Capsid inhibitors for treatment of HIV

Abstract

The present invention relates to a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof for use in the treatment of HIV infection in a patient suffering from multi-drug resistant HIV infection undergoing a large amount of treatment. # imgabs0 #

Description

[0001] This application is a divisional application of the patent application with the filing date of July 15, 2019, application number 201980047511.X, and title "Capsid Inhibitors for the Treatment of HIV".

[0002] Cross-reference to Related Applications

[0003] This application claims the benefit of U.S. Provisional Application No. 62 / 698,611, filed on July 16, 2018, the entire content of which is incorporated herein by reference in its entirety. Technical Field

[0004] The present disclosure relates to methods for treating human immunodeficiency virus (HIV) infection in patients who have experienced extensive treatment (e.g., patients with multi-drug resistant HIV infections). Background Art

[0005] The viral capsid protein (CA) is critical for multiple stages of the HIV life cycle. During virus maturation after HIV protease processing of the Gag polyprotein, CA self-assembles into the conical core characteristic of the mature HIV-1 virion. The capsid core contains viral RNA, nucleocapsid, reverse transcriptase, and integrase. The inability to produce a proper core precludes infectivity. In addition, CA contributes to multiple important processes in the early stages of HIV replication, including regulating the proper disassembly (uncoating) kinetics of the capsid core to ensure an important role in efficient and effective viral DNA synthesis by coupled reverse transcription, and facilitating the active transport of the pre-integration complex into the nuclear compartment to support viral DNA integration into transcriptionally active loci. Defects in the normal function of the capsid ultimately inhibit efficient nuclear uptake and viral DNA integration into the host genome.

[0006] There are currently many antiretroviral drugs available to combat HIV infection. These drugs can be classified into several categories based on the viral proteins they target or their mode of action. Used alone, these drugs can effectively reduce viral replication. However, this effect is only temporary because the virus readily develops resistance to all known agents used as monotherapy. In many patients, combination therapy has proven to be highly effective in both reducing the virus and suppressing the emergence of resistance. In the United States, where combination therapy is widely used, the number of HIV-related deaths has declined sharply (Palella, F.J.; Delany, K.M.; Moorman, A.C.; Loveless, M.O.; Furher, J.; Satten, g.A.; Aschman, D.J.; Holmberg, S.D.; N. Engl. J. Med. 1998, 338:853-860).

[0007] Despite the success of antiretroviral combination therapies, a significant portion of patients lose virological, immunological, or clinical benefits due to current treatment regimens, leading to treatment failure and a rebound in the detectable amount of HIV in the blood. Preliminary studies indicate that approximately 30 - 50% of patients ultimately fail at least one drug in the regimen. The emergence of viral drug resistance can lead to treatment failure. Viral drug resistance can be caused by the replication rate of HIV-1 during the infection process, along with the relatively high viral mutation rate associated with the viral polymerase, and the lack of adherence of HIV-infected individuals when taking prescription drugs. Due to the structural similarity of drugs within the antiretroviral class, cross-resistance is typically seen among other members of the class (e.g., virological failure in a regimen containing a non-nucleoside reverse transcriptase inhibitor (NNRTI) leads to cross-resistance to other first-generation NNRTI agents). As patients repeatedly experience virological failure during antiretroviral combination therapy, their virus develops extensive multi-class antiretroviral drug resistance, which limits the effectiveness of the next round of antiretroviral therapy. Many treatment-experienced patients are resistant to several classes of antiretroviral drugs, and often there are not even two drugs that can remain fully active to form the core of a new effective antiretroviral treatment regimen. Typically, these patients have limited options for alternative treatments and are at risk of significant morbidity and mortality.

[0008] Accordingly, there is a need for safe and effective therapies for heavily pre-treated patients with limited treatment options due to antiretroviral drug resistance. SUMMARY OF THE INVENTION

[0009] The present disclosure relates to methods of treating human immunodeficiency virus (HIV) infection in heavily pre-treated patients. The method comprises administering to the patient a therapeutically effective amount of a compound of formula (Ia) or formula (Ib):

[0010]

[0011] or a pharmaceutically acceptable salt thereof.

[0012] In some embodiments, the HIV infection is an HIV-1 infection characterized by an HIV-1 mutant being resistant to one or more antiretroviral drugs. In some embodiments, the HIV infection is an HIV-1 infection characterized by an HIV-1 mutant being resistant to two or more antiretroviral drugs. In some embodiments, the HIV infection is an HIV-1 infection characterized by an HIV-1 mutant being resistant to three or more antiretroviral drugs.

[0013] In some embodiments, the HIV-1 mutants are resistant to protease inhibitors (PIs), nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs), non-nucleoside or non-nucleotide reverse transcriptase inhibitors (NNRTIs), or integrase strand transfer inhibitors (INSTIs). In certain embodiments, the HIV-1 mutants resistant to protease inhibitors are selected from I50V, I84V / L90M, G48V / V82A / L90M, and G48V / V82S. In certain embodiments, the HIV-1 mutants resistant to nucleoside or nucleotide reverse transcriptase inhibitors are selected from K65R, M184V, and 6TAM. In certain embodiments, the 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 certain embodiments, the HIV-1 mutants resistant to integrase strand transfer inhibitors are selected from Y143R, E138K / Q148K, G140S / Q148R, E92Q / N155H, N155H / Q148R, and R263K / M50I.

[0014] In some embodiments, the patient is infected with HIV-1 that is resistant to at least one antiretroviral drug. In some embodiments, the patient is infected with multi-drug resistant HIV-1 that is resistant to at least one antiretroviral drug in each of at least two different classes of antiretroviral drugs. In some embodiments, the patient is infected with multi-drug resistant HIV-1 that is resistant to at least one antiretroviral drug in 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), and integrase strand transfer inhibitors (INSTIs).

[0015] In some embodiments, the NRTIs are selected from: emtricitabine, lamivudine (3TC), zidovudine (azidothymidine (AZT)), didanosine (ddI), zalcitabine, tenofovir, tenofovir alafenamide, tenofovir disoproxil fumarate, stavudine (d4T), zalcitabine (dideoxycytidine, ddC), and abacavir.

[0016] In some embodiments, the NNRTIs are selected from efavirenz, etravirine, rilpivirine, nevirapine, and delavirdine.

[0017] In some embodiments, the PI is selected from: amprenavir, atazanavir, darunavir, fosamprenavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, and tipranavir.

[0018] In some embodiments, the INSTI is selected from raltegravir, elvitegravir, dolutegravir, and bictegravir.

[0019] In some embodiments of the method, the patient has been previously 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.

[0020] In some embodiments, the patient's previous HIV treatment regimen has failed, including administration of at least one antiretroviral drug. In certain embodiments, the previous treatment regimen includes administration of at least one antiretroviral drug from each of two different classes of antiretroviral drugs. In certain embodiments, the previous treatment regimen includes 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).

[0021] In certain embodiments of the method, the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof is administered orally, subcutaneously, intramuscularly, or intravenously.

[0022] In some embodiments, the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof is administered orally at a concentration of about 20 mg / mL to about 100 mg / mL. In some embodiments, the compound of formula (Ia) or formula (Ib) is formulated as a hard gelatin capsule. In some embodiments, the compound of formula (Ia) or formula (Ib) is formulated as a soft gelatin capsule. In some embodiments, the compound of formula (Ia) or formula (Ib) is formulated as a tablet.

[0023] In some embodiments, the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof is administered subcutaneously. In some embodiments, the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof is administered subcutaneously at a concentration of about 50 mg / mL to about 500 mg / mL. In some embodiments, the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof is formulated as a solution preparation. In some embodiments, the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof is formulated as an aqueous suspension. In some embodiments, the compound of formula (Ia) is the sodium salt. In some embodiments, the compound of formula (Ib) is the trifluoroacetate salt.

[0024] In some embodiments of the method, the compound of formula (Ia) or formula (Ib) is formulated with one or more other compounds selected from HIV protease inhibitors, HIV non-nucleoside or non-nucleotide inhibitors of reverse transcriptase, HIV nucleoside or nucleotide inhibitors of reverse transcriptase, HIV integrase inhibitors, HIV non-catalytic site (or allosteric) integrase inhibitors, HIV nucleoside reverse transcriptase translocation inhibitors, and pharmacokinetic enhancers. In some embodiments, the HIV nucleoside reverse transcriptase translocation inhibitor is 4'-ethynyl-2-fluoro-2'-deoxyadenosine triphosphate (MK-8591).

[0025] In some embodiments, the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof is administered once daily. In some embodiments, the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof is administered once every 1 week, every 2 weeks, every 4 weeks, every 8 weeks, every 12 weeks, every 16 weeks, every 20 weeks, every 24 weeks, or every 48 weeks.

[0026] In some embodiments of the method, the viral load of the patient at the start of administration of the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof is greater than about 200 copies of HIV-1 RNA / mL, greater than about 500 copies of HIV-1 RNA / mL, greater than about 750 copies of HIV-1 RNA / mL, greater than about 1000 copies of HIV-1 RNA / mL, or greater than about 2000 copies of HIV-1 RNA / mL.

[0027] In some embodiments, at the start of administration of the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof, the patient's HIV treatment regimen including administration of at least one antiretroviral drug is about to fail.

[0028] In some embodiments of the method, administration of a compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof results in a decrease in viral load in a patient. In some embodiments, the viral load is decreased by about 0.5 log 10 to about 2.5 log 10 about 24 weeks after administration of the compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof, compared to the viral load at the start of administration of the compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof. In some embodiments, the viral load is decreased by about 0.5 log 10 about 24 weeks after administration of the compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof, compared to the viral load at the start of administration of the compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof. 10 about 1 log 10 about 1.5 log 10 about 2 log 10 or about 2.5 log

[0029] In some embodiments, the viral load in the patient is about 200 copies of HIV-1 RNA / mL or less about 24 weeks after administration of the compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof. In some embodiments, the viral load of the patient is about 50 copies of HIV-1 RNA / mL or less about 24 weeks after administration of the compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof.

[0030] In some embodiments, the patient is treated concurrently with at least one additional antiretroviral drug. In some embodiments, the additional antiretroviral drug is selected from nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), integrase strand transfer inhibitors (INSTIs), gp41 fusion inhibitors, CCR5 co-receptor antagonists, and combinations thereof.

[0031] In some embodiments, the NRTIs are selected from: emtricitabine, lamivudine (3TC), zidovudine (azidothymidine (AZT)), didanosine (ddI), zalcitabine, tenofovir, tenofovir alafenamide, tenofovir disoproxil fumarate, stavudine (d4T), zalcitabine (dideoxycytidine, ddC), and abacavir.

[0032] In some embodiments, the NNRTIs are selected from: efavirenz, etravirine, rilpivirine, nevirapine, and delavirdine.

[0033] In some embodiments, the PI is selected from: amprenavir, atazanavir, darunavir, fosamprenavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, and tipranavir.

[0034] In some embodiments, the INSTI is selected from raltegravir, elvitegravir, dolutegravir, and bictegravir.

[0035] In some embodiments, the gp41 fusion inhibitor is selected from: aboceptiv, enfuvirtide, BMS-986197, biosimilar of enfuvirtide, biosimilar of enfuvirtide, HIV-1 fusion inhibitor (P26-Bapc), ITV-1, ITV-2, ITV-3, ITV-4, PIE-12 trimer, and sifuvirtide.

[0036] In some embodiments, the CCR5 co-receptor antagonist is selected from: apaviroc, vicriviroc, maraviroc, cenicriviroc, PRO-140, alacatamivir (RAP-101), neviroc (TD-0232), anti-GP120 / CD4 or CCR5 bispecific antibody, B-07, MB-66, polypeptide C25P, TD-0680, and vMIP (Haimipu).

[0037] Also included in the present disclosure is a method for treating human immunodeficiency virus type 1 (HIV-1) infection in heavily treated patients with multi-drug resistant HIV-1, the method comprising administering to the patient a therapeutically effective amount of a compound of formula (Ia) or formula (Ib):

[0038]

[0039] or a pharmaceutically acceptable salt thereof, wherein the patient has previously been treated with an HIV treatment regimen comprising administration of at least one antiretroviral drug and the treatment regimen has failed; administration of the compound reduces the patient's HIV viral load.

[0040] In some embodiments of the method, the multi-drug resistant HIV-1 is resistant to at least one antiretroviral drug of each of two different classes of antiretroviral drugs. In some embodiments of the method, the multi-drug resistant HIV-1 is resistant to at least one antiretroviral drug of each of three different classes of antiretroviral drugs. In some embodiments, the different classes of antiretroviral drugs are selected from nucleoside reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI), protease inhibitors (PI), and integrase strand transfer inhibitors (INSTI).

[0041] In some embodiments, the patient has been previously 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. In some embodiments, the previous treatment regimen includes administering at least one antiretroviral drug from each of two different classes of antiretroviral drugs. In some embodiments, the previous treatment regimen includes administering 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).

[0042] The present disclosure provides a method of treating human immunodeficiency virus-1 (HIV-1) infection in heavily pre-treated patients with multi-drug resistant HIV-1, the method comprising administering to the patient a therapeutically effective amount of a compound of formula (Ia) or formula (Ib):

[0043]

[0044] or a pharmaceutically acceptable salt thereof, wherein the multi-drug resistant HIV-1 is resistant to at least one antiretroviral drug from each of two different classes of antiretroviral drugs, wherein 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); the patient has previously received treatment with an HIV treatment regimen that included administering at least one antiretroviral drug, but the treatment regimen has failed; at the start of administration of the compound of formula (Ia) or formula (Ib), the patient's viral load is greater than about 200 copies of HIV-1 RNA / mL; and administering the compound reduces the patient's HIV viral load.

[0045] Also provided is a method of reducing the viral load associated with HIV infection in heavily pre-treated patients with multi-drug resistant HIV, the method comprising administering to the patient a therapeutically effective amount of a compound of formula (Ia) or formula (Ib):

[0046]

[0047] or a pharmaceutically acceptable salt thereof.

[0048] Other embodiments of the present disclosure are disclosed herein. Brief Description of the Drawings

[0050] Figure 1 showing the compound of formula (Ia) 11H NMR (400 MHz, methanol-d 4 ): N-((S)-1-(3-(4-chloro-3-methylsulfonamido)-1-(2,2,2-trifluoroethyl)-1H-indazol-7-yl)-6-(3-methyl-3-(methylsulfonyl)but-1-yn-1-yl)pyridin-2-yl)-2-(3,5-difluorophenyl)ethyl)-2-((3bS,4aR)-5,5-difluoro-3-(trifluoromethyl)-3b,4,4a,5-tetrahydro-1H-cyclopropa[3,4]cyclopenta[1,2-c]pyrazol-1-yl)acetamide.

[0051] Figure 2 shows the 1 1H NMR (400 MHz, methanol-d 4 ): N-((S)-1-(3-(4-chloro-3-(cyclopropanesulfonamido)-1-(2,2-difluoroethyl)-1H-indazol-7-yl)-6-(3-methyl-3-(methylsulfonyl)but-1-yn-1-yl)pyridin-2-yl)-2-(3,5-difluorophenyl)ethyl)-2-((3bS,4aR)-5,5-difluoro-3-(trifluoromethyl)-3b,4,4a,5-tetrahydro-1H-cyclopropa[3,4]cyclopenta[1,2-c]pyrazol-1-yl)acetamide.

[0052] Figure 3 shows the plasma concentration-time profiles of the 400 mg / mL compound of formula (Ia) in 10% ethanol, 13% water and 77% PEG 200 when subcutaneously administered to dogs and rats at 12 mg / kg and 50 mg / kg, respectively.

[0053] Figure 4 shows the plasma concentration-time profile of the 300 mg / mL compound of formula (Ia) in 15% water and 85% PEG 300 when subcutaneously administered to rats at 50 mg / kg.

[0054] Figure 5 shows the plasma concentration-time profiles of the 400 mg / mL compound of formula (Ia) in 15% water and 85% PEG 300 when subcutaneously administered to dogs at 12 mg / kg.

[0055] Figure 6 shows the plasma concentration-time profiles of the 300 mg / mL sodium salt of the compound of formula (Ia) in a formulation of 22.6% water / 50% PEG 300 / 1.1% NaOH / 26.3% of formula (Ia) when subcutaneously administered to dogs at 12 mg / kg.

[0056] Figure 7Aand 7B show the plasma concentration-time profiles of 300 mg / ml of the compound of formula (Ia) in a solution of 9.8 w / w% water, 65.0 w / w% PEG 300 and 25.2 w / w% of the compound of formula (Ia) when administered subcutaneously at 50 mg / kg in rats ( Figure 7A ) and at 12 mg / kg subcutaneously in dogs ( Figure 7B ).

[0057] Figure 8A and 8B show the plasma concentration-time profiles of 150 mg / ml of the compound of formula (Ia) in a solution of 27.92 w / w% water, 58.04 w / w% PEG 300, 13.47 w / w% of the compound of formula (Ia) and 0.58 w / w% NaOH when administered subcutaneously at 50 mg / kg in rats ( Figure 8A ) and at 12 mg / kg subcutaneously in dogs ( Figure 8B ).

[0058] Figure 9A and 9B show the plasma concentration-time profiles of 300 mg / ml of the compound of formula (Ia) in a solution of 23.2 w / w% water, 50.0 w / w% PEG 300, 25.7 w / w% of the compound of formula (Ia) and 1.1 w / w% NaOH when administered subcutaneously at 50 mg / kg in rats ( Figure 9A ) and at 12 mg / kg subcutaneously in dogs ( Figure 9B ).

[0059] Figure 10A and 10B show the plasma concentration-time profiles of 50 mg / mL of the compound of formula (Ia) in a solution of 30.07 w / w% water, 64.40 w / w% PEG 300, 4.68 w / w% of the sodium salt of the compound of formula (Ia) and 0.85 w / w% poloxamer 188 when administered subcutaneously at 50 mg / kg in rats ( Figure 10A ) and at 6 mg / kg subcutaneously in dogs ( Figure 10B ).

[0060] Figure 11A and 11B show the plasma concentration-time profiles of 50 mg / mL of the compound of formula (Ia) in a solution of 30.07 w / w% water, 64.40 w / w% PEG 300, 4.68 w / w% of the sodium salt of the compound of formula (Ia) and 0.85 w / w% poloxamer 188 when administered subcutaneously at 50 mg / kg in rats ( Figure 11A ) and at 6 mg / kg subcutaneously in dogs ( Figure 11B) The graph showing the change of plasma concentration of the compound of formula (Ia) at 75 mg / ml over time in a solution of 29.21 w / w% water, 62.55 w / w% PEG 300, 6.97 w / w% sodium salt of the compound of formula (Ia), and 1.68 w / w% poloxamer 188.

[0061] Figure 12A and 12B showing when administered subcutaneously at 50 mg / kg in rats ( Figure 12A ) and at 6 mg / kg subcutaneously in dogs ( Figure 12B ) The graph showing the change of plasma concentration of the compound of formula (Ia) at 100 mg / ml over time in a solution of 28.36 w / w% water, 60.73 w / w% PEG 300, 9.23 w / w% sodium salt of the compound of formula (Ia), and 1.68 w / w% poloxamer 188.

[0062] Figure 13A and 13B showing when administered subcutaneously at 50 mg / kg in rats ( Figure 13A ) and at 6 mg / kg subcutaneously in dogs ( Figure 13B ) The graph showing the change of plasma concentration of the compound of formula (Ia) at 125 mg / ml over time in a solution of 27.51 w / w% water, 58.92 w / w% PEG 300, 11.48 w / w% sodium salt of the compound of formula (Ia), and 2.09 w / w% poloxamer 188.

[0063] Figure 14A showing when administered subcutaneously at 50 mg / kg in rats, the graph showing the change of plasma concentration of the compound of formula (Ia) at 150 mg / ml over time in a solution of 26.6 w / w% water, 56.97 w / w% PEG 300, 13.39 w / w% of the compound of formula (Ia), 0.57 w / w% NaOH, and 2.49 w / w% poloxamer 188. Figure 14B showing when administered subcutaneously at 6 mg / kg in dogs, the graph showing the change of plasma concentration of the compound of formula (Ia) at 150 mg / ml over time in a solution of 26.6 w / w% water, 56.97 w / w% PEG 300, 13.39 w / w% of the compound of formula (Ia), 0.57 w / w% NaOH, and 2.49 w / w% poloxamer 188.

[0064] Figure 15A and 15B showing when administered subcutaneously at 50 mg / kg in rats ( Figure 15A ) and at 6 mg / kg subcutaneously in dogs ( Figure 15B) When administered orally to dogs as a liquid-filled capsule at a fixed dose of 7.5 mg, the plasma concentration-time profile of the compound of formula (Ia) in 100% monocaprylyl decaglyceride.

[0065] Figure 16 The graph showing the plasma concentration-time profile of the compound of formula (Ia) when administered orally to dogs at a fixed dose of 7.5 mg as a liquid-filled capsule.

[0066] Figure 17 The graph showing the plasma concentration-time profile of the tablets prepared from a spray-dried dispersion of the sodium salt of the compound of formula (Ia) (the composition described in Table T has an outer film coating made of II White 85F18422, and the outer film coating provides a 3% weight increase based on the weight of the uncoated tablets) when administered orally to dogs at a fixed dose of 300 mg. Detailed Description

[0067] Subject to the following description, the present disclosure should be regarded as an example of the claimed subject matter and is not intended to limit the appended claims to the specific embodiments shown. The headings used throughout this disclosure are for convenience only and should not be construed as limiting the claims in any way. The embodiments shown under any heading may be combined with the embodiments shown under any other heading. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. When using a trade name herein, it is intended to independently include the trade name product and one or more active pharmaceutical ingredients of the trade name product. The reference herein to a "about" value or parameter includes (and describes) embodiments directed to that value or parameter itself. In certain embodiments, the term "about" includes the indicated amount ± 10%. In other embodiments, the term "about" includes the indicated amount ± 8%. In other embodiments, the term "about" includes the indicated amount ± 5%. In other embodiments, the term "about" includes the indicated amount ± 3%. In certain other embodiments, the term "about" includes the indicated amount ± 1%. Additionally, the term "about X" includes a description of "X".

[0068] As used herein and in the appended claims, the singular forms "a" and "the" include plural objects unless the context clearly indicates otherwise. Thus, for example, reference to "a compound" includes a plurality of such compounds, reference to "an assay" includes reference to one or more assays, and so on.

[0069] As a further example, reference to "pharmaceutically acceptable excipients" includes a single pharmaceutically acceptable excipient and multiple pharmaceutically acceptable excipients.

[0070] As used herein, "HIV" or "human immunodeficiency virus" refers to HIV-1 and / or HIV-2.

[0071] As used herein, "heavily pre-treated patients" refers to HIV-infected patients with limited treatment options due to multi-drug resistant HIV infection. For example, in some embodiments, "heavily pre-treated patients" are HIV patients who have developed resistance to antiretroviral drugs in at least one class selected from NRTIs, NNRTIs, PIs, and INSTIs.

[0072] In some embodiments, "multi-drug resistant HIV infection" refers to resistance to antiretroviral drugs in at least one class selected from NRTIs, NNRTIs, PIs, and INSTIs. In some embodiments, "multi-drug resistant HIV infection" refers to resistance to at least one antiretroviral drug in two classes of antiretroviral drugs selected from NRTIs, NNRTIs, PIs, and INSTIs. In some embodiments, "multi-drug resistant HIV infection" refers to resistance to at least one antiretroviral drug in three classes of antiretroviral drugs selected from NRTIs, NNRTIs, PIs, and INSTIs. In some embodiments, "multi-drug resistant HIV infection" refers to resistance to at least one antiretroviral drug in each of the four classes of antiretroviral drugs selected from NRTIs, NNRTIs, PIs, and INSTIs.

[0073] As used herein, the term "NRTI" refers to a nucleoside reverse transcriptase inhibitor or a nucleotide reverse transcriptase inhibitor.

[0074] As used herein, the term "NNRTI" refers to a non-nucleoside reverse transcriptase inhibitor or a non-nucleotide reverse transcriptase inhibitor.

[0075] As used herein, the term "PI" refers to a protease inhibitor.

[0076] As used herein, the term "INSTI" refers to an integrase strand transfer inhibitor.

[0077] As used herein, when referring to an HIV therapy or an HIV treatment regimen, the terms "failure" or "failed" refer to a treatment outcome that precludes future use of the same agent or class in an HIV patient. This may be due to an inadequate initial viral response due to pre-existing viral resistance, viral rebound due to the emergence of viral resistance, or the inability of the patient to continue treatment due to intolerance or safety issues.

[0078] As used herein, the term "C" max " refers to the maximum plasma / serum concentration of the observed drug.

[0079] "Pharmaceutically acceptable" refers to compounds, salts, compositions, dosage forms, and other materials that can be used to prepare pharmaceutical compositions suitable for veterinary or human drugs.

[0080] "Pharmaceutically acceptable excipients" include, but are not limited to, any adjuvant, carrier, excipient, glidant, sweetening agent, diluent, preservative, dye / colorant, flavoring agent, surfactant, wetting agent, dispersing agent, suspending agent, stabilizing agent, isotonic agent, solvent, or emulsifying agent that has been approved by the U.S. Food and Drug Administration for use in humans or livestock.

[0081] "Pharmaceutically acceptable salts" are salts of compounds that are pharmaceutically acceptable and have (or can be converted to have) the desired pharmacological activity of the parent compound. Such salts include acid addition salts formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, etc.; or acid addition salts formed with organic acids such as acetic acid, benzenesulfonic acid, benzoic acid, camphorsulfonic acid, citric acid, ethanesulfonic acid, fumaric acid, glucoheptanoic acid, gluconic acid, lactic acid, maleic acid, malonic acid, mandelic acid, methanesulfonic acid, 2-naphthalenesulfonic acid, oleic acid, palmitic acid, propionic acid, stearic acid, succinic acid, tartaric acid, p-toluenesulfonic acid, trifluoroacetic acid, trimethylacetic acid, etc.; and protons present in the parent compound are replaced by metal ions such as alkali metal ions (e.g., sodium or potassium), alkaline earth metal ions (e.g., calcium or magnesium), or aluminum ions; or coordinated with organic bases such as diethanolamine, triethanolamine, N-methylglucosamine, etc. Also included in this definition are ammonium salts and substituted ammonium salts or quaternary ammonium salts (e.g., quaternary ammonium salts containing the N,N,N-trimethylethanolammonium (choline) cation). A representative non-limiting list of pharmaceutically acceptable salts can be found in S.M. Berge et al., J. Pharma Sci., 66(1), 1-19 (1977) and Remington: The Science and Practice of Pharmacy, R. Hendrickson, ed., 21st edition, Lippincott, Williams & Wilkins, Philadelphia, PA, (2005), page 732, Table 38-5, both of which are incorporated herein by reference.

[0082] "Patient" refers to humans, livestock (e.g., dogs and cats), farm animals (e.g., cows, horses, sheep, goats, and pigs), laboratory animals (e.g., mice, rats, hamsters, guinea pigs, pigs, rabbits, dogs, and monkeys, etc.).

[0083] As used herein, "treating" or "treatment" is a method for obtaining a beneficial or desired result. For the purposes of this disclosure, beneficial or desired results include, but are not limited to, alleviating symptoms and / or reducing the severity of symptoms and / or preventing the worsening of symptoms associated with a disease or medical condition.

[0084] In one embodiment, "treating" or "treatment" includes one or more of the following: a) inhibiting a disease or medical condition (e.g., alleviating one or more symptoms caused by the disease or medical condition, and / or reducing the severity of the disease or medical condition); b) slowing or preventing the development of one or more symptoms associated with the disease or medical condition (e.g., stabilizing the disease or medical condition, delaying the worsening or progression of the disease or medical condition); and / or c) alleviating the disease or medical condition, such as causing the regression of clinical symptoms, improving the disease state, delaying the progression of the disease, enhancing the quality of life, and / or prolonging the survival period.

[0085] As used herein, the term "therapeutically effective amount" or "effective amount" refers to an amount effective to elicit a desired biological or medical response, including the amount of a compound when administered to a patient to treat a disease, sufficient to effect such treatment of the disease, or sufficient to protect it from the invasion or onset of the disease. The effective amount will vary depending on the compound, the disease, its severity, and the age, weight, etc. of the patient being treated. The effective amount can include a range of amounts. As understood in the art, the effective amount can be in one or more doses, e.g., a single dose or multiple doses may be required to achieve the desired therapeutic result. The effective amount can be considered in the case of administering one or more therapeutic agents, and in the case of co-administration with one or more other drugs, a single agent can be administered in an effective amount to achieve the desired or beneficial result. Due to the combined action of the compounds (e.g., additive or synergistic effects), the appropriate dose of any co-administered compound can optionally be reduced.

[0086] Unless otherwise clearly defined, even if only one tautomer is explicitly indicated, this disclosure includes all tautomers of the compounds detailed herein (e.g., both tautomeric forms are intended and described by presenting one tautomeric form, where a pair of two tautomers can exist). For example, if a compound containing an amide is mentioned (e.g., by structure or chemical name), it should be understood that the corresponding imino tautomer is included in this disclosure and described as the same as when the amide is explicitly recited alone or together with the imino form. In cases where there are more than two tautomers, even if only a single tautomeric form is depicted by chemical name and / or structure, this disclosure includes all such tautomers.

[0087] Those skilled in the art will understand that the present disclosure also includes that any compound disclosed herein (e.g., a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof) may be enriched with one or more isotopes at a ratio higher than the natural isotope ratio on any or all atoms, such as but not limited to deuterium ( 2 H or D).

[0088] Compounds are also disclosed in which 1 to n hydrogen atoms attached to carbon atoms may be replaced by deuterium atoms or D, where n is the number of hydrogen atoms in the molecule. As is known in the art, deuterium atoms are non-radioactive isotopes of hydrogen atoms. Such compounds can increase resistance to metabolism and can thus be used to increase the half-life of the compound when administered to a mammal. See, e.g., Foster, “Deuterium Isotope Effects in Studies of Drug Metabolism,” Trends Pharmacol. Sci., 5(12):524-527 (1984). Such compounds are synthesized by methods known in the art, such as by using starting materials in which one or more hydrogen atoms have been replaced by deuterium.

[0089] Examples of isotopes that can be incorporated into the disclosed compounds also 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. Substitution with positron-emitting isotopes (such as 11 C, 18 F, 15 O, and 13 N) can be used in positron emission tomography (PET) studies to examine the occupancy of substrate receptors. Isotopically labeled compounds of formula (Ia) or formula (Ib) or pharmaceutically acceptable salts thereof can generally be prepared by conventional techniques known to those skilled in the art or by methods similar to those described in the following embodiments, using appropriate isotopically labeled reagents in place of the previously used unlabeled reagents, as described below.

[0090] The compounds described herein may have chiral centers and / or geometric isomeric centers (E- and Z-isomers), and it is to be understood that all such optical isomers, enantiomers, diastereomers and geometric isomers are included. When a compound is represented in its chiral form, it is to be understood that the embodiment includes, but is not limited to, specific diastereomeric or enantiomerically enriched forms. In cases where chirality is not specified but is present, it is to be understood that the embodiment is directed to specific diastereomeric or enantiomerically enriched forms; or racemic or non-racemic mixtures of such compounds.

[0091] Also provided are pharmaceutically acceptable hydrates, solvates, tautomeric forms, polymorphs and prodrugs of the compounds described herein.

[0092] In one embodiment, the present disclosure relates to the use of a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof in the treatment of an infection caused by an HIV virus, comprising administering a therapeutically effective amount to a patient in need, wherein the patient is a patient who has undergone extensive treatment and has a multi-drug resistant HIV infection.

[0093] The present disclosure includes the use of a compound of formula (Ia) having the following structure N-((S)-1-(3-(4-chloro-3-(methylsulfonamido)-1-(2,2,2-trifluoroethyl)-1H-indazol-7-yl)-6-(3-methyl-3-(methylsulfonyl)but-1-yn-1-yl)pyridin-2-yl)-2-(3,5-difluorophenyl)ethyl)-2-((3bS,4aR)-5,5-difluoro-3-(trifluoromethyl)-3b,4,4a,5-tetrahydro-1H-cyclopropa[3,4]cyclopenta[1,2-c]pyrazol-1-yl)acetamide:

[0094]

[0095] or a pharmaceutically acceptable salt thereof, for the treatment of HIV infection in a patient who has undergone extensive treatment and has a multi-drug resistant HIV infection.

[0096] The present disclosure also includes the use of a compound of formula (Ib) having the following structure N-((S)-1-(3-(4-chloro-3-(cyclopropanesulfonamido)-1-(2,2-difluoroethyl)-1H)-indazol-7-yl)-6-(3-methyl-3-(methylsulfonyl)but-1-yn-1-yl)pyridin-2-yl)-2-(3,5-difluorophenyl)ethyl)-2-((3bS,4aR)-3-(difluoromethyl)-5,5-difluoro-3b,4,4a,5-tetrahydro-1H-cyclopropa[3,4]cyclopenta[1,2-c]pyrazol-1-yl)acetamide:

[0097]

[0098] or a pharmaceutically acceptable salt thereof, for treating HIV infection in heavily pre-treated patients with multi-drug resistant HIV infection.

