 50% to about 90% of the total weight of the dosage form.

38. The oral dosage form according to any one of claims 31 to 37, wherein the filler is present in an amount of about 55% to about 85% of the total weight of the dosage form.

39. The oral dosage form according to any one of claims 31 to 38, wherein the filler is present in an amount of about 81% to about 83% of the total weight of the dosage form.

40. The oral dosage form according to any one of claims 31 to 39, wherein the filler is present in an amount of about 82% of the total weight of the dosage form.

41. The oral dosage form according to any one of claims 31 to 38, wherein the filler is present in an amount of about 58% to about 60% of the total weight of the dosage form.

42. The oral dosage form according to any one of claims 31 to 38 and 41, wherein the filler is present in an amount of about 59% of the total weight of the dosage form.

43. The oral dosage form according to any one of claims 32 to 42, wherein the lactose is present in an amount of about 20% to about 50% or about 25% to about 45% of the total weight of the dosage form.

44. The oral dosage form according to any one of claims 32 to 43, wherein the lactose is present in an amount of about 25% to about 35% of the total weight of the dosage form.

45. The oral dosage form according to any one of claims 32 to 44, wherein the lactose is present in an amount of about 29% to about 31% of the total weight of the dosage form.

46. ​​The oral dosage form according to any one of claims 32 to 45, wherein the lactose is present in an amount of about 30% of the total weight of the dosage form.

47. The oral dosage form according to any one of claims 32 to 43, wherein the lactose is present in an amount of about 35% to about 45% of the total weight of the dosage form.

48. The oral dosage form according to any one of claims 32 to 43 and 47, wherein the lactose is present in an amount of about 40% to about 42% of the total weight of the dosage form.

49. The oral dosage form according to any one of claims 32 to 43, 47 and 48, wherein the lactose is present in an amount of about 41% of the total weight of the dosage form.

50. The oral dosage form according to any one of claims 32 to 49, wherein the microcrystalline cellulose is present in an amount of about 20% to about 50% or about 25% to about 45% of the total weight of the dosage form.

51. The oral dosage form according to any one of claims 32 to 50, wherein the microcrystalline cellulose is present in an amount of about 25% to about 35% of the total weight of the dosage form.

52. The oral dosage form according to any one of claims 32 to 51, wherein the microcrystalline cellulose is present in an amount of about 29% to about 31% of the total weight of the dosage form.

53. The oral dosage form according to any one of claims 32 to 52, wherein the microcrystalline cellulose is present in an amount of about 30% of the total weight of the dosage form.

54. The oral dosage form according to any one of claims 32 to 50, wherein the microcrystalline cellulose is present in an amount of about 35% to about 45% of the total weight of the dosage form.

55. The oral dosage form according to any one of claims 32 to 50 and 54, wherein the microcrystalline cellulose is present in an amount of about 40% to about 42% of the total weight of the dosage form.

56. The oral dosage form according to any one of claims 32 to 50, 54 and 55, wherein the microcrystalline cellulose is present in an amount of about 41% of the total weight of the dosage form.

57. The oral dosage form according to any one of claims 32 to 56, wherein the filler comprises a mixture of lactose and microcrystalline cellulose, wherein the weight ratio of lactose to microcrystalline cellulose is about 2:3 to about 3:

2.

58. The oral dosage form according to any one of claims 32 to 57, wherein the filler comprises a mixture of lactose and microcrystalline cellulose, wherein the weight ratio of lactose to microcrystalline cellulose is about 1:

1.

59. The oral dosage form according to any one of claims 31 to 58, wherein the disintegrant comprises starch, pregelatinized starch, hydroxypropyl starch, cellulose, crosspovidone, sodium carboxymethyl starch, croscarmellose sodium, or combinations thereof.

60. The oral dosage form according to any one of claims 31 to 59, wherein the disintegrant comprises pregelatinized starch.

61. The oral dosage form according to any one of claims 31 to 60, wherein the disintegrant comprises croscarmellose sodium.

62. The oral dosage form according to any one of claims 31 to 61, wherein the disintegrant comprises cropovidone.

63. The oral dosage form according to any one of claims 31 to 62, wherein the disintegrant is present in an amount of about 1% to about 50%, about 1% to about 20%, about 1% to about 15%, about 1% to about 10%, about 5% to about 15%, or about 5% to about 8% of the total weight of the dosage form.

