Neuroactive steroid formulations and methods of use thereof

Abstract

Described herein are pharmaceutical compositions comprising Compound I and pharmaceutically acceptable salts thereof, and methods of use thereof for treating conditions associated with modulation of NMDA receptors.

Description

[0001] Cross-reference to related applications

[0002] This application claims priority and benefit to U.S. Provisional Application No. 63 / 463,540, filed May 2, 2023, the disclosure of which is incorporated herein by reference in its entirety. Background Technology

[0003] NMDA receptors are highly expressed in the central nervous system and are involved in excitatory synaptic transmission. Activation of these receptors contributes to synaptic plasticity in some cases and promotes excitotoxicity in others. These receptors are ligand-gated ion channels that allow Ca2+ ionization to occur after binding to the neurotransmitters glutamate and glycine. 2+ Influx is fundamental to excitatory neurotransmission and normal central nervous system function. NMDA receptors are heteromeric complexes composed of NR1, NR2, and / or NR3 subunits and possess distinct recognition sites for exogenous and endogenous ligands. These recognition sites include binding sites for glycine, glutamate agonists, and modulators. Positive modulators can be used as therapeutic agents, with potential clinical applications including as cognitive enhancers and for treating mental illnesses in which glutamatergic transmission is impaired or deficient (see, for example, Horak et al., J. Neuroscience, 2004, 24(46), 10318-10325). Conversely, negative modulators can be used as therapeutic agents, with potential clinical applications including treating mental illnesses in which glutamatergic transmission is pathologically enhanced (e.g., treatment-resistant depression).

[0004] There is still a need for pharmaceutical compositions that can be used to treat central nervous system disorders associated with NMDA receptor modulation. Summary of the Invention

[0005] This document describes a pharmaceutical composition comprising compound I and its method of use. It also describes the use of the pharmaceutical composition in the manufacture of a medicament for treating diseases or conditions associated with NMDA receptor modulation. Compound I is an NMDA modulator. This document further describes a pharmaceutical composition comprising compound I for the treatment of diseases or conditions associated with NMDA receptor modulation.

[0006] One aspect of this disclosure provides a pharmaceutical composition comprising:

[0007] a) Compound I:

[0008]

[0009] Compound I;

[0010] or a pharmaceutically acceptable salt thereof; and b) one or more glycerides, wherein the glycerides comprise monoglycerides between about 30% w / w and about 100% w / w.

[0011] In some embodiments, the pharmaceutical composition comprises compound I. In some embodiments, the pharmaceutical composition comprises a pharmaceutically acceptable salt of compound I. In some embodiments, the pharmaceutical composition comprises about 0.2% w / w to about 0.4% w / w of compound I. In some embodiments, the pharmaceutical composition comprises about 0.25% w / w to about 0.35% w / w of compound I. In some embodiments, the pharmaceutical composition comprises about 0.3% w / w of compound I. In some embodiments, the pharmaceutical composition comprises 0.3% w / w of compound I. In some embodiments, the pharmaceutical composition comprises about 3 mg / g of compound I. In some embodiments, the pharmaceutical composition comprises 3 mg / g of compound I.

[0012] In some embodiments, one or more glycerides are selected from the group consisting of mono / dicaprylic / capric glyceride, mono / dicaprylic / capric glyceride, type I monocaprylic glyceride, type I monocaprylic glyceride, type I monocaprylic / capric glyceride, monolinoleic glyceride, and combinations thereof. In some embodiments, one or more glycerides are selected from the group consisting of monocaprylic glyceride, monolinoleic glyceride, and combinations thereof. In some embodiments, the pharmaceutical composition comprises monocaprylic glyceride. In some embodiments, the pharmaceutical composition comprises monolinoleic glyceride. In some embodiments, the pharmaceutical composition comprises both monocaprylic glyceride and monolinoleic glyceride.

[0013] In some embodiments, the amount of one or more glycerides is from about 20% w / w to about 80% w / w. In some embodiments, the amount of one or more glycerides is from about 20% w / w to about 60% w / w.