[0099] In some embodiments, the compound is a pharmaceutically acceptable salt of a compound of formula (Ia) or formula (Ib). Non-limiting examples of pharmaceutically acceptable salts of compounds of formula (Ia) and formula (Ib) include sodium salts and trifluoroacetate salts. In some embodiments, the compound of formula (Ia) is a sodium salt. In some embodiments, the compound of formula (Ib) is a trifluoroacetate salt.

[0100] The compounds used in the methods disclosed herein (e.g., compounds of formula (Ia) or formula (Ib) or pharmaceutically acceptable salts thereof) are active against major HIV-1 mutants selected by protease inhibitors (PIs), nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and / or integrase inhibitors (INSTIs).

[0101] Therapeutic Methods

[0102] The present disclosure provides a method for treating human immunodeficiency virus (HIV) infection in heavily pre-treated patients, the method comprising administering to the patient a therapeutically effective amount of a compound of formula (Ia) or formula (Ib):

[0103]

[0104] or a pharmaceutically acceptable salt thereof.

[0105] In the disclosed methods, the heavily pre-treated patients are infected with multi-drug resistant HIV. In some embodiments, the heavily pre-treated patients have multi-drug resistant HIV infection and are on a failed HIV treatment regimen. In some embodiments, the heavily pre-treated patients have a viral load greater than about 1,000 copies of HIV RNA / mL.

[0106] In some embodiments, the HIV infection is an HIV-1 infection. In some embodiments, the HIV-1 infection is characterized by an HIV-1 mutant that is resistant to antiretroviral drugs, for example, one, two, three, four, or more classes of antiretroviral drugs (such as PI, NRTI, NNRTI, INSTI, etc.). In some embodiments, the HIV-1 infection is characterized by an HIV-1 mutant that is resistant to one or more classes of antiretroviral drugs. In some embodiments, the HIV-1 infection is characterized by an HIV-1 mutant that is resistant to two or more classes of antiretroviral drugs. In some embodiments, the HIV-1 infection is characterized by an HIV-1 mutant that is resistant to three or more classes of antiretroviral drugs.

[0107] In some embodiments, the HIV-1 infection is characterized by an HIV-1 mutant, including but not limited to:

[0108] (a) An HIV-1 mutant resistant to PI (such as I50V, I84V / L90M, G48V / V82A / L90M, G48V / V82S, etc.);

[0109] (b) An HIV-1 mutant resistant to NRTI (such as K65R, M184V, 6TAM, etc.);

[0110] (c) An HIV-1 mutant resistant to NNRTI (such as K103N, Y181C, Y188L, L100I / K103N, K103N / Y181C, etc.); and / or

[0111] (d) An HIV-1 mutant resistant to INSTI (Y143R, E138K / Q148K, G140S / Q148R, E92Q / N155H, N155H / Q148R, R263K / M50I, etc.).

[0112] In some embodiments, the patient is infected with HIV-1 that is resistant to at least one antiretroviral drug. In some embodiments, the patient is infected with multi-drug resistant HIV-1. In some embodiments, the patient is infected with multi-drug resistant HIV-1 that is resistant to at least one, two, three, four or more antiretroviral drugs. In some embodiments, the patient is infected with multi-drug resistant HIV-1 that is resistant to at least one antiretroviral drug of each of two different classes of antiretroviral drugs. In some embodiments, the patient is infected with multi-drug resistant HIV-1 that is resistant to at least one antiretroviral drug of 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). In some embodiments, the different classes of antiretroviral drugs are selected from NRTIs, NNRTIs, and PIs. In some embodiments, the patient is infected with multi-drug resistant HIV-1 that is resistant to at least one NRTI and at least one NNRTI. In some embodiments, the patient is infected with multi-drug resistant HIV-1 that is resistant to at least one NRTI and at least one PI. In some embodiments, the patient is infected with multi-drug resistant HIV-1 that is resistant to at least one NRTI and at least one INSTI. In some embodiments, the patient is infected with multi-drug resistant HIV-1 that is resistant to at least one NNRTI and at least one PI. In some embodiments, the patient is infected with multi-drug resistant HIV-1 that is resistant to at least one NNRTI and at least one INSTI. In some embodiments, the patient is infected with multi-drug resistant HIV-1 that is resistant to at least one PI and at least one INSTI. In some embodiments, the patient is infected with multi-drug resistant HIV-1 that is resistant to at least one NRTI, at least one NNRTI, and at least one PI. In some embodiments, the patient is infected with multi-drug resistant HIV-1 that is resistant to at least one NRTI, at least one NNRTI, and at least one INSTI. In some embodiments, the patient is infected with multi-drug resistant HIV-1 that is resistant to at least one NRTI, at least one PI, and at least one INSTI. In some embodiments, the patient is infected with multi-drug resistant HIV-1 that is resistant to at least one NNRTI, at least one PI, and at least one INSTI. In some embodiments, the patient is infected with multi-drug resistant HIV-1 that is resistant to at least one NRTI, at least one NNRTI, at least one PI, and at least one INSTI.

[0113] In some embodiments, the patient is infected with multi-drug resistant HIV-1 that is resistant to at least one antiretroviral drug NRTI. Examples of NRTIs include, but are not limited to: emtricitabine (FTC; ), lamivudine (3TC; ), zidovudine (azidothymidine (AZT); ), didanosine (ddl; ), zalcitabine (dideoxycytidine, ddC; tenofovir, tenofovir alafenamide tenofovir disoproxil fumarate stavudine (d4T; ), zalcitabine (dideoxycytidine, ddC; ), and abacavir

[0114] In some embodiments, the patient is infected with multi-drug resistant HIV-1 that is resistant to at least one antiretroviral drug NNRTI. Examples of NNRTIs include, but are not limited to: efavirenz etravirine rilpivirine nevirapine and delavirdine

[0115] In some embodiments, the patient is infected with multi-drug resistant HIV-1 that is resistant to at least one antiretroviral drug PI. Examples of PIs include, but are not limited to: amprenavir atazanavir darunavir fosamprenavir indinavir lopinavir nelfinavir ritonavir saquinavir and tipranavir

[0116] In some embodiments, the patient is infected with multi-drug resistant HIV-1 that is resistant to at least one antiretroviral drug INSTI. Examples of INSTIs include, but are not limited to: raltegravir elvitegravir dolutegravir cabotegravir, and bictegravir.

[0117] In some embodiments, the patient is infected with multi-drug resistant HIV-1 that is resistant to at least one antiretroviral drug, a gp4l fusion inhibitor. Examples of gp4l fusion inhibitors include, but are not limited to: abacavir, enfuvirtide, BMS-986197, biosimilar enfuvirtide, biosimilar of enfuvirtide, HIV-1 fusion inhibitor (P26-Bapc), ITV-1, ITV-2, ITV-3, ITV-4, PIE-12 trimer, and T-20.

[0118] In some embodiments, the patient is infected with multi-drug resistant HIV-1 that is resistant to at least one antiretroviral drug, a CCR5 co-receptor antagonist. Examples of CCR5 co-receptor antagonists include, but are not limited to: apaviroc, vicriviroc, maraviroc, cenicriviroc, PRO-140, aldavert (RAP-101), niveraprevir (TD-0232), anti-GP120 / CD4 or CCR5 bispecific antibody, B-07, MB-66, peptide C25P, TD-0680, and vMIP (Haimipu).

[0119] In some embodiments of the disclosed method, prior to treatment with a compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof, the patient has previously been treated with at least one antiretroviral drug. In some embodiments, the patient has previously been treated with at least one antiretroviral drug for at least 3 months, such as at least 4 months, at least 5 months, at least 6 months, at least 7 months, at least 8 months, at least 9 months, at least 10 months, at least 11 months, at least 12 months, at least 18 months, or at least 24 months. In some embodiments, the patient has previously been treated with at least one antiretroviral drug for at least 3 months. In some embodiments, the patient has previously been treated with at least one antiretroviral drug for at least 6 months. In some embodiments, the patient has previously been treated with at least one antiretroviral drug for at least 9 months. In some embodiments, the patient has previously been treated with at least one antiretroviral drug for at least 12 months. In some embodiments, the patient has previously been treated with at least one antiretroviral drug for at least 18 months. In some embodiments, the patient has previously been treated with at least one antiretroviral drug for at least 24 months. In some embodiments, the patient has previously been treated with at least one antiretroviral drug for at least 30 months. In some embodiments, the patient has previously been treated with at least one antiretroviral drug for at least 36 months.

[0120] In some embodiments of the disclosed method, the patient's HIV treatment regimen has failed or is about to fail prior to treatment with a compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof. In some embodiments, the previous HIV treatment regimen included administration of at least one antiretroviral drug. In some embodiments, the HIV-infected patient has relapsed after an initial response to a previous HIV treatment regimen, such as antiretroviral therapy. In some embodiments, prior to treatment with a compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof, after about 48 weeks of therapy (such as antiretroviral therapy), the patient's viral load is greater than about 50 copies of HIV RNA / mL.

[0121] In some embodiments, the previous treatment regimen included administration of at least one antiretroviral drug from each of two different classes of antiretroviral drugs. In some embodiments, the previous treatment regimen included 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). In some embodiments, the different classes of antiretroviral drugs are selected from NRTIs, NNRTIs, and PIs. In some embodiments, the previous treatment regimen included administration of at least one NRTI and at least one NNRTI. In some embodiments, the previous treatment regimen included administration of at least one NRTI and at least one PI. In some embodiments, the previous treatment regimen included administration of at least one NRTI and at least one INSTI. In some embodiments, the previous treatment regimen included administration of at least one NNRTI and at least one PI. In some embodiments, the previous treatment regimen included administration of at least one NNRTI and at least one INSTI. In some embodiments, the previous treatment regimen included administration of at least one PI and at least one INSTI. In some embodiments, the previous treatment regimen included administration of at least one NRTI, at least one NNRTI, and at least one PI. In some embodiments, the previous treatment regimen included administration of at least one NRTI, at least one NNRTI, and at least one INSTI. In some embodiments, the previous treatment regimen included administration of at least one NRTI, at least one PI, and at least one INSTI. In some embodiments, the previous treatment regimen included administration of at least one NNRTI, at least one PI, and at least one INSTI.

[0122] In some embodiments, the previous treatment regimen included administration of at least one antiretroviral drug that is a gp41 fusion inhibitor.

[0123] In some embodiments, the previous treatment regimen includes administering at least one antiretroviral drug that is a CCR5 co-receptor antagonist.

[0124] In some embodiments, the previous treatment regimen includes administering at least one antiretroviral drug that is an NRTI. Examples of NRTIs include, but are not limited to: emtricitabine (FTC; ), lamivudine (3TC; ), zidovudine (azidothymidine (AZT); ), didanosine (ddI; ), zalcitabine (dideoxycytidine, ddC; tenofovir, tenofovir alafenamide tenofovir disoproxil fumarate stavudine (d4T; ), abacavir ), and abacavir

[0125] In some embodiments, the previous treatment regimen includes administering at least one antiretroviral drug that is an NNRTI. Examples of NNRTIs include, but are not limited to: efavirenz etravirine rilpivirine nevirapine and delavirdine

[0126] In some embodiments, the previous treatment regimen includes administering at least one antiretroviral drug that is a PI. Examples of PIs include, but are not limited to: amprenavir atazanavir darunavir fosamprenavir indinavir lopinavir nelfinavir ritonavir saquinavir and tipranavir

[0127] In some embodiments, the previous treatment regimen includes administering at least one antiretroviral drug that is an INSTI. Examples of INSTIs include, but are not limited to: raltegravir elvitegravir dolutegravir cabotegravir, and bictegravir.

[0128] In some embodiments, the previous treatment regimen included administration of at least one antiretroviral drug that is a gp41 fusion inhibitor. Examples of gp41 fusion inhibitors include, but are not limited to: abacavir, enfuvirtide, BMS-986197, biosimilar enfuvirtide, biosimilar enfuvirtide, HIV-1 fusion inhibitor (P26-Bapc), ITV-1, ITV-2, ITV-3, ITV-4, PIE-12 trimer, and T-20.

[0129] In some embodiments, the previous treatment regimen included administration of at least one antiretroviral drug that is a CCR5 co-receptor antagonist. Examples of CCR5 co-receptor antagonists include, but are not limited to: aplaviroc, vicriviroc, maraviroc, saniviroc, PRO-140, alaclavir (RAP-101), niveraprevir (TD-0232), anti-GP120 / CD4 or CCR5 bispecific antibody, B-07, MB-66, polypeptide C25P, TD-0680, and vMIP (Haimipu).

[0130] In some embodiments of the disclosed method, when initiating administration of a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof, heavily pre-treated patients infected with HIV have a viral load of from about 200 copies of HIV-1 RNA / mL (c / mL) to about 1,000,000 c / mL, such as a viral load of from about 200 c / mL to about 500,000 c / mL, from about 200 c / mL to about 250,000 c / mL, from about 200 c / mL to about 100,000 c / mL, from about 200 c / mL to about 50,000 c / mL, from about 200 c / mL to about 25,000 c / mL, from about 200 c / mL to about 10,000 c / mL, from about 200 c / mL to about 5,000 c / mL, from about 200 c / mL to about 3,000 c / mL, from about 200 c / mL to about 2,000 c / mL, from about 200 c / mL to about 1,000 c / mL, from about 200 c / mL to about 750 c / mL, from about 200 c / mL to about 500 c / mL, from about 500 c / mL to about 1,000,000 c / mL, from about 500 c / mL to about 500,000 c / mL, from about 500 c / mL to about 250,000 c / mL, from about 500 c / mL to about 100,000 c / mL, from about 500 c / mL to about 50,000 c / mL, from about 500 c / mL to about 25,000 c / mL, from about 500 c / mL to about 10,000 c / mL, from about 500 c / mL to about 5,000 c / mL, from about 500 c / mL to about 3,000 c / mL, from about 500 c / mL to about 2,000 c / mL, from about 500 c / mL to about 1,000 c / mL, from about 500 c / mL to about 750 c / mL, from about 750 c / mL to about 1,000,000 c / mL, from about 750 c / mL to about 500,000 c / mL, from about 750 c / mL to about 250,000 c / mL, from about 750 c / mL to about 100,000 c / mL, from about 750 c / mL to about 50,000 c / mL, from about 750 c / mL to about 25,000 c / mL, from about 750 c / mL to about 10,000 c / mL, from about 750 c / mL to about 5,000 c / mL, from about 750 c / mL to about 3,000 c / mL, from about 750 c / mL to about 2,000 c / mL, from about 750 c / mL to about 1,000 c / mL, from about 1,000 c / mL to about 1,000,000 c / mL, from about 1,000 c / mL to about 500,000 c / mL, from about 1,000 c / mL to about 250,000 c / mL, from about 1,000 c / mL to about 100,000 c / mL, from about 1,000 c / mL to about 50,000 c / mL, from about 1,000 c / mL to about 25,000 c / mL, from about 1,from 000 c / mL to about 10,000 c / mL, about 1,000 c / mL to about 5,000 c / mL, about 1,000 c / mL to about 3,000 c / mL, about 1,000 c / mL to about 2,000 c / mL, about 2,000 c / mL to about 1,000,000 c / mL, about 2,000 c / mL to about 500,000 c / mL, about 2,000 c / mL to about 250,000 c / mL, about 2,000 c / mL to about 100,000 c / mL, about 2,000 c / mL to about 50,000 c / mL, about 2,000 c / mL to about 25,000 c / mL, about 2,000 c / mL to about 10,000 c / mL, about 2,000 c / mL to about 5,000 c / mL, about 2,000 c / mL to about 3,000 c / mL, about 3,000 c / mL to about 1,000,000 c / mL, about 3,000 c / mL to about 500,000 c / mL, about 3,000 c / mL to about 250,000 c / mL, about 3,000 c / mL to about 100,000 c / mL, about 3,000 c / mL to about 50,000 c / mL, about 3,000 c / mL to about 25,000 c / mL, about 3,000 c / mL to about 10,000 c / mL, about 3,000 c / mL to about 5,000 c / mL, about 5,000 c / mL to about 1,000,000 c / mL, about 5,000 c / mL to about 500,000 c / mL, about 5,000 c / mL to about 250,000 c / mL, about 5,000 c / mL to about 100,000 c / mL, about 5,000 c / mL to about 50,000 c / mL, about 5,000 c / mL to about 25,000 c / mL, about 5,000 c / mL to about 10,000 c / mL, about 10,000 c / mL to about 1,000,000 c / mL, about 10,000 c / mL to about 500,000 c / mL, about 10,000 c / mL to about 250,000 c / mL, about 10,000 c / mL to about 100,000 c / mL, about 10,000 c / mL to about 50,000 c / mL, about 10,000 c / mL to about 25,000 c / mL, about 25,000 c / mL to about 1,000,000 c / mL, about 25,000 c / mL to about 500,000 c / mL, about 25,000 c / mL to about 250,000 c / mL, about 25,000 c / mL to about 100,000 c / mL, about 25,000 c / mL to about 50,000 c / mL, about 50,000 c / mL to about 1,000,000 c / mL, about 50,000 c / mL to about 500,000 c / mL, about 50,000 c / mL to about 250,from about 0 c / mL, from about 50,000 c / mL to about 100,000 c / mL, from about 100,000 c / mL to about 1,000,000 c / mL, from about 100,000 c / mL to about 500,000 c / mL, from about 100,000 c / mL to about 250,000 c / mL, from about 250,000 c / mL to about 1,000,000 c / mL, from about 250,000 c / mL to about 500,000 c / mL or from about 500,000 c / mL to about 1,000,000 c / mL.,

[0131] In some embodiments, at the start of administration of a compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof, the viral load of the patient is greater than about 200 copies of HIV-1 RNA / mL (c / mL), for example at the start of administration of a compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof the viral load is greater than about 500 c / mL, about 750 c / mL, about 1,000 c / mL, about 2,000 c / mL, about 3,000 c / mL, about 5,000 c / mL, about 10,000 c / mL, about 25,000 c / mL, about 50,000 c / mL, about 100,000 c / mL, about 250,000 c / mL, about 500,000 c / mL or greater than about 1,000,000 c / mL. In some embodiments, at the start of administration of a compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof, the viral load of the patient is greater than about 200 c / mL. In some embodiments, at the start of administration of a compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof, the viral load of the patient is greater than about 500 c / mL. In some embodiments, at the start of administration of a compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof, the viral load of the patient is greater than about 750 c / mL. In some embodiments, at the start of administration of a compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof, the viral load of the patient is greater than about 1,000 c / mL. In some embodiments, at the start of administration of a compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof, the viral load of the patient is greater than about 2,000 c / mL.

[0132] A compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof can be administered to a patient according to an effective dosing regimen for a desired period or duration, such as at least about one day, at least about one week, at least about one month, at least about 2 months, at least about 3 months, at least about 4 months, at least about 6 months or at least about 12 months or longer. In some embodiments, the compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof is administered on a daily or intermittent schedule. In some embodiments, the compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof is administered once a week. In some embodiments, the compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof is administered twice a month (i.e., every two weeks). In some embodiments, the compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof is administered once a month. In some embodiments, the compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof is administered once every two months. In some embodiments, the compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof is administered once every three months. In some embodiments, the compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof is administered once every four months. In some embodiments, the compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof is administered once every five months. In some embodiments, the compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof is administered once every 6 months. In some embodiments, the compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof is administered once every five months. In some embodiments, the compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof is administered once every 12 months.

[0133] In some embodiments, the compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof is administered once every nine months.

[0134] In some embodiments of the disclosed methods, administration of a compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof results in a reduction in viral load in a patient. In some embodiments, the viral load is reduced by about 0.5 log 10 to about 2.5 log 10 . For example, compared to the viral load at the start of administration of a compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof, after a certain time of administration of the compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof, the viral load is reduced by about 0.5 log 10 , about 1 log 10, about 1.5 log 10 , about 2 log 10 or about 2.5 log 10 . In some embodiments, the viral load is reduced by about 0.5 log about 24 weeks after administration of a compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof, compared to the viral load at the start of administration of the compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof 10 . In some embodiments, the viral load is reduced by about 1 log about 24 weeks after administration of a compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof, compared to the viral load at the start of administration of the compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof 10 . In some embodiments, the viral load is reduced by about 1.5 log about 24 weeks after administration of a compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof, compared to the viral load at the start of administration of the compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof 10 . In some embodiments, the viral load is reduced by about 2 log about 24 weeks after administration of a compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof, compared to the viral load at the start of administration of the compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof 10 . In some embodiments, the viral load is reduced by about 2.5 log about 24 weeks after administration of a compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof, compared to the viral load at the start of administration of the compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof 10 .

[0135] In some embodiments of the disclosed method, after a certain period of time following administration of a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof, the viral load in a patient is about 200 c / mL or lower, such as about 175 c / mL or lower, about 150 c / mL or lower, about 125 c / mL or lower, about 100 c / mL or lower, about 75 c / mL or lower or about 50 c / mL or lower. In some embodiments, after about 24 weeks following administration of a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof, the viral load of the patient is about 200 c / mL or lower. In some embodiments, after about 24 weeks following administration of a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof, the viral load of the patient is about 200 c / mL or lower. In some embodiments, after about 24 weeks following administration of a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof, the viral load of the patient is about 100 c / mL or lower. In some embodiments, after about 24 weeks following administration of a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof, the viral load of the patient is about 50 c / mL or lower.

[0136] In certain embodiments of the disclosed method, patients who have undergone extensive treatment receive treatment with at least one other antiretroviral drug. In some embodiments, the antiretroviral drugs are selected from NRTIs, NNRTIs, PIs, INSTIs, gp41 fusion inhibitors, and CCR5 co-receptor antagonists.

[0137] In some embodiments, the patient is treated simultaneously with at least one NRTI. Examples of NRTIs include, but are not limited to: emtricitabine (FTC; ), lamivudine (3TC; ), zidovudine (azidothymidine (AZT); ), didanosine (ddI; ), zalcitabine (dideoxycytidine, ddC; ), tenofovir, tenofovir alafenamide tenofovir disoproxil fumarate stavudine (d4T; ), abacavir ), and

[0138] In some embodiments, the patient is treated simultaneously with at least one NNRTI. Examples of NNRTIs include, but are not limited to: efavirenz etravirine rilpivirine nevirapine and delavirdine

[0139] In some embodiments, a patient is treated with at least one PI concurrently. Examples of PIs include, but are not limited to: amprenavir atazanavir darunavir fosamprenavir indinavir lopinavir nelfinavir ritonavir saquinavir and tipranavir

[0140] In some embodiments, a patient is treated with at least one INSTI concurrently. Examples of INSTIs include, but are not limited to: raltegravir elvitegravir dolutegravir cabotegravir, and bictegravir.

[0141] In some embodiments, a patient is treated with at least one gp41 fusion inhibitor concurrently. Examples of gp41 fusion inhibitors include, but are not limited to: aboceptiv, enfuvirtide, BMS-986197, biosimilar of enfuvirtide, biosimilar of enfuvirtide, HIV-1 fusion inhibitor (P26-Bapc), ITV-1, ITV-2, ITV-3, ITV-4, PIE-12 trimer, and T-20.

[0142] In some embodiments, a patient is treated with at least one CCR5 co-receptor antagonist concurrently. Examples of CCR5 co-receptor antagonists include, but are not limited to: apaviroc, vicriviroc, maraviroc, cenicriviroc, PRO-140, alacatavir (RAP-101), nilacatavir (TD-0232), anti-GP120 / CD4 or CCR5 bispecific antibody, B-07, MB-66, peptide C25P, TD-0680, and vMIP (haimipu).

[0143] The present disclosure also provides a method for treating HIV-1 infection in a patient with multi-drug resistant HIV-1 who has undergone extensive treatment, the method comprising administering to a patient who has previously been treated with an HIV treatment regimen a therapeutically effective amount of a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof, the previous treatment regimen comprising administration of at least one antiretroviral drug and the treatment regimen having failed. In some embodiments, the HIV treatment regimen comprises administration of at least one antiretroviral drug, such as those described herein. In some embodiments of the method, administration of the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof results in a decrease in the patient's HIV viral load.

[0144] Also disclosed is a method of treating HIV-1 infection in patients with multi-drug resistant HIV-1 who have undergone extensive treatment, the method comprising administering to a patient who has previously received treatment with an HIV treatment regimen, a therapeutically effective amount of a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof, the previous treatment regimen comprising administering at least one antiretroviral drug and the treatment regimen having failed, wherein the multi-drug resistant HIV-1 is resistant to at least one antiretroviral drug from each of at least two different classes of antiretroviral drugs. In some embodiments, the different classes of antiretroviral drugs are selected from NRTI, NNRTI, PI, and INSTI. In some embodiments, at the start of administration of the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof, the patient's viral load is greater than about 200 c / mL, and administration of the compound results in a decrease in the patient's HIV viral load.

[0145] In some embodiments, also disclosed is a method of treating HIV-1 infection in patients with multi-drug resistant HIV-1 who have undergone extensive treatment, the method comprising administering to a patient who has previously received treatment with an HIV treatment regimen, a therapeutically effective amount of a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof, the previous treatment regimen comprising administering at least one antiretroviral drug and the treatment regimen having failed, wherein the multi-drug resistant HIV-1 is resistant to at least one antiretroviral drug from each of at least three different classes of antiretroviral drugs. In some embodiments, the different classes of antiretroviral drugs are selected from NRTI, NNRTI, PI, and INSTI. In some embodiments, at the start of administration of the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof, the patient's viral load is greater than about 200 c / mL, and administration of the compound results in a decrease in the patient's HIV viral load.

[0146] Pharmaceutical Compositions

[0147] The pharmaceutical compositions disclosed herein comprise a compound disclosed herein (e.g., a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof) and one or more pharmaceutically acceptable excipients and optionally other therapeutic agents. The pharmaceutical composition containing the active ingredient can be in any form suitable for the intended method of administration.

[0148] A pharmaceutical composition comprising a compound disclosed herein (e.g., a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof) can be prepared with conventional carriers (e.g., inactive ingredients or excipients), which can be selected according to conventional practices. Tablets can contain excipients including glidants, fillers, binders, etc. Aqueous compositions can be prepared in a sterile form and, when intended to be delivered by a route other than oral administration, are generally isotonic. All compositions can optionally contain excipients such as those described in Handbook of Pharmaceutical Excipients, 5th Edition, by Rowe et al., American Pharmaceutical Association, 1986. Excipients can include ascorbic acid and other antioxidants, chelating agents (e.g., EDTA), carbohydrates (e.g., dextrin, hydroxyalkylcellulose, hydroxyalkylmethylcellulose, stearic acid, etc.).

[0149] In some embodiments, tablets can contain excipients including glidants, fillers, binders, polymers, etc. Injectable solutions and suspensions can be prepared in a sterile form and, when intended to be delivered by a route other than oral administration, are generally isotonic. All compositions can optionally contain excipients such as those described in Handbook of Pharmaceutical Excipients, 5th Edition, by Rowe et al., American Pharmaceutical Association, 1986. Excipients can include ascorbic acid and other antioxidants, chelating agents (e.g., EDTA), carbohydrates (e.g., dextrin, hydroxyalkylcellulose, hydroxyalkylmethylcellulose, stearic acid, etc.).

[0150] Although the active ingredient (e.g., a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof) can be administered alone, it is preferably presented as a pharmaceutical composition. Compositions for veterinary and human use comprise at least a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof and one or more acceptable carriers and optionally other therapeutic ingredients. In one embodiment, the pharmaceutical composition comprises a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable excipient, and a therapeutically effective amount of one or more (e.g., one, two, three, or four; or one or two; or one to three; or one to four) other therapeutic agents as defined herein. In some embodiments, the pharmaceutical composition comprises a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable excipient, and one other therapeutic ingredient. A carrier is "acceptable" in the sense that it is compatible with the other ingredients of the composition and physiologically innocuous to its recipient.

[0151] In some embodiments, the pharmaceutical compositions disclosed herein comprise a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable excipient, and an additional therapeutic agent selected from tenofovir alafenamide, tenofovir alafenamide hemifumarate, and bictegravir. In some embodiments, the pharmaceutical compositions disclosed herein comprise a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable excipient, and an additional therapeutic agent selected from tenofovir alafenamide hemifumarate and bictegravir.

[0152] In some embodiments, the pharmaceutical compositions disclosed herein comprise a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable excipient, and tenofovir alafenamide. In some embodiments, the pharmaceutical compositions disclosed herein comprise a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable excipient, and tenofovir alafenamide hemifumarate. In some embodiments, the pharmaceutical compositions disclosed herein comprise a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable excipient, and bictegravir.

[0153] In some embodiments, the pharmaceutical compositions disclosed herein comprise a compound of formula (Ia) or formula (Ib), a pharmaceutically acceptable excipient, and an additional therapeutic agent selected from tenofovir alafenamide, tenofovir alafenamide hemifumarate, and bictegravir. In some embodiments, the pharmaceutical compositions disclosed herein comprise a compound of formula (Ia) or formula (Ib), a pharmaceutically acceptable excipient, and an additional therapeutic agent selected from tenofovir alafenamide hemifumarate and bictegravir. In some embodiments, the pharmaceutical compositions disclosed herein comprise a compound of formula (Ia) or formula (Ib), a pharmaceutically acceptable excipient, and tenofovir alafenamide. In some embodiments, the pharmaceutical compositions disclosed herein comprise a compound of formula (Ia) or formula (Ib), a pharmaceutically acceptable excipient, and tenofovir alafenamide hemifumarate. In some embodiments, the pharmaceutical compositions disclosed herein comprise a compound of formula (Ia) or formula (Ib), a pharmaceutically acceptable excipient, and bictegravir.

[0154] In some embodiments, the pharmaceutical compositions disclosed herein comprise the sodium salt of a compound of formula (Ia), a pharmaceutically acceptable excipient, and an additional therapeutic agent selected from tenofovir alafenamide, tenofovir alafenamide hemifumarate, and bictegravir. In some embodiments, the pharmaceutical compositions disclosed herein comprise the sodium salt of a compound of formula (Ia), a pharmaceutically acceptable excipient, and an additional therapeutic agent selected from tenofovir alafenamide hemifumarate and bictegravir. In some embodiments, the pharmaceutical compositions disclosed herein comprise the sodium salt of a compound of formula (Ia), a pharmaceutically acceptable excipient, and tenofovir alafenamide. In some embodiments, the pharmaceutical compositions disclosed herein comprise the sodium salt of a compound of formula (Ia), a pharmaceutically acceptable excipient, and tenofovir alafenamide hemifumarate. In some embodiments, the pharmaceutical compositions disclosed herein comprise the sodium salt of a compound of formula (Ia), a pharmaceutically acceptable excipient, and bictegravir.

[0155] In some embodiments, the pharmaceutical compositions disclosed herein comprise the trifluoroacetate salt of a compound of formula (Ib), a pharmaceutically acceptable excipient, and an additional therapeutic agent selected from tenofovir alafenamide, tenofovir alafenamide hemifumarate, and bictegravir. In some embodiments, the pharmaceutical compositions disclosed herein comprise the trifluoroacetate salt of a compound of formula (Ib), a pharmaceutically acceptable excipient, and an additional therapeutic agent selected from tenofovir alafenamide hemifumarate and bictegravir. In some embodiments, the pharmaceutical compositions disclosed herein comprise the trifluoroacetate salt of a compound of formula (Ib), a pharmaceutically acceptable excipient, and tenofovir alafenamide. In some embodiments, the pharmaceutical compositions disclosed herein comprise the trifluoroacetate salt of a compound of formula (Ib), a pharmaceutically acceptable excipient, and tenofovir alafenamide hemifumarate. In some embodiments, the pharmaceutical compositions disclosed herein comprise the trifluoroacetate salt of a compound of formula (Ib), a pharmaceutically acceptable excipient, and bictegravir.

[0156] The compositions include those suitable for various routes of administration. The compositions may be conveniently presented in unit dosage form and may be prepared by any method well known in the pharmaceutical art. Such methods include the step of bringing into association the active ingredient (e.g., a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof) with one or more inactive ingredients (e.g., a carrier, a pharmaceutical excipient, etc.). The compositions may be prepared by uniformly and intimately bringing into association the active ingredient with a liquid carrier or a finely divided solid carrier or both, and then, if necessary, shaping the product. Techniques and formulations are generally found in Remington: The Science and Practice of Pharmacy, 21st Edition, Lippincott Williams and Wilkins, Philadelphia, PA, 2006.