64. The oral dosage form according to any one of claims 31 to 63, wherein the disintegrant is present in an amount of about 3% to about 7% of the total weight of the dosage form.

65. The oral dosage form according to any one of claims 31 to 64, wherein the disintegrant is present in an amount of about 5% of the total weight of the dosage form.

66. The oral dosage form according to any one of claims 31 to 65, wherein the lubricant comprises stearic acid, sodium stearoyl fumarate, magnesium stearate, or a combination thereof.

67. The oral dosage form according to any one of claims 31 to 66, wherein the lubricant comprises magnesium stearate.

68. The oral dosage form according to any one of claims 31 to 67, wherein the lubricant is present in an amount of about 0.01% to about 10%, about 0.1% to about 5%, or about 0.1% to about 2% of the total weight of the dosage form.

69. The oral dosage form according to any one of claims 31 to 68, wherein the lubricant is present in an amount of about 1% to about 2% of the total weight of the dosage form.

70. The oral dosage form according to any one of claims 31 to 69, wherein the lubricant is present in an amount of about 1.5% of the total weight of the dosage form.

71. The oral dosage form according to any one of claims 31 to 70, wherein the binder comprises cellulose, starch, gelatin, gum arabic, or a combination thereof.

72. The oral dosage form according to any one of claims 31 to 71, wherein the binder comprises cellulose.

73. The oral dosage form according to any one of claims 31 to 72, wherein the binder comprises hydroxypropyl cellulose.

74. The oral dosage form according to any one of claims 31 to 73, wherein the binder is present in an amount of about 1% to about 10% of the total weight of the dosage form.

75. The oral dosage form according to any one of claims 31 to 74, wherein the binder is present in an amount of about 2% to about 6% of the total weight of the dosage form.

76. The oral dosage form according to any one of claims 31 to 75, wherein the binder is present in an amount of about 4% of the total weight of the dosage form.

77. The oral dosage form according to any one of claims 31 to 76, wherein the surfactant comprises sodium lauryl sulfate, d-α-tocopherol polyethylene glycol 1000 succinate (TPGS), or a combination thereof.

78. The oral dosage form according to any one of claims 31 to 77, wherein the pH adjuster is an alkaline excipient.

79. The oral dosage form according to any one of claims 31 to 78, wherein the pH adjuster is sodium bicarbonate.

80. The oral dosage form according to any one of claims 1 to 79, wherein the one or more excipients include fillers, disintegrants, and lubricants.

81. The oral dosage form according to any one of claims 1 to 80, wherein the one or more excipients include fillers, disintegrants, lubricants, and binders.

82. The oral dosage form according to claim 80 or 81, wherein the filler comprises lactose and microcrystalline cellulose, the disintegrant comprises croscarmellose sodium, and the lubricant comprises magnesium stearate.

83. The oral dosage form according to claim 81 or 82, wherein the filler comprises lactose and microcrystalline cellulose, the disintegrant comprises croscarmellose sodium, the lubricant comprises magnesium stearate, and the binder comprises hydroxypropyl cellulose.

84. A solid oral dosage form comprising about 5 mg to about 1400 mg of a compound of formula I: I Or a pharmaceutically acceptable salt thereof, wherein the amount is based on the free acid form; filler; Disintegrant; Adhesives; and Lubricant.

85. The oral dosage form according to any one of claims 31 to 84, wherein the oral dosage form comprises: About 5% by weight to about 35% by weight of the compound of Formula I or a pharmaceutically acceptable salt thereof; The filler, approximately 50% to approximately 90% by weight; The disintegrant is present in about 1% to about 10% by weight. The adhesive is said to be from about 1% by weight to about 10% by weight; and The lubricant is used in amounts of about 0.1% to about 5% by weight.

86. The oral dosage form according to any one of claims 1 to 85, wherein the oral dosage form comprises: About 5% by weight to about 35% by weight of the compound of Formula I or a pharmaceutically acceptable salt thereof; Approximately 20% by weight to approximately 50% by weight of lactose; Approximately 20% to approximately 50% by weight of microcrystalline cellulose; From about 1% to about 10% by weight of croscarmellose sodium; Hydroxypropyl cellulose, about 1% by weight to about 10% by weight; and Magnesium stearate, approximately 0.1% to approximately 2% by weight.