[0014] In some embodiments, the amount of glyceryl monocaprylate in the composition is from about 50% w / w to about 80% w / w. In some embodiments, the amount of glyceryl monocaprylate is from about 55% w / w to about 60% w / w. In some embodiments, the amount of glyceryl monocaprylate is about 50% w / w. In some embodiments, the amount of glyceryl monocaprylate is 50% w / w. In some embodiments, the amount of glyceryl monocaprylate is about 60% w / w. In some embodiments, the amount of glyceryl monocaprylate is 60% w / w. In some embodiments, the amount of glyceryl monolinoleate is from about 20% w / w to about 30% w / w. In some embodiments, the amount of glyceryl monolinoleate is about 20% w / w. In some embodiments, the amount of glyceryl monolinoleate is 20% w / w. In some embodiments, the amount of glyceryl monolinoleate is about 22.5% w / w. In some embodiments, the amount of glyceryl monolinoleate is 22.5% w / w.

[0015] In some embodiments, the pharmaceutical composition further comprises stearoyl polyoxyethylene-32 glyceride. In some embodiments, the amount of stearoyl polyoxyethylene-32 glyceride is from about 5% w / w to about 20% w / w. In some embodiments, the amount of stearoyl polyoxyethylene-32 glyceride is from about 10% w / w to about 20% w / w. In some embodiments, the amount of stearoyl polyoxyethylene-32 glyceride is about 7.5% w / w. In some embodiments, the amount of stearoyl polyoxyethylene-32 glyceride is 7.5% w / w. In some embodiments, the amount of stearoyl polyoxyethylene-32 glyceride is about 10% w / w. In some embodiments, the amount of stearoyl polyoxyethylene-32 glyceride is 10% w / w. In some embodiments, the amount of stearoyl polyoxyethylene-32 glyceride is about 20% w / w. In some embodiments, the amount of stearoyl polyoxyethylene-32 glyceride is 20% w / w.

[0016] In some embodiments, the composition further comprises a surfactant. In some embodiments, the amount of surfactant is from about 10% w / w to about 25% w / w. In some embodiments, the amount of surfactant is about 10% w / w. In some embodiments, the amount of surfactant is 10% w / w. In some embodiments, the amount of surfactant is about 20% w / w. In some embodiments, the amount of surfactant is 20% w / w. In some embodiments, the surfactant is vitamin E TPGS.

[0017] In some embodiments, the pharmaceutical composition further comprises an antioxidant. In some embodiments, the amount of antioxidant is from about 0.005% w / w to about 0.02% w / w. In some embodiments, the amount of antioxidant is about 0.005% w / w. In some embodiments, the amount of antioxidant is 0.005% w / w. In some embodiments, the amount of antioxidant is about 0.01% w / w. In some embodiments, the amount of antioxidant is 0.01% w / w. In some embodiments, the amount of antioxidant is 0.01% w / w. In some embodiments, the amount of antioxidant is about 0.02% w / w. In some embodiments, the amount of antioxidant is 0.02% w / w. In some embodiments, the antioxidant is butylated hydroxyanisole (BHA).

[0018] In some embodiments, this disclosure provides a pharmaceutical composition comprising: a) about 0.3% w / w of compound I, b) about 60% w / w of caprylic acid glyceride, c) about 20% w / w of linoleic acid glyceride, d) about 20% w / w of vitamin ETPGS, and e) about 0.01% w / w of butylated hydroxyanisole. In some embodiments, this disclosure provides a pharmaceutical composition comprising: a) about 0.3% w / w of compound I, b) about 50% w / w of caprylic acid glyceride, c) about 22.5% w / w of linoleic acid glyceride, d) about 20% w / w of vitamin ETPGS, e) about 7.5% w / w of stearoyl polyoxyethylene-32 glyceride, and f) about 0.01% w / w of butylated hydroxyanisole.