[0157] The compositions suitable for oral administration described herein can be presented in discrete units (unit dosage forms), including but not limited to capsules, cachets or tablets, each containing a predetermined amount of the active ingredient.

[0158] When formulated for oral administration, tablets, troches, lozenges, aqueous or oily suspensions, dispersible powders or granules, emulsions, hard or soft capsules, syrups or elixirs can be prepared. Compositions for oral use can be prepared by any of the methods known in the art for the preparation of pharmaceutical compositions. Such compositions may contain one or more agents, including sweetening agents, flavoring agents, coloring agents and preserving agents, to provide palatable formulations. Tablets containing the active ingredient mixed with non-toxic pharmaceutically acceptable excipients suitable for the manufacture of tablets are acceptable. These excipients can be, for example, inert diluents such as calcium carbonate or sodium carbonate, lactose, lactose monohydrate, croscarmellose sodium, povidone, calcium phosphate or sodium phosphate; granulating and disintegrating agents such as corn starch or alginic acid; binding agents such as cellulose, microcrystalline cellulose, starch, gelatin or gum arabic; lubricating agents such as magnesium stearate, stearic acid or talc. Tablets can be uncoated or can be coated by known techniques including microencapsulation to delay disintegration and absorption in the gastrointestinal tract and thus provide a sustained action over a longer period. For example, delayed release materials such as glyceryl monostearate or glyceryl distearate used alone or in combination with waxes can be used.

[0159] In some embodiments, disclosed herein are oral dosage forms (e.g., tablets) that can be prepared from hot melt extrusion or spray dried dispersion (SDD) technologies.

[0160] In some embodiments, disclosed herein are capsules containing powders, beads or granules that contain the active ingredient mixed with non-toxic pharmaceutically acceptable excipients suitable for the manufacture of hard or soft capsules. These excipients can be, for example, inert diluents such as calcium carbonate or sodium carbonate, lactose, lactose monohydrate, croscarmellose sodium, povidone, calcium phosphate or sodium phosphate; granulating and disintegrating agents such as corn starch or alginic acid; binding agents such as cellulose, microcrystalline cellulose, starch, gelatin or gum arabic; lubricating agents such as magnesium stearate, stearic acid or talc. In some embodiments, the capsule is a hard capsule. In some embodiments, the capsule is a soft capsule.

[0161] In some embodiments, disclosed herein are hard or soft capsules filled with a liquid or semi-solid mixture comprising an active ingredient admixed with a non-toxic pharmaceutically acceptable excipient suitable for manufacturing hard or soft capsules. These excipients can be, for example, solubilizing oils such as corn oil, sesame oil or sunflower oil; medium-chain triglycerides and related esters such as those derived from palm kernel oil or coconut oil; self-emulsifying lipid systems (SEDDS or SMEDDS) such as triglyceride caprylate or polyethylene glycol esters of propylene glycol monocaprylate and medium-chain triglycerides; viscosity modifiers such as cetyl alcohol, sterols, glyceryl stearate; mixtures of medium-chain glycerol monoesters and glycerol diesters; mixtures of glycerol monoesters, glycerol di-esters and glycerol triesters such as caprylic / capric glycerol monoesters and glycerol di-esters; solubilizers and surfactants such as polyethylene glycol, propylene glycol, glycerol, ethanol, polyethoxylated castor oil, poloxamer or polysorbate. In some embodiments, the capsule is a hard capsule. In some embodiments, the capsule is a soft capsule.

[0162] In some embodiments, the hard or soft capsule comprises a compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable excipients. In some embodiments, one or more pharmaceutically acceptable excipients of the hard or soft capsules disclosed herein are water-soluble and / or water-insoluble. Examples of water-soluble excipients include, but are not limited to: dimethylacetamide (DMA), dimethyl sulfoxide (DMSO), ethanol, N-methyl-2-pyrrolidone (NMP), PEG 300, PEG 400, PEG 600, propylene glycol, hydroxypropyl-β-cyclodextrin, sulfobutyl ether-β-cyclodextrin, glycerol, diethylene glycol monoethyl ether (e.g. HP) and phospholipids. Examples of phospholipids include, but are not limited to, hydrogenated soy phosphatidylcholine (HSPC), distearoyl phosphatidylglycerol (DSPG), L-α-dimyristoyl phosphatidylcholine (DMPC) and L-α-dimyristoyl phosphatidylglycerol (DMPG). Examples of water-insoluble excipients include, but are not limited to, beeswax, oleic acid, soy fatty acids, vitamin E, corn oil, mono-di-tri-glycerides, medium-chain C 8-10 glycerol monoesters and glycerol di-esters, propylene glycol dicaprylate / dicaprate, monoglyceride linoleate, monoglyceride oleate, long-chain triglycerides and medium-chain triglycerides. Examples of long-chain triglycerides include, but are not limited to: sesame oil, castor oil, corn oil, cottonseed oil, olive oil, peanut oil, peppermint oil, soybean oil, hydrogenated soybean oil and hydrogenated vegetable oil. Examples of medium-chain triglycerides include, but are not limited to, caprylic / capric triglyceride derived from coconut oil or palm kernel oil.

[0163] In some embodiments, one or more pharmaceutically acceptable excipients of the hard capsules or soft capsules disclosed herein include one or more surfactants. Examples of surfactants include, but are not limited to: d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), polysorbate 20, polysorbate 80, polyoxyl 35 castor oil (e.g., EL), polyoxyl 40 hydrogenated castor oil (e.g., RH 40, RH 60), HS-15, sorbitan monooleate (e.g., 20), PEG 300 caprylic / capric glycerides (e.g., 767), PEG 400 caprylic / capric glycerides (e.g., ), PEG 300 glyceryl oleate (e.g., M-1944CS), PEG 300 glyceryl linoleate (e.g., M-2125CS), PEG 300 glyceryl laurate (e.g., M2130CS), polyoxyl 8 stearate (e.g., PEG 400 monostearate), polyoxyl 40 stearate (e.g., PEG 1750 monostearate), povidone K-90, polyoxyl stearate type I (e.g., 48 / 16), polyglyceryl-3 dioleate, propylene glycol monolaurate type I, propylene glycol monolaurate type II, propylene glycol monocaprylate type II (e.g., Capryol TM 90), propylene glycol monocaprylate type I (e.g., Capryol TM PGMC), lauroyl polyglyceryl ester (e.g., 44 / 14), stearoyl polyglyceryl ester (e.g., 50 / 13), poloxamer 124, poloxamer 188, and poloxamer 407.

[0164] The pharmaceutical compositions of the present disclosure can be in the form of a sterile injectable preparation, such as a solution or a sterile injectable aqueous or oily suspension. The suspension can be formulated according to known techniques using those suitable dispersing or wetting agents and suspending agents that have been mentioned herein. The sterile injectable preparation can also be a sterile injectable solution or suspension in a non-toxic parenterally acceptable diluent or solvent, such as a solution in 1,3-butanediol or prepared in the form of a lyophilized powder. Acceptable vehicles and solvents that can be used include water, Ringer's solution, and isotonic sodium chloride solution. Additionally, sterile fixed oils can conventionally be used as a solvent or a suspending medium. For this purpose, any mild fixed oil can be used, including synthetic mono- or di-glycerides of fatty acids. Additionally, fatty acids such as oleic acid can also be used in the preparation of injectables.

[0165] In some embodiments, the sterile injection preparations disclosed herein can also be sterile injection solutions or suspensions prepared from reconstituted lyophilized powders in a non-toxic parenterally acceptable diluent or solvent, such as a solution in 1,3-butanediol. Acceptable vehicles and solvents that can be used include water, Ringer's solution, and isotonic sodium chloride solution. Additionally, sterile fixed oils can conventionally be used as a solvent or suspending medium. For this purpose, any mild fixed oil can be used, including synthetic mono- or di-glycerides of fatty acids. Additionally, fatty acids such as oleic acid can also be used in the preparation of injectables. Preparations suitable for parenteral administration include aqueous and non-aqueous sterile injection solutions, which can contain antioxidants, buffers, bacteriostatic agents, and solutes (which render the preparation isotonic with the blood of the intended recipient), and aqueous and non-aqueous sterile suspensions (which can include suspending and thickening agents). In certain embodiments, the suspension is a micro-suspension. In certain embodiments, the suspension is a nano-suspension.

[0166] In some embodiments, the pharmaceutical compositions of the present disclosure can be in the form of solution preparations. In some embodiments, the solution comprises N-methyl-2-pyrrolidone (NMP), polyethylene glycol (PEG), water, and / or tetraethylene glycol. In some embodiments, the solution comprises PEG 200, ethanol, and water. In some embodiments, the solution comprises PEG 300 and water. In some embodiments, the amount of water in the solution comprising PEG 300 and water is about 25 w / w%, about 23 w / w%, about 20 w / w%, about 17 w / w%, about 15 w / w%, about 10 w / w%, about 9 w / w%, about 8 w / w%, or about 5 w / w%. In some embodiments, the amount of PEG 300 in the solution comprising PEG 300 and water is about 90 w / w%, about 85 w / w%, about 80 w / w%, about 75 w / w%, about 70 w / w%, about 65 w / w%, about 60 w / w%, about 55 w / w%, about 50 w / w%, or about 45 w / w%. In some embodiments, the solution comprising PEG 300 and water comprises about 85 w / w% of PEG 300 and about 15 w / w% of water. In some embodiments, the solution comprising PEG 300 and water further comprises a base. In some embodiments, the solution comprising PEG 300 and water further comprises an inorganic base. In some embodiments, the inorganic base is sodium hydroxide or sodium ethoxide. In some embodiments, the amount of sodium hydroxide or sodium ethoxide is about 3 w / w%, about 2 w / w%, about 1 w / w%, or about 0.5 w / w%.

[0167] In some embodiments, formulations suitable for parenteral administration (e.g., intramuscular (IM) and subcutaneous (SC) administration) will contain one or more excipients. The excipients should be compatible with the other ingredients in the formulation and physiologically innocuous to its recipient. Examples of suitable excipients are well known to those skilled in the art of parenteral formulations and can be found, for example, in the Handbook of Pharmaceutical Excipients (eds. Rowe, Sheskey & Quinn), 6th Edition, 2009.

[0168] Examples of solubilizing excipients in parenteral formulations (e.g., SC or IM formulations) include, but are not limited to, polysorbates (e.g., polysorbate 20 or 80) and poloxamers (e.g., poloxamer 338, 188, or 207). In some embodiments, parenteral administration (e.g., SC or IM formulations) comprising a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof and a poloxamer are disclosed herein. In some embodiments, the poloxamer is poloxamer 338. In some embodiments, the poloxamer is poloxamer 188. In some embodiments, the amount of poloxamer in the parenteral administration disclosed herein is less than about 5%, such as less than about 3%, about 2%, about 1%, or about 0.5%.

[0169] In certain embodiments, the excipients include N-methyl-2-pyrrolidone (NMP), dimethyl sulfoxide, polyethylene glycol, and / or tetraethylene glycol / tetraethylene glycol.

[0170] Generally, poloxamers are synthetic nonionic triblock linear copolymers having a central hydrophobic chain of polyoxypropylene flanked by two hydrophilic polyoxypropylene chains, in certain cases in a weight ratio of 4:2:4. Thus, in certain embodiments, the compositions disclosed herein include a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof and a block copolymer consisting of one polyoxypropylene chain segment and two hydrophilic polyoxypropylene chain segments. In certain embodiments, the ratio of the polyoxypropylene chain segment to the two hydrophilic polyoxypropylene chain segments is 4:2:4 (hydrophilic polyoxypropylene: polyoxypropylene: hydrophilic polyoxypropylene). Poloxamers are generally considered to have the following structure: where a and b are integers. For example, a is between about 2 and about 130, and b is between about 15 and about 67. For example, the molecular weight of poloxamer 188 should be understood to be about 7680 to about 9510 daltons (where a is about 80 and b is about 27) (e.g., see International Journal of PharmTech Research, Volume 1, Number 2, pages 299 - 303, April - June 2009). In certain cases, the average molecular weight of poloxamer 188 is about 8400 Da. The molecular weight of poloxamer 338 is about 12700 Da to about 17400 Da (where a is about 141 and b is about 44).

[0171] In some embodiments, poloxamer is a synthetic nonionic triblock linear copolymer having a central hydrophobic poly(propylene oxide) (PPO) chain flanked by two poly(ethylene oxide) (PEO) hydrophilic chains, in certain cases in a weight ratio of 4:2:4. Thus, in certain embodiments, the compositions disclosed herein include a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof and a block copolymer consisting of one PPO block and two PEO blocks. In certain embodiments, the ratio of the PPO block to the two PEO blocks is 4:2:4 (PEO:PPO:PEO). Poloxamer is generally understood to have the following structure: where a and b are integers. For example, a ranges from about 2 to about 130 and b ranges from about 15 to about 67. For example, poloxamer 188 is understood to have a molecular weight of from about 7,680 to about 9,510 daltons (where a is about 80 and b is about 27) (see, e.g., International Journal of PharmTech Research, Volume 1, No. 2, pages 299 - 303, April - June 2009). In certain cases, the average molecular weight of poloxamer 188 is about 8,400 daltons. Poloxamer 338 has a molecular weight of from about 12,700 Da to about 17,400 Da (where a is about 141 and b is about 44).

[0172] In some embodiments, the pharmaceutical compositions disclosed herein comprise a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof, poloxamer, and a pharmaceutically acceptable excipient. In certain embodiments, the pharmaceutical compositions disclosed herein comprise a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof, poloxamer 188, and a pharmaceutically acceptable excipient. In some embodiments, the pharmaceutical compositions disclosed herein do not comprise poloxamer. In some embodiments, the pharmaceutical compositions disclosed herein do not comprise poloxamer 188. In some embodiments, the pharmaceutical compositions disclosed herein are solutions comprising a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient. In some embodiments, the pharmaceutical compositions disclosed herein are solutions comprising a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof, poloxamer, and a pharmaceutically acceptable excipient. In some embodiments, the pharmaceutical compositions disclosed herein are solutions comprising a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof, poloxamer 188, and a pharmaceutically acceptable excipient. In some embodiments, the pharmaceutical compositions disclosed herein are solutions that do not comprise poloxamer. In some embodiments, the pharmaceutical compositions disclosed herein are solutions that do not comprise poloxamer 188.

[0173] Examples of excipients in parenteral formulations (e.g., SC or IM formulations) include polyethylene glycol. Generally, polyethylene glycol (PEG) is a polyether having the general formula H-(O-CH 2 -CH 2 )n-OH. In certain embodiments, the PEG can be "capped" with an alkyl group. In those embodiments, the capped PEG has the formula alkyl-(O-CH 2 -CH 2 ) n -O-alkyl (e.g., CH 3 -(O-CH 2 -CH 2 ) n -OCH 3 ). The pharmaceutical compositions of the present disclosure can comprise a PEG having an average molecular weight of from about 100 to about 1000. In some embodiments, the average molecular weight of the PEG in the pharmaceutical composition is from about 100 to about 800. In some embodiments, the average molecular weight of the PEG in the pharmaceutical composition is from about 200 to about 600. In some embodiments, the average molecular weight of the PEG in the pharmaceutical composition is about 400. In some embodiments, the average molecular weight of the PEG in the pharmaceutical composition is about 300. In some embodiments, the average molecular weight of the PEG in the pharmaceutical composition is about 200. In some embodiments of the pharmaceutical composition, PEGs of different molecular weights can be combined to obtain one or more desired properties (e.g., viscosity). Specific examples of PEGs include, but are not limited to, PEG 100, PEG 200, PEG 300, PEG 400, PEG 500, and PEG 600. PEG 100 refers, for example, to polyethylene glycol having an average molecular weight of about 100. As described above, in some embodiments, the pharmaceutical compositions disclosed herein comprising a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof are in solution form.

[0174] In some embodiments, the concentration of the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof in the solutions disclosed herein is from about 50 mg / ml to about 500 mg / ml. In some embodiments, the concentration of the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof in the solutions disclosed herein is from about 75 mg / ml to about 500 mg / ml. In some embodiments, the concentration of the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof in the solutions disclosed herein is from about 50 mg / ml to about 400 mg / ml. In some embodiments, the concentration of the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof in the solutions disclosed herein is from about 50 mg / ml to about 300 mg / ml. In some embodiments, the concentration of the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof in the solutions disclosed herein is from about 75 mg / ml to about 400 mg / ml. In some embodiments, the concentration of the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof in the solutions disclosed herein is from about 75 mg / ml to about 300 mg / ml.

[0175] In some embodiments, the concentration of the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof in the solutions disclosed herein is about 50 mg / ml, about 55 mg / ml, about 60 mg / ml, about 65 mg / ml, about 70 mg / ml, about 75 mg / mL, about 80 mg / mL, about 85 mg / mL, about 90 mg / mL, about 95 mg / mL, about 100 mg / mL, about 105 mg / mL, about 110 mg / mL, about 115 mg / mL, about 120 mg / mL, about 125 mg / mL, about 130 mg / mL, about 135 mg / mL, about 140 mg / mL, about 145 mg / mL, about 150 mg / mL, about 155 mg / mL, about 160 mg / mL, about 165 mg / mL, about 170 mg / mL, about 175 mg / mL, about 180 mg / mL, about 185 mg / mL, about 190 mg / mL, about 195 mg / mL, about 200 mg / mL, about 205 mg / mL, about 210 mg / mL, about 215 mg / mL, about 220 mg / mL, about 225 mg / mL, about 230 mg / mL, about 235 mg / mL, about 240 mg / mL, about 245 mg / mL, about 250 mg / mL, about 255 mg / mL, about 260 mg / mL, about 265 mg / mL, about 270 mg / mL, about 275 mg / mL, about 280 mg / mL, about 285 mg / mL, about 290 mg / mL, about 295 mg / mL, about 300 mg / mL, about 325 mg / mL, about 350 mg / mL, about 375 mg / mL, about 400 mg / mL, about 425 mg / mL, about 450 mg / mL, about 475 mg / mL or about 500 mg / mL. In some embodiments, the concentration of the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof in the solutions disclosed herein is about 50 mg / ml. In some embodiments, the concentration of the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof in the solutions disclosed herein is about 75 mg / ml. In some embodiments, the concentration of the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof in the solutions disclosed herein is about 100 mg / ml. In some embodiments, the concentration of the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof in the solutions disclosed herein is about 125 mg / ml. In some embodiments, the concentration of the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof in the solutions disclosed herein is about 150 mg / ml. In some embodiments, the concentration of the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof in the solutions disclosed herein is about 175 mg / ml.In some embodiments, the concentration of the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof in the solution disclosed herein is about 200 mg / ml. In some embodiments, the concentration of the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof in the solution disclosed herein is about 225 mg / ml. In some embodiments, the concentration of the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof in the solution disclosed herein is about 250 mg / ml. In some embodiments, the concentration of the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof in the solution disclosed herein is about 275 mg / ml. In some embodiments, the concentration of the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof in the solution disclosed herein is about 300 mg / ml. In some embodiments, the concentration of the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof in the solution disclosed herein is about 325 mg / ml. In some embodiments, the concentration of the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof in the solution disclosed herein is about 350 mg / ml. In some embodiments, the concentration of the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof in the solution disclosed herein is about 375 mg / ml. In some embodiments, the concentration of the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof in the solution disclosed herein is about 400 mg / ml. In some embodiments, the concentration of the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof in the solution disclosed herein is about 425 mg / ml. In some embodiments, the concentration of the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof in the solution disclosed herein is about 450 mg / ml. In some embodiments, the concentration of the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof in the solution disclosed herein is about 475 mg / ml. In some embodiments, the concentration of the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof in the solution disclosed herein is about 500 mg / ml.

[0176] In some embodiments, the solutions disclosed herein comprise a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof, PEG 300, and water. In some embodiments, the solutions disclosed herein comprise a compound of formula (Ia) or a pharmaceutically acceptable salt thereof, PEG 300, and water. In some embodiments, the solutions disclosed herein comprise a compound of formula (Ib) or a pharmaceutically acceptable salt thereof, PEG 300, and water. In some embodiments, the solutions disclosed herein comprise the sodium salt of a compound of formula (Ia), PEG 300, and water. In some embodiments, the solutions disclosed herein comprise the trifluoroacetate salt of a compound of formula (Ib), PEG 300, and water. In some embodiments, the solutions disclosed herein comprise a compound of formula (Ib), PEG 300, and water.

[0177] In some embodiments, the solution disclosed herein comprises a compound of formula (Ia), PEG 300, and water. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, and water, the compound of formula (Ia) is from about 50 mg / ml to about 500 mg / ml. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, and water, the concentration of the compound of formula (Ia) is from about 50 mg / ml to about 400 mg / ml. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, and water, the concentration of the compound of formula (Ia) is from about 50 mg / ml to about 300 mg / ml. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, and water, the concentration of the compound of formula (Ia) is from about 75 mg / ml to about 300 mg / ml. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, and water, the concentration of the compound of formula (Ia) is about 50 mg / ml. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, and water, the concentration of the compound of formula (Ia) is about 75 mg / ml. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, and water, the concentration of the compound of formula (Ia) is about 100 mg / ml. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, and water, the concentration of the compound of formula (Ia) is about 125 mg / ml. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, and water, the concentration of the compound of formula (Ia) is about 150 mg / ml. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, and water, the concentration of the compound of formula (Ia) is about 175 mg / mL. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, and water, the concentration of the compound of formula (Ia) is about 200 mg / ml. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, and water, the concentration of the compound of formula (Ia) is about 225 mg / ml. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, and water, the concentration of the compound of formula (Ia) is about 250 mg / ml. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, and water, the concentration of the compound of formula (Ia) is about 275 mg / ml. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, and water, the concentration of the compound of formula (Ia) is about 300 mg / ml. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, and water, the concentration of the compound of formula (Ia) is about 325 mg / mL.In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, and water, the concentration of the compound of formula (Ia) is about 350 mg / ml. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, and water, the concentration of the compound of formula (Ia) is about 375 mg / ml. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, and water, the concentration of the compound of formula (Ia) is about 400 mg / ml. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, and water, the concentration of the compound of formula (Ia) is about 425 mg / ml. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, and water, the concentration of the compound of formula (Ia) is about 450 mg / ml. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, and water, the concentration of the compound of formula (Ia) is about 475 mg / ml. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, and water, the concentration of the compound of formula (Ia) is about 500 mg / ml.

[0178] In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, and water, the amount of water is from about 5 w / w% to about 15 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, and water, the amount of water is from about 5 w / w% to about 10 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, and water, the amount of water is from about 8 w / w% to about 12 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, and water, the amount of water is from about 9 w / w% to about 10 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, and water, the amount of water is about 8.0 w / w%, about 8.1 w / w%, about 8.2 w / w%, about 8.3 w / w%, about 8.4 w / w%, about 8.5 w / w%, about 8.6 w / w%, about 8.7 w / w%, about 8.8 w / w%, about 8.9 w / w%, about 9.0 w / w%, about 9.1 w / w%, about 9.2 w / w%, about 9.3 w / w%, about 9.4 w / w%, about 9.5 w / w%, about 9.6 w / w%, about 9.7 w / w%, about 9.8 w / w%, about 9.9 w / w%, about 10.0 w / w%, about 10.1 w / w%, about 10.2 w / w%, about 10.3 w / w%, about 10.4 w / w%, about 10.5 w / w%, about 10.6 w / w%, about 10.7 w / w%, about 10.8 w / w%, about 10.9 w / w%, about 11.0 w / w%, about 11.1 w / w%, about 11.2 w / w%, about 11.3 w / w%, about 11.4 w / w%, about 11.5 w / w%, about 11.6 w / w%, about 11.7 w / w%, about 11.8 w / w%, about 11.9 w / w%, or about 12.0 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, and water, the amount of water is about 9.0 w / w%, about 9.1 w / w%, about 9.2 w / w%, about 9.3 w / w%, about 9.4 w / w%, about 9.5 w / w%, about 9.6 w / w%, about 9.7 w / w%, about 9.8 w / w%, about 9.9 w / w%, or about 10.0 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, and water, the amount of water is about 9.5 w / w%, about 9.6 w / w%, about 9.7 w / w%, about 9.8 w / w%, about 9.9 w / w%, or about 10.0 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, and water, the amount of water is about 9.8 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, and water, the amount of water is about 10 w / w%.

[0179] In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, and water, the amount of PEG 300 is from about 50 w / w% to about 85 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, and water, the amount of PEG 300 is from about 60 w / w% to about 80 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, and water, the amount of PEG 300 is from about 60 w / w% to about 70 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, and water, the amount of PEG 300 is about 50 w / w%, about 55 w / w%, about 60 w / w%, about 65 w / w%, about 70 w / w%, about 75 w / w%, about 80 w / w%, or about 85 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, and water, the amount of PEG 300 is about 65 w / w%. In some embodiments, the amount of PEG 300 in a solution comprising a compound of formula (Ia), PEG 300, and water is about 65.0 w / w%.

[0180] In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, and water, the amount of the compound of formula (Ia) is from about 15 w / w% to about 35 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, and water, the amount of the compound of formula (Ia) is from about 20 w / w% to about 35 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, and water, the amount of the compound of formula (Ia) is from about 24 w / w% to about 26 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, and water, the amount of the compound of formula (Ia) is about 24.5 w / w%, about 24.6 w / w%, about 24.7 w / w%, about 24.8 w / w%, about 24.9 w / w%, about 25.0 w / w%, about 25.1 w / w%, about 25.2 w / w%, about 25.3 w / w%, about 25.4 w / w%, or about 25.5 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, and water, the amount of the compound of formula (Ia) is about 25 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, and water, the amount of the compound of formula (Ia) is about 25.2 w / w%.

[0181] In some embodiments, the solution disclosed herein comprises from about 5 w / w% to about 15 w / w% water, from about 50 w / w% to about 85 w / w% PEG 300, and from about 15 w / w% to about 35 w / w% of the compound of formula (Ia). In some embodiments, the solution comprises from about 5 w / w% to about 10 w / w% water, from about 60 w / w% to about 80 w / w% PEG 300, and from about 20 w / w% to about 35 w / w% of the compound of formula (Ia). In some embodiments, the solution comprises from about 8 w / w% to about 12 w / w% water, from about 60 w / w% to about 70 w / w% PEG 300, and from about 15 w / w% to about 35 w / w% of the compound of formula (Ia). In some embodiments, the solution comprises from about 9 w / w% to about 10 w / w% water, from about 60 w / w% to about 70 w / w% PEG 300, and from about 24 w / w% to about 26 w / w% of the compound of formula (Ia). In some embodiments, the solution comprises about 9.8 w / w% water, about 65.0 w / w% PEG 300, and about 25.2 w / w% of the compound of formula (Ia). In some embodiments, the solution comprises about 10 w / w% water, about 65.0 w / w% PEG 300, and about 25 w / w% of the compound of formula (Ia).

[0182] In some embodiments, the solution disclosed herein comprises the sodium salt of the compound of formula (Ia), PEG 300, and water. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, and water, the concentration of the compound of formula (Ia) is from about 50 mg / ml to about 500 mg / ml. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, and water, the concentration of the compound of formula (Ia) is from about 50 mg / ml to about 300 mg / ml. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, and water, the concentration of the compound of formula (Ia) is from about 75 mg / ml to about 300 mg / ml. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, and water, the concentration of the compound of formula (Ia) is about 50 mg / ml. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, and water, the concentration of the compound of formula (Ia) is about 75 mg / ml. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, and water, the concentration of the compound of formula (Ia) is about 100 mg / ml. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, and water, the concentration of the compound of formula (Ia) is about 125 mg / ml. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, and water, the concentration of the compound of formula (Ia) is about 150 mg / ml. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, and water, the concentration of the compound of formula (Ia) is about 175 mg / ml. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, and water, the concentration of the compound of formula (Ia) is about 200 mg / ml. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, and water, the concentration of the compound of formula (Ia) is about 225 mg / ml. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, and water, the concentration of the compound of formula (Ia) is about 250 mg / ml. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, and water, the concentration of the compound of formula (Ia) is about 275 mg / ml. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, and water, the concentration of the compound of formula (Ia) is about 300 mg / ml. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, and water, the concentration of the compound of formula (Ia) is about 325 mg / ml.In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, and water, the concentration of the compound of formula (Ia) is about 350 mg / ml. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, and water, the concentration of the compound of formula (Ia) is about 375 mg / ml. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, and water, the concentration of the compound of formula (Ia) is about 400 mg / ml. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, and water, the concentration of the compound of formula (Ia) is about 425 mg / ml. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, and water, the concentration of the compound of formula (Ia) is about 450 mg / ml. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, and water, the concentration of the compound of formula (Ia) is about 475 mg / ml. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, and water, the concentration of the compound of formula (Ia) is about 500 mg / ml.

[0183] In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, and water, the amount of water is from about 10 w / w% to about 40 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, and water, the amount of water is from about 15 w / w% to about 35 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, and water, the amount of water is from about 20 w / w% to about 30 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, and water, the amount of water is from about 21 w / w% to about 29 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, and water, the amount of water is from about 23.4 w / w% to about 27.5 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, and water, the amount of water is from about 23.41 w / w% to about 27.47 w / w%.In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, and water, the amount of water is about 22.0 w / w%, about 22.1 w / w%, about 22.2 w / w%, about 22.3 w / w%, about 22.4 w / w%, about 22.5 w / w%, about 22.6 w / w%, about 22.7 w / w%, about 22.8 w / w%, about 22.9 w / w%, about 23.0 w / w%, about 23.1 w / w%, about 23.2 w / w%, about 23.3 w / w%, about 23.4 w / w%, about 23.5 w / w%, about 23.6 w / w%, about 23.7 w / w%, about 23.8 w / w%, about 23.9 w / w%, about 24.0 w / w%, about 24.1 w / w%, about 24.2 w / w%, about 24.3 w / w%, about 24.4 w / w%, about 24.5 w / w%, about 24.6 w / w%, about 24.7 w / w%, about 24.8 w / w%, about 24.9 w / w%, about 25.0 w / w%, about 25.1 w / w%, about 25.2 w / w%, about 25.3 w / w%, about 25.4 w / w%, about 25.5 w / w%, about 25.6 w / w%, about 25.7 w / w%, about 25.8 w / w%, about 25.9 w / w%, about 26.0 w / w%, about 26.1 w / w%, about 26.2 w / w%, about 26.3 w / w%, about 26.4 w / w%, about 26.5 w / w%, about 26.6 w / w%, about 26.7 w / w%, about 26.8 w / w%, about 26.9 w / w%, about 27.0 w / w%, about 27.1 w / w%, about 27.2 w / w%, about 27.3 w / w%, about 27.4 w / w%, about 27.5 w / w%, about 27.6 w / w%, about 27.7 w / w%, about 27.8 w / w%, about 27.9 w / w%, about 28.0 w / w%, about 28.1 w / w%, about 28.2 w / w%, about 28.3 w / w%, about 28.4 w / w%, about 28.5 w / w%, about 28.6 w / w%, about 28.7 w / w%, about 28.8 w / w%, about 28.9 w / w%, or about 29.0 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, and water, the amount of water is about 23.4 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, and water, the amount of water is about 23.41 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, and water, the amount of water is about 27.47 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, and water, the amount of water is about 27.5 w / w%.

[0184] In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, and water, the amount of PEG 300 is from about 35 w / w% to about 75 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, and water, the amount of PEG 300 is from about 45 w / w% to about 65 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, and water, the amount of PEG 300 is from about 48 w / w% to about 60 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, and water, the amount of PEG 300 is from about 50 w / w% to about 59 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, and water, the amount of PEG 300 is from about 50.1 w / w% to about 58.8 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, and water, the amount of PEG 300 is from about 50.13 w / w% to about 58.84 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, and water, the amount of PEG 300 is about 45 w / w%, about 46 w / w%, about 47 w / w%, 48 w / w%, about 49 w / w%, about 50 w / w%, about 51 w / w%, about 52 w / w%, about 53 w / w%, about 54 w / w%, about 55 w / w%, about 56 w / w%, about 57 w / w%, about 58 w / w%, about 59 w / w%, about 60 w / w%, about 61 w / w%, about 62 w / w%, about 63 w / w%, about 64 w / w% or about 65 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, and water, the amount of PEG 300 is about 50.1 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, and water, the amount of PEG 300 is about 50.13 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, and water, the amount of PEG 300 is about 58.8 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, and water, the amount of PEG 300 is about 58.84 w / w%.