87. The oral dosage form according to any one of claims 84 to 86, wherein the oral dosage form comprises: About 5% by weight to about 35% by weight of the compound of formula I; Approximately 25% by weight to approximately 45% by weight of lactose; Approximately 25% to approximately 45% by weight of microcrystalline cellulose; Approximately 3% to approximately 7% by weight of croscarmellose sodium; About 2% by weight to about 6% by weight of hydroxypropyl cellulose; and Magnesium stearate, approximately 0.1% to approximately 2% by weight.

88. The oral dosage form according to any one of claims 84 to 87, wherein the oral dosage form comprises: About 5% by weight to about 10% by weight of the compound of formula I; Approximately 35% to approximately 45% by weight of lactose; Approximately 35% to approximately 45% by weight of microcrystalline cellulose; Approximately 3% to approximately 7% by weight of croscarmellose sodium; About 2% by weight to about 6% by weight of hydroxypropyl cellulose; and Magnesium stearate, approximately 0.1% to approximately 2% by weight.

89. The oral dosage form according to any one of claims 84 to 88, wherein the oral dosage form comprises: Approximately 7.4% by weight of the compound of formula I; Approximately 41% by weight of lactose; Approximately 41% by weight of microcrystalline cellulose; Approximately 5% by weight of cross-linked sodium carboxymethyl cellulose; Approximately 4% by weight of hydroxypropyl cellulose; and Approximately 1.5% by weight of magnesium stearate.

90. The oral dosage form according to any one of claims 84 to 87, wherein the oral dosage form comprises: About 28% by weight to about 32% by weight of the compound of formula I; Approximately 25% by weight to approximately 35% by weight of lactose; Approximately 25% to approximately 35% by weight of microcrystalline cellulose; Approximately 3% to approximately 7% by weight of croscarmellose sodium; About 2% by weight to about 6% by weight of hydroxypropyl cellulose; and Magnesium stearate, approximately 0.1% to approximately 2% by weight.

91. The oral dosage form according to any one of claims 83 to 87 and 89, wherein the oral dosage form comprises: Approximately 30% by weight of the compound of formula I; Approximately 30% by weight of lactose; Approximately 30% by weight of microcrystalline cellulose; Approximately 5% by weight of cross-linked sodium carboxymethyl cellulose; Approximately 4% by weight of hydroxypropyl cellulose; and Approximately 1.5% by weight of magnesium stearate.

92. The oral dosage form according to any one of claims 31 to 91, wherein the oral dosage form comprises: The compound of formula I in amounts from about 5 mg to about 500 mg; The filler in amounts from about 60 mg to about 1000 mg; The disintegrant in amounts of about 1 mg to about 100 mg; The adhesive, in amounts from about 1 mg to about 80 mg; and The lubricant is present in amounts of approximately 0.5 mg to approximately 30 mg.

93. The oral dosage form according to claim 92, wherein the oral dosage form comprises: The compound of formula I in amounts from about 5 mg to about 500 mg; Lactose in amounts ranging from approximately 30 mg to approximately 500 mg; Microcrystalline cellulose in amounts ranging from approximately 30 mg to approximately 500 mg; Sodium croscarmellose in amounts ranging from approximately 1 mg to approximately 100 mg; Hydroxypropyl cellulose in amounts from about 1 mg to about 80 mg; and Magnesium stearate in amounts from about 0.5 mg to about 30 mg.

94. The oral dosage form according to any one of claims 31 to 93, wherein the oral dosage form comprises: The compound of formula I in amounts from about 10 mg to about 450 mg; The filler in an amount of about 90 mg to about 900 mg; The disintegrant is present in amounts of approximately 5 mg to approximately 80 mg. The adhesive, in an amount of about 5 mg to about 60 mg; and The lubricant is present in amounts of approximately 0.5 mg to approximately 25 mg.

95. The oral dosage form according to claim 94, wherein the oral dosage form comprises: The compound of formula I in amounts from about 10 mg to about 450 mg; Approximately 45 mg to approximately 450 mg of lactose; Microcrystalline cellulose in amounts of approximately 45 mg to approximately 450 mg; Approximately 5 mg to approximately 80 mg of croscarmellose sodium; Hydroxypropyl cellulose in amounts from about 5 mg to about 60 mg; and Magnesium stearate in amounts from about 0.5 mg to about 25 mg.