[0019] In some embodiments, the pharmaceutical composition is an oral dosage form. In some embodiments, the pharmaceutical composition is a lipid formulation. In some embodiments, the oral dosage form is a soft gelatin capsule, a hard-shell capsule, or an oral liquid.

[0020] On one hand, this disclosure provides a soft gelatin capsule comprising: a) compound I:

[0021]

[0022] Compound I;

[0023] a) or a pharmaceutically acceptable salt thereof; and b) one or more glycerides, wherein the glycerides comprise monoglycerides between about 30% w / w and about 100% w / w. In some embodiments, the soft gelatin capsule comprises compound I. In some embodiments, the soft gelatin capsule comprises a pharmaceutically acceptable salt of compound I. In some embodiments, the soft gelatin capsule comprises about 0.2% w / w to about 0.4% w / w of compound I. In some embodiments, the soft gelatin capsule comprises about 0.25% w / w to about 0.35% w / w of compound I. In some embodiments, the soft gelatin capsule comprises about 0.3% w / w of compound I. In some embodiments, the soft gelatin capsule comprises 0.3% w / w of compound I. In some embodiments, the soft gelatin capsule comprises about 3 mg / g of compound I. In some embodiments, the soft gelatin capsule comprises about 3 mg / g of compound I.

[0024] In some embodiments, one or more glycerides in the soft gelatin capsule are selected from the group consisting of glyceryl mono / dicaprylate, glyceryl mono / dicaprylate, glyceryl type 1 caprylate, glyceryl type 1 caprylate, glyceryl type 1 caprylate, glyceryl monocaprylate, glyceryl monolinoleate, and combinations thereof. In some embodiments, one or more glycerides in the soft gelatin capsule are selected from the group consisting of glyceryl monocaprylate, glyceryl monolinoleate, and combinations thereof. In some embodiments, the soft gelatin capsule comprises glyceryl monocaprylate. In some embodiments, the soft gelatin capsule comprises glyceryl monolinoleate. In some embodiments, the soft gelatin capsule comprises glyceryl monocaprylate and glyceryl monolinoleate. In some embodiments, the amount of one or more glycerides in the soft gelatin capsule is from about 20% w / w to about 80% w / w. In some embodiments, the amount of one or more glycerides in the soft gelatin capsule is from about 20% w / w to about 60% w / w. In some embodiments, the amount of glyceryl monocaprylate in the soft gelatin capsule is from about 50% w / w to about 80% w / w. In some embodiments, the amount of caprylic / caprylic acid glyceride in the soft gelatin capsule is about 55% w / w to about 60% w / w. In some embodiments, the amount of caprylic / caprylic acid glyceride in the soft gelatin capsule is about 50% w / w. In some embodiments, the amount of caprylic / caprylic acid glyceride in the soft gelatin capsule is 50% w / w. In some embodiments, the amount of caprylic / caprylic acid glyceride in the soft gelatin capsule is about 60% w / w. In some embodiments, the amount of caprylic / caprylic acid glyceride in the soft gelatin capsule is 60% w / w. In some embodiments, the amount of linoleic acid glyceride in the soft gelatin capsule is about 20% w / w to about 30% w / w. In some embodiments, the amount of linoleic acid glyceride in the soft gelatin capsule is about 20% w / w. In some embodiments, the amount of linoleic acid glyceride in the soft gelatin capsule is 20% w / w. In some embodiments, the amount of linoleic acid glyceride in the soft gelatin capsule is about 22.5% w / w. In some embodiments, the amount of monolinoleic acid glycerides in the soft gelatin capsules is 22.5% w / w.