[0185] In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, and water, the amount of the sodium salt of the compound of formula (Ia) is from about 5 w / w% to about 35 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, and water, the amount of the sodium salt of the compound of formula (Ia) is from about 10 w / w% to about 30 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, and water, the amount of the sodium salt of the compound of formula (Ia) is from about 11 w / w% to about 28 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, and water, the amount of the sodium salt of the compound of formula (Ia) is from about 13 w / w% to about 27 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, and water, the amount of the sodium salt of the compound of formula (Ia) is from about 13.69 w / w% to about 26.46 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, and water, the amount of the sodium salt of the compound of formula (Ia) is from about 13.7 w / w% to about 26.5 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, and water, the amount of the sodium salt of the compound of formula (Ia) is about 13.0 w / w%, about 13.1 w / w%, about 13.2 w / w%, about 13.3 w / w%, about 13.4 w / w%, about 13.5 w / w%, about 13.6 w / w%, about 13.7 w / w%, about 13.8 w / w%, about 13.9 w / w%, about 14.0 w / w%, about 14.1 w / w%, about 14.2 w / w%, about 14.3 w / w%, about 14.4 w / w%, about 14.5 w / w%, about 14.6 w / w%, about 14.7 w / w%, about 14.8 w / w%, about 14.9 w / w%, about 15.0 w / w%, about 15.1 w / w%, about 15.2 w / w%, about 15.3 w / w%, about 15.4 w / w%, about 15.5 w / w%, about 15.6 w / w%, about 15.7 w / w%, about 15.8 w / w%, about 15.9 w / w%, about 16.0 w / w%, about 16.1 w / w%, about 16.2 w / w%, about 16.3 w / w%, about 16.4 w / w%, about 16.5 w / w%, about 16.6 w / w%, about 16.7 w / w%, about 16.8 w / w%, about 16.9 w / w%, about 17.0 w / w%, about 17.1 w / w%, about 17.2 w / w%, about 17.3 w / w%, about 17.4 w / w%, about 17.5 w / w%, about 17.6 w / w%, about 17.7 w / w%, about 17.8 w / w%, about 17.9 w / w%, about 18.0 w / w%, about 18.1 w / w%, about 18.2 w / w%, about 18.3 w / w%, about 18.4 w / w%, about 18.5 w / w%, about 18.6 w / w%, about 18.7 w / w%, about 18.8 w / w%, about 18.9 w / w%, about 19.0 w / w%, about 19.1 w / w%, about 19.2 w / w%, about 19.3 w / w%, about 19.4 w / w%, about 19.5 w / w%, about 19.6 w / w%, about 19.7 w / w%, about 19.8 w / w%, about 19.9 w / w%, about 20.0 w / w%, about 21.1 w / w%, about 21.2 w / w%, about 21.3 w / w%, about 21.4 w / w%, about 21.5 w / w%, about 21.6 w / w%, about 21.7 w / w%, about 21.8 w / w%, about 21.9 w / w%, about 22.0 w / w%, about 22.1 w / w%, about 22.2 w / w%, about 22.3 w / w%, about 22.4 w / w%, about 22.5 w / w%, about 22.6 w / w%, about 22.7 w / w%, about 22.8 w / w%, about 22.9 w / w%, about 23.0 w / w%, about 23.1 w / w%, about 23.2 w / w%, about 23.3 w / w%, about 23.4 w / w%, about 23.5 w / w%, about 23.6 w / w%, about 23.7 w / w%, about 23.8 w / w%, about 23.9 w / w%, about 24.0 w / w%, about 24.1 w / w%, about 24.2 w / w%, about 24.3 w / w%, about 24.4 w / w%, about 24.5 w / w%, about 24.6 w / w%, about 24.7 w / w%, about 24.8 w / w%, about 24.9 w / w%, about 25.0 w / w%, about 25.1 w / w%, about 25.2 w / w%, about 25.3 w / w%, about 25.4 w / w%, about 25.5 w / w%, about 25.6 w / w%, about 25.7 w / w%, about 25.8 w / w%, about 25.9 w / w%, about 26.0 w / w%, about 26.1 w / w%, about 26.2 w / w%, about 26.3 w / w%, about 26.4 w / w%, about 26.5 w / w%, about 26.6 w / w%, about 26.7 w / w%, about 26.8 w / w%, about 26.9 w / w%, about 27.0 w / w%, about 27.1 w / w%, about 27.2 w / w%, about 27.3 w / w%, about 27.4 w / w%, about 27.5 w / w%, about 27.6 w / w%, about 27.7 w / w%, about 27.8 w / w%, about 27.9 w / w%, about 28.0 w / w%, about 28.1 w / w%, about 28.2 w / w%, about 28.3 w / w%, about 28.4 w / w%, about 28.5 w / w%, about 28.6 w / w%, about 28.7 w / w%, about 28.8 w / w%, about 28.9 w / w% or about 29.0 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, and water, the amount of the sodium salt of the compound of formula (Ia) is about 13.69 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, and water, the amount of the sodium salt of the compound of formula (Ia) is about 13.7 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, and water, the amount of the sodium salt of the compound of formula (Ia) is about 26.46 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, and water, the amount of the sodium salt of the compound of formula (Ia) is about 26.5 w / w%.

[0186] In some embodiments, the solution disclosed herein comprises from about 10 w / w% to about 40 w / w% water, from about 35 w / w% to about 75 w / w% PEG 300, and from about 5 w / w% to about 35 w / w% sodium salt of the compound of formula (Ia). In some embodiments, the solution comprises from about 15 w / w% to about 35 w / w% water, from about 45 w / w% to about 65 w / w% PEG 300, and from about 10 w / w% to about 30 w / w% sodium salt of the compound of formula (Ia). In some embodiments, the solution comprises from about 20 w / w% to about 30 w / w% water, from about 48 w / w% to about 60 w / w% PEG 300, and from about 11 w / w% to about 28 w / w% sodium salt of the compound of formula (Ia). In some embodiments, the solution comprises from about 21 w / w% to about 29 w / w% water, from about 50 w / w% to about 59 w / w% PEG 300, and from about 13 w / w% to about 27 w / w% sodium salt of the compound of formula (Ia). In some embodiments, the solution comprises from about 23.4 w / w% to about 27.5 w / w% water, from about 50.1 w / w% to about 58.8 w / w% PEG 300, and from about 13.7 w / w% to about 26.5 w / w% sodium salt of the compound of formula (Ia). In some embodiments, the solution comprises from about 23.41 w / w% to about 27.47 w / w% water, from about 50.13 w / w% to about 58.84 w / w% PEG 300, and from about 13.69 w / w% to about 26.46 w / w% sodium salt of the compound of formula (Ia). In some embodiments, the solution comprises about 27.5 w / w% water, about 58.8 w / w% PEG 300, and about 13.7 w / w% sodium salt of the compound of formula (Ia). In some embodiments, the solution comprises about 27.47 w / w% water, about 58.84 w / w% PEG 300, and about 13.69 w / w% sodium salt of the compound of formula (Ia). In some embodiments, the solution comprises about 23.4 w / w% water, about 50.1 w / w% PEG 300, and about 26.5 w / w% sodium salt of the compound of formula (Ia). In some embodiments, the solution comprises about 23.41 w / w% water, about 50.13 w / w% PEG 300, and about 26.46 w / w% sodium salt of the compound of formula (Ia).

[0187] In some embodiments, the solution disclosed herein comprises a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof, PEG 300, poloxamer 188, and water. In some embodiments, the solution disclosed herein comprises a compound of formula (Ia) or a pharmaceutically acceptable salt thereof, PEG 300, poloxamer 188, and water. In some embodiments, the solution disclosed herein comprises a compound of formula (Ib) or a pharmaceutically acceptable salt thereof, PEG 300, poloxamer 188, and water. In some embodiments, the solution disclosed herein comprises a compound of formula (Ia), PEG 300, poloxamer 188, and water. In some embodiments, the solution disclosed herein comprises the trifluoroacetate salt of a compound of formula (Ib), PEG 300, poloxamer 188, and water. In some embodiments, the solution disclosed herein comprises a compound of formula (Ib), PEG 300, poloxamer 188, and water.

[0188] In some embodiments, the solution disclosed herein comprises the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the concentration of the compound of formula (Ia) is from about 50 mg / ml to about 500 mg / ml. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the concentration of the compound of formula (Ia) is from about 50 mg / ml to about 400 mg / ml. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the concentration of the compound of formula (Ia) is from about 50 mg / ml to about 300 mg / ml. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the concentration of the compound of formula (Ia) is from about 75 mg / ml to about 300 mg / ml. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the concentration of the compound of formula (Ia) is about 50 mg / mL. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the concentration of the compound of formula (Ia) is about 75 mg / ml. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the concentration of the compound of formula (Ia) is about 100 mg / ml. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the concentration of the compound of formula (Ia) is about 125 mg / ml. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the concentration of the compound of formula (Ia) is about 150 mg / mL. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the concentration of the compound of formula (Ia) is about 175 mg / ml. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the concentration of the compound of formula (Ia) is about 200 mg / ml. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the concentration of the compound of formula (Ia) is about 225 mg / ml. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the concentration of the compound of formula (Ia) is about 250 mg / mL.In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the concentration of the compound of formula (Ia) is about 275 mg / mL. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the concentration of the compound of formula (Ia) is about 300 mg / ml. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the concentration of the compound of formula (Ia) is about 325 mg / ml. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the concentration of the compound of formula (Ia) is about 350 mg / ml. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the concentration of the compound of formula (Ia) is about 375 mg / ml. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the concentration of the compound of formula (Ia) is about 400 mg / ml. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the concentration of the compound of formula (Ia) is about 425 mg / ml. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the concentration of the compound of formula (Ia) is about 450 mg / ml. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the concentration of the compound of formula (Ia) is about 475 mg / ml. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the concentration of the compound of formula (Ia) is about 500 mg / ml.

[0189] In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of water is from about 10 w / w% to about 45 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of water is from about 15 w / w% to about 35 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of water is from about 20 w / w% to about 35 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of water is from about 20 w / w% to about 31 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of water is from about 21.9 w / w% to about 30.1 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of water is from about 21.87 w / w% to 30.07 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of water is about 19.0 w / w%, about 19.1 w / w%, about 19.2 w / w%, about 19.3 w / w%, about 19.4 w / w%, about 19.5 w / w%, about 19.6 w / w%, about 19.7 w / w%, about 19.8 w / w%, about 19.9 w / w%, about 20.0 w / w%, about 20.1 w / w%, about 20.2 w / w%, about 20.3 w / w%, about 20.4 w / w%, about 20.5 w / w%, about 20.6 w / w%, about 20.7 w / w%, about 20.8 w / w%, about 20.9 w / w%, about 21.0 w / w%, about 21.1 w / w%, about 21.2 w / w%, about 21.3 w / w%, about 21.4 w / w%, about 21.5 w / w%, about 21.6 w / w%, about 21.7 w / w%, about 21.8 w / w%, about 21.9 w / w%, about 22.0 w / w%, about 22.1 w / w%, about 22.2 w / w%, about 22.3 w / w%, about 22.4 w / w%, about 22.5 w / w%, about 22.6 w / w%, about 22.7 w / w%, about 22.8 w / w%, about 22.9 w / w%, about 23.0 w / w%, about 23.1 w / w%, about 23.2 w / w%, about 23.3 w / w%, about 23.4 w / w%, about 23.5 w / w%, about 23.6 w / w%, about 23.7 w / w%, about 23.8 w / w%, about 23.9 w / w%, about 24.0 w / w%, about 24.1 w / w%, about 24.2 w / w%, about 24.3 w / w%, about 24.4 w / w%, about 24.5 w / w%, about 24.6 w / w%, about 24.7 w / w%, about 24.8 w / w%, about 24.9 w / w%, about 25.0 w / w%, about 25.1 w / w%, about 25.2 w / w%, about 25.3 w / w%, about 25.4 w / w%, about 25.5 w / w%, about 25.6 w / w%, about 25.7 w / w%, about 25.8 w / w%, about 25.9 w / w%, about 26.0 w / w%, about 26.1 w / w%, about 26.2 w / w%, about 26.3 w / w%, about 26.4 w / w%, about 26.5 w / w%, about 26.6 w / w%, about 26.7 w / w%, about 26.8 w / w%, about 26.9 w / w%, about 27.0 w / w%, about 27.1 w / w%, about 27.2 w / w%, about 27.3 w / w%, about 27.4 w / w%, about 27.5 w / w%, about 27.6 w / w%, about 27.7 w / w%, about 27.8 w / w%, about 27.9 w / w%, about 28.0 w / w%, about 28.1 w / w%, about 28.2 w / w%, about 28.3 w / w%, about 28.4 w / w%, about 28.5 w / w%, about 28.6 w / w%, about 28.7 w / w%, about 28.8 w / w%, about 28.9 w / w%, about 29.0 w / w%, about 29.1 w / w%, about 29.2 w / w%, about 29.3 w / w%, about 29.4 w / w%, about 29.5 w / w%, about 29.6 w / w%, about 29.7 w / w%, about 29.8 w / w%, about 29.9 w / w%, about 30.0 w / w%, about 30.1 w / w%, about 30.2 w / w%, about 30.3 w / w%, about 30.4 w / w%, about 30.5 w / w%, about 30.6 w / w%, about 30.7 w / w%, about 30.8 w / w%, about 30.9 w / w%, about 31.0 w / w%, about 31.1 w / w%, about 31.2 w / w%, about 31.3 w / w%, about 31.4 w / w%, about 31.5 w / w%, about 31.6 w / w%, about 31.7 w / w%, about 31.8 w / w%, about 31.9 w / w%, about 32.0 w / w%, about 32.1 w / w%, about 32.2 w / w%, about 32.3 w / w%, about 32.4 w / w%, about 32.5 w / w%, about 32.6 w / w%, about 32.7 w / w%, about 32.8 w / w%, about 32.9 w / w% or about 33.0 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of water is about 21.87 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of water is about 21.9 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of water is about 26.68 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of water is about 26.7 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of water is about 27.5 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of water is about 27.51 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of water is about 28.36 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of water is about 28.4 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of water is about 29.2 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of water is about 29.21 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of water is about 30.07 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of water is about 30.1 w / w%.

[0190] In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of PEG 300 is from about 30 w / w% to about 85 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of PEG 300 is from about 35 w / w% to about 75 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of PEG 300 is from about 40 w / w% to about 70 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of PEG 300 is from about 45 w / w% to about 68 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of PEG 300 is from about 46.8 w / w% to about 64.4 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of PEG 300 is from about 46.84 w / w% to about 64.40 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of PEG 300 is about 40 w / w%, about 41 w / w%, about 42 w / w%, about 43 w / w%, about 44 w / w%, about 45 w / w%, about 46 w / w%, about 47 w / w%, about 48 w / w%, about 49 w / w%, about 50 w / w%, about 51 w / w%, about 52 w / w%, about 53 w / w%, about 54 w / w%, about 55 w / w%, about 56 w / w%, about 57 w / w%, about 58 w / w%, about 59 w / w%, about 60 w / w%, about 61 w / w%, about 62 w / w%, about 63 w / w%, about 64 w / w%, about 65 w / w%, about 66 w / w%, about 67 w / w%, about 68 w / w%, about 69 w / w%, or about 70 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of PEG 300 is about 46.8 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of PEG 300 is about 46.84 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of PEG 300 is about 57.1 w / w%.In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of PEG 300 is about 57.13 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of PEG 300 is about 58.9 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of PEG 300 is about 58.92 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of PEG 300 is about 60.7 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of PEG 300 is about 60.73 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of PEG 300 is about 62.55 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of PEG 300 is about 62.6 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of PEG 300 is about 64.4 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of PEG 300 is about 64.40 w / w%.

[0191] In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of the sodium salt of the compound of formula (Ia) is from about 0.5 w / w% to about 40 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of the sodium salt of the compound of formula (Ia) is from about 1 w / w% to about 35 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of the sodium salt of the compound of formula (Ia) is from about 1 w / w% to about 30 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of the sodium salt of the compound of formula (Ia) is from about 3 w / w% to about 28 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of the sodium salt of the compound of formula (Ia) is from about 4 w / w% to about 27 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of the sodium salt of the compound of formula (Ia) is from about 4.68 w / w% to about 26.47 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of the sodium salt of the compound of formula (Ia) is from about 4.7 w / w% to about 26.5 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of the sodium salt of the compound of formula (Ia) is about 3.0 w / w%, about 3.1 w / w%, about 3.2 w / w%, about 3.3 w / w%, about 3.4 w / w%, about 3.5 w / w%, about 3.6 w / w%, about 3.7 w / w%, about 3.8 w / w%, about 3.9 w / w%, about 4.0 w / w%, about 4.1 w / w%, about 4.2 w / w%, about 4.3 w / w%, about 4.4 w / w%, about 4.5 w / w%, about 4.6 w / w%, about 4.7 w / w%, about 4.8 w / w%, about 4.9 w / w%, about 5.0 w / w%, about 5.1 w / w%, about 5.2 w / w%, about 5.3 w / w%, about 5.4 w / w%, about 5.5 w / w%, about 5.6 w / w%, about 5.7 w / w%, about 5.8 w / w%, about 5.9 w / w%, about 6.0 w / w%, about 6.1 w / w%, about 6.2 w / w%, about 6.3 w / w%, about 6.4 w / w%, about 6.5 w / w%, about 6.6 w / w%, about 6.7 w / w%, about 6.8 w / w%, about 6.9 w / w%, about 7.0 w / w%, about 7.1 w / w%, about 7.2 w / w%, about 7.3 w / w%, about 7.4 w / w%, about 7.5 w / w%, about 7.6 w / w%, about 7.7 w / w%, about 7.8 w / w%, about 7.9 w / w%, about 8.0 w / w%, about 8.1 w / w%, about 8.2 w / w%, about 8.3 w / w%, about 8.4 w / w%, about 8.5 w / w%, about 8.6 w / w%, about 8.7 w / w%, about 8.8 w / w%, about 8.9 w / w%, about 9.0 w / w%, about 9.1 w / w%, about 9.2 w / w%, about 9.3 w / w%, about 9.4 w / w%, about 9.5 w / w%, about 9.6 w / w%, about 9.7 w / w%, about 9.8 w / w%, about 9.9 w / w%, about 10.0 w / w%, about 10.1 w / w%, about 10.2 w / w%, about 10.3 w / w%, about 10.4 w / w%, about 10.5 w / w%, about 10.6 w / w%, about 10.7 w / w%, about 10.8 w / w%, about 10.9 w / w%, about 11.0 w / w%, about 11.1 w / w%, about 11.2 w / w%, about 11.3 w / w%, about 11.4 w / w%, about 11.5 w / w%, about 11.6 w / w%, about 11.7 w / w%, about 11.8 w / w%, about 11.9 w / w%, about 12.0 w / w%, about 12.1 w / w%, about 12.2 w / w%, about 12.3 w / w%, about 12.4 w / w%, about 12.5 w / w%, about 12.6 w / w%, about 12.7 w / w%, about 12.8 w / w%, about 12.9 w / w%, about 13.0 w / w%, about 13.1 w / w%, about 13.2 w / w%, about 13.3 w / w%, about 13.4 w / w%, about 13.5 w / w%, about 13.6 w / w%, about 13.7 w / w%, about 13.8 w / w%, about 13.9 w / w%, about 14.0 w / w%, about 14.1 w / w%, about 14.2 w / w%, about 14.3 w / w%, about 14.4 w / w%, about 14.5 w / w%, about 14.6 w / w%, about 14.7 w / w%, about 14.8 w / w%, about 14.9 w / w%, about 15.0 w / w%, about 15.1 w / w%, about 15.2 w / w%, about 15.3 w / w%, about 15.4 w / w%, about 15.5 w / w%, about 15.6 w / w%, about 15.7 w / w%, about 15.8 w / w%, about 15.9 w / w%, about 16.0 w / w%, about 16.1 w / w%, about 16.2 w / w%, about 16.3 w / w%, about 16.4 w / w%, about 16.5 w / w%, about 16.6 w / w%, about 16.7 w / w%, about 16.8 w / w%, about 16.9 w / w%, about 17.0 w / w%, about 17.1 w / w%, about 17.2 w / w%, about 17.3 w / w%, about 17.4 w / w%, about 17.5 w / w%, about 17.6 w / w%, about 17.7 w / w%, about 17.8 w / w%, about 17.9 w / w%, about 18.0 w / w%, about 18.1 w / w%, about 18.2 w / w%, about 18.3 w / w%, about 18.4 w / w%, about 18.5 w / w%, about 18.6 w / w%, about 18.7 w / w%, about 18.8 w / w%, about 18.9 w / w%, about 19.0 w / w%, about 19.1 w / w%, about 19.2 w / w%, about 19.3 w / w%, about 19.4 w / w%, about 19.5 w / w%, about 19.6 w / w%, about 19.7 w / w%, about 19.8 w / w%, about 19.9 w / w%, about 20.0 w / w%, about 20.1 w / w%, about 20.2 w / w%, about 20.3 w / w%, about 20.4 w / w%, about 20.5 w / w%, about 20.6 w / w%, about 20.7 w / w%, about 20.8 w / w%, about 20.9 w / w%, about 21.0 w / w%, about 21.1 w / w%, about 21.2 w / w%, about 21.3 w / w%, about 21.4 w / w%, about 21.5 w / w%, about 21.6 w / w%, about 21.7 w / w%, about 21.8 w / w%, about 21.9 w / w%, about 22.0 w / w%, about 22.1 w / w%, about 22.2 w / w%, about 22.3 w / w%, about 22.4 w / w%, about 22.5 w / w%, about 22.6 w / w%, about 22.7 w / w%, about 22.8 w / w%, about 22.9 w / w%, about 23.0 w / w%, about 23.1 w / w%, about 23.2 w / w%, about 23.3 w / w%, about 23.4 w / w%, about 23.5 w / w%, about 23.6 w / w%, about 23.7 w / w%, about 23.8 w / w%, about 23.9 w / w%, about 24.0 w / w%, about 24.1 w / w%, about 24.2 w / w%, about 24.3 w / w%, about 24.4 w / w%, about 24.5 w / w%, about 24.6 w / w%, about 24.7 w / w%, about 24.8 w / w%, about 24.9 w / w%, about 25.0 w / w%, about 25.1 w / w%, about 25.2 w / w%, about 25.3 w / w%, about 25.4 w / w%, about 25.5 w / w%, about 25.6 w / w%, about 25.7 w / w%, about 25.8 w / w%, about 25.9 w / w%, about 26.0 w / w%, about 26.1 w / w%, about 26.2 w / w%, about 26.3 w / w%, about 26.4 w / w%, about 26.5 w / w%, about 26.6 w / w%, about 26.7 w / w%, about 26.8 w / w%, about 26.9 w / w%, about 27.0 w / w%, about 27.1 w / w%, about 27.2 w / w%, about 27.3 w / w%, about 27.4 w / w%, about 27.5 w / w%, about 27.6 w / w%, about 27.7 w / w%, about 27.8 w / w%, about 27.9 w / w%, about 28.0 w / w%, about 28.1 w / w%, about 28.2 w / w%, about 28.3 w / w%, about 28.4 w / w%, about 28.5 w / w%, about 28.6 w / w%, about 28.7 w / w%, about 28.8 w / w%, about 28.9 w / w% or about 29.0 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of the sodium salt of the compound of formula (Ia) is about 4.68 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of the sodium salt of the compound of formula (Ia) is about 4.7 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of the sodium salt of the compound of formula (Ia) is about 6.97 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of the sodium salt of the compound of formula (Ia) is about 7 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of the sodium salt of the compound of formula (Ia) is about 9.2 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of the sodium salt of the compound of formula (Ia) is about 9.23 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of the sodium salt of the compound of formula (Ia) is about 11.48 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of the sodium salt of the compound of formula (Ia) is about 11.5 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of the sodium salt of the compound of formula (Ia) is about 13.7 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of the sodium salt of the compound of formula (Ia) is about 13.70 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of the sodium salt of the compound of formula (Ia) is about 26.47 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of the sodium salt of the compound of formula (Ia) is about 26.5 w / w%.

[0192] In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of poloxamer 188 is from about 0.1 w / w% to about 10 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of poloxamer 188 is from about 0.3 w / w% to about 8 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of poloxamer 188 is from about 0.5 w / w% to about 7 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of poloxamer 188 is from about 0.6 w / w% to about 7 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of poloxamer 188 is from about 0.85 w / w% to about 4.82 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of poloxamer 188 is from about 0.9 w / w% to about 4.8 w / w%.In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of poloxamer 188 is about 0.5 w / w%, about 0.6 w / w%, about 0.7 w / w%, about 0.8 w / w%, about 0.9 w / w%, about 1.0 w / w%, about 1.1 w / w%, about 1.2 w / w%, about 1.3 w / w%, about 1.4 w / w%, about 1.5 w / w%, about 1.6 w / w%, about 1.7 w / w%, about 1.8 w / w%, about 1.9 w / w%, about 2.0 w / w%, about 2.1 w / w%, about 2.2 w / w%, about 2.3 w / w%, about 2.4 w / w%, about 2.5 w / w%, about 2.6 w / w%, about 2.7 w / w%, about 2.8 w / w%, about 2.9 w / w%, about 3.0 w / w%, about 3.1 w / w%, about 3.2 w / w%, about 3.3 w / w%, about 3.4 w / w%, about 3.5 w / w%, about 3.6 w / w%, about 3.7 w / w%, about 3.8 w / w%, about 3.9 w / w%, about 4.0 w / w%, about 4.1 w / w%, about 4.2 w / w%, about 4.3 w / w%, about 4.4 w / w%, about 4.5 w / w%, about 4.6 w / w%, about 4.7 w / w%, about 4.8 w / w%, about 4.9 w / w%, about 5.0 w / w%, about 5.1 w / w%, about 5.2 w / w%, about 5.3 w / w%, about 5.4 w / w%, about 5.5 w / w%, about 5.6 w / w%, about 5.7 w / w%, about 5.8 w / w%, about 5.9 w / w%, about 6.0 w / w%, about 6.1 w / w%, about 6.2 w / w%, about 6.3 w / w%, about 6.4 w / w%, about 6.5 w / w%, about 6.6 w / w%, about 6.7 w / w%, about 6.8 w / w%, about 6.9 w / w%, or about 7.0 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of poloxamer 188 is about 0.85 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of poloxamer 188 is about 0.9 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of poloxamer 188 is about 1.27 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of poloxamer 188 is about 1.3 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of poloxamer 188 is about 1.68 w / w%.In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of poloxamer 188 is about 1.7 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of poloxamer 188 is about 2.09 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of poloxamer 188 is about 2.1 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of poloxamer 188 is about 2.49 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of poloxamer 188 is about 2.5 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of poloxamer 188 is about 4.8 w / w%. In some embodiments, in a solution comprising the sodium salt of the compound of formula (Ia), PEG 300, poloxamer 188, and water, the amount of poloxamer 188 is about 4.82 w / w%.

[0193] In some embodiments, the solution disclosed herein comprises from about 10 w / w% to about 45 w / w% water, from about 30 w / w% to about 85 w / w% PEG 300, from about 0.5 w / w% to about 40 w / w% sodium salt of the compound of formula (Ia), and from about 0.1 w / w% to about 10 w / w% poloxamer 188. In some embodiments, the solution comprises from about 15 w / w% to about 35 w / w% water, from about 35 w / w% to about 75 w / w% PEG 300, from about 1 w / w% to about 35 w / w% sodium salt of the compound of formula (Ia), and from about 0.3 w / w% to about 8 w / w% poloxamer 188. In some embodiments, the solution comprises from about 20 w / w% to about 35 w / w% water, from about 40 w / w% to about 70 w / w% PEG 300, from about 1 w / w% to about 30 w / w% sodium salt of the compound of formula (Ia), and from about 0.5 w / w% to about 7 w / w% poloxamer 188. In some embodiments, the solution comprises from about 20 w / w% to about 31 w / w% water, from about 45 w / w% to about 68 w / w% PEG 300, from about 3 w / w% to about 28 w / w% sodium salt of the compound of formula (Ia), and from about 0.6 w / w% to about 7 w / w% poloxamer 188. In some embodiments, the solution comprises from about 21.9 w / w% to about 30.1 w / w% water, from about 46.8 w / w% to about 64.4 w / w% PEG 300, from about 4.7 w / w% to about 26.5 w / w% sodium salt of the compound of formula (Ia), and from about 0.9 w / w% to about 4.8 w / w% poloxamer 188. In some embodiments, the solution comprises from about 21.87 w / w% to about 30.07 w / w% water, from about 46.84 w / w% to about 64.40 w / w% PEG 300, from about 4.68 w / w% to about 26.47 w / w% sodium salt of the compound of formula (Ia), and from 0.85 w / w% to about 4.82 w / w% poloxamer 188. In some embodiments, the solution comprises about 30.1 w / w% water, about 64.4 w / w% PEG 300, about 4.7 w / w% sodium salt of the compound of formula (Ia), and about 0.9 w / w% poloxamer 188. In some embodiments, the solution comprises about 30.07 w / w% water, about 64.40 w / w% PEG 300, about 4.68 w / w% sodium salt of the compound of formula (Ia), and about 0.85 w / w% poloxamer 188. In some embodiments, the solution comprises about 29.2 w / w% water, about 62.6 w / w% PEG 300, about 7 w / w% sodium salt of the compound of formula (Ia), and about 1.3 w / w% poloxamer 188.In some embodiments, the solution comprises about 29.21 w / w% water, about 62.55 w / w% PEG 300, about 6.97 w / w% sodium salt of the compound of formula (Ia), and about 1.27 w / w% poloxamer 188. In some embodiments, the solution comprises about 28.4 w / w% water, about 60.7 w / w% PEG 300, about 9.2 w / w% sodium salt of the compound of formula (Ia), and about 1.7 w / w% poloxamer 188. In some embodiments, the solution comprises about 28.36 w / w% water, about 60.73 w / w% PEG 300, about 9.23 w / w% sodium salt of the compound of formula (Ia), and about 1.68 w / w% poloxamer 188. In some embodiments, the solution comprises about 27.5 w / w% water, about 58.9 w / w% PEG 300, about 11.5 w / w% sodium salt of the compound of formula (Ia), and about 2.1 w / w% poloxamer 188. In some embodiments, the solution comprises about 27.51 w / w% water, about 58.92 w / w% PEG 300, about 11.48 w / w% sodium salt of the compound of formula (Ia), and about 2.09 w / w% poloxamer 188. In some embodiments, the solution comprises about 26.7 w / w% water, about 57.1 w / w% PEG 300, about 13.7 w / w% sodium salt of the compound of formula (Ia), and about 2.5 w / w% poloxamer 188. In some embodiments, the solution comprises about 26.68 w / w% water, about 57.13 w / w% PEG 300, about 13.70 w / w% sodium salt of the compound of formula (Ia), and about 2.49 w / w% poloxamer 188. In some embodiments, the solution comprises about 21.9 w / w% water, about 46.8 w / w% PEG 300, about 26.5 w / w% sodium salt of the compound of formula (Ia), and about 4.8 w / w% poloxamer 188. In some embodiments, the solution comprises about 21.87 w / w% water, about 46.84 w / w% PEG 300, about 26.47 w / w% sodium salt of the compound of formula (Ia), and about 4.82 w / w% poloxamer 188.

[0194] In some embodiments, the parenteral formulations (e.g., SC or IM formulations) disclosed herein are aqueous suspensions. In some embodiments, the parenteral formulations (e.g., SC or IM formulations) disclosed herein are aqueous suspensions comprising a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof and saline. In some embodiments, the parenteral formulations (e.g., SC or IM formulations) disclosed herein are aqueous suspensions comprising a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof, saline, and a suspending agent. In some embodiments, the parenteral formulations (e.g., SC or IM formulations) disclosed herein are aqueous suspensions comprising a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof, saline, and poloxamer (e.g., poloxamer 338, 188, or 207).

[0195] In some embodiments, there is provided a suspension comprising a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof in poloxamer and saline. In some embodiments, the concentration of poloxamer in saline is from about 0.1% to about 20%. In some embodiments, the concentration of poloxamer in saline is from about 0.1% to about 10%. In some embodiments, the concentration of poloxamer in saline is about 0.1%, about 0.2%, about 0.3%, about 0.4%, about 0.5%, about 0.6%, about 0.7%, about 0.8%, about 0.9%, about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, or about 10%. In certain embodiments, the concentration of poloxamer in saline is about 2%. In certain embodiments, the poloxamer is poloxamer 188. In certain embodiments, the compound is a compound of formula (Ia) or a pharmaceutically acceptable salt thereof. In certain embodiments, the compound is a compound of formula (Ia). In certain embodiments, the compound is the sodium salt of a compound of formula (Ia). In certain embodiments, the compound is a compound of formula (Ib) or a pharmaceutically acceptable salt thereof. In certain embodiments, the compound is a compound of formula (Ib). In certain embodiments, the compound is the trifluoroacetate salt of a compound of formula (Ib).