96. The oral dosage form according to any one of claims 31 to 95, wherein the oral dosage form comprises: The compound of formula I in amounts of about 10 mg to about 250 mg; The filler in an amount of about 90 mg to about 500 mg; The disintegrant is administered in amounts of approximately 5 mg to approximately 45 mg. The adhesive, in amounts of about 5 mg to about 35 mg; and The lubricant is present in amounts of approximately 0.5 mg to approximately 20 mg.

97. The oral dosage form according to claim 96, wherein the oral dosage form comprises: The compound of formula I in amounts of about 10 mg to about 250 mg; Approximately 45 mg to approximately 250 mg of lactose; Microcrystalline cellulose in amounts of approximately 45 mg to approximately 250 mg; Sodium croscarmellose, in amounts ranging from approximately 5 mg to approximately 45 mg; Hydroxypropyl cellulose in amounts from approximately 5 mg to approximately 35 mg; and Magnesium stearate in amounts from about 0.5 mg to about 20 mg.

98. The oral dosage form according to claim 96 or 97, wherein the oral dosage form comprises: Approximately 10 mg of the compound of formula I; Approximately 55 mg of lactose; Approximately 55 mg of microcrystalline cellulose; Approximately 7 mg of croscarmellose sodium; Approximately 5 mg of hydroxypropyl cellulose; and Approximately 2 mg of magnesium stearate.

99. The oral dosage form according to claim 96 or 97, wherein the oral dosage form comprises: Approximately 50 mg of the compound of formula I; Approximately 49 mg of lactose; Approximately 49 mg of microcrystalline cellulose; Approximately 8 mg of croscarmellose sodium; Approximately 7 mg of hydroxypropyl cellulose; and Approximately 2.5 mg of magnesium stearate.

100. The oral dosage form according to claim 96 or 97, wherein the oral dosage form comprises: Approximately 250 mg of the compound of formula I; Approximately 246 mg of lactose; Approximately 246 mg of microcrystalline cellulose; Approximately 42 mg of croscarmellose sodium; Approximately 33 mg of hydroxypropyl cellulose; and Approximately 12 mg of magnesium stearate.

101. The oral dosage form according to any one of claims 92 to 95, wherein the oral dosage form comprises: Approximately 325 mg of the compound of formula I; Approximately 320 mg of lactose; Approximately 320 mg of microcrystalline cellulose; Approximately 54 mg of croscarmellose sodium; Approximately 43 mg of hydroxypropyl cellulose; and Approximately 16 mg of magnesium stearate.

102. The oral dosage form according to any one of claims 92 to 95, wherein the oral dosage form comprises: Approximately 450 mg of the compound of formula I; Approximately 444 mg of lactose; Approximately 444 mg of microcrystalline cellulose; Approximately 75 mg of croscarmellose sodium; Approximately 60 mg of hydroxypropyl cellulose; and Approximately 22 mg of magnesium stearate.

103. The oral dosage form according to any one of claims 31 to 102, wherein the dosage form is a tablet comprising a core and a film coating; and wherein the core comprises: The compound of Formula I or a pharmaceutically acceptable salt thereof; The filler; The disintegrant; The adhesive; and the lubricant.

104. The oral dosage form of claim 103, wherein the film coating comprises Opadry. ® II.

105. The oral dosage form according to claim 103 or 104, wherein the film coating comprises Opadry. ® IIBeige.

106. The oral dosage form according to any one of claims 103 to 105, wherein the oral dosage form comprises about 1% to about 5% by weight of the film coating.

107. The oral dosage form according to any one of claims 1 to 106, wherein the compound of formula I or a pharmaceutically acceptable salt thereof is micronized.

108. The oral dosage form according to any one of claims 1 to 107, wherein the compound of formula I or a pharmaceutically acceptable salt thereof has a particle size distribution of about 1 μm to about 150 μm. 90 .

109. The oral dosage form according to any one of claims 1 to 108, wherein the compound of formula I or a pharmaceutically acceptable salt thereof has a particle size distribution of about 5 μm to about 125 μm. 90 .

110. The oral dosage form according to any one of claims 1 to 109, wherein the compound of formula I or a pharmaceutically acceptable salt thereof has a particle size distribution of about 5 μm to about 60 μm. 90 .

111. The oral dosage form according to any one of claims 1 to 110, wherein the compound of formula I or a pharmaceutically acceptable salt thereof has a particle size distribution of about 5 μm to about 15 μm. 90 .

112. The oral dosage form according to any one of claims 1 to 111, wherein the compound of formula I or a pharmaceutically acceptable salt thereof is spray-dried.