[0025] In some embodiments, the soft gelatin capsule further comprises stearoyl polyoxyethylene-32 glyceryl ester. In some embodiments, the amount of stearoyl polyoxyethylene-32 glyceryl ester in the soft gelatin capsule is from about 5% w / w to about 20% w / w. In some embodiments, the amount of stearoyl polyoxyethylene-32 glyceryl ester in the soft gelatin capsule is from about 10% w / w to about 20% w / w. In some embodiments, the amount of stearoyl polyoxyethylene-32 glyceryl ester in the soft gelatin capsule is about 7.5% w / w. In some embodiments, the amount of stearoyl polyoxyethylene-32 glyceryl ester in the soft gelatin capsule is 7.5% w / w. In some embodiments, the amount of stearoyl polyoxyethylene-32 glyceryl ester in the soft gelatin capsule is about 10% w / w. In some embodiments, the amount of stearoyl polyoxyethylene-32 glyceryl ester in the soft gelatin capsule is 10% w / w. In some embodiments, the amount of stearoyl polyoxyethylene-32 glyceryl ester in the soft gelatin capsule is about 20% w / w. In some embodiments, the amount of stearoyl polyoxyethylene-32 glyceryl ester in the soft gelatin capsule is 20% w / w.

[0026] In some embodiments, the soft gelatin capsule further comprises a surfactant. In some embodiments, the amount of surfactant in the soft gelatin capsule is from about 10% w / w to about 25% w / w. In some embodiments, the amount of surfactant in the soft gelatin capsule is about 10% w / w. In some embodiments, the amount of surfactant in the soft gelatin capsule is 10% w / w. In some embodiments, the amount of surfactant in the soft gelatin capsule is about 20% w / w. In some embodiments, the amount of surfactant in the soft gelatin capsule is 20% w / w. In some embodiments, the surfactant is vitamin E TPGS.

[0027] In some embodiments, the soft gelatin capsules further comprise an antioxidant. In some embodiments, the amount of antioxidant in the soft gelatin capsule is about 0.005% w / w to about 0.02% w / w. In some embodiments, the amount of antioxidant in the soft gelatin capsule is about 0.005% w / w. In some embodiments, the amount of antioxidant in the soft gelatin capsule is 0.005% w / w. In some embodiments, the amount of antioxidant in the soft gelatin capsule is about 0.01% w / w. In some embodiments, the amount of antioxidant in the soft gelatin capsule is 0.01% w / w. In some embodiments, the amount of antioxidant in the soft gelatin capsule is 0.01% w / w. In some embodiments, the amount of antioxidant in the soft gelatin capsule is about 0.02% w / w. In some embodiments, the amount of antioxidant in the soft gelatin capsule is 0.02% w / w. In some embodiments, the antioxidant is butylated hydroxyanisole (BHA).

[0028] In some embodiments, this disclosure provides a soft gelatin capsule comprising: a) about 0.3% w / w of Compound I, b) about 60% w / w of glyceryl monocaprylate, c) about 20% w / w of glyceryl monolinoleate, d) about 20% w / w of vitamin ETPGS, and e) about 0.01% w / w of butylated hydroxyanisole. In some embodiments, this disclosure provides a soft gelatin capsule comprising: a) about 0.3% w / w of Compound I, b) about 50% w / w of glyceryl monocaprylate, c) about 22.5% w / w of glyceryl monolinoleate, d) about 20% w / w of vitamin ETPGS, e) about 7.5% w / w of stearoyl polyoxyethylene-32 glyceride, and f) about 0.01% w / w of butylated hydroxyanisole.

[0029] On the one hand, this disclosure provides a pharmaceutical composition comprising a therapeutically effective amount of compound I.

[0030] (Compound I)

[0031] Or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier thereof;

[0032] When administered to a subject, the drug composition provides one or more of the following pharmacokinetic parameters:

[0033] a) C between approximately 8 and approximately 25 ng / mL max ;

[0034] b) AUC between approximately 100 and approximately 450 ng*h / mL last ;

[0035] c) AUC between approximately 100 and approximately 500 ng*h / mL inf ;

[0036] d) t between approximately 2 and approximately 8 hours max ;or

[0037] e) Bioavailability between approximately 70% and approximately 100%.

[0038] On the one hand, this disclosure provides a method for treating a subject with Huntington's disease, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition disclosed herein.