[0196] In some embodiments, suspensions of a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof in poloxamer and mannitol are provided. In some embodiments, the concentration of poloxamer in mannitol is from about 0.1% to about 20%. In some embodiments, the concentration of poloxamer in mannitol is from about 0.1% to about 10%. In some embodiments, the concentration of poloxamer in mannitol is about 0.1%, about 0.2%, about 0.3%, about 0.4%, about 0.5%, about 0.6%, about 0.7%, about 0.8%, about 0.9%, about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9% or about 10%. In certain embodiments, the concentration of poloxamer in mannitol is about 2%. In certain embodiments, the poloxamer is poloxamer 188. In certain embodiments, the compound is a compound of formula (Ia) or a pharmaceutically acceptable salt thereof. In certain embodiments, the compound is a compound of formula (Ia). In certain embodiments, the compound is the sodium salt of a compound of formula (Ia). In certain embodiments, the compound is a compound of formula (Ib) or a pharmaceutically acceptable salt thereof. In certain embodiments, the compound is a compound of formula (Ib). In certain embodiments, the compound is the trifluoroacetate salt of a compound of formula (Ib).

[0197] In certain embodiments, the composition is formulated as a solid dosage form. In some embodiments, the solid dosage form is a solid injectable dosage form, such as a solid depot form.

[0198] In certain embodiments, the active ingredient (such as a compound of formula (Ia) or formula (Ib)) is present in the free acid form. In certain embodiments, the active ingredient (such as a compound of formula (Ia) or formula (Ib)) is present in the sodium salt form. In certain embodiments, the active ingredient (such as a compound of formula (Ia) or formula (Ib)) is present in the trifluoroacetate salt form. In some embodiments, the active ingredient is a compound of formula (Ia). In some embodiments, the active ingredient is a compound of formula (Ib).

[0199] In certain embodiments, the pharmaceutical compositions disclosed herein are parenteral formulations. In certain embodiments, the formulation is administered subcutaneously to a patient in need thereof. In certain embodiments, the formulation is administered intramuscularly to a patient in need thereof.

[0200] In certain embodiments, the parenteral formulation comprises N-methyl-2-pyrrolidone (NMP). In certain embodiments, the parenteral formulation consists essentially of N-methyl-2-pyrrolidone. In certain embodiments, the parenteral formulation comprises dimethyl sulfoxide (DMSO). In some embodiments, the parenteral formulation comprises polyethylene glycol (PEG) or tetraethylene glycol. In some embodiments, the solution comprises PEG 200, ethanol, and water. In some embodiments, the solution comprises PEG 300 and water. In some embodiments, the solution comprises poloxamer in saline. In some embodiments, the solution comprises 2% poloxamer 188 in physiological saline.

[0201] In certain embodiments, the parenteral formulation comprises a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof and water. In certain embodiments, the parenteral formulation comprises a compound of formula (Ia) or a pharmaceutically acceptable salt thereof and water. In certain embodiments, the parenteral formulation comprises a compound of formula (Ib) or a pharmaceutically acceptable salt thereof and water. In certain embodiments, the parenteral formulation further comprises an alcohol. In certain embodiments, the alcohol is ethanol. In certain embodiments, the parenteral formulation further comprises polyethylene glycol. In certain embodiments, the polyethylene glycol has an average molecular weight of about 200 g / mol (e.g., polyethylene glycol 200). In certain embodiments, the parenteral formulation further comprises an inorganic base. In certain embodiments, the inorganic base is sodium hydroxide (NaOH). In certain embodiments, the inorganic base is sodium ethoxide (NaOEt). In certain embodiments, the formulation comprises from about 0.1 molar equivalent to about 1.5 molar equivalents of the inorganic base. In certain embodiments, the formulation comprises from about 0.5 molar equivalent to about 1.5 molar equivalents of the inorganic base. In certain embodiments, the formulation comprises from about 0.75 molar equivalent to about 1.2 molar equivalents of the inorganic base. In certain embodiments, the formulation comprises about 1.0 molar equivalent of the inorganic base. In certain embodiments, the formulation comprises about 1.2 molar equivalents of the inorganic base. In some embodiments, the inorganic base is NaOH or NaOEt.

[0202] In certain embodiments, the parenteral formulation comprises a compound of formula (Ia) or a pharmaceutically acceptable salt thereof, water, and polyethylene glycol PEG 300. In certain embodiments, the parenteral formulation comprises a compound of formula (Ib) or a pharmaceutically acceptable salt thereof, water, and polyethylene glycol PEG 300.

[0203] In certain embodiments, the parenteral formulation comprises a compound of formula (Ia) or a pharmaceutically acceptable salt thereof, water, polyethylene glycol PEG 300 (polyethylene glycol having an average molecular weight of 300 g / mol), and NaOH. In certain embodiments, the parenteral formulation comprises a compound of formula (Ia) or a pharmaceutically acceptable salt thereof, water, polyethylene glycol (PEG) 300, and NaOEt. In certain embodiments, the formulation comprises from about 0.1 molar equivalent to about 1.5 molar equivalents of NaOH or NaOEt. In certain embodiments, the formulation comprises from about 0.5 molar equivalent to about 1.5 molar equivalents of NaOH or NaOEt. In certain embodiments, the formulation comprises from about 0.75 molar equivalent to about 1.2 molar equivalents of NaOH or NaOEt. In certain embodiments, the formulation comprises about 1.0 molar equivalent of NaOH or NaOEt. In certain embodiments, the formulation comprises about 1.2 molar equivalents of NaOH or NaOEt.

[0204] In certain embodiments, the parenteral formulation is a solution formulation comprising a mixture of ethanol, water, and polyethylene glycol. In certain embodiments, the parenteral formulation is a solution formulation comprising a mixture of ethanol, water, and PEG 200. In certain embodiments, the solution formulation comprises from about 5% to about 20% ethanol, from about 5% to about 20% water, and from about 60% to about 90% PEG 200. In certain embodiments, the solution formulation comprises from about 10% to about 15% ethanol, from about 10% to about 15% water, and from about 70% to about 80% PEG 200. In certain embodiments, the solution formulation comprises about 10% ethanol, about 12% water, and about 78% PEG 200. In certain embodiments, the solution formulation further comprises an inorganic base. In certain embodiments, the solution formulation comprises about 10% ethanol, about 13% water, and about 77% PEG 200. In certain embodiments, the solution formulation further comprises an inorganic base. In certain embodiments, the formulation comprises from about 0.1 molar equivalent to about 1.5 molar equivalents of the inorganic base. In certain embodiments, the formulation comprises from about 0.5 molar equivalent to about 1.5 molar equivalents of the inorganic base. In certain embodiments, the formulation comprises from about 1.0 molar equivalent to about 1.2 molar equivalents of the inorganic base. In certain embodiments, the formulation comprises about 1.2 molar equivalents of the inorganic base. In certain embodiments, the inorganic base is sodium hydroxide or sodium ethoxide. In certain embodiments, the inorganic base is sodium hydroxide.

[0205] In certain embodiments, the parenteral formulation is a solution formulation comprising a mixture of water and polyethylene glycol. In certain embodiments, the parenteral formulation is a solution formulation comprising a mixture of water and PEG 300. In certain embodiments, the solution formulation comprises from about 5% w / w to about 25% w / w water and from about 75% w / w to about 95% w / w PEG 300. In some embodiments, the solution formulation further comprises an inorganic base. In certain embodiments, the formulation comprises from about 0.1 molar equivalents to about 1.5 molar equivalents of the inorganic base. In certain embodiments, the formulation comprises from about 0.5 molar equivalents to about 1.5 molar equivalents of the inorganic base. In certain embodiments, the formulation comprises from about 0.75 molar equivalents to about 1.2 molar equivalents of the inorganic base. In certain embodiments, the formulation comprises about 1.0 molar equivalent of the inorganic base. In certain embodiments, the formulation comprises about 1.2 molar equivalents of the inorganic base. In certain embodiments, the inorganic base is sodium hydroxide or sodium ethoxide. In certain embodiments, the inorganic base is sodium hydroxide.

[0206] In some embodiments, the solutions disclosed herein comprise a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof, PEG 300, sodium hydroxide, and water. In some embodiments, the solutions disclosed herein comprise a compound of formula (Ia) or a pharmaceutically acceptable salt thereof, PEG 300, sodium hydroxide, and water. In some embodiments, the solutions disclosed herein comprise a compound of formula (Ib) or a pharmaceutically acceptable salt thereof, PEG 300, sodium hydroxide, and water. In some embodiments, the solutions disclosed herein comprise the sodium salt of a compound of formula (Ia), PEG 300, sodium hydroxide, and water. In some embodiments, the solutions disclosed herein comprise the trifluoroacetate salt of a compound of formula (Ib), PEG 300, sodium hydroxide, and water. In some embodiments, the solutions disclosed herein comprise a compound of formula (Ib), PEG 300, sodium hydroxide, and water.

[0207] In some embodiments, the solution disclosed herein comprises a compound of formula (Ia), PEG 300, sodium hydroxide, and water. In some embodiments, in the solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, and water, the concentration of the compound of formula (Ia) is from about 50 mg / ml to about 500 mg / ml. In some embodiments, in the solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, and water, the concentration of the compound of formula (Ia) is from about 50 mg / ml to about 400 mg / ml. In some embodiments, in the solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, and water, the concentration of the compound of formula (Ia) is from about 50 mg / ml to about 300 mg / ml. In some embodiments, in the solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, and water, the concentration of the compound of formula (Ia) is from about 75 mg / ml to about 300 mg / ml. In some embodiments, in the solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, and water, the concentration of the compound of formula (Ia) is about 50 mg / ml. In some embodiments, in the solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, and water, the concentration of the compound of formula (Ia) is about 75 mg / ml. In some embodiments, in the solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, and water, the concentration of the compound of formula (Ia) is about 100 mg / ml. In some embodiments, in the solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, and water, the concentration of the compound of formula (Ia) is about 125 mg / ml. In some embodiments, in the solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, and water, the concentration of the compound of formula (Ia) is about 150 mg / ml. In some embodiments, in the solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, and water, the concentration of the compound of formula (Ia) is about 175 mg / ml. In some embodiments, in the solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, and water, the concentration of the compound of formula (Ia) is about 200 mg / ml. In some embodiments, in the solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, and water, the concentration of the compound of formula (Ia) is about 225 mg / ml. In some embodiments, in the solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, and water, the concentration of the compound of formula (Ia) is about 250 mg / ml. In some embodiments, in the solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, and water, the concentration of the compound of formula (Ia) is about 275 mg / ml.In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, and water, the concentration of the compound of formula (Ia) is about 300 mg / ml. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, and water, the concentration of the compound of formula (Ia) is about 325 mg / ml. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, and water, the concentration of the compound of formula (Ia) is about 350 mg / ml. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, and water, the concentration of the compound of formula (Ia) is about 375 mg / ml. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, and water, the concentration of the compound of formula (Ia) is about 400 mg / ml. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, and water, the concentration of the compound of formula (Ia) is about 425 mg / ml. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, and water, the concentration of the compound of formula (Ia) is about 450 mg / ml. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, and water, the concentration of the compound of formula (Ia) is about 475 mg / ml. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, and water, the concentration of the compound of formula (Ia) is about 500 mg / ml.

[0208] In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, and water, the amount of water is from about 10 w / w% to about 40 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, and water, the amount of water is from about 15 w / w% to about 35 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, and water, the amount of water is from about 20 w / w% to about 30 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, and water, the amount of water is from about 21 w / w% to about 29 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, and water, the amount of water is from about 23.2 w / w% to about 27.9 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, and water, the amount of water is from about 23.2 w / w% to about 27.92 w / w%.In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, and water, the amount of water is about 22.0 w / w%, about 22.1 w / w%, about 22.2 w / w%, about 22.3 w / w%, about 22.4 w / w%, about 22.5 w / w%, about 22.6 w / w%, about 22.7 w / w%, about 22.8 w / w%, about 22.9 w / w%, about 23.0 w / w%, about 23.1 w / w%, about 23.2 w / w%, about 23.3 w / w%, about 23.4 w / w%, about 23.5 w / w%, about 23.6 w / w%, about 23.7 w / w%, about 23.8 w / w%, about 23.9 w / w%, about 24.0 w / w%, about 24.1 w / w%, about 24.2 w / w%, about 24.3 w / w%, about 24.4 w / w%, about 24.5 w / w%, about 24.6 w / w%, about 24.7 w / w%, about 24.8 w / w%, about 24.9 w / w%, about 25.0 w / w%, about 25.1 w / w%, about 25.2 w / w%, about 25.3 w / w%, about 25.4 w / w%, about 25.5 w / w%, about 25.6 w / w%, about 25.7 w / w%, about 25.8 w / w%, about 25.9 w / w%, about 26.0 w / w%, about 26.1 w / w%, about 26.2 w / w%, about 26.3 w / w%, about 26.4 w / w%, about 26.5 w / w%, about 26.6 w / w%, about 26.7 w / w%, about 26.8 w / w%, about 26.9 w / w%, about 27.0 w / w%, about 27.1 w / w%, about 27.2 w / w%, about 27.3 w / w%, about 27.4 w / w%, about 27.5 w / w%, about 27.6 w / w%, about 27.7 w / w%, about 27.8 w / w%, about 27.9 w / w%, about 28.0 w / w%, about 28.1 w / w%, about 28.2 w / w%, about 28.3 w / w%, about 28.4 w / w%, about 28.5 w / w%, about 28.6 w / w%, about 28.7 w / w%, about 28.8 w / w%, about 28.9 w / w%, or about 29.0 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, and water, the amount of water is about 23.2 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, and water, the amount of water is about 27.9 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, and water, the amount of water is about 27.92 w / w%.

[0209] In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, and water, the amount of PEG 300 is from about 35 w / w% to about 75 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, and water, the amount of PEG 300 is from about 45 w / w% to about 65 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, and water, the amount of PEG 300 is from about 48 w / w% to about 60 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, and water, the amount of PEG 300 is from about 49 w / w% to about 59 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, and water, the amount of PEG 300 is from about 50.0 w / w% to about 58.0 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, and water, the amount of PEG 300 is from about 50.0 w / w% to about 58.04 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, and water, the amount of PEG 300 is about 45 w / w%, about 46 w / w%, about 47 w / w%, about 48 w / w%, about 49 w / w%, about 50 w / w%, about 51 w / w%, about 52 w / w%, about 53 w / w%, about 54 w / w%, about 55 w / w%, about 56 w / w%, about 57 w / w%, about 58 w / w%, about 59 w / w%, about 60 w / w%, about 61 w / w%, about 62 w / w%, about 63 w / w%, about 64 w / w% or about 65 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, and water, the amount of PEG 300 is about 50.0 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, and water, the amount of PEG 300 is about 58.0 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, and water, the amount of PEG 300 is about 58.04 w / w%.

[0210] In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, and water, the amount of the compound of formula (Ia) is from about 5 w / w% to about 35 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, and water, the amount of the compound of formula (Ia) is from about 10 w / w% to about 30 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, and water, the amount of the compound of formula (Ia) is from about 11 w / w% to about 28 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, and water, the amount of the compound of formula (Ia) is from about 13 w / w% to about 27 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, and water, the amount of the compound of formula (Ia) is from about 13.5 w / w% to about 25.7 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, and water, the amount of the compound of formula (Ia) is from about 13.47 w / w% to about 25.7 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, and water, the amount of the compound of formula (Ia) is about 13.0 w / w%, about 13.1 w / w%, about 13.2 w / w%, about 13.3 w / w%, about 13.4 w / w%, about 13.5 w / w%, about 13.6 w / w%, about 13.7 w / w%, about 13.8 w / w%, about 13.9 w / w%, about 14.0 w / w%, about 14.1 w / w%, about 14.2 w / w%, about 14.3 w / w%, about 14.4 w / w%, about 14.5 w / w%, about 14.6 w / w%, about 14.7 w / w%, about 14.8 w / w%, about 14.9 w / w%, about 15.0 w / w%, about 15.1 w / w%, about 15.2 w / w%, about 15.3 w / w%, about 15.4 w / w%, about 15.5 w / w%, about 15.6 w / w%, about 15.7 w / w%, about 15.8 w / w%, about 15.9 w / w%, about 16.0 w / w%, about 16.1 w / w%, about 16.2 w / w%, about 16.3 w / w%, about 16.4 w / w%, about 16.5 w / w%, about 16.6 w / w%, about 16.7 w / w%, about 16.8 w / w%, about 16.9 w / w%, about 17.0 w / w%, about 17.1 w / w%, about 17.2 w / w%, about 17.3 w / w%, about 17.4 w / w%, about 17.5 w / w%, about 17.6 w / w%, about 17.7 w / w%, about 17.8 w / w%, about 17.9 w / w%, about 18.0 w / w%, about 18.1 w / w%, about 18.2 w / w%, about 18.3 w / w%, approximately 18.4 w / w%, approximately 18.5 w / w%, approximately 18.6 w / w%, approximately 18.7 w / w%, approximately 18.8 w / w%, approximately 18.9 w / w%, approximately 19.0 w / w%, approximately 19.1 w / w%, approximately 19.2 w / w%, approximately 19.3 w / w%, approximately 19.4 w / w%, approximately 19.5 w / w%, approximately 19.6 w / w%, approximately 19.7 w / w%, approximately 19.8 w / w%, approximately 19.9 w / w%, approximately 20.0 w / w%, approximately 21.1 w / w%, approximately 21.2 w / w%, approximately 21.3 w / w%, approximately 21.4 w / w%, approximately 21.5 w / w%, approximately 21.6 w / w%, approximately 21.7 w / w%, approximately 21.8 w / w%, approximately 21.9 w / w%, approximately 22.0 w / w%, approximately 22.1 w / w%, approximately 22.2 w / w%, approximately 22.3 w / w%, approximately 22.4 w / w%, approximately 22.5 w / w%, approximately 22.6 w / w%, approximately 22.7 w / w%, approximately 22.8 w / w%, approximately 22.9 w / w%, approximately 23.0 w / w%, approximately 23.1 w / w%, approximately 23.2 w / w%, approximately 23.3 w / w%, approximately 23.4 w / w%, approximately 23.5 w / w%, approximately 23.6 w / w%, approximately 23.7 w / w%, approximately 23.8 w / w%, approximately 23.9 w / w%, approximately 24.0 w / w%, approximately 24.1 w / w%, approximately 24.2 w / w%, approximately 24.3 w / w%, approximately 24.4 w / w%, approximately 24.5 w / w%, approximately 24.6 w / w%, approximately 24.7 w / w%, approximately 24.8 w / w%, approximately 24.9 w / w%, approximately 25.0 w / w%, approximately 25.1 w / w%, approximately 25.2 w / w%, approximately 25.3 w / w%, approximately 25.4 w / w%, approximately 25.5 w / w%, approximately 25.6 w / w%, approximately 25.7 w / w%, approximately 25.8 w / w%, approximately 25.9 w / w%, approximately 26.0 w / w%, approximately 26.1 w / w%, approximately 26.2 w / w%, approximately 26.3 w / w%, approximately 26.4 w / w%, approximately 26.5 w / w%, approximately 26.6 w / w%, approximately 26.7 w / w%, approximately 26.8 w / w%, approximately 26.9 w / w%, approximately 27.0 w / w%, approximately 27.1 w / w%, approximately 27.2 w / w%, approximately 27.3 w / w%, approximately 27.4 w / w%, approximately 27.5 w / w%, approximately 27.6 w / w%, approximately 27.7 w / w%, approximately 27.8 w / w%, approximately 27.9 w / w%, approximately 28.0 w / w%, approximately 28.1 w / w%, approximately 28.2 w / w%, approximately 28.3 w / w%, approximately 28.4 w / w%, approximately 28.5 w / w%, approximately 28.6 w / w%, approximately 28.7 w / w%, approximately 28.8 w / w%, approximately 28.9 w / w% or approximately 29.0 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, and water, the amount of the compound of formula (Ia) is about 13.47 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, and water, the amount of the compound of formula (Ia) is about 13.5 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, and water, the amount of the compound of formula (Ia) is about 25.7 w / w%.

[0211] In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, and water, the amount of sodium hydroxide is from about 0.05 w / w% to about 0.2 w / w. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, and water, the amount of sodium hydroxide is from about 0.1 w / w% to about 1.5 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, and water, the amount of sodium hydroxide is from about 0.3 w / w% to about 1.3 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, and water, the amount of sodium hydroxide is from about 0.5 w / w% to about 1.2 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, and water, the amount of sodium hydroxide is from about 0.6 w / w% to about 1.1 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, and water, the amount of sodium hydroxide is from about 0.58 w / w% to about 1.1 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, and water, the amount of sodium hydroxide is about 0.1 w / w%, about 0.2 w / w%, about 0.3 w / w%, about 0.4 w / w%, about 0.5 w / w%, about 0.6 w / w%, about 0.7 w / w%, about 0.8 w / w%, about 0.9 w / w%, about 1.0 w / w%, about 1.1 w / w%, about 1.2 w / w%, about 1.3 w / w%, about 1.4 w / w%, about 1.5 w / w%, about 1.6 w / w%, about 1.7 w / w%, about 1.8 w / w%, about 1.9 w / w% or about 2.0 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, and water, the amount of sodium hydroxide is about 0.58 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, and water, the amount of sodium hydroxide is about 0.6 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, and water, the amount of sodium hydroxide is about 1.1 w / w%. In some embodiments, the solutions disclosed herein comprise from about 10 w / w% to about 40 w / w% water, from about 35 w / w% to about 75 w / w% PEG 300, from about 5 w / w% to about 35 w / w% of the compound of formula (Ia), and from about 0.05 w / w% to about 2 w / w% sodium hydroxide. In some embodiments, the solution comprises from about 15 w / w% to about 35 w / w% water, from about 45 w / w% to about 65 w / w% PEG 300, from about 10 w / w% to about 30 w / w% of the compound of formula (Ia), and from about 0.1 w / w% to about 1.5 w / w% sodium hydroxide.In some embodiments, the solution comprises from about 20 w / w% to about 30 w / w% water, from about 48 w / w% to about 60 w / w% PEG 300, from about 11 w / w% to about 28 w / w% of the compound of formula (Ia), and from about 0.3 w / w% to about 1.3 w / w% sodium hydroxide. In some embodiments, the solution comprises from about 21 w / w% to about 29 w / w% water, from about 49 w / w% to about 59 w / w% PEG 300, from about 13 w / w% to about 27 w / w% of the compound of formula (Ia), and from about 0.5 w / w% to about 1.2 w / w% sodium hydroxide. In some embodiments, the solution comprises from about 23.2 w / w% to about 27.9 w / w% water, from about 50 w / w% to about 58 w / w% PEG 300, from about 13.5 w / w% to about 25.7 w / w% of the compound of formula (Ia), and from about 0.6 w / w% to about 1.1 w / w% sodium hydroxide. In some embodiments, the solution comprises from about 23.2 w / w% to about 27.92 w / w% water, from about 50.0 w / w% to about 58.04 w / w% PEG 300, from about 13.47 w / w% to about 25.7 w / w% of the compound of formula (Ia), and from about 0.58 w / w% to about 1.1 w / w% sodium hydroxide. In some embodiments, the solution comprises about 27.9 w / w% water, about 58 w / w% PEG 300, about 13.5 w / w% of the compound of formula (Ia), and about 0.6 w / w% sodium hydroxide. In some embodiments, the solution comprises about 27.92 w / w% water, about 58.04 w / w% PEG 300, about 13.47 w / w% of the compound of formula (Ia), and about 0.58 w / w% sodium hydroxide. In some embodiments, the solution comprises about 23.2 w / w% water, about 50.0 w / w% PEG 300, about 25.7 w / w% of the compound of formula (Ia), and about 1.1 w / w% sodium hydroxide.

[0212] In some embodiments, in a solution comprising the compound of formula (Ia), PEG 300, sodium hydroxide, and water, in the presence of sodium hydroxide, the compound of formula (Ia) is ionized in situ to the sodium salt of the compound of formula (Ia). Thus, in some embodiments, the compound of formula (Ia) is present as the sodium salt of the compound of formula (Ia) in a solution comprising the compound of formula (Ia), PEG 300, sodium hydroxide, and water.

[0213] In some embodiments, the pharmaceutical compositions disclosed herein comprise a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof, poloxamer, and a pharmaceutically acceptable excipient. In some embodiments, the pharmaceutical compositions disclosed herein comprise a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof, poloxamer 188, and a pharmaceutically acceptable excipient. In some embodiments, the pharmaceutical compositions disclosed herein are solutions comprising a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof, poloxamer, and a pharmaceutically acceptable excipient. In some embodiments, the pharmaceutical compositions disclosed herein are solutions comprising a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof, poloxamer 188, and a pharmaceutically acceptable excipient.

[0214] In some embodiments, the solutions disclosed herein comprise a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof, PEG 300, sodium hydroxide, poloxamer 188, and water. In some embodiments, the solutions disclosed herein comprise a compound of formula (Ia) or a pharmaceutically acceptable salt thereof, PEG 300, sodium hydroxide, poloxamer 188, and water. In some embodiments, the solutions disclosed herein comprise a compound of formula (Ib) or a pharmaceutically acceptable salt thereof, PEG 300, sodium hydroxide, poloxamer 188, and water. In some embodiments, the solutions disclosed herein comprise the sodium salt of a compound of formula (Ia), PEG300, sodium hydroxide, poloxamer 188, and water. In some embodiments, the solutions disclosed herein comprise the trifluoroacetate salt of a compound of formula (Ib), PEG 300, sodium hydroxide, poloxamer 188, and water.

[0215] In some embodiments, the solution disclosed herein comprises a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the concentration of the compound of formula (Ia) is from about 50 mg / ml to about 500 mg / ml. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the concentration of the compound of formula (Ia) is from about 50 mg / mL to about 400 mg / mL. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the concentration of the compound of formula (Ia) is from about 50 mg / ml to about 300 mg / ml. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the concentration of the compound of formula (Ia) is from about 75 mg / ml to about 300 mg / ml. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the concentration of the compound of formula (Ia) is about 50 mg / ml. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the concentration of the compound of formula (Ia) is about 75 mg / ml. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the concentration of the compound of formula (Ia) is about 100 mg / ml. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the concentration of the compound of formula (Ia) is about 125 mg / ml. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the concentration of the compound of formula (Ia) is about 150 mg / ml. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the concentration of the compound of formula (Ia) is about 175 mg / ml. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the concentration of the compound of formula (Ia) is about 200 mg / ml. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the concentration of the compound of formula (Ia) is about 225 mg / ml. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the concentration of the compound of formula (Ia) is about 250 mg / ml.In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the concentration of the compound of formula (Ia) is about 275 mg / ml. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the concentration of the compound of formula (Ia) is about 300 mg / ml. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the concentration of the compound of formula (Ia) is about 325 mg / ml. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the concentration of the compound of formula (Ia) is about 350 mg / ml. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the concentration of the compound of formula (Ia) is about 375 mg / ml. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the concentration of the compound of formula (Ia) is about 400 mg / ml. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the concentration of the compound of formula (Ia) is about 425 mg / ml. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the concentration of the compound of formula (Ia) is about 450 mg / ml. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the concentration of the compound of formula (Ia) is about 475 mg / ml. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the concentration of the compound of formula (Ia) is about 500 mg / ml.

[0216] In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the amount of water is from about 10 w / w% to about 45 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the amount of water is from about 15 w / w% to about 35 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the amount of water is from about 20 w / w% to about 35 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the amount of water is from about 20 w / w% to about 31 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the amount of water is from about 22 w / w% to about 30.1 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the amount of water is from about 21.97 w / w% to 30.07 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the amount of water is about 19.0 w / w%, about 19.1 w / w%, about 19.2 w / w%, about 19.3 w / w%, about 19.4 w / w%, about 19.5 w / w%, about 19.6 w / w%, about 19.7 w / w%, about 19.8 w / w%, about 19.9 w / w%, about 20.0 w / w%, about 20.1 w / w%, about 20.2 w / w%, about 20.3 w / w%, about 20.4 w / w%, about 20.5 w / w%, about 20.6 w / w%, about 20.7 w / w%, about 20.8 w / w%, about 20.9 w / w%, about 21.0 w / w%, about 21.1 w / w%, about 21.2 w / w%, about 21.3 w / w%, about 21.4 w / w%, about 21.5 w / w%, about 21.6 w / w%, about 21.7 w / w%, about 21.8 w / w%, about 21.9 w / w%, about 22.0 w / w%, about 22.1 w / w%, about 22.2 w / w%, about 22.3 w / w%, about 22.4 w / w%, about 22.5 w / w%, about 22.6 w / w%, about 22.7 w / w%, about 22.8 w / w%, about 22.9 w / w%, about 23.0 w / w%, about 23.1 w / w%, about 23.2 w / w%, about 23.3 w / w%, about 23.4 w / w%, about 23.5 w / w%, about 23.6 w / w%, about 23.7 w / w%, about 23.8 w / w%, about 23.9 w / w%, about 24.0 w / w%, about 24.1 w / w%, about 24.2 w / w%, about 24.3 w / w%, about 24.4 w / w%, about 24.5 w / w%, about 24.6 w / w%, about 24.7 w / w%, about 24.8 w / w%, about 24.9 w / w%, about 25.0 w / w%, about 25.1 w / w%, about 25.2 w / w%, about 25.3 w / w%, about 25.4 w / w%, about 25.5 w / w%, about 25.6 w / w%, about 25.7 w / w%, about 25.8 w / w%, about 25.9 w / w%, about 26.0 w / w%, about 26.1 w / w%, about 26.2 w / w%, about 26.3 w / w%, about 26.4 w / w%, about 26.5 w / w%, about 26.6 w / w%, about 26.7 w / w%, about 26.8 w / w%, about 26.9 w / w%, about 27.0 w / w%, about 27.1 w / w%, about 27.2 w / w%, about 27.3 w / w%, about 27.4 w / w%, about 27.5 w / w%, about 27.6 w / w%, about 27.7 w / w%, about 27.8 w / w%, about 27.9 w / w%, about 28.0 w / w%, about 28.1 w / w%, about 28.2 w / w%, about 28.3 w / w%, about 28.4 w / w%, about 28.5 w / w%, about 28.6 w / w%, about 28.7 w / w%, about 28.8 w / w%, about 28.9 w / w%, about 29.0 w / w%, about 29.1 w / w%, about 29.2 w / w%, about 29.3 w / w%, about 29.4 w / w%, about 29.5 w / w%, about 29.6 w / w%, about 29.7 w / w%, about 29.8 w / w%, about 29.9 w / w%, about 30.0 w / w%, about 30.1 w / w%, about 30.2 w / w%, about 30.3 w / w%, about 30.4 w / w%, about 30.5 w / w%, about 30.6 w / w%, about 30.7 w / w%, about 30.8 w / w%, about 30.9 w / w%, about 31.0 w / w%, about 31.1 w / w%, about 31.2 w / w%, about 31.3 w / w%, about 31.4 w / w%, about 31.5 w / w%, about 31.6 w / w%, about 31.7 w / w%, about 31.8 w / w%, about 31.9 w / w%, about 32.0 w / w%, about 32.1 w / w%, about 32.2 w / w%, about 32.3 w / w%, about 32.4 w / w%, about 32.5 w / w%, about 32.6 w / w%, about 32.7 w / w%, about 32.8 w / w%, about 32.9 w / w% or about 33.0 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the amount of water is about 21.97 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the amount of water is about 22 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the amount of water is about 30.07 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the amount of water is about 30.1 w / w%.

[0217] In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the amount of PEG 300 is from about 30 w / w% to about 85 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the amount of PEG 300 is from about 35 w / w% to about 75 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the amount of PEG 300 is from about 40 w / w% to about 70 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the amount of PEG 300 is from about 45 w / w% to about 68 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the amount of PEG 300 is from about 47.1 w / w% to about 64.4 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the amount of PEG 300 is from about 47.05 w / w% to about 64.41 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the amount of PEG 300 is about 40 w / w%, about 41 w / w%, about 42 w / w%, about 43 w / w%, about 44 w / w%, about 45 w / w%, about 46 w / w%, about 47 w / w%, about 48 w / w%, about 49 w / w%, about 50 w / w%, about 51 w / w%, about 52 w / w%, about 53 w / w%, about 54 w / w%, about 55 w / w%, about 56 w / w%, about 57 w / w%, about 58 w / w%, about 59 w / w%, about 60 w / w%, about 61 w / w%, about 62 w / w%, about 63 w / w%, about 64 w / w%, about 65 w / w%, about 66 w / w%, about 67 w / w%, about 68 w / w%, about 69 w / w%, or about 70 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the amount of PEG 300 is about 47.05 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the amount of PEG 300 is about 47.1 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the amount of PEG 300 is about 64.4 w / w%.In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the amount of PEG 300 is about 64.41 w / w%.