113. The oral dosage form according to any one of claims 1 to 112, wherein the compound of formula I or a pharmaceutically acceptable salt thereof is spray-dried in a dispersion having one or more polymers.

114. The oral dosage form according to claim 113, wherein the one or more polymers comprise neutral polymers or charged polymers.

115. The oral dosage form according to claim 113 or 114, wherein the one or more polymers are selected from copovidone, povidone, hydroxypropyl methylcellulose, hydroxypropyl methylcellulose phthalate, hydroxypropyl methylcellulose acetate succinate, cellulose acetate phthalate, (meth)acrylate polymers, or combinations thereof.

116. The oral dosage form according to claim 115, wherein the (meth)acrylate polymer comprises a methacrylate-methyl methacrylate copolymer, a methacrylate-ethyl acrylate copolymer, or a combination thereof.

117. The oral dosage form according to any one of claims 113 to 116, wherein the one or more polymers comprise copovidone.

118. The oral dosage form according to any one of claims 113 to 117, wherein the dispersion comprises about 40% to about 60% by weight of a compound of formula I or a pharmaceutically acceptable salt thereof and about 40% to about 60% by weight of one or more polymers.

119. The oral dosage form according to any one of claims 113 to 118, wherein the dispersion comprises about 50% by weight of a compound of formula I or a pharmaceutically acceptable salt thereof and about 50% by weight of one or more of the polymers.

120. The oral dosage form according to any one of claims 1 to 119, wherein the oral dosage form comprises a compound of formula I.

121. The oral dosage form according to claim 120, wherein the compound of formula I is crystalline.

122. The oral dosage form according to claim 121, wherein the compound of formula I is in crystalline form I.

123. The oral dosage form according to claim 122, wherein the crystalline form I is characterized in that the X-ray powder diffraction (XRPD) pattern includes °2-θ peaks (± 0.2° 2-θ) at 7.0°, 13.9° and 27.9°.

124. The oral dosage form of claim 123, wherein the XPRD pattern further comprises 2-θ peaks (± 0.2° 2-θ) at 12.3°, 17.4° and 24.6°.

125. The oral dosage form according to claim 123 or 124, wherein the XPRD pattern further comprises 2-θ peaks (± 0.2° 2-θ) at 21.4°, 23.2° and 29.2°.

126. The oral dosage form according to claim 120, wherein the compound of formula I is amorphous.

127. The oral dosage form according to any one of claims 1 to 119, wherein the oral dosage form comprises a pharmaceutically acceptable salt of a compound of formula I.

128. The oral dosage form according to any one of claims 1 to 119 and 127, wherein the oral dosage form comprises a sodium salt of the compound of formula I.

129. The oral dosage form according to any one of claims 1 to 119 and 127, wherein the oral dosage form comprises an n-butanamine salt of the compound of formula I.

130. The oral dosage form according to any one of claims 1 to 119 and 127, wherein the oral dosage form comprises an ammonium salt of the compound of formula I.

131. An oral dosage form according to any one of claims 1 to 119 and 127, wherein the oral dosage form comprises an aminobutanetriol salt of the compound of formula I.

132. The oral dosage form according to any one of claims 127 to 131, wherein the salt of the compound of formula I is crystalline.

133. The oral dosage form according to any one of claims 127 to 131, wherein the salt of the compound of formula I is amorphous.

134. A pharmaceutical composition comprising: About 5% by weight to about 35% by weight of compounds of formula I; I Or its pharmaceutically acceptable salt; Approximately 50% to approximately 90% by weight of fillers; From about 1% to about 10% by weight of disintegrant; Adhesives of about 1% to about 10% by weight; and Lubricant of about 0.1% to about 5% by weight.

135. The pharmaceutical composition according to claim 134, wherein the pharmaceutical composition comprises: About 5% by weight to about 35% by weight of the compound of Formula I or a pharmaceutically acceptable salt thereof; Approximately 20% by weight to approximately 50% by weight of lactose; Approximately 20% to approximately 50% by weight of microcrystalline cellulose; From about 1% to about 10% by weight of croscarmellose sodium; Hydroxypropyl cellulose, about 1% by weight to about 10% by weight; and Magnesium stearate, approximately 0.1% to approximately 2% by weight.