[0039] On the one hand, this disclosure provides a method for treating cognitive impairment in a subject suffering from Huntington's disease, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition disclosed herein.

[0040] On one hand, this disclosure provides a method for treating mild cognitive impairment (MCI) associated with Huntington's disease in a subject, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition disclosed herein.

[0041] On the one hand, this disclosure provides a method for improving executive function in a subject suffering from mild cognitive impairment (MCI) associated with Huntington's disease, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition disclosed herein.

[0042] On the one hand, this disclosure provides a method for improving the working memory of a subject suffering from mild cognitive impairment (MCI) associated with Huntington's disease, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition disclosed herein.

[0043] On the one hand, this disclosure provides a method for improving learning in subjects with mild cognitive impairment (MCI) associated with Huntington's disease, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition disclosed herein.

[0044] On the one hand, this disclosure provides a method for improving the learning and working memory of subjects suffering from mild cognitive impairment (MCI) associated with Huntington's disease, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition disclosed herein.

[0045] On the one hand, this disclosure provides a method for improving cognition in a subject suffering from Huntington's disease, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition disclosed herein.

[0046] On the one hand, this disclosure provides a method for slowing cognitive decline in subjects suffering from Huntington's disease, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition disclosed herein.

[0047] On the one hand, this disclosure provides a method for treating a subject with Parkinson's disease, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition disclosed herein.

[0048] On the one hand, this disclosure provides a method for treating cognitive impairment in a subject suffering from Parkinson's disease, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition disclosed herein.

[0049] On one hand, this disclosure provides a method for treating mild cognitive impairment (MCI) associated with Parkinson's disease in a subject, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition disclosed herein.

[0050] On the one hand, this disclosure provides a method for improving executive function in a subject suffering from mild cognitive impairment (MCI) associated with Parkinson's disease, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition disclosed herein.

[0051] On the one hand, this disclosure provides a method for improving the working memory of a subject suffering from mild cognitive impairment (MCI) associated with Parkinson's disease, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition disclosed herein.

[0052] On the one hand, this disclosure provides a method for improving learning in subjects suffering from mild cognitive impairment (MCI) associated with Parkinson's disease, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition disclosed herein.

[0053] On the one hand, this disclosure provides a method for improving the learning and working memory of subjects suffering from mild cognitive impairment (MCI) associated with Parkinson's disease, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition disclosed herein.

[0054] On the one hand, this disclosure provides a method for improving cognition in a subject suffering from Parkinson's disease, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition disclosed herein.

[0055] On the one hand, this disclosure provides a method for slowing cognitive decline in a subject suffering from Parkinson's disease, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition disclosed herein.

[0056] On the one hand, this disclosure provides a method for treating Alzheimer's disease in a subject, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition disclosed herein.

[0057] On the one hand, this disclosure provides a method for treating cognitive impairment in a subject suffering from Alzheimer's disease, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition disclosed herein.

[0058] On one hand, this disclosure provides a method for treating mild cognitive impairment (MCI) associated with Alzheimer's disease in a subject, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition disclosed herein.

[0059] On one hand, this disclosure provides a method for improving executive function in a subject suffering from mild cognitive impairment (MCI) associated with Alzheimer's disease, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition disclosed herein.

[0060] On the one hand, this disclosure provides a method for improving the working memory of a subject suffering from mild cognitive impairment (MCI) associated with Alzheimer's disease, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition disclosed herein.

[0061] On the one hand, this disclosure provides a method for improving learning in subjects suffering from mild cognitive impairment (MCI) associated with Alzheimer's disease, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition disclosed herein.

[0062] On the one hand, this disclosure provides a method for improving the learning and working memory of subjects suffering from mild cognitive impairment (MCI) associated with Alzheimer's disease, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition disclosed herein.

[0063] On the one hand, this disclosure provides a method for improving the cognition of a subject suffering from Alzheimer's disease, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition disclosed herein.