[0218] In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the amount of the compound of formula (Ia) is from about 0.5 w / w% to about 40 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the amount of the compound of formula (Ia) is from about 1 w / w% to about 35 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the amount of the compound of formula (Ia) is from about 1 w / w% to about 30 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the amount of the compound of formula (Ia) is from about 3 w / w% to about 28 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the amount of the compound of formula (Ia) is from about 4 w / w% to about 26 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the amount of the compound of formula (Ia) is from about 4.6 w / w% to about 25.2 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the amount of the compound of formula (Ia) is from about 4.57 w / w% to about 25.21 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the amount of the compound of formula (Ia) is about 3.0 w / w%, about 3.1 w / w%, about 3.2 w / w%, about 3.3 w / w%, about 3.4 w / w%, about 3.5 w / w%, about 3.6 w / w%, about 3.7 w / w%, about 3.8 w / w%, about 3.9 w / w%, about 4.0 w / w%, 4.1 w / w%, about 4.2 w / w%, about 4.3 w / w%, about 4.4 w / w%, about 4.5 w / w%, about 4.6 w / w%, about 4.7 w / w%, about 4.8 w / w%, about 4.9 w / w%, about 5.0 w / w%, about 5.1 w / w%, about 5.2 w / w%, about 5.3 w / w%, about 5.4 w / w%, about 5.5 w / w%, about 5.6 w / w%, about 5.7 w / w%, about 5.8 w / w%, about 5.9 w / w%, about 6.0 w / w%, about 6.1 w / w%, about 6.2 w / w%, about 6.3 w / w%, about 6.4 w / w%, about 6.5 w / w%, about 6.6 w / w%, about 6.7 w / w%, about 6.8 w / w%, about 6.9 w / w%, about 7.0 w / w%, about 7.1 w / w%, about 7.2 w / w%, about 7.3 w / w%, about 7.4 w / w%, about 7.5 w / w%, approximately 7.6 w / w%, approximately 7.7 w / w%, approximately 7.8 w / w%, approximately 7.9 w / w%, approximately 7.9 w / w% / w%, approximately 8.1 w / w%, approximately 8.2 w / w%, approximately 8.3 w / w%, approximately 8.4 w / w%, approximately 8.5 w / w%, approximately 8.6 w / w%, approximately 8.6 w / w w%, approximately 8.8 w / w%, approximately 8.9 w / w%, approximately 9.0 w / w%, approximately 9.1 w / w%, approximately 9.2 w / w%, approximately 9.3 w / w%, approximately 9.4 w / w%, approximately 9.5 w / w%, approximately 9.5 w / w%, approximately 9.7 w / w%, approximately 9.8 w / w%, approximately 9.9 w / w%, approximately 10.0 w / w%, approximately 10.1 w / w%, approximately 10.2 w / w%, approximately 10.3 w / w%, approximately 10.4 w / w%, approximately 10.5 w / w%, approximately 10.6 w / w%, approximately 10.7 w / w%, approximately 10.8 w / w%, approximately 10.9 w / w%, approximately 11.0 w / w%, approximately 11.1 w / w%, approximately 11.2 w / w%, approximately 11.3 w / w%, approximately 11.4 w / w%, approximately 11.5 w / w%, approximately 11.6 w / w%, approximately 11.7 w / w%, approximately 11.8 w / w%, approximately 11.9 w / w%, approximately 12.0 w / w%, approximately 12.1 w / w%, approximately 12.2 w / w%, approximately 12.3 w / w%, approximately 12.4 w / w%, approximately 12.5 w / w%, approximately 12.6 w / w%, approximately 12.7 w / w%, approximately 12.8 w / w%, approximately 12.9 w / w%, approximately 13.0 w / w%, approximately 13.1 w / w%, approximately 13.2 w / w%, approximately 13.3 w / w%, approximately 13.4 w / w%, approximately 13.5 w / w%, approximately 13.6 w / w%, approximately 13.7 w / w%, approximately 13.8 w / w%, approximately 13.9 w / w%, approximately 14.0 w / w%, approximately 14.1 w / w%, approximately 14.2 w / w%, approximately 14.3 w / w%, approximately 14.4 w / w%, approximately 14.5 w / w%, approximately 14.6 w / w%, approximately 14.7 w / w%, approximately 14.8 w / w%, approximately 14.9 w / w%, approximately 15.0 w / w%, approximately 15.1 w / w%, approximately 15.2 w / w%, approximately 15.3 w / w%, approximately 15.4 w / w%, approximately 15.5 w / w%, approximately 15.6 w / w%, approximately 15.7 w / w%, approximately 15.8 w / w%, approximately 15.9 w / w%, approximately 16.0 w / w%, approximately 16.1 w / w%, approximately 16.2 w / w%, approximately 16.3 w / w%, approximately 16.4 w / w%, approximately 16.5 w / w%, approximately 16.6 w / w%, approximately 16.7 w / w%, approximately 16.8 w / w%, approximately 16.9 w / w%, approximately 17.0 w / w%, approximately 17.1 w / w%, approximately 17.2 w / w%, approximately 17.3 w / w%, approximately 17.4 w / w%, approximately 17.5 w / w%, approximately 17.6 w / w%, approximately 17.7 w / w%, approximately 17.8 w / w%, approximately 17.9 w / w%, approximately 18.0 w / w%, approximately 18.1 w / w%, approximately 18.2 w / w%, approximately 18.3 w / w%, approximately 18.4 w / w%, approximately 18.5 w / w%, approximately 18.6 w / w%, approximately 18.7 w / w%, approximately 18.8 w / w%, approximately 18.9 w / w%, approximately 19.0 w / w%, approximately 19.1 w / w%, approximately 19.2 w / w%, approximately 19.3 w / w%, approximately 19.4 w / w%, approximately 19.5 w / w%, approximately 19.6 w / w%, approximately 19.7 w / w%, approximately 19.8 w / w%, approximately 19.9 w / w%, approximately 20.0 w / w%, approximately 21.1 w / w%, approximately 21.2 w / w%, approximately 21.3 w / w%, approximately 21.4 w / w%, approximately 21.5 w / w%, approximately 21.6 w / w%, approximately 21.7 w / w%, approximately 21.8 w / w%, approximately 21.9 w / w%, approximately 22.0 w / w%, approximately 22.1 w / w%, approximately 22.2 w / w%, approximately 22.3 w / w%, approximately 22.4 w / w%, approximately 22.5 w / w%, approximately 22.6 w / w%, approximately 22.7 w / w%, approximately 22.8 w / w%, approximately 22.9 w / w%, approximately 23.0 w / w%, approximately 23.1 w / w%, approximately 23.2 w / w%, approximately 23.3 w / w%, approximately 23.4 w / w%, approximately 23.5 w / w%, approximately 23.6 w / w%, approximately 23.7 w / w%, approximately 23.8 w / w%, approximately 23.9 w / w%, approximately 24.0 w / w%, approximately 24.1 w / w%, approximately 24.2 w / w%, approximately 24.3 w / w%, approximately 24.4 w / w%, approximately 24.5 w / w%, approximately 24.6 w / w%, approximately 24.7 w / w%, approximately 24.8 w / w%, approximately 24.9 w / w%, approximately 25.0 w / w%, approximately 25.1 w / w%, approximately 25.2 w / w%, approximately 25.3 w / w%, approximately 25.4 w / w%, approximately 25.5 w / w%, approximately 25.6 w / w%, approximately 25.7 w / w%, approximately 25.8 w / w%, approximately 25.9 w / w%, approximately 26.0 w / w%, approximately 26.1 w / w%, approximately 26.2 w / w%, approximately 26.3 w / w%, approximately 26.4 w / w%, approximately 26.5 w / w%, approximately 26.6 w / w%, approximately 26.7 w / w%, approximately 26.8 w / w%, approximately 26.9 w / w%, approximately 27.0 w / w%, approximately 27.1 w / w%, approximately 27.2 w / w%, approximately 27.3 w / w%, approximately 27.4 w / w%, approximately 27.5 w / w%, approximately 27.6 w / w%, approximately 27.7 w / w%, approximately 27.8 w / w%, approximately 27.9 w / w%, approximately 28.0 w / w%, approximately 28.1 w / w%, approximately 28.2 w / w%, approximately 28.3 w / w%, approximately 28.4 w / w%, approximately 28.5 w / w%, approximately 28.6 w / w%, approximately 28.7 w / w%, about 28.8 w / w%, about 28.9 w / w% or about 29.0 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188 and water, the amount of the compound of formula (Ia) is about 4.57 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188 and water, the amount of the compound of formula (Ia) is about 4.6 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188 and water, the amount of the compound of formula (Ia) is about 25.2 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188 and water, the amount of the compound of formula (Ia) is about 25.21 w / w%.

[0219] In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the amount of sodium hydroxide is from about 0.01 w / w% to about 3.0 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the amount of sodium hydroxide is from about 0.01 w / w% to about 2.0 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the amount of sodium hydroxide is from about 0.05 w / w% to about 1.5 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the amount of sodium hydroxide is from about 0.05 w / w% to about 1.2 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the amount of sodium hydroxide is from about 0.1 w / w% to about 1.1 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the amount of sodium hydroxide is from about 0.10 w / w% to about 1.08 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the amount of sodium hydroxide is about 0.01 w / w%, about 0.02 w / w%, about 0.03 w / w%, about 0.04 w / w%, about 0.05 w / w%, about 0.06 w / w%, about 0.07 w / w%, about 0.08 w / w%, about 0.09 w / w%, about 0.1 w / w%, about 0.2 w / w%, about 0.3 w / w%, about 0.4 w / w%, about 0.5 w / w%, about 0.6 w / w%, about 0.7 w / w%, about 0.8 w / w%, about 0.9 w / w%, about 1.0 w / w%, about 1.1 w / w%, about 1.2 w / w%, about 1.3 w / w%, about 1.4 w / w%, about 1.5 w / w%, about 1.6 w / w%, about 1.7 w / w%, about 1.8 w / w%, about 1.9 w / w% or about 2.0 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the amount of sodium hydroxide is about 0.1 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the amount of sodium hydroxide is about 0.10 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the amount of sodium hydroxide is about 1.08 w / w%.In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the amount of sodium hydroxide is about 1.1 w / w%.

[0220] In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the amount of poloxamer 188 is from about 0.1 w / w% to about 10 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the amount of poloxamer 188 is from about 0.3 w / w% to about 8 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the amount of poloxamer 188 is from about 0.5 w / w% to about 7 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the amount of poloxamer 188 is from about 0.6 w / w% to about 7 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the amount of poloxamer 188 is from about 0.85 w / w% to about 4.69 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the amount of poloxamer 188 is from about 0.9 w / w% to about 4.7 w / w%.In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the amount of poloxamer 188 is about 0.5 w / w%, about 0.6 w / w%, about 0.7 w / w%, about 0.8 w / w%, about 0.9 w / w%, about 1.0 w / w%, about 1.1 w / w%, about 1.2 w / w%, about 1.3 w / w%, about 1.4 w / w%, about 1.5 w / w%, about 1.6 w / w%, about 1.7 w / w%, about 1.8 w / w%, about 1.9 w / w%, about 2.0 w / w%, about 2.1 w / w%, about 2.2 w / w%, about 2.3 w / w%, about 2.4 w / w%, about 2.5 w / w%, about 2.6 w / w%, about 2.7 w / w%, about 2.8 w / w%, about 2.9 w / w%, about 3.0 w / w%, about 3.1 w / w%, about 3.2 w / w%, about 3.3 w / w%, about 3.4 w / w%, about 3.5 w / w%, about 3.6 w / w%, about 3.7 w / w%, about 3.8 w / w%, about 3.9 w / w%, about 4.0 w / w%, about 4.1 w / w%, about 4.2 w / w%, 4.3 w / w%, about 4.4 w / w%, about 4.5 w / w%, about 4.6 w / w%, about 4.7 w / w%, about 4.8 w / w%, about 4.9 w / w%, about 5.0 w / w%, about 5.1 w / w%, about 5.2 w / w%, about 5.3 w / w%, about 5.4 w / w%, about 5.5 w / w%, about 5.6 w / w%, about 5.7 w / w%, about 5.8 w / w%, about 5.9 w / w%, about 6.0 w / w%, about 6.1 w / w%, about 6.2 w / w%, about 6.3 w / w%, about 6.4 w / w%, about 6.5 w / w%, about 6.6 w / w%, about 6.7 w / w%, about 6.8 w / w%, about 6.9 w / w%, or about 7.0 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the amount of poloxamer 188 is about 0.85 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the amount of poloxamer 188 is about 0.9 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the amount of poloxamer 188 is about 4.69 w / w%. In some embodiments, in a solution comprising a compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, the amount of poloxamer 188 is about 4.7 w / w%.

[0221] In some embodiments, the solution disclosed herein comprises from about 10 w / w% to about 45 w / w% water, from about 30 w / w% to about 85 w / w% PEG 300, from about 0.5 w / w% to about 40 w / w% of the compound of formula (Ia), from about 0.01 w / w% to about 3.0 w / w% sodium hydroxide, and from about 0.1 w / w% to about 10 w / w% poloxamer 188. In some embodiments, the solution comprises from about 15 w / w% to about 35 w / w% water, from about 35 w / w% to about 75 w / w% PEG 300, from about 1 w / w% to about 35 w / w% of the compound of formula (Ia), from about 0.01 w / w% to about 2.0 w / w% sodium hydroxide, and from about 0.3 w / w% to about 8 w / w% poloxamer 188. In some embodiments, the solution comprises from about 20 w / w% to about 35 w / w% water, from about 40 w / w% to about 70 w / w% PEG 300, from about 1 w / w% to about 30 w / w% of the compound of formula (Ia), from about 0.05 w / w% to about 1.5 w / w% sodium hydroxide, and from about 0.5 w / w% to about 7 w / w% poloxamer 188. In some embodiments, the solution comprises from about 20 w / w% to about 31 w / w% water, from about 45 w / w% to about 68 w / w% PEG 300, from about 3 w / w% to about 28 w / w% of the compound of formula (Ia), from about 0.05 w / w% to about 1.2 w / w% sodium hydroxide, and from about 0.6 w / w% to about 7 w / w% poloxamer 188.

[0222] In some embodiments, the solution comprises from about 22 w / w% to about 30.1 w / w% water, from about 47.1 w / w% to about 64.4 w / w% PEG 300, from about 4.6 w / w% to about 25.2 w / w% of the compound of formula (Ia), from about 0.1 w / w% to about 1.1 w / w% sodium hydroxide, and from about 0.9 w / w% to about 4.7 w / w% poloxamer 188. In some embodiments, the solution comprises from about 21.97 w / w% to about 30.07 w / w% water, from about 47.05 w / w% to about 64.41 w / w% PEG 300, from about 4.57 w / w% to about 25.21 w / w% of the compound of formula (Ia), from about 0.10 w / w% to about 1.08 w / w% sodium hydroxide, and from about 0.85 w / w% to about 4.69 w / w% poloxamer 188. In some embodiments, the solution comprises about 30.1 w / w% water, about 64.4 w / w% PEG 300, about 4.6 w / w% of the compound of formula (Ia), about 0.1 w / w% sodium hydroxide, and about 0.9 w / w% poloxamer 188. In some embodiments, the solution comprises about 30.07 w / w% water, about 64.41 w / w% PEG 300, about 4.57 w / w% of the compound of formula (Ia), about 0.10 w / w% sodium hydroxide, and about 0.85 w / w% poloxamer 188. In some embodiments, the solution comprises about 22 w / w% water, about 47.1 w / w% PEG 300, about 25.2 w / w% of the compound of formula (Ia), about 1.1 w / w% sodium hydroxide, and about 4.7 w / w% poloxamer 188. In some embodiments, the solution comprises about 21.97 w / w% water, about 47.05 w / w% PEG 300, about 25.21 w / w% of the compound of formula (Ia), about 1.08 w / w% sodium hydroxide, and about 4.69 w / w% poloxamer 188.

[0223] In some embodiments, in a solution comprising the compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water, in the presence of sodium hydroxide, the compound of formula (Ia) is ionized in situ to the sodium salt of the compound of formula (Ia). Thus, in some embodiments, the compound of formula (Ia) is present as the sodium salt of the compound of formula (Ia) in a solution comprising the compound of formula (Ia), PEG 300, sodium hydroxide, poloxamer 188, and water.

[0224] In some embodiments, the solution formulation comprises from about 50 mg / mL of a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof. In some embodiments, the solution formulation comprises from about 75 mg / mL of a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof. In some embodiments, the solution formulation comprises from about 125 mg / mL of a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof. In some embodiments, the solution formulation comprises from about 175 mg / mL of a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof. In some embodiments, the solution formulation comprises from about 225 mg / mL of a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof. In some embodiments, the solution formulation comprises from about 250 mg / mL of a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof. In some embodiments, the solution formulation comprises from about 275 mg / mL of a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof. In some embodiments, the solution formulation comprises from about 325 mg / mL of a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof. In some embodiments, the solution formulation comprises from about 350 mg / mL of a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof. In some embodiments, the solution formulation comprises from about 375 mg / mL of a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof.

[0225] In some embodiments, the solution formulation comprises from about 100 mg / mL of a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof. In some embodiments, the solution formulation comprises from about 150 mg / mL of a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof. In some embodiments, the solution formulation comprises from about 200 mg / mL of a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof. In some embodiments, the solution formulation comprises from about 300 mg / mL of a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof. In some embodiments, the solution formulation comprises from about 400 mg / mL of a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof.

[0226] In some embodiments, the solution formulation comprises from about 425 mg / mL of a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof. In some embodiments, the solution formulation comprises from about 450 mg / mL of a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof. In some embodiments, the solution formulation comprises from about 475 mg / mL of a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof. In some embodiments, the solution formulation comprises from about 500 mg / mL of a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof.

[0227] In some embodiments, the solutions disclosed herein are administered by subcutaneous injection. In some embodiments, the solutions disclosed herein are administered by intramuscular injection.

[0228] In certain embodiments, an oral formulation of a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof and at least one excipient is provided. The excipient(s) may include ethanol, medium-chain triglycerides, vitamin E d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), monocaprylyl decaglyceride, glycerol, and / or a pharmaceutically acceptable oil. Examples of suitable medium-chain triglycerides include, but are not limited to, MIGLYOL 810, MIGLYOL 821, and MIGLYOL 840. Examples of suitable pharmaceutically acceptable oils include, but are not limited to, sesame oil, castor oil, safflower oil, vegetable oil, and soybean oil. The oral formulations disclosed herein may include any combination of one or more suitable excipients. The excipients together may be present in an amount greater than about 65% by weight of the total oral formulation, greater than about 70% by weight of the total oral formulation, greater than about 80% by weight of the total oral formulation, greater than about 90% by weight of the total oral formulation, or greater than about 95% by weight of the total oral formulation.

[0229] In some embodiments, an oral formulation of a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof and at least one excipient is prepared as a hard capsule or a soft capsule. In some embodiments, the hard capsule or soft capsule contains a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof, and one or more excipients selected from the group consisting of: ethanol, propylene glycol, glycerol, d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), polyoxyl 35 castor oil (e.g. EL), monocaprylyl decaglyceride (e.g. MCM), PEG 400 caprylic / capric glycerides (e.g. ), PEG 400, diethylene glycol monoethyl ether (e.g. ), monocaprylyl propylene glycol ester type II (e.g. 90), glycerol monooctanoate type 40 (e.g. Peceol TM ), medium-chain triglycerides (e.g. 812N), glycerol mono-linoleate (e.g. ), and polysorbate 80. In some embodiments, the hard capsule or soft capsule contains a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof, and one or more excipients selected from the group consisting of: ethanol, medium-chain triglycerides (e.g., 812N), d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), monocaprylyl decaglyceride (e.g., MCM), PEG 400 caprylic / capric glycerides (e.g., ), and PEG 400.

[0230] In some embodiments, the hard capsule or soft capsule further comprises a capsule shell. In some embodiments, the capsule shell comprises one or more pharmaceutically acceptable excipients. In some embodiments, one or more pharmaceutically acceptable excipients of the capsule shell are selected from the group consisting of: gelatin shell, plasticizer, opacifying agent, and coloring agent. Plasticizers, opacifying agents, and coloring agents are well known in the art. In some embodiments, the capsule shell comprises one or more pharmaceutically acceptable excipients selected from the group consisting of: gelatin, glycerol, titanium dioxide, and iron oxide. In some embodiments, the iron oxide includes iron oxide (yellow).

[0231] In some embodiments, an oral formulation of a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof is provided. In certain embodiments, the oral formulation comprises a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof and monocaprylyl decaglyceride. In certain embodiments, the oral formulation comprises a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof, about 5% to about 20% ethanol, about 10% to about 30% vitamin E TPGS, and about 50% to about 85% MIGLYOL 812. In some embodiments, the oral formulation comprises a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof, about 8% to about 15% ethanol, about 15% to about 25% vitamin E TPGS, and about 60% to about 77% MIGLYOL 812. In certain embodiments, the oral formulation comprises a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof in about 10% ethanol, about 20% vitamin E TPGS, and about 70% MIGLYOL 812. In certain embodiments, the oral formulation is prepared as a hard gelatin capsule. In certain embodiments, the oral formulation is prepared as a soft gelatin capsule.

[0232]

[0233] In some embodiments, the hard or soft gelatin capsules disclosed herein comprise a compound of formula (Ib) or a pharmaceutically acceptable salt thereof and monocaprylyl decaglycerol. In some embodiments, the hard or soft gelatin capsules disclosed herein comprise the trifluoroacetate salt of a compound of formula (Ib) and monocaprylyl decaglycerol.

[0234] In some embodiments, the hard or soft gelatin capsules disclosed herein contain a compound of formula (Ia) and glyceryl monocaprylate decanoate. In some embodiments, in a hard or soft gelatin capsule containing a compound of formula (Ia) and glyceryl monocaprylate decanoate, the concentration of the compound of formula (Ia) is from about 10 mg / ml to about 500 mg / ml. In some embodiments, in a hard or soft gelatin capsule containing a compound of formula (Ia) and glyceryl monocaprylate decanoate, the concentration of the compound of formula (Ia) is from about 10 mg / ml to about 400 mg / ml. In some embodiments, in a hard or soft gelatin capsule containing a compound of formula (Ia) and glyceryl monocaprylate decanoate, the concentration of the compound of formula (Ia) is from about 50 mg / ml to about 300 mg / ml. In some embodiments, in a hard or soft gelatin capsule containing a compound of formula (Ia) and glyceryl monocaprylate decanoate, the concentration of the compound of formula (Ia) is from about 75 mg / ml to about 300 mg / ml. In some embodiments, in a hard or soft gelatin capsule containing a compound of formula (Ia) and glyceryl monocaprylate decanoate, the concentration of the compound of formula (Ia) is from about 50 mg / ml to about 200 mg / ml. In some embodiments, in a hard or soft gelatin capsule containing a compound of formula (Ia) and glyceryl monocaprylate decanoate, the concentration of the compound of formula (Ia) is from about 50 mg / ml to about 100 mg / ml. In some embodiments, in a hard or soft gelatin capsule containing a compound of formula (Ia) and glyceryl monocaprylate decanoate, the concentration of the compound of formula (Ia) is about 10 mg / ml. In some embodiments, in a hard or soft gelatin capsule containing a compound of formula (Ia) and glyceryl monocaprylate decanoate, the concentration of the compound of formula (Ia) is about 20 mg / ml. In some embodiments, in a hard or soft gelatin capsule containing a compound of formula (Ia) and glyceryl monocaprylate decanoate, the concentration of the compound of formula (Ia) is about 30 mg / ml. In some embodiments, in a hard or soft gelatin capsule containing a compound of formula (Ia) and glyceryl monocaprylate decanoate, the concentration of the compound of formula (Ia) is about 40 mg / ml. In some embodiments, in a hard or soft gelatin capsule containing a compound of formula (Ia) and glyceryl monocaprylate decanoate, the concentration of the compound of formula (Ia) is about 50 mg / ml. In some embodiments, in a hard or soft gelatin capsule containing a compound of formula (Ia) and glyceryl monocaprylate decanoate, the concentration of the compound of formula (Ia) is about 75 mg / ml. In some embodiments, in a hard or soft gelatin capsule containing a compound of formula (Ia) and glyceryl monocaprylate decanoate, the concentration of the compound of formula (Ia) is about 100 mg / ml. In some embodiments, in a hard or soft gelatin capsule containing a compound of formula (Ia) and glyceryl monocaprylate decanoate, the concentration of the compound of formula (Ia) is about 125 mg / ml.In some embodiments, in a hard or soft gelatin capsule containing the compound of formula (Ia) and monocaprylyl decaglyceride, the concentration of the compound of formula (Ia) is about 150 mg / ml. In some embodiments, in a hard or soft gelatin capsule containing the compound of formula (Ia) and monocaprylyl decaglyceride, the concentration of the compound of formula (Ia) is about 175 mg / ml. In some embodiments, in a hard or soft gelatin capsule containing the compound of formula (Ia) and monocaprylyl decaglyceride, the concentration of the compound of formula (Ia) is about 200 mg / ml. In some embodiments, in a hard or soft gelatin capsule containing the compound of formula (Ia) and monocaprylyl decaglyceride, the concentration of the compound of formula (Ia) is about 225 mg / ml. In some embodiments, in a hard or soft gelatin capsule containing the compound of formula (Ia) and monocaprylyl decaglyceride, the concentration of the compound of formula (Ia) is about 250 mg / ml. In some embodiments, in a hard or soft gelatin capsule containing the compound of formula (Ia) and monocaprylyl decaglyceride, the concentration of the compound of formula (Ia) is about 275 mg / ml. In some embodiments, in a hard or soft gelatin capsule containing the compound of formula (Ia) and monocaprylyl decaglyceride, the concentration of the compound of formula (Ia) is about 300 mg / ml. In some embodiments, in a hard or soft gelatin capsule containing the compound of formula (Ia) and monocaprylyl decaglyceride, the concentration of the compound of formula (Ia) is about 325 mg / ml. In some embodiments, in a hard or soft gelatin capsule containing the compound of formula (Ia) and monocaprylyl decaglyceride, the concentration of the compound of formula (Ia) is about 350 mg / ml. In some embodiments, in a hard or soft gelatin capsule containing the compound of formula (Ia) and monocaprylyl decaglyceride, the concentration of the compound of formula (Ia) is about 375 mg / ml. In some embodiments, in a hard or soft gelatin capsule containing the compound of formula (Ia) and monocaprylyl decaglyceride, the concentration of the compound of formula (Ia) is about 400 mg / ml. In some embodiments, in a hard or soft gelatin capsule containing the compound of formula (Ia) and monocaprylyl decaglyceride, the concentration of the compound of formula (Ia) is about 425 mg / ml. In some embodiments, in a hard or soft gelatin capsule containing the compound of formula (Ia) and monocaprylyl decaglyceride, the concentration of the compound of formula (Ia) is about 450 mg / ml. In some embodiments, in a hard or soft gelatin capsule containing the compound of formula (Ia) and monocaprylyl decaglyceride, the concentration of the compound of formula (Ia) is about 475 mg / ml. In some embodiments, in a hard or soft gelatin capsule containing the compound of formula (Ia) and monocaprylyl decaglyceride, the concentration of the compound of formula (Ia) is about 500 mg / ml.

[0235] In some embodiments, in a hard or soft gelatin capsule containing a compound of formula (Ia) and monocaprylyl decanoate, the amount of monocaprylyl decanoate is from about 30 w / w% to about 85 w / w%. In some embodiments, in a hard or soft gelatin capsule containing a compound of formula (Ia) and monocaprylyl decanoate, the amount of monocaprylyl decanoate is from about 40 w / w% to about 80 w / w%. In some embodiments, in a hard or soft gelatin capsule containing a compound of formula (Ia) and monocaprylyl decanoate, the amount of monocaprylyl decanoate is from about 50 w / w% to about 80 w / w%. In some embodiments, in a hard or soft gelatin capsule containing a compound of formula (Ia) and monocaprylyl decanoate, the amount of monocaprylyl decanoate is from about 60 w / w% to about 70 w / w%. In some embodiments, in a hard or soft gelatin capsule containing a compound of formula (Ia) and monocaprylyl decanoate, the amount of monocaprylyl decanoate is about 65.9 w / w%. In some embodiments, in a hard or soft gelatin capsule containing a compound of formula (Ia) and monocaprylyl decanoate, the amount of monocaprylyl decanoate is about 65.94 w / w%.

[0236] In some embodiments, in a hard or soft gelatin capsule containing a compound of formula (Ia) and monocaprylyl decanoate, the amount of the compound of formula (Ia) is from about 1 w / w% to about 40 w / w%. In some embodiments, in a hard or soft gelatin capsule containing a compound of formula (Ia) and monocaprylyl decanoate, the amount of the compound of formula (Ia) is from about 1 w / w% to about 35 w / w%. In some embodiments, in a hard or soft gelatin capsule containing a compound of formula (Ia) and monocaprylyl decanoate, the amount of the compound of formula (Ia) is from about 2 w / w% to about 30 w / w%. In some embodiments, in a hard or soft gelatin capsule containing a compound of formula (Ia) and monocaprylyl decanoate, the amount of the compound of formula (Ia) is from about 3 w / w% to about 28 w / w%. In some embodiments, in a hard or soft gelatin capsule containing a compound of formula (Ia) and monocaprylyl decanoate, the amount of the compound of formula (Ia) is about 3.4 w / w%. In some embodiments, in a hard or soft gelatin capsule containing a compound of formula (Ia) and monocaprylyl decanoate, the amount of the compound of formula (Ia) is about 3.42 w / w%.

[0237] In some embodiments, the hard gelatin or soft gelatin capsules containing the compound of formula (Ia) and monocaprylyl decaglycerol further comprise a capsule shell. In some embodiments, the capsule shell comprises one or more pharmaceutically acceptable excipients. In some embodiments, the one or more pharmaceutically acceptable excipients of the capsule shell are selected from the group consisting of: gelatin shell, plasticizer, opacifying agent, and coloring agent. In some embodiments, the hard gelatin or soft gelatin capsules containing the compound of formula (Ia) and monocaprylyl decaglycerol further comprise one or more pharmaceutically acceptable excipients selected from gelatin, glycerol, titanium dioxide, and iron oxide. In some embodiments, the hard gelatin or soft gelatin capsules containing the compound of formula (Ia) and monocaprylyl decaglycerol further comprise gelatin. In some embodiments, the hard gelatin or soft gelatin capsules containing the compound of formula (Ia) and monocaprylyl decaglycerol further comprise glycerol. In some embodiments, the hard gelatin or soft gelatin capsules containing the compound of formula (Ia) and monocaprylyl decaglycerol further comprise titanium dioxide. In some embodiments, the hard gelatin or soft gelatin capsules containing the compound of formula (Ia) and monocaprylyl decaglycerol further comprise iron oxide. In some embodiments, the hard gelatin or soft gelatin capsules containing the compound of formula (Ia) and monocaprylyl decaglycerol further comprise gelatin and glycerol. In some embodiments, the hard gelatin or soft gelatin capsules containing the compound of formula (Ia) and monocaprylyl decaglycerol further comprise gelatin, glycerol, and titanium dioxide. In some embodiments, the hard gelatin or soft gelatin capsules containing the compound of formula (Ia), monocaprylyl decaglycerol, gelatin, glycerol, titanium dioxide, and iron oxide comprise iron oxide (yellow).

[0238] In some embodiments, in a hard or soft gelatin capsule comprising a compound of formula (Ia), monocaprylyl glycerol, gelatin, glycerol, titanium dioxide, and iron oxide, the amount of gelatin is from about 10 w / w% to about 40 w / w%. In some embodiments, in a hard or soft gelatin capsule comprising a compound of formula (Ia), monocaprylyl glycerol, gelatin, glycerol, titanium dioxide, and iron oxide, the amount of gelatin is from about 10 w / w% to about 30 w / w%. In some embodiments, in a hard or soft gelatin capsule comprising a compound of formula (Ia), monocaprylyl glycerol, gelatin, glycerol, titanium dioxide, and iron oxide, the amount of gelatin is from about 15 w / w% to about 25 w / w%. In some embodiments, in a hard or soft gelatin capsule comprising a compound of formula (Ia), monocaprylyl glycerol, gelatin, glycerol, titanium dioxide, and iron oxide, the amount of gelatin is from about 18 w / w% to about 22 w / w%. In some embodiments, in a hard or soft gelatin capsule comprising a compound of formula (Ia), monocaprylyl glycerol, gelatin, glycerol, titanium dioxide, and iron oxide, the amount of gelatin is about 19.6 w / w%. In some embodiments, in a hard or soft gelatin capsule comprising a compound of formula (Ia), monocaprylyl glycerol, gelatin, glycerol, titanium dioxide, and iron oxide, the amount of gelatin is about 19.60 w / w%.