136. The pharmaceutical composition according to claim 134 or 135, wherein the pharmaceutical composition comprises: About 5% by weight to about 35% by weight of the compound of formula I; Approximately 25% by weight to approximately 45% by weight of lactose; Approximately 25% to approximately 45% by weight of microcrystalline cellulose; Approximately 3% to approximately 7% by weight of croscarmellose sodium; About 2% by weight to about 6% by weight of hydroxypropyl cellulose; and Magnesium stearate, approximately 0.1% to approximately 2% by weight.

137. The pharmaceutical composition according to any one of claims 134 to 136, wherein the pharmaceutical composition comprises: About 5% by weight to about 10% by weight of the compound of formula I; Approximately 35% to approximately 45% by weight of lactose; Approximately 35% to approximately 45% by weight of microcrystalline cellulose; Approximately 3% to approximately 7% by weight of croscarmellose sodium; About 2% by weight to about 6% by weight of hydroxypropyl cellulose; and Magnesium stearate, approximately 0.1% to approximately 2% by weight.

138. The pharmaceutical composition according to any one of claims 134 to 137, wherein the pharmaceutical composition comprises: Approximately 7.4% by weight of the compound of formula I; Approximately 41% by weight of lactose; Approximately 41% by weight of microcrystalline cellulose; Approximately 5% by weight of cross-linked sodium carboxymethyl cellulose; Approximately 4% by weight of hydroxypropyl cellulose; and Approximately 1.5% by weight of magnesium stearate.

139. The pharmaceutical composition according to any one of claims 134 to 136, wherein the pharmaceutical composition comprises: About 28% by weight to about 32% by weight of the compound of formula I; Approximately 25% by weight to approximately 35% by weight of lactose; Approximately 25% to approximately 35% by weight of microcrystalline cellulose; Approximately 3% to approximately 7% by weight of croscarmellose sodium; About 2% by weight to about 6% by weight of hydroxypropyl cellulose; and Magnesium stearate, approximately 0.1% to approximately 2% by weight.

140. The pharmaceutical composition according to any one of claims 134 to 136 and 139, wherein the pharmaceutical composition comprises: Approximately 30% by weight of the compound of formula I; Approximately 30% by weight of lactose; Approximately 30% by weight of microcrystalline cellulose; Approximately 5% by weight of cross-linked sodium carboxymethyl cellulose; Approximately 4% by weight of hydroxypropyl cellulose; and Approximately 1.5% by weight of magnesium stearate.

141. The pharmaceutical composition according to any one of claims 134 to 140, wherein the compound of formula I has crystalline form I.

142. The pharmaceutical composition according to any one of claims 135 to 141, wherein the lactose is lactose monohydrate.

143. The pharmaceutical composition according to any one of claims 135 to 142, wherein the weight ratio of lactose to microcrystalline cellulose is about 1:

1.

144. A method for treating or preventing HIV infection in a person, the method comprising orally administering to the person a solid oral dosage form according to any one of claims 1 to 133 or a pharmaceutical composition according to any one of claims 134-143.

145. The method of claim 144, wherein the solid oral dosage form or pharmaceutical composition is administered once every 1 day, every 2 days, every 3 days, every 4 days, every 5 days, every 6 days, every 7 days, every 8 days, every 9 days, or every 10 days.

146. The method of claim 144 or 145, wherein the solid oral dosage form or pharmaceutical composition is administered once weekly (QW).

147. The method according to any one of claims 144 to 146, the method comprising administering a dose of about 10 mg to about 1500 mg of a compound of formula I or a pharmaceutically acceptable salt thereof, wherein the dose is based on the free acid form.

148. The method according to any one of claims 144 to 147, the method comprising administering a dose of about 10 mg to about 1350 mg of a compound of formula I or a pharmaceutically acceptable salt thereof, wherein the dose is based on the free acid form.

149. The method according to any one of claims 144 to 148, the method comprising administering a dose of about 50 mg to about 500 mg of a compound of formula I or a pharmaceutically acceptable salt thereof, wherein the dose is based on the free acid form.

150. The method according to any one of claims 144 to 149, the method comprising administering a dose of about 500 mg to about 1000 mg of a compound of formula I or a pharmaceutically acceptable salt thereof, wherein the dose is based on the free acid form.

151. The method according to any one of claims 144 to 150, the method comprising administering a dose of about 200 mg to about 300 mg of a compound of formula I or a pharmaceutically acceptable salt thereof, wherein the dose is based on the free acid form.