[0064] On the one hand, this disclosure provides a method for slowing cognitive decline in a subject suffering from Alzheimer's disease, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition disclosed herein.

[0065] On one hand, this disclosure provides a method for treating mild dementia associated with Alzheimer's disease in a subject, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition disclosed herein.

[0066] On the one hand, this disclosure provides a method for improving executive function in a subject suffering from mild dementia associated with Alzheimer's disease, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition disclosed herein.

[0067] On the one hand, this disclosure provides a method for improving the working memory of a subject suffering from mild dementia associated with Alzheimer's disease, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition disclosed herein.

[0068] On the one hand, this disclosure provides a method for improving learning in subjects suffering from mild dementia associated with Alzheimer's disease, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition disclosed herein.

[0069] On the one hand, this disclosure provides a method for improving the learning and working memory of a subject suffering from mild dementia associated with Alzheimer's disease, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition disclosed herein.

[0070] On the one hand, this disclosure provides a method for treating Huntington's disease in a subject, the method comprising administering to the subject a therapeutically effective amount of a soft gelatin capsule disclosed herein.

[0071] On the one hand, this disclosure provides a method for treating cognitive impairment in a subject with Huntington's disease, the method comprising administering to the subject a therapeutically effective amount of soft gelatin capsules disclosed herein.

[0072] On one hand, this disclosure provides a method for treating mild cognitive impairment (MCI) associated with Huntington's disease in a subject, the method comprising administering to the subject a therapeutically effective amount of soft gelatin capsules disclosed herein.

[0073] On one hand, this disclosure provides a method for improving executive function in subjects with mild cognitive impairment (MCI) associated with Huntington's disease, the method comprising administering to the subject a therapeutically effective amount of soft gelatin capsules disclosed herein.

[0074] On the one hand, this disclosure provides a method for improving working memory in subjects with mild cognitive impairment (MCI) associated with Huntington's disease, the method comprising administering to the subject a therapeutically effective amount of soft gelatin capsules disclosed herein.

[0075] On the one hand, this disclosure provides a method for improving learning in subjects with mild cognitive impairment (MCI) associated with Huntington's disease, the method comprising administering to the subject a therapeutically effective amount of soft gelatin capsules disclosed herein.

[0076] On the one hand, this disclosure provides a method for improving learning and working memory in subjects with mild cognitive impairment (MCI) associated with Huntington's disease, the method comprising administering to the subject a therapeutically effective amount of soft gelatin capsules disclosed herein.

[0077] On the one hand, this disclosure provides a method for improving cognition in a subject suffering from Huntington's disease, the method comprising administering to the subject a therapeutically effective amount of soft gelatin capsules disclosed herein.

[0078] On the one hand, this disclosure provides a method for slowing cognitive decline in subjects with Huntington's disease, the method comprising administering to the subject a therapeutically effective amount of soft gelatin capsules disclosed herein.

[0079] On the one hand, this disclosure provides a method for treating Parkinson's disease in a subject, the method comprising administering to the subject a therapeutically effective amount of soft gelatin capsules disclosed herein.

[0080] On the one hand, this disclosure provides a method for treating cognitive impairment in a subject with Parkinson's disease, the method comprising administering to the subject a therapeutically effective amount of soft gelatin capsules disclosed herein.

[0081] On one hand, this disclosure provides a method for treating mild cognitive impairment (MCI) associated with Parkinson's disease in a subject, the method comprising administering to the subject a therapeutically effective amount of soft gelatin capsules disclosed herein.

[0082] On the one hand, this disclosure provides a method for improving executive function in subjects with mild cognitive impairment (MCI) associated with Parkinson's disease, the method comprising administering to the subject a therapeutically effective amount of soft gelatin capsules disclosed herein.

[0083] On the one hand, this disclosure provides a method for improving working memory in subjects with mild cognitive impairment (MCI) associated with Parkinson's disease, the method comprising administering to the subject a therapeutically effective amount of soft gelatin capsules disclosed herein.