[0239] In some embodiments, in a hard or soft gelatin capsule comprising a compound of formula (Ia), monocaprylyl glycerol, gelatin, glycerol, titanium dioxide, and iron oxide, the amount of glycerol is from about 3 w / w% to about 25 w / w%. In some embodiments, in a hard or soft gelatin capsule comprising a compound of formula (Ia), monocaprylyl glycerol, gelatin, glycerol, titanium dioxide, and iron oxide, the amount of glycerol is from about 5 w / w% to about 20 w / w%. In some embodiments, in a hard or soft gelatin capsule comprising a compound of formula (Ia), monocaprylyl glycerol, gelatin, glycerol, titanium dioxide, and iron oxide, the amount of glycerol is from about 5 w / w% to about 15 w / w%. In some embodiments, in a hard or soft gelatin capsule comprising a compound of formula (Ia), monocaprylyl glycerol, gelatin, glycerol, titanium dioxide, and iron oxide, the amount of glycerol is from about 8 w / w% to about 12 w / w%. In some embodiments, in a hard or soft gelatin capsule comprising a compound of formula (Ia), monocaprylyl glycerol, gelatin, glycerol, titanium dioxide, and iron oxide, the amount of glycerol is about 10.8 w / w%. In some embodiments, in a hard or soft gelatin capsule comprising a compound of formula (Ia), monocaprylyl glycerol, gelatin, glycerol, titanium dioxide, and iron oxide, the amount of glycerol is about 10.80 w / w%.

[0240] In some embodiments, in a hard or soft gelatin capsule comprising a compound of formula (Ia), monocaprylyl decaglycerin, gelatin, glycerol, titanium dioxide, and iron oxide, the amount of titanium dioxide is from about 0.01 w / w% to about 2 w / w%. In some embodiments, in a hard or soft gelatin capsule comprising a compound of formula (Ia), monocaprylyl decaglycerin, gelatin, glycerol, titanium dioxide, and iron oxide, the amount of titanium dioxide is from about 0.05 w / w% to about 1.5 w / w%. In some embodiments, in a hard or soft gelatin capsule comprising a compound of formula (Ia), monocaprylyl decaglycerin, gelatin, glycerol, titanium dioxide, and iron oxide, the amount of titanium dioxide is from about 0.1 w / w% to about 1.0 w / w%. In some embodiments, in a hard or soft gelatin capsule comprising a compound of formula (Ia), monocaprylyl decaglycerin, gelatin, glycerol, titanium dioxide, and iron oxide, the amount of titanium dioxide is from about 0.1 w / w% to about 0.5 w / w%. In some embodiments, in a hard or soft gelatin capsule comprising a compound of formula (Ia), monocaprylyl decaglycerin, gelatin, glycerol, titanium dioxide, and iron oxide, the amount of titanium dioxide is about 0.2 w / w%. In some embodiments, in a hard or soft gelatin capsule comprising a compound of formula (Ia), monocaprylyl decaglycerin, gelatin, glycerol, titanium dioxide, and iron oxide, the amount of titanium dioxide is about 0.22 w / w%.

[0241] In some embodiments, in a hard or soft gelatin capsule comprising a compound of formula (Ia), monocaprylyl decaglycerin, gelatin, glycerol, titanium dioxide, and iron oxide, the amount of iron oxide is from about 0.01 w / w% to about 1 w / w%. In some embodiments, in a hard or soft gelatin capsule comprising a compound of formula (Ia), monocaprylyl decaglycerin, gelatin, glycerol, titanium dioxide, and iron oxide, the amount of iron oxide is from about 0.01 w / w% to about 0.5 w / w%. In some embodiments, in a hard or soft gelatin capsule comprising a compound of formula (Ia), monocaprylyl decaglycerin, gelatin, glycerol, titanium dioxide, and iron oxide, the amount of iron oxide is from about 0.01 w / w% to about 0.15 w / w%. In some embodiments, in a hard or soft gelatin capsule comprising a compound of formula (Ia), monocaprylyl decaglycerin, gelatin, glycerol, titanium dioxide, and iron oxide, the amount of iron oxide is from about 0.01 w / w% to about 0.1 w / w%. In some embodiments, in a hard or soft gelatin capsule comprising a compound of formula (Ia), monocaprylyl decaglycerin, gelatin, glycerol, titanium dioxide, and iron oxide, the amount of iron oxide is about 0.02 w / w%.

[0242] In some embodiments, the hard gelatin or soft capsules disclosed herein comprise from about 30 w / w% to about 85 w / w% of glyceryl monocaprylate decanoate and from about 1 w / w% to about 40 w / w% of the compound of formula (Ia). In some embodiments, the hard gelatin or soft capsules disclosed herein comprise from about 40 w / w% to about 80 w / w% of glyceryl monocaprylate decanoate and from about 1 w / w% to about 35 w / w% of the compound of formula (Ia). In some embodiments, the hard gelatin or soft capsules disclosed herein comprise from about 50 w / w% to about 80 w / w% of glyceryl monocaprylate decanoate and from about 2 w / w% to about 30 w / w% of the compound of formula (Ia). In some embodiments, the hard gelatin or soft capsules disclosed herein comprise from about 60 w / w% to about 70 w / w% of glyceryl monocaprylate decanoate and from about 3 w / w% to about 28 w / w% of the compound of formula (Ia). In some embodiments, the hard gelatin or soft capsules disclosed herein comprise about 65.9 w / w% of glyceryl monocaprylate decanoate and about 3.4 w / w% of the compound of formula (Ia). In some embodiments, the hard gelatin or soft capsules disclosed herein comprise about 65.94 w / w% of glyceryl monocaprylate decanoate and about 3.42 w / w% of the compound of formula (Ia).

[0243] In some embodiments, the hard gelatin or soft capsules disclosed herein comprise from about 30 w / w% to about 85 w / w% of glyceryl monocaprylate decanoate, from about 1 w / w% to about 40 w / w% of the compound of formula (Ia), from about 10 w / w% to about 40 w / w% of gelatin, from about 3 w / w% to about 25 w / w% of glycerol, from about 0.01 w / w% to about 2 w / w% of titanium dioxide and from about 0.01 w / w% to about 1 w / w% of iron oxide. In some embodiments, the hard gelatin or soft capsules disclosed herein comprise from about 40 w / w% to about 80 w / w% of glyceryl monocaprylate decanoate, from about 1 w / w% to about 35 w / w% of the compound of formula (Ia), from about 10 w / w% to about 30 w / w% of gelatin, from about 5 w / w% to about 20 w / w% of glycerol, from about 0.05 w / w% to about 1.5 w / w% of titanium dioxide and from about 0.01 w / w% to about 0.5 w / w% of iron oxide. In some embodiments, the hard gelatin or soft capsules disclosed herein comprise from about 50 w / w% to about 80 w / w% of glyceryl monocaprylate decanoate, from about 2 w / w% to about 30 w / w% of the compound of formula (Ia), from about 15 w / w% to about 25 w / w% of gelatin, from about 5 w / w% to about 15 w / w% of glycerol, from about 0.1 w / w% to about 1.0 w / w% of titanium dioxide and from about 0.01 w / w% to about 0.15 w / w% of iron oxide. In some embodiments, the hard gelatin or soft capsules disclosed herein comprise from about 60 w / w% to about 70 w / w% of glyceryl monocaprylate decanoate, from about 3 w / w% to about 28 w / w% of the compound of formula (Ia), from about 18 w / w% to about 22 w / w% of gelatin, from about 8 w / w% to about 12 w / w% of glycerol, from about 0.1 w / w% to about 0.5 w / w% of titanium dioxide and from about 0.01 w / w% to about 0.1 w / w% of iron oxide. In some embodiments, the hard gelatin or soft capsules disclosed herein comprise about 65.9 w / w% of glyceryl monocaprylate decanoate, about 3.4 w / w% of the compound of formula (Ia), about 19.6 w / w% of gelatin, about 10.8 w / w% of glycerol, about 0.2 w / w% of titanium dioxide and about 0.02 w / w% of iron oxide. In some embodiments, the hard gelatin or soft capsules disclosed herein comprise about 65.94 w / w% of glyceryl monocaprylate decanoate, about 3.42 w / w% of the compound of formula (Ia), about 19.60 w / w% of gelatin, about 10.80 w / w% of glycerol, about 0.22 w / w% of titanium dioxide and about 0.02 w / w% of iron oxide.

[0244] In some embodiments, in a hard or soft gelatin capsule comprising a compound of formula (Ia), monocaprylyl decanoate, gelatin, glycerol, titanium dioxide, and iron oxide, the iron oxide comprises iron oxide (yellow). In some embodiments, the hard or soft gelatin capsules disclosed herein comprise about 65.9 w / w% monocaprylyl decanoate, about 3.4 w / w% of the compound of formula (Ia), about 19.6 w / w% gelatin, about 10.8 w / w% glycerol, about 0.2 w / w% titanium dioxide, and about 0.02 w / w% iron oxide (yellow). In some embodiments, the hard or soft gelatin capsules disclosed herein comprise about 65.94 w / w% monocaprylyl decanoate, about 3.42 w / w% of the compound of formula (Ia), about 19.60 w / w% gelatin, about 10.80 w / w% glycerol, about 0.22 w / w% titanium dioxide, and about 0.02 w / w% iron oxide (yellow).

[0245] In some embodiments, the hard gelatin or soft gelatin capsules disclosed herein comprise the sodium salt of the compound of formula (Ia) and glycerol monocaprylate decanoate. In some embodiments, in a hard gelatin or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia) and glycerol monocaprylate decanoate, the concentration of the compound of formula (Ia) is from about 10 mg / ml to about 500 mg / ml. In some embodiments, in a hard gelatin or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia) and glycerol monocaprylate decanoate, the concentration of the compound of formula (Ia) is from about 10 mg / ml to about 400 mg / ml. In some embodiments, in a hard gelatin or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia) and glycerol monocaprylate decanoate, the concentration of the compound of formula (Ia) is from about 50 mg / ml to about 300 mg / ml. In some embodiments, in a hard gelatin or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia) and glycerol monocaprylate decanoate, the concentration of the compound of formula (Ia) is from about 75 mg / ml to about 300 mg / ml. In some embodiments, in a hard gelatin or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia) and glycerol monocaprylate decanoate, the concentration of the compound of formula (Ia) is about 10 mg / ml. In some embodiments, in a hard gelatin or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia) and glycerol monocaprylate decanoate, the concentration of the compound of formula (Ia) is about 20 mg / ml. In some embodiments, in a hard gelatin or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia) and glycerol monocaprylate decanoate, the concentration of the compound of formula (Ia) is about 30 mg / ml. In some embodiments, in a hard gelatin or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia) and glycerol monocaprylate decanoate, the concentration of the compound of formula (Ia) is about 40 mg / ml. In some embodiments, in a hard gelatin or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia) and glycerol monocaprylate decanoate, the concentration of the compound of formula (Ia) is about 50 mg / ml. In some embodiments, in a hard gelatin or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia) and glycerol monocaprylate decanoate, the concentration of the compound of formula (Ia) is about 75 mg / ml. In some embodiments, in a hard gelatin or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia) and glycerol monocaprylate decanoate, the concentration of the compound of formula (Ia) is about 100 mg / ml. In some embodiments, in a hard gelatin or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia) and glycerol monocaprylate decanoate, the concentration of the compound of formula (Ia) is about 125 mg / ml. In some embodiments, in a hard gelatin or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia) and glycerol monocaprylate decanoate, the concentration of the compound of formula (Ia) is about 150 mg / ml. In some embodiments, in a hard gelatin or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia) and glycerol monocaprylate decanoate, the concentration of the compound of formula (Ia) is about 175 mg / ml.In some embodiments, in a hard or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia) and glyceryl monocaprylate decanoate, the concentration of the compound of formula (Ia) is about 200 mg / ml. In some embodiments, in a hard or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia) and glyceryl monocaprylate decanoate, the concentration of the compound of formula (Ia) is about 225 mg / ml. In some embodiments, in a hard or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia) and glyceryl monocaprylate decanoate, the concentration of the compound of formula (Ia) is about 250 mg / ml. In some embodiments, in a hard or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia) and glyceryl monocaprylate decanoate, the concentration of the compound of formula (Ia) is about 275 mg / ml. In some embodiments, in a hard or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia) and glyceryl monocaprylate decanoate, the concentration of the compound of formula (Ia) is about 300 mg / ml. In some embodiments, in a hard or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia) and glyceryl monocaprylate decanoate, the concentration of the compound of formula (Ia) is about 325 mg / ml. In some embodiments, in a hard or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia) and glyceryl monocaprylate decanoate, the concentration of the compound of formula (Ia) is about 350 mg / ml. In some embodiments, in a hard or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia) and glyceryl monocaprylate decanoate, the concentration of the compound of formula (Ia) is about 375 mg / ml. In some embodiments, in a hard or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia) and glyceryl monocaprylate decanoate, the concentration of the compound of formula (Ia) is about 400 mg / ml. In some embodiments, in a hard or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia) and glyceryl monocaprylate decanoate, the concentration of the compound of formula (Ia) is about 425 mg / ml. In some embodiments, in a hard or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia) and glyceryl monocaprylate decanoate, the concentration of the compound of formula (Ia) is about 450 mg / ml. In some embodiments, in a hard or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia) and glyceryl monocaprylate decanoate, the concentration of the compound of formula (Ia) is about 475 mg / ml. In some embodiments, in a hard or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia) and glyceryl monocaprylate decanoate, the concentration of the compound of formula (Ia) is about 500 mg / ml.

[0246] In some embodiments, in a hard or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia) and monocaprylyl decaglycerol, the amount of monocaprylyl decaglycerol is from about 30 w / w% to about 99 w / w%. In some embodiments, in a hard or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia) and monocaprylyl decaglycerol, the amount of monocaprylyl decaglycerol is from about 50 w / w% to about 99 w / w%. In some embodiments, in a hard or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia) and monocaprylyl decaglycerol, the amount of monocaprylyl decaglycerol is from about 60 w / w% to about 99 w / w%. In some embodiments, in a hard or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia) and monocaprylyl decaglycerol, the amount of monocaprylyl decaglycerol is from about 75 w / w% to about 98 w / w%. In some embodiments, in a hard or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia) and monocaprylyl decaglycerol, the amount of monocaprylyl decaglycerol is from about 80.09 w / w% to about 94.85 w / w%. In some embodiments, in a hard or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia) and monocaprylyl decaglycerol, the amount of monocaprylyl decaglycerol is from about 80.1 w / w% to about 94.9 w / w%. In some embodiments, in a hard or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia) and monocaprylyl decaglycerol, the amount of monocaprylyl decaglycerol is about 80.09 w / w%. In some embodiments, in a hard or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia) and monocaprylyl decaglycerol, the amount of monocaprylyl decaglycerol is about 80.1 w / w%. In some embodiments, in a hard or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia) and monocaprylyl decaglycerol, the amount of monocaprylyl decaglycerol is about 94.85 w / w%. In some embodiments, in a hard or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia) and monocaprylyl decaglycerol, the amount of monocaprylyl decaglycerol is about 94.9 w / w%.

[0247] In some embodiments, in a hard or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia) and monocaprylyl decaglycerin, the amount of the sodium salt of the compound of formula (Ia) is from about 1 w / w% to about 40 w / w%. In some embodiments, in a hard or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia) and monocaprylyl decaglycerin, the amount of the sodium salt of the compound of formula (Ia) is from about 1 w / w% to about 35 w / w%. In some embodiments, in a hard or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia) and monocaprylyl decaglycerin, the amount of the sodium salt of the compound of formula (Ia) is from about 2 w / w% to about 30 w / w%. In some embodiments, in a hard or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia) and monocaprylyl decaglycerin, the amount of the sodium salt of the compound of formula (Ia) is from about 3 w / w% to about 28 w / w%. In some embodiments, in a hard or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia) and monocaprylyl decaglycerin, the amount of the sodium salt of the compound of formula (Ia) is about 5.15 w / w%. In some embodiments, in a hard or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia) and monocaprylyl decaglycerin, the amount of the sodium salt of the compound of formula (Ia) is about 5.2 w / w%. In some embodiments, in a hard or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia) and monocaprylyl decaglycerin, the amount of the sodium salt of the compound of formula (Ia) is about 19.9 w / w%. In some embodiments, in a hard or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia) and monocaprylyl decaglycerin, the amount of the sodium salt of the compound of formula (Ia) is about 19.91 w / w%.

[0248] In some embodiments, a hard or soft gelatin capsule containing the sodium salt of the compound of formula (Ia) and monocaprylyl decaglycerin further includes a capsule shell. In some embodiments, the capsule shell contains one or more pharmaceutically acceptable excipients. In some embodiments, one or more pharmaceutically acceptable excipients of the capsule shell are selected from gelatin shells, plasticizers, opacifying agents, and colorants. In some embodiments, a hard or soft gelatin capsule containing the sodium salt of the compound of formula (Ia) and monocaprylyl decaglycerin further contains one or more pharmaceutically acceptable excipients selected from gelatin, glycerol, titanium dioxide, and iron oxide. In some embodiments, a hard or soft gelatin capsule containing the sodium salt of the compound of formula (Ia) and monocaprylyl decaglycerin further contains gelatin. In some embodiments, a hard or soft gelatin capsule containing the sodium salt of the compound of formula (Ia) and monocaprylyl decaglycerin further contains glycerol. In some embodiments, a hard or soft gelatin capsule containing the sodium salt of the compound of formula (Ia) and monocaprylyl decaglycerin further contains titanium dioxide. In some embodiments, a hard or soft gelatin capsule containing the sodium salt of the compound of formula (Ia) and monocaprylyl decaglycerin further contains iron oxide. In some embodiments, a hard or soft gelatin capsule containing the sodium salt of the compound of formula (Ia) and monocaprylyl decaglycerin further contains gelatin and glycerol. In some embodiments, a hard or soft gelatin capsule containing the sodium salt of the compound of formula (Ia) and monocaprylyl decaglycerin further contains gelatin, glycerol, and titanium dioxide. In some embodiments, a hard or soft gelatin capsule containing the sodium salt of the compound of formula (Ia), monocaprylyl decaglycerin, gelatin, glycerol, titanium dioxide, and iron oxide contains iron oxide (yellow).

[0249] In some embodiments, in a hard or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia), monocaprylyl decanoate, gelatin, glycerol, titanium dioxide, and iron oxide, the amount of gelatin is from about 10 w / w% to about 40 w / w%. In some embodiments, in a hard or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia), monocaprylyl decanoate, gelatin, glycerol, titanium dioxide, and iron oxide, the amount of gelatin is from about 10 w / w% to about 30 w / w%. In some embodiments, in a hard or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia), monocaprylyl decanoate, gelatin, glycerol, titanium dioxide, and iron oxide, the amount of gelatin is from about 15 w / w% to about 25 w / w%. In some embodiments, in a hard or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia), monocaprylyl decanoate, gelatin, glycerol, titanium dioxide, and iron oxide, the amount of gelatin is from about 18 w / w% to about 22 w / w%. In some embodiments, in a hard or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia), monocaprylyl decanoate, gelatin, glycerol, titanium dioxide, and iron oxide, the amount of gelatin is about 19.6 w / w%. In some embodiments, in a hard or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia), monocaprylyl decanoate, gelatin, glycerol, titanium dioxide, and iron oxide, the amount of gelatin is about 19.60 w / w%.

[0250] In some embodiments, in a hard or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia), monocaprylyl decanoate, gelatin, glycerol, titanium dioxide, and iron oxide, the amount of glycerol is from about 3 w / w% to about 25 w / w%. In some embodiments, in a hard or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia), monocaprylyl decanoate, gelatin, glycerol, titanium dioxide, and iron oxide, the amount of glycerol is from about 5 w / w% to about 20 w / w%. In some embodiments, in a hard or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia), monocaprylyl decanoate, gelatin, glycerol, titanium dioxide, and iron oxide, the amount of glycerol is from about 5 w / w% to about 15 w / w%. In some embodiments, in a hard or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia), monocaprylyl decanoate, gelatin, glycerol, titanium dioxide, and iron oxide, the amount of glycerol is from about 8 w / w% to about 12 w / w%. In some embodiments, in a hard or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia), monocaprylyl decanoate, gelatin, glycerol, titanium dioxide, and iron oxide, the amount of glycerol is about 10.8 w / w%. In some embodiments, in a hard or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia), monocaprylyl decanoate, gelatin, glycerol, titanium dioxide, and iron oxide, the amount of glycerol is about 10.80 w / w%.

[0251] In some embodiments, in a hard or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia), monocaprylyl glycerol, gelatin, glycerol, titanium dioxide, and iron oxide, the amount of titanium dioxide is from about 0.01 w / w% to about 2 w / w%. In some embodiments, in a hard or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia), monocaprylyl glycerol, gelatin, glycerol, titanium dioxide, and iron oxide, the amount of titanium dioxide is from about 0.05 w / w% to about 1.5 w / w%. In some embodiments, in a hard or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia), monocaprylyl glycerol, gelatin, glycerol, titanium dioxide, and iron oxide, the amount of titanium dioxide is from about 0.1 w / w% to about 1.0 w / w%. In some embodiments, in a hard or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia), monocaprylyl glycerol, gelatin, glycerol, titanium dioxide, and iron oxide, the amount of titanium dioxide is from about 0.1 w / w% to about 0.5 w / w%. In some embodiments, in a hard or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia), monocaprylyl glycerol, gelatin, glycerol, titanium dioxide, and iron oxide, the amount of titanium dioxide is about 0.2 w / w%. In some embodiments, in a hard or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia), monocaprylyl glycerol, gelatin, glycerol, titanium dioxide, and iron oxide, the amount of titanium dioxide is about 0.22 w / w%.

[0252] In some embodiments, in a hard or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia), monocaprylyl glycerol, gelatin, glycerol, titanium dioxide, and iron oxide, the amount of iron oxide is from about 0.01 w / w% to about 1 w / w%. In some embodiments, in a hard or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia), monocaprylyl glycerol, gelatin, glycerol, titanium dioxide, and iron oxide, the amount of iron oxide is from about 0.01 w / w% to about 0.5 w / w%. In some embodiments, in a hard or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia), monocaprylyl glycerol, gelatin, glycerol, titanium dioxide, and iron oxide, the amount of iron oxide is from about 0.01 w / w% to about 0.15 w / w%. In some embodiments, in a hard or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia), monocaprylyl glycerol, gelatin, glycerol, titanium dioxide, and iron oxide, the amount of iron oxide is from about 0.01 w / w% to about 0.1 w / w%. In some embodiments, in a hard or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia), monocaprylyl glycerol, gelatin, glycerol, titanium dioxide, and iron oxide, the amount of iron oxide is about 0.02 w / w%.

[0253] In some embodiments, the hard or soft gelatin capsules disclosed herein comprise from about 30 w / w% to about 99 w / w% of glycerol monocaprylate and from about 1 w / w% to about 40 w / w% of the sodium salt of the compound of formula (Ia). In some embodiments, the hard or soft gelatin capsules disclosed herein comprise from about 50 w / w% to about 99 w / w% of glycerol monocaprylate and from about 1 w / w% to about 35 w / w% of the sodium salt of the compound of formula (Ia). In some embodiments, the hard or soft gelatin capsules disclosed herein comprise from about 60 w / w% to about 99 w / w% of glycerol monocaprylate and from about 2 w / w% to about 30 w / w% of the sodium salt of the compound of formula (Ia). In some embodiments, the hard or soft gelatin capsules disclosed herein comprise from about 75 w / w% to about 98 w / w% of glycerol monocaprylate and from about 3 w / w% to about 28 w / w% of the sodium salt of the compound of formula (Ia). In some embodiments, the hard or soft gelatin capsules disclosed herein comprise from about 80.09 w / w% to about 94.85 w / w% of glycerol monocaprylate and from about 5.15 w / w% to about 19.91 w / w% of the sodium salt of the compound of formula (Ia). In some embodiments, the hard or soft gelatin capsules disclosed herein comprise from about 80.1 w / w% to about 94.9 w / w% of glycerol monocaprylate and from about 5.2 w / w% to about 19.9 w / w% of the sodium salt of the compound of formula (Ia). In some embodiments, the hard or soft gelatin capsules disclosed herein comprise about 94.85 w / w% of glycerol monocaprylate and about 5.15 w / w% of the sodium salt of the compound of formula (Ia). In some embodiments, the hard or soft gelatin capsules disclosed herein comprise about 94.9 w / w% of glycerol monocaprylate and about 5.2 w / w% of the sodium salt of the compound of formula (Ia). In some embodiments, the hard or soft gelatin capsules disclosed herein comprise about 80.09 w / w% of glycerol monocaprylate and about 19.91 w / w% of the sodium salt of the compound of formula (Ia). In some embodiments, the hard or soft gelatin capsules disclosed herein comprise about 80.1 w / w% of glycerol monocaprylate and about 19.9 w / w% of the sodium salt of the compound of formula (Ia).

[0254] In some embodiments, the iron oxide in the hard or soft gelatin capsule comprising the sodium salt of the compound of formula (Ia), glycerol monocaprylate, gelatin, glycerol, titanium dioxide and iron oxide comprises iron oxide (yellow).

[0255] In some embodiments, the hard or soft gelatin capsules disclosed herein can be taken with food. In some embodiments, the hard or soft gelatin capsules disclosed herein exhibit C max increase when taken with food (compared to when not taken with food). In some embodiments, the hard or soft gelatin capsules disclosed herein exhibit Cmax Increased by about 2 - 10 times. In some embodiments, the hard gelatin or soft gelatin capsules disclosed herein show C when taken with food (compared to when not taken with food). max Increased by about 2 times. In some embodiments, the hard gelatin or soft gelatin capsules disclosed herein show C when taken with food (compared to when not taken with food). max Increased by about 3 times. In some embodiments, the hard gelatin or soft gelatin capsules disclosed herein show C when taken with food (compared to when not taken with food). max Increased by about 4 times. In some embodiments, the hard gelatin or soft gelatin capsules disclosed herein show C when taken with food (compared to when not taken with food). max Increased by about 5 times. In some embodiments, the hard gelatin or soft gelatin capsules disclosed herein show C when taken with food (compared to when not taken with food). max Increased by about 6 times. In some embodiments, the hard gelatin or soft gelatin capsules disclosed herein show C when taken with food (compared to when not taken with food). max Increased by about 7 times. In some embodiments, the hard gelatin or soft gelatin capsules disclosed herein show C when taken with food (compared to when not taken with food). max Increased by about 8 times.

[0256] In some embodiments, the food taken with the hard gelatin or soft gelatin capsules disclosed herein includes any food from low - fat to high - fat. In some embodiments, the food taken with the hard gelatin or soft gelatin capsules disclosed herein includes any low - fat food. In some embodiments, the food taken with the hard gelatin or soft gelatin capsules disclosed herein includes any medium - fat food. In some embodiments, the food taken with the hard gelatin or soft gelatin capsules disclosed herein includes any high - fat food. In some embodiments, the food taken with the hard gelatin or soft gelatin capsules disclosed herein is low - fat. In some embodiments, the food taken with the hard gelatin or soft gelatin capsules disclosed herein is medium - fat. In some embodiments, the food taken with the hard gelatin or soft gelatin capsules disclosed herein is high - fat.

[0257] In some embodiments, the hard gelatin or soft gelatin capsules disclosed herein are hard gelatin capsules. In some embodiments, the hard gelatin or soft gelatin capsules disclosed herein are soft gelatin capsules.

[0258] In some embodiments, an oral formulation of a compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof disclosed herein is a tablet prepared from a spray-dried dispersion of the compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof. In some embodiments, the amount of the compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof in the tablet disclosed herein is from about 5 mg to about 500 mg. In some embodiments, the amount of the compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof in the tablet disclosed herein is from about 25 mg to about 500 mg. In some embodiments, the amount of the compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof in the tablet disclosed herein is from about 25 mg to about 400 mg. In some embodiments, the amount of the compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof in the tablet disclosed herein is from about 25 mg to about 300 mg. In some embodiments, the amount of the compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof in the tablet disclosed herein is from about 50 mg to about 500 mg. In some embodiments, the amount of the compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof in the tablet disclosed herein is from about 75 mg to about 500 mg. In some embodiments, the amount of the compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof in the tablet disclosed herein is from about 50 mg to about 400 mg. In some embodiments, the amount of the compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof in the tablet disclosed herein is from about 50 mg to about 300 mg. In some embodiments, the amount of the compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof in the tablet disclosed herein is from about 75 mg to about 400 mg. In some embodiments, the amount of the compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof in the tablet disclosed herein is from about 75 mg to about 300 mg.In some embodiments, the amount of the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof in the tablets disclosed herein is about 5 mg, about 10 mg, about 15 mg, about 20 mg, about 25 mg, about 30 mg, about 35 mg, about 40 mg, about 45 mg, about 50 mg, about 55 mg, about 60 mg, about 65 mg, about 70 mg, about 75 mg, about 80 mg, about 85 mg, about 90 mg, about 95 mg, about 100 mg, about 105 mg, about 110 mg, about 115 mg, about 120 mg, about 125 mg, about 130 mg, about 135 mg, about 140 mg, about 145 mg, about 150 mg, about 155 mg, about 160 mg, about 165 mg, 170 mg, about 175 mg, about 180 mg, about 185 mg, about 190 mg, about 195 mg, about 200 mg, 205 mg, about 210 mg, about 215 mg, about 220 mg, about 225 mg, about 230 mg, about 235 mg, about 240 mg, about 245 mg, about 250 mg, about 255 mg, about 260 mg, about 265 mg, about 270 mg, about 275 mg, about 280 mg, about 285 mg, about 290 mg, about 295 mg, about 300 mg, about 305 mg, about 310 mg, about 315 mg, about 320 mg, about 325 mg, about 330 mg, about 335 mg, about 340 mg, about 345 mg, about 350 mg, about 355 mg, about 360 mg, about 365 mg, about 370 mg, about 375 mg, about 380 mg, about 385 mg, about 390 mg, about 395 mg, about 400 mg, about 405 mg, about 410 mg, about 415 mg, about 420 mg, about 425 mg, about 430 mg, about 435 mg, about 440 mg, about 445 mg, about 450 mg, about 455 mg, about 460 mg, about 465 mg, about 470 mg, about 475 mg, about 480 mg, about 485 mg, about 490 mg, about 495 mg or about 500 mg. In some embodiments, the amount of the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof in the tablets disclosed herein is about 5 mg. In some embodiments, the amount of the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof in the tablets disclosed herein is about 10 mg. In some embodiments, the amount of the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof in the tablets disclosed herein is about 20 mg. In some embodiments, the amount of the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof in the tablets disclosed herein is about 25 mg. In some embodiments, the amount of the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof in the tablets disclosed herein is about 30 mg.In some embodiments, the amount of the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof in the tablets disclosed herein is about 40 mg. In some embodiments, the amount of the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof in the tablets disclosed herein is about 50 mg. In some embodiments, the amount of the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof in the tablets disclosed herein is about 75 mg. In some embodiments, the amount of the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof in the tablets disclosed herein is about 100 mg. In some embodiments, the amount of the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof in the tablets disclosed herein is about 125 mg. In some embodiments, the amount of the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof in the tablets disclosed herein is about 150 mg. In some embodiments, the amount of the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof in the tablets disclosed herein is about 175 mg. In some embodiments, the amount of the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof in the tablets disclosed herein is about 200 mg. In some embodiments, the amount of the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof in the tablets disclosed herein is about 225 mg. In some embodiments, the amount of the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof in the tablets disclosed herein is about 250 mg. In some embodiments, the amount of the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof in the tablets disclosed herein is about 275 mg. In some embodiments, the amount of the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof in the tablets disclosed herein is about 300 mg. In some embodiments, the amount of the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof in the tablets disclosed herein is about 325 mg. In some embodiments, the amount of the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof in the tablets disclosed herein is about 350 mg. In some embodiments, the amount of the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof in the tablets disclosed herein is about 375 mg. In some embodiments, the amount of the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof in the tablets disclosed herein is about 400 mg. In some embodiments, the amount of the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof in the tablets disclosed herein is about 425 mg. In some embodiments, the amount of the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof in the tablets disclosed herein is about 450 mg. In some embodiments, the amount of the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof in the tablets disclosed herein is about 475 mg.In some embodiments, the amount of the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof in the tablets disclosed herein is about 500 mg.

[0259] In some embodiments, the tablets disclosed herein comprise a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable excipients. In some embodiments, the tablets disclosed herein comprise a compound of formula (Ia) or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable excipients. In some embodiments, the tablets disclosed herein comprise a compound of formula (Ia) and one or more pharmaceutically acceptable excipients. In some embodiments, the tablets disclosed herein comprise the sodium salt of the compound of formula (Ia) and one or more pharmaceutically acceptable excipients. In some embodiments, the tablets disclosed herein comprise a compound of formula (Ib) and one or more pharmaceutically acceptable excipients. In some embodiments, the tablets disclosed herein comprise the trifluoroacetate salt of the compound of formula (Ib) and one or more pharmaceutically acceptable excipients.