152. The method according to any one of claims 144 to 146, the method comprising administering a dose of about 5 mg to about 1000 mg of the compound of formula I or a pharmaceutically acceptable salt thereof, wherein the dose is based on the free acid form.

153. The method according to any one of claims 144 to 146, the method comprising administering a dose of about 5 mg to about 500 mg of the compound of formula I or a pharmaceutically acceptable salt thereof, wherein the dose is based on the free acid form.

154. The method according to any one of claims 144 to 148, the method comprising administering a dose of about 10 mg to about 450 mg of a compound of formula I or a pharmaceutically acceptable salt thereof, wherein the dose is based on the free acid form.

155. The method according to any one of claims 144 to 148, the method comprising administering a dose of about 10 mg to about 250 mg of a compound of formula I or a pharmaceutically acceptable salt thereof, wherein the dose is based on the free acid form.

156. The method according to any one of claims 144 to 149, the method comprising administering a dose of about 10 mg of the compound of formula I or a pharmaceutically acceptable salt thereof, wherein the dose is based on the free acid form.

157. The method according to any one of claims 144 to 149, the method comprising administering a dose of about 50 mg of the compound of formula I or a pharmaceutically acceptable salt thereof, wherein the dose is based on the free acid form.

158. The method according to any one of claims 144 to 149, the method comprising administering a dose of about 250 mg of the compound of formula I or a pharmaceutically acceptable salt thereof, wherein the dose is based on the free acid form.

159. The method according to any one of claims 144 to 148, the method comprising administering a dose of about 325 mg of the compound of formula I or a pharmaceutically acceptable salt thereof, wherein the dose is based on the free acid form.

160. The method according to any one of claims 144 to 148, the method comprising administering a dose of about 400 mg to about 700 mg of a compound of formula I or a pharmaceutically acceptable salt thereof, wherein the dose is based on the free acid form.

161. The method according to any one of claims 144 to 148 and 160, the method comprising administering a dose of about 400 mg to about 500 mg of a compound of formula I or a pharmaceutically acceptable salt thereof, wherein the dose is based on the free acid form.

162. The method according to any one of claims 144 to 148, 160 and 161, the method comprising administering a dose of about 450 mg of the compound of formula I or a pharmaceutically acceptable salt thereof, wherein the dose is based on the free acid form.

163. The method according to any one of claims 144 to 148 and 160, the method comprising administering a dose of about 600 mg to about 700 mg of the compound of formula I or a pharmaceutically acceptable salt thereof, wherein the dose is based on the free acid form.

164. The method according to any one of claims 144 to 148, 160 and 163, the method comprising administering a dose of about 650 mg of the compound of formula I or a pharmaceutically acceptable salt thereof, wherein the dose is based on the free acid form.

165. The method according to any one of claims 144 to 162, wherein the person is infected with HIV.

166. The method according to any one of claims 144 to 163, wherein the person has an HIV-1 RNA copy number of less than about 50 copies / mL.

167. The method according to any one of claims 144 to 164, wherein the method comprises administering one, two, three, or four additional therapeutic agents to the person.

168. The method of claim 167, wherein the additional therapeutic agent is selected from the group consisting of: HIV protease inhibitors, non-nucleoside or non-nucleotide inhibitors of HIV reverse transcriptase, nucleoside or nucleotide inhibitors of HIV reverse transcriptase, HIV capsid inhibitors, gp41 inhibitors, CXCR4 inhibitors, gp120 inhibitors, CCR5 inhibitors, latency reversal agents, capsid polymerization inhibitors, HIV bNAb, TLR7 agonists, pharmacokinetic enhancers, other drugs for treating HIV, or combinations thereof.

169. Use of the oral dosage form according to any one of claims 1 to 133 for the treatment or prevention of HIV infection.

170. Use of the pharmaceutical composition according to any one of claims 134 to 143 for the treatment or prevention of HIV infection.

171. The oral dosage form according to any one of claims 1 to 133, for use in a method of treating or preventing HIV infection.

172. The pharmaceutical composition according to any one of claims 134 to 143, for use in a method of treating or preventing HIV infection.

173. Use of the oral dosage form according to any one of claims 1 to 133 in the manufacture of a medicament for the treatment or prevention of HIV infection.

174. Use of the pharmaceutical composition according to any one of claims 134 to 143 in the manufacture of a medicament for treating or preventing HIV infection.

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