[0260] The pharmaceutically acceptable excipients of the tablets disclosed herein should be compatible with the other components of the formulation and physiologically harmless to the recipient. Examples of suitable excipients are well known to those skilled in the art of tablet formulations and can be found, for example, in the Handbook of Pharmaceutical Excipients (eds. Rowe, Sheskey & Quinn), 6th Edition, 2009. As used herein, the term "excipient" refers in particular to alkalizing agents, solubilizers, glidants, fillers, binders, lubricants, diluents, preservatives, surfactants, dispersants, etc. The term also includes agents such as sweeteners, flavoring agents, coloring agents and preservatives. Such components will generally be present in the tablets in a mixture form.

[0261] Examples of solubilizers include, but are not limited to: surfactants (including ionic and non-ionic surfactants) such as sodium lauryl sulfate, cetrimonium bromide, polysorbates (e.g., polysorbate 20 or 80), poloxamers (e.g., poloxamer 188 or 207) and polyethylene glycol. Examples of lubricants, glidants and flow aids include, but are not limited to: magnesium stearate, calcium stearate, stearic acid, hydrogenated vegetable oil, glyceryl palmitostearate, glyceryl behenate, sodium stearyl fumarate, colloidal silica and talc. Examples of disintegrants include, but are not limited to: starch, cellulose, cross-linked PVP, sodium starch glycolate, cross-linked sodium carboxymethyl cellulose, etc. Examples of fillers (also referred to as fillers or diluents) include, but are not limited to: starch, maltodextrin, polyols (e.g., lactose) and cellulose. Examples of binders include, but are not limited to: cross-linked PVP, HPMC, microcrystalline cellulose, sucrose, starch, etc.

[0262] In some embodiments, the tablets disclosed herein comprise a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable excipients selected from matrix formers, surfactants, fillers, disintegrants, and lubricants. In some embodiments, the tablets comprise from about 1 w / w% to about 10 w / w% of a matrix former. In some embodiments, the matrix former comprises copovidone. In some embodiments, the tablets comprise from about 0.01 w / w% to about 10 w / w% of a surfactant. In some embodiments, the surfactant comprises poloxamer 407. In some embodiments, the tablets comprise from about 25 - 85 w / w% of one or more fillers. In some embodiments, the one or more fillers comprise microcrystalline cellulose and / or mannitol. In some embodiments, the tablets comprise from about 1 w / w% to about 30 w / w% of a disintegrant. In some embodiments, the disintegrant comprises sodium croscarmellose. In some embodiments, the tablets comprise from about 0.01 w / w% to about 10 w / w% of a lubricant. In some embodiments, the lubricant comprises magnesium stearate.

[0263] The tablets disclosed herein can be uncoated or coated (in which case they include an outer film coating). Although uncoated tablets can be used, it is more common to provide coated tablets, in which case a conventional non-enteric coating can be used. Film coatings are known in the art and can consist of hydrophilic polymeric materials, but are not limited to polysaccharide materials such as hydroxypropyl methylcellulose (HPMC), methylcellulose, hydroxyethylcellulose (HEC), hydroxypropylcellulose (HPC), poly(vinyl alcohol-co-ethylene glycol), and other water-soluble polymers. Although the water-soluble materials contained in the film coatings of the tablets disclosed herein can include a single polymeric material, it can also be formed using a mixture of more than one polymer. The coating can be white or colored. Suitable coatings include, but are not limited to, polymeric film coatings such as those comprising polyvinyl alcohol such as II (including partially hydrolyzed PVA, titanium dioxide, polyethylene glycol 3350, and talc, and optionally a colorant such as iron oxide or indigo carmine or yellow iron oxide or FD&C yellow #6). The amount of the coating is generally about 1 - 8% of the weight of the uncoated tablet.

[0264] In some embodiments, the tablets disclosed herein comprise a compound of formula (Ia) or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable excipients. In some embodiments, the one or more pharmaceutically acceptable excipients are selected from the group consisting of copovidone, poloxamer 407, microcrystalline cellulose, mannitol, croscarmellose sodium, and magnesium stearate. In some embodiments, the one or more pharmaceutically acceptable excipients include copovidone. In some embodiments, the one or more pharmaceutically acceptable excipients include poloxamer 407. In some embodiments, the one or more pharmaceutically acceptable excipients include microcrystalline cellulose. In some embodiments, the one or more pharmaceutically acceptable excipients include mannitol. In some embodiments, the one or more pharmaceutically acceptable excipients include croscarmellose sodium. In some embodiments, the one or more pharmaceutically acceptable excipients include magnesium stearate. In some embodiments, the one or more pharmaceutically acceptable excipients include copovidone and poloxamer 407. In some embodiments, the one or more pharmaceutically acceptable excipients include copovidone, poloxamer 407, and microcrystalline cellulose. In some embodiments, the one or more pharmaceutically acceptable excipients include copovidone, poloxamer 407, microcrystalline cellulose, and mannitol. In some embodiments, the one or more pharmaceutically acceptable excipients include copovidone, poloxamer 407, microcrystalline cellulose, mannitol, and croscarmellose sodium. In some embodiments, the one or more pharmaceutically acceptable excipients include copovidone, poloxamer 407, microcrystalline cellulose, mannitol, croscarmellose sodium, and magnesium stearate.

[0265] In some embodiments, the tablets disclosed herein comprise a compound of formula (Ia) or a pharmaceutically acceptable salt thereof, copovidone, poloxamer 407, microcrystalline cellulose, mannitol, croscarmellose sodium, and magnesium stearate. In some embodiments, the tablets disclosed herein comprise a compound of formula (Ib) or a pharmaceutically acceptable salt thereof, copovidone, poloxamer 407, microcrystalline cellulose, mannitol, croscarmellose sodium, and magnesium stearate. In some embodiments, the tablets disclosed herein comprise the trifluoroacetate salt of a compound of formula (Ib), copovidone, poloxamer 407, microcrystalline cellulose, mannitol, croscarmellose sodium, and magnesium stearate. In some embodiments, the tablets disclosed herein comprise a compound of formula (Ia), copovidone, poloxamer 407, microcrystalline cellulose, mannitol, croscarmellose sodium, and magnesium stearate. In some embodiments, the tablets disclosed herein comprise a compound of formula (Ib), copovidone, poloxamer 407, microcrystalline cellulose, mannitol, croscarmellose sodium, and magnesium stearate.

[0266] In some embodiments, the tablets disclosed herein comprise the sodium salt of the compound of formula (Ia), crospovidone, poloxamer 407, microcrystalline cellulose, mannitol, sodium carboxymethylcellulose cross-linked, and magnesium stearate. In some embodiments, in a tablet comprising the sodium salt of the compound of formula (Ia), crospovidone, poloxamer 407, microcrystalline cellulose, mannitol, sodium carboxymethylcellulose cross-linked, and magnesium stearate, the amount of the compound of formula (Ia) is from about 5 mg to about 500 mg. In some embodiments, in a tablet comprising the sodium salt of the compound of formula (Ia), crospovidone, poloxamer 407, microcrystalline cellulose, mannitol, sodium carboxymethylcellulose cross-linked, and magnesium stearate, the amount of the compound of formula (Ia) is from about 25 mg to about 500 mg. In some embodiments, in a tablet comprising the sodium salt of the compound of formula (Ia), crospovidone, poloxamer 407, microcrystalline cellulose, mannitol, sodium carboxymethylcellulose cross-linked, and magnesium stearate, the amount of the compound of formula (Ia) is from about 25 mg to about 400 mg. In some embodiments, in a tablet comprising the sodium salt of the compound of formula (Ia), crospovidone, poloxamer 407, microcrystalline cellulose, mannitol, sodium carboxymethylcellulose cross-linked, and magnesium stearate, the amount of the compound of formula (Ia) is from about 25 mg to about 300 mg. In some embodiments, in a tablet comprising the sodium salt of the compound of formula (Ia), crospovidone, poloxamer 407, microcrystalline cellulose, mannitol, sodium carboxymethylcellulose cross-linked, and magnesium stearate, the amount of the compound of formula (Ia) is from about 50 mg to about 300 mg. In some embodiments, in a tablet comprising the sodium salt of the compound of formula (Ia), crospovidone, poloxamer 407, microcrystalline cellulose, mannitol, sodium carboxymethylcellulose cross-linked, and magnesium stearate, the amount of the compound of formula (Ia) is about 5 mg. In some embodiments, in a tablet comprising the sodium salt of the compound of formula (Ia), crospovidone, poloxamer 407, microcrystalline cellulose, mannitol, sodium carboxymethylcellulose cross-linked, and magnesium stearate, the amount of the compound of formula (Ia) is about 10 mg. In some embodiments, in a tablet comprising the sodium salt of the compound of formula (Ia), crospovidone, poloxamer 407, microcrystalline cellulose, mannitol, sodium carboxymethylcellulose cross-linked, and magnesium stearate, the amount of the compound of formula (Ia) is about 20 mg. In some embodiments, in a tablet comprising the sodium salt of the compound of formula (Ia), crospovidone, poloxamer 407, microcrystalline cellulose, mannitol, sodium carboxymethylcellulose cross-linked, and magnesium stearate, the amount of the compound of formula (Ia) is about 25 mg. In some embodiments, in a tablet comprising the sodium salt of the compound of formula (Ia), crospovidone, poloxamer 407, microcrystalline cellulose, mannitol, sodium carboxymethylcellulose cross-linked, and magnesium stearate, the amount of the compound of formula (Ia) is about 30 mg.In some embodiments, in a tablet comprising the sodium salt of the compound of formula (Ia), crospovidone, poloxamer 407, microcrystalline cellulose, mannitol, sodium carboxymethyl starch, and magnesium stearate, the amount of the compound of formula (Ia) is about 40 mg. In some embodiments, in a tablet comprising the sodium salt of the compound of formula (Ia), crospovidone, poloxamer 407, microcrystalline cellulose, mannitol, sodium carboxymethyl starch, and magnesium stearate, the amount of the compound of formula (Ia) is about 50 mg. In some embodiments, in a tablet comprising the sodium salt of the compound of formula (Ia), crospovidone, poloxamer 407, microcrystalline cellulose, mannitol, sodium carboxymethyl starch, and magnesium stearate, the amount of the compound of formula (Ia) is about 75 mg. In some embodiments, in a tablet comprising the sodium salt of the compound of formula (Ia), crospovidone, poloxamer 407, microcrystalline cellulose, mannitol, sodium carboxymethyl starch, and magnesium stearate, the amount of the compound of formula (Ia) is about 100 mg. In some embodiments, in a tablet comprising the sodium salt of the compound of formula (Ia), crospovidone, poloxamer 407, microcrystalline cellulose, mannitol, sodium carboxymethyl starch, and magnesium stearate, the amount of the compound of formula (Ia) is about 125 mg. In some embodiments, in a tablet comprising the sodium salt of the compound of formula (Ia), crospovidone, poloxamer 407, microcrystalline cellulose, mannitol, sodium carboxymethyl starch, and magnesium stearate, the amount of the compound of formula (Ia) is about 150 mg. In some embodiments, in a tablet comprising the sodium salt of the compound of formula (Ia), crospovidone, poloxamer 407, microcrystalline cellulose, mannitol, sodium carboxymethyl starch, and magnesium stearate, the amount of the compound of formula (Ia) is about 175 mg. In some embodiments, in a tablet comprising the sodium salt of the compound of formula (Ia), crospovidone, poloxamer 407, microcrystalline cellulose, mannitol, sodium carboxymethyl starch, and magnesium stearate, the amount of the compound of formula (Ia) is about 200 mg. In some embodiments, in a tablet comprising the sodium salt of the compound of formula (Ia), crospovidone, poloxamer 407, microcrystalline cellulose, mannitol, sodium carboxymethyl starch, and magnesium stearate, the amount of the compound of formula (Ia) is about 225 mg. In some embodiments, in a tablet comprising the sodium salt of the compound of formula (Ia), crospovidone, poloxamer 407, microcrystalline cellulose, mannitol, sodium carboxymethyl starch, and magnesium stearate, the amount of the compound of formula (Ia) is about 250 mg. In some embodiments, in a tablet comprising the sodium salt of the compound of formula (Ia), crospovidone, poloxamer 407, microcrystalline cellulose, mannitol, sodium carboxymethyl starch, and magnesium stearate, the amount of the compound of formula (Ia) is about 275 mg. In some embodiments, in a tablet comprising the sodium salt of the compound of formula (Ia), crospovidone, poloxamer 407, microcrystalline cellulose, mannitol, sodium carboxymethyl starch, and magnesium stearate, the amount of the compound of formula (Ia) is about 300 mg.In some embodiments, in a tablet comprising the sodium salt of the compound of formula (Ia), copovidone, poloxamer 407, microcrystalline cellulose, mannitol, croscarmellose sodium, and magnesium stearate, the amount of the compound of formula (Ia) is about 325 mg. In some embodiments, in a tablet comprising the sodium salt of the compound of formula (Ia), copovidone, poloxamer 407, microcrystalline cellulose,...

Claims

1. A method for treating human immunodeficiency virus (HIV) infection in patients who have undergone extensive treatment, the method comprising administering to the patient a therapeutically effective amount of a compound of formula (Ia) or formula (Ib): or a pharmaceutically acceptable salt thereof.

2. The method according to claim 1, wherein the HIV infection is an HIV-1 infection characterized in that the HIV-1 mutant is resistant to one or more antiretroviral drugs.

3. The method according to claim 1, wherein the HIV infection is an HIV-1 infection characterized in that the HIV-1 mutant is resistant to two or more antiretroviral drugs.

4. The method according to claim 1, wherein the HIV infection is an HIV-1 infection characterized in that the HIV-1 mutant is resistant to three or more antiretroviral drugs.

5. The method according to any one of claims 1-4, wherein 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).

6. The method according to claim 5, wherein the HIV-1 mutants resistant to protease inhibitors are selected from I50V, I84V / L90M, G48V / V82A / L90M, and G48V / V82S.

7. The method according to claim 5, wherein the HIV-1 mutants resistant to nucleoside or nucleotide reverse transcriptase inhibitors are selected from K65R, M184V, and 6TAM.

8. The method according to claim 5, wherein the HIV-1 mutants resistant to non-nucleoside or non-nucleotide reverse transcriptase inhibitors are selected from K103N, Y181C, Y188L, L100I / K103N, and K103N / Y181C.

9. The method according to claim 5, wherein the HIV-1 mutants resistant to integrase strand transfer inhibitors are selected from Y143R, E138K / Q148K, G140S / Q148R, E92Q / N155H, N155H / Q148R, and R263K / M50I.

10. The method according to any one of claims 1 to 9, wherein the patient is infected with HIV-1 that is resistant to at least one antiretroviral drug.

11. The method according to any one of claims 1 to 10, wherein the patient is infected with multi-drug resistant HIV-1, which is resistant to at least one antiretroviral drug of each of two different classes of antiretroviral drugs, wherein the different classes of antiretroviral drugs are selected from nucleoside or nucleotide reverse transcriptase inhibitors (NRTI), non-nucleoside or non-nucleotide reverse transcriptase inhibitors (NNRTI), protease inhibitors (PI), and integrase strand transfer inhibitors (INSTI).

12. The method according to any one of claims 1 to 10, wherein the patient is infected with multi-drug resistant HIV-1, and the HIV-1 is resistant to at least one antiretroviral drug from each of three different classes of antiretroviral drugs, wherein 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).

13. The method according to claim 11 or claim 12, wherein 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), and protease inhibitors (PIs).

14. The method according to any one of claims 11 to 13, wherein the NRTI is selected from emtricitabine, lamivudine (3TC), zidovudine (azidothymidine (AZT)), didanosine (ddl), zalcitabine, tenofovir, tenofovir alafenamide, tenofovir disoproxil fumarate, stavudine (d4T), zalcitabine (dideoxycytidine, ddC), and abacavir.

15. The method according to any one of claims 11 to 13, wherein the NNRTI is selected from efavirenz, etravirine, rilpivirine, nevirapine, and delavirdine.

16. The method according to any one of claims 11 to 13, wherein the PI is selected from amprenavir, atazanavir, darunavir, fosamprenavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, and tipranavir.

17. The method according to any one of claims 11 to 13, wherein the INSTI is selected from raltegravir, elvitegravir, dolutegravir, cabotegravir, and bictegravir.

18. The method according to any one of claims 10 to 17, wherein the patient has been previously treated with at least one antiretroviral drug for at least 3 months.

19. The method according to any one of claims 10 to 17, wherein the patient has been previously treated with at least one antiretroviral drug for at least 6 months.

20. The method according to any one of claims 10 to 17, wherein the patient has been previously treated with at least one antiretroviral drug for at least 9 months.

21. The method according to any one of claims 10 to 17, wherein the patient has been previously treated with at least one antiretroviral drug for at least 12 months.

22. The method according to any one of claims 10 to 21, wherein the patient's previous HIV treatment regimen has failed, and the previous HIV treatment regimen includes administering at least one antiretroviral drug.

23. The method according to claim 22, wherein the previous treatment regimen comprises administering at least one antiretroviral drug from each of two different classes of antiretroviral drugs, wherein 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).

24. The method according to claim 22, wherein the previous treatment regimen comprises administering at least one antiretroviral drug from each of three different classes of antiretroviral drugs, wherein 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).

25. The method according to claim 23 or claim 24, wherein the different classes of antiretroviral drugs are selected from nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors (PIs).

26. The method according to any one of claims 1-25, wherein the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof is administered orally, subcutaneously, intramuscularly, or intravenously.

27. The method according to claim 26, wherein the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof is administered orally.

28. The method according to claim 27, wherein the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof is administered orally at a concentration of about 20 mg / mL to about 100 mg / mL.

29. The method according to claim 28, wherein the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof is administered orally at a concentration of about 30 mg / mL.

30. The method according to claim 28, wherein the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof is administered orally at a concentration of about 50 mg / mL.

31. The method according to any one of claims 27-30, wherein the compound of formula (Ia) or formula (Ib) is formulated as a hard gelatin capsule.

32. The method according to any one of claims 27-30, wherein the compound of formula (Ia) or formula (Ib) is formulated as a soft gelatin capsule.

33. The method according to claim 27, wherein the compound of formula (Ia) or formula (Ib) is formulated as a tablet.

34. The method according to claim 26, wherein the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof is administered subcutaneously.

35. The method according to claim 34, wherein the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof is administered subcutaneously at a concentration of about 50 mg / mL to about 500 mg / mL.

36. The method according to claim 35, wherein the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof is administered subcutaneously at a concentration of about 100 mg / mL.

37. The method according to claim 35, wherein the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof is administered subcutaneously at a concentration of about 150 mg / mL.

38. The method according to claim 35, wherein the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof is administered subcutaneously at a concentration of about 300 mg / mL.

39. The method according to any one of claims 34 - 38, wherein the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof is formulated into a solution preparation.

40. The method according to any one of claims 34 - 38, wherein the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof is formulated into an aqueous suspension.

41. The method according to claim 39 or claim 40, wherein the compound of formula (Ia) is a sodium salt.

42. The method according to claim 39 or claim 40, wherein the compound of formula (Ib) is a trifluoroacetate salt.

43. The method according to any one of claims 26 - 42, wherein the compound of formula (Ia) or formula (Ib) is formulated together with one or more other compounds selected from HIV protease inhibitors, HIV non - nucleoside or non - nucleotide reverse transcriptase inhibitors, HIV nucleoside or nucleotide reverse transcriptase inhibitors, HIV integrase inhibitors, HIV non - catalytic site (or allosteric) integrase inhibitors, HIV nucleoside reverse transcriptase translocation inhibitors, and pharmacokinetic enhancers.

44. The method according to claim 43, wherein the compound of formula (Ia) or formula (Ib) is formulated together with an HIV nucleoside reverse transcriptase translocation inhibitor.

45. The method according to claim 44, wherein the HIV nucleoside reverse transcriptase translocation inhibitor is 4’ - ethynyl - 2 - fluoro - 2 - deoxyadenosine triphosphate (MK - 8591).

46. The method according to any one of claims 1 - 45, wherein the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof is administered once a day.

47. The method according to any one of claims 1 - 45, wherein the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof is administered once every 1 week, every 2 weeks, every 4 weeks, every 8 weeks, every 12 weeks, every 16 weeks, every 20 weeks, every 24 weeks, or every 48 weeks.

48. The method according to claim 47, wherein the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof is administered once every 4 weeks.

49. The method according to claim 47, wherein the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof is administered once every 8 weeks.

50. The method according to claim 47, wherein the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof is administered once every 12 weeks.

51. The method according to any one of claims 1 to 50, wherein at the start of administration of the compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof, the viral load of the patient is greater than about 200 copies of HIV-1 RNA / mL.

52. The method according to any one of claims 1 to 50, wherein at the start of administration of the compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof, the viral load of the patient is greater than about 500 copies of HIV-1 RNA / mL.

53. The method according to any one of claims 1 to 50, wherein at the start of administration of the compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof, the viral load of the patient is greater than about 750 copies of HIV-1 RNA / mL.

54. The method according to any one of claims 1 to 50, wherein at the start of administration of the compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof, the viral load of the patient is greater than about 1000 copies of HIV-1 RNA / mL.

55. The method according to any one of claims 1 to 50, wherein at the start of administration of the compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof, the viral load of the patient is greater than about 2000 copies of HIV-1 RNA / mL.

56. The method according to any one of claims 1 to 50, wherein at the start of administration of the compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof, the patient's HIV treatment regimen comprising administration of at least one antiretroviral drug is about to fail.

57. The method according to any one of claims 51 - 56, wherein administration of the compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof results in a reduction in viral load in the patient.

58. The method according to claim 57, wherein the viral load is reduced by about 0.5 log 10 to about 2.5 log 10 after administration of the compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof for about 24 weeks, as compared to the viral load at the start of administration of the compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof.

59. The method according to claim 57, wherein the viral load is reduced by about 0.5 log after administration of the compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof for about 24 weeks as compared to the viral load at the start of administration of the compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof. 10 .

60. The method according to claim 57, wherein the viral load is reduced by about 1 log after administration of the compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof for about 24 weeks, compared to the viral load at the start of administration of the compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof. 10 .

61. The method according to claim 57, wherein the viral load is reduced by about 1.5 log after administration of the compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof for about 24 weeks as compared to the viral load at the start of administration of the compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof. 10 .

62. The method according to claim 57, wherein the viral load is reduced by about 2 log after administration of the compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof for about 24 weeks as compared to the viral load at the start of administration of the compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof. 10 .

63. The method according to claim 57, wherein the viral load is reduced by about 2.5 log after administration of the compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof for about 24 weeks, compared to the viral load at the start of administration of the compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof. 10 .

64. The method according to claim 57, wherein at about 24 weeks after administration of the compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof, the viral load in the patient is about 200 copies of HIV-1 RNA / mL or lower.

65. The method according to claim 57, wherein at about 24 weeks after administration of the compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof, the viral load in the patient is about 50 copies of HIV-1 RNA / mL or lower.

66. The method according to any one of claims 1 - 65, wherein the patient is treated concurrently with at least one additional antiretroviral drug.

67. The method according to claim 66, wherein the additional antiretroviral drug is selected from nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), integrase strand transfer inhibitors (INSTIs), gp41 fusion inhibitors, CCR5 co-receptor antagonists, and combinations thereof.

68. The method according to claim 67, wherein the NRTI is selected from emtricitabine, lamivudine (3TC), zidovudine (azidothymidine (AZT)), didanosine (ddI), zalcitabine, tenofovir, tenofovir alafenamide, tenofovir disoproxil fumarate, stavudine (d4T), zalcitabine (dideoxycytidine, ddC), and abacavir.

69. The method according to claim 67, wherein the NNRTI is selected from efavirenz, etravirine, rilpivirine, nevirapine, and delavirdine.

70. The method according to claim 67, wherein the PI is selected from amprenavir, atazanavir, darunavir, fosamprenavir, indinavir, lopinavir / ritonavir, nelfinavir, ritonavir, saquinavir, and tipranavir.

71. The method according to claim 67, wherein the INSTI is selected from raltegravir, elvitegravir, dolutegravir, and bictegravir.

72. The method according to claim 67, wherein the gp41 fusion inhibitor is selected from abacavir, enfuvirtide, BMS-986197, biosimilar of enfuvirtide, biosimilar of enfuvirtide, HIV-1 fusion inhibitor (P26-Bapc), ITV-1, ITV-2, ITV-3, ITV-4, PIE-12 trimer, and sifuvirtide.

73. The method according to claim 67, wherein the CCR5 co-receptor antagonist is selected from apaviroc, vicriviroc, maraviroc, cenicriviroc, PRO-140, alacavir (RAP-101), nifivirine (TD-0232), anti-GP120 / CD4 or CCR5 bispecific antibody, B-07, MB-66, polypeptide C25P, TD-0680, and vMTP (Haimipu).

74. A method for treating human immunodeficiency virus-1 (HIV-1) infection in heavily pre-treated patients with multi-drug resistant HIV-1, the method comprising administering to the patient a therapeutically effective amount of a compound of formula (Ia) or formula (Ib): or a pharmaceutically acceptable salt thereof, wherein: the patient has previously been treated with an HIV treatment regimen comprising administration of at least one antiretroviral drug, and the treatment regimen has failed; and administration of the compound results in a reduction in the patient's HIV viral load.

75. The method according to claim 74, wherein the multi-drug resistant HIV-1 is resistant to at least one antiretroviral drug from each of two different classes of antiretroviral drugs, wherein the different classes of antiretroviral drugs are selected from nucleoside reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI), protease inhibitors (PI), and integrase strand transfer inhibitors (INSTI).

76. The method according to claim 74, wherein the multi-drug resistant HIV-1 is resistant to at least one antiretroviral drug of each of three different classes of antiretroviral drugs, wherein 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).

77. The method according to claim 75 or claim 76, wherein the different classes of antiretroviral drugs are selected from nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors (PIs).

78. The method according to claim 77, wherein the NRTIs are selected from emtricitabine, lamivudine (3TC), zidovudine (azidothymidine (AZT)), didanosine (ddI), zalcitabine, tenofovir, tenofovir alafenamide, tenofovir disoproxil fumarate, stavudine (d4T), zalcitabine (dideoxycytidine, ddC), and abacavir.

79. The method according to claim 77, wherein the NNRTIs are selected from efavirenz, etravirine, rilpivirine, nevirapine, and delavirdine.

80. The method according to claim 77, wherein the PIs are selected from amprenavir, atazanavir, darunavir, fosamprenavir, indinavir, lopinavir / ritonavir, nelfinavir, ritonavir, saquinavir, and tipranavir.

81. The method according to claim 77, wherein the INSTIs are selected from raltegravir, elvitegravir, dolutegravir, cabotegravir, and bictegravir.

82. The method according to any one of claims 74 - 81, wherein 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.

83. The method according to any one of claims 74 - 82, wherein the previous treatment regimen comprises administering at least one antiretroviral drug of each of two different classes of antiretroviral drugs, wherein 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).

84. The method according to any one of claims 74 - 82, wherein the previous treatment regimen comprises administering at least one antiretroviral drug of each of three different classes of antiretroviral drugs, wherein 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).

85. The method according to claim 83 or claim 84, wherein the different classes of antiretroviral drugs are selected from nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors (PIs).

86. A method of treating human immunodeficiency virus type 1 (HIV-1) infection in heavily pre-treated patients with multi-drug resistant HIV-1, the method comprising administering to the patient a therapeutically effective amount of a compound of formula (Ia) or (Ib): or a pharmaceutically acceptable salt thereof, wherein: the multi-drug resistant HIV-1 is resistant to at least one antiretroviral drug of each of two different classes of antiretroviral drugs, wherein 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); the patient has previously been treated with an HIV treatment regimen comprising administration of at least one antiretroviral drug, and the treatment regimen has failed; at the start of administration of the compound of formula (Ia) or formula (Ib), the patient's viral load is greater than about 200 copies of HIV-1 RNA / mL; and administration of the compound results in a reduction in the patient's HIV viral load.

87. A method of reducing the viral load associated with HIV infection in heavily pre-treated patients with multi-drug resistant HIV, the method comprising administering to the patient a therapeutically effective amount of a compound of formula (Ia) or (Ib): or a pharmaceutically acceptable salt thereof.

88. A pharmaceutical composition comprising a compound of formula (Ia) or (Ib): or a pharmaceutically acceptable salt thereof, wherein the pharmaceutical composition is in solution form and the solution comprises PEG 300 and water.

89. The pharmaceutical composition according to claim 88, wherein the solution comprises about 5 w / w% to about 15 w / w% water, about 50 w / w% to about 85 w / w% PEG 300, and about 15 w / w% to about 35 w / w% of the compound of formula (Ia).

90. The pharmaceutical composition according to claim 88, wherein the solution comprises about 10 w / w% to about 40 w / w% water, about 35 w / w% to about 75 w / w% PEG 300, and about 5 w / w% to about 35 w / w% of the sodium salt of the compound of formula (Ia).

91. The pharmaceutical composition according to claim 88, wherein the solution further comprises sodium hydroxide.

92. The pharmaceutical composition according to claim 91, wherein the solution comprises about 10 w / w% to about 40 w / w% water, about 35 w / w% to about 75 w / w% PEG 300, about 5 w / w% to about 35 w / w% of the compound of formula (Ia), and about 0.05 w / w% to about 2 w / w% sodium hydroxide.

93. A pharmaceutical composition in solution form, wherein the solution comprises about 10 w / w% to about 45 w / w% water, about 30 w / w% to about 85 w / w% PEG 300, about 0.5 w / w% to about 40 w / w% sodium salt of the compound of formula (Ia), and about 0.1 w / w% to about 10 w / w% poloxamer 188, wherein the compound of formula (Ia) has the following structure:

94. A pharmaceutical composition in solution form, wherein the solution comprises about 10 w / w% to about 45 w / w% water, about 30 w / w% to about 85 w / w% PEG 300, about 0.5 w / w% to about 40 w / w% of the compound of formula (Ia), about 0.01 w / w% to about 3.0 w / w% sodium hydroxide, and about 0.1 w / w% to about 10 w / w% poloxamer 188, wherein the compound of formula (Ia) has the following structure:

95. An oral formulation comprising a compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof and monocaprylyl decaglyceride.

96. The oral formulation according to claim 95, wherein the oral formulation is prepared as a hard gelatin capsule or a soft gelatin capsule.

97. The hard gelatin capsule or soft gelatin capsule according to claim 96, wherein the hard gelatin capsule or soft gelatin capsule comprises about 30 w / w% to about 85 w / w% monocaprylyl decaglyceride and about 1 w / w% to about 40 w / w% of the compound of formula (Ia).

98. The hard gelatin capsule or soft gelatin capsule according to claim 96, wherein the hard gelatin capsule or soft gelatin capsule comprises about 30 w / w% to about 99 w / w% monocaprylyl decaglyceride and about 1 w / w% to about 40 w / w% sodium salt of the compound of formula (Ia).

99. The hard gelatin capsule or soft gelatin capsule according to any one of claims 96 - 98, wherein the concentration of the compound of formula (Ia) is about 10 mg / mL to about 500 mg / mL.

100. The hard gelatin capsule or soft gelatin capsule according to any one of claims 96 - 99, further comprising a capsule shell.

101. The hard gelatin capsule or soft gelatin capsule according to claim 100, wherein the shell comprises gelatin, glycerol, titanium dioxide, and iron oxide.

102. A tablet comprising a compound of formula (Ia) or formula (Ib) or: a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients, wherein the tablet is prepared by spray - drying dispersion technology.

103. The tablet according to claim 102, wherein the amount of the compound of formula (Ia) or formula (Ib) or a pharmaceutically acceptable salt thereof is about 5 mg to about 500 mg.

104. The tablet according to any one of claims 102 - 103, wherein the tablet comprises the sodium salt of the compound of formula (Ia).

105. The tablet according to any one of claims 102 - 104, wherein the tablet comprises from about 5 w / w% to about 45 w / w% of the sodium salt of the compound of formula (Ia), from about 1 w / w% to about 10 w / w% of copovidone, from about 0.01 w / w% to about 10 w / w% of poloxamer 407, from about 5 w / w% to about 45 w / w% of microcrystalline cellulose, from about 15 w / w% to about 70 w / w% of mannitol, from about 1 w / w% to about 30 w / w% of croscarmellose sodium, and from about 0.01 w / w% to about 10 w / w% of magnesium stearate.

106. The tablet according to any one of claims 102 - 105, wherein the tablet further comprises an outer film coating.

107. The tablet according to claim 106, wherein the outer film coating provides a weight gain of from about 1% to about 8% based on the uncoated tablet.

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