[0084] On the one hand, this disclosure provides a method for improving learning in subjects with mild cognitive impairment (MCI) associated with Parkinson's disease, the method comprising administering to the subject a therapeutically effective amount of soft gelatin capsules disclosed herein.

[0085] On the one hand, this disclosure provides a method for improving learning and working memory in subjects with mild cognitive impairment (MCI) associated with Parkinson's disease, the method comprising administering to the subject a therapeutically effective amount of soft gelatin capsules disclosed herein.

[0086] On the one hand, this disclosure provides a method for improving cognition in a subject suffering from Parkinson's disease, the method comprising administering to the subject a therapeutically effective amount of soft gelatin capsules disclosed herein.

[0087] On the one hand, this disclosure provides a method for slowing cognitive decline in subjects with Parkinson's disease, the method comprising administering to the subject a therapeutically effective amount of soft gelatin capsules disclosed herein.

[0088] On the one hand, this disclosure provides a method for treating Alzheimer's disease in a subject, the method comprising administering to the subject a therapeutically effective amount of soft gelatin capsules disclosed herein.

[0089] On the one hand, this disclosure provides a method for treating cognitive impairment in a subject with Alzheimer's disease, the method comprising administering to the subject a therapeutically effective amount of soft gelatin capsules disclosed herein.

[0090] On one hand, this disclosure provides a method for treating mild cognitive impairment (MCI) associated with Alzheimer's disease in a subject, the method comprising administering to the subject a therapeutically effective amount of soft gelatin capsules disclosed herein.

[0091] On one hand, this disclosure provides a method for improving executive function in subjects with mild cognitive impairment (MCI) associated with Alzheimer's disease, the method comprising administering to the subject a therapeutically effective amount of soft gelatin capsules disclosed herein.

[0092] On the one hand, this disclosure provides a method for improving the working memory of subjects suffering from mild cognitive impairment (MCI) associated with Alzheimer's disease, the method comprising administering to the subject a therapeutically effective amount of soft gelatin capsules disclosed herein.

[0093] On the one hand, this disclosure provides a method for improving learning in subjects suffering from mild cognitive impairment (MCI) associated with Alzheimer's disease, the method comprising administering to the subject a therapeutically effective amount of soft gelatin capsules disclosed herein.

[0094] On the one hand, this disclosure provides a method for improving the learning and working memory of subjects suffering from mild cognitive impairment (MCI) associated with Alzheimer's disease, the method comprising administering to the subject a therapeutically effective amount of soft gelatin capsules disclosed herein.

[0095] On the one hand, this disclosure provides a method for improving cognition in subjects suffering from Alzheimer's disease, the method comprising administering to the subject a therapeutically effective amount of soft gelatin capsules disclosed herein.

[0096] On the one hand, this disclosure provides a method for slowing cognitive decline in subjects with Alzheimer's disease, the method comprising administering to the subject a therapeutically effective amount of soft gelatin capsules disclosed herein.

[0097] On the one hand, this disclosure provides a method for treating mild dementia associated with Alzheimer's disease, the method comprising administering to a subject a therapeutically effective amount of soft gelatin capsules disclosed herein.

[0098] On one hand, this disclosure provides a method for improving executive function in a subject suffering from mild dementia associated with Alzheimer's disease, the method comprising administering to the subject a therapeutically effective amount of soft gelatin capsules disclosed herein.

[0099] On the one hand, this disclosure provides a method for improving working memory in subjects suffering from mild dementia associated with Alzheimer's disease, the method comprising administering to the subject a therapeutically effective amount of soft gelatin capsules disclosed herein.

[0100] On the one hand, this disclosure provides a method for improving learning in subjects with mild dementia associated with Alzheimer's disease, the method comprising administering to the subject a therapeutically effective amount of soft gelatin capsules disclosed herein.

[0101] On the one hand, this disclosure provides a method for improving the learning and working memory of subjects with mild dementia associated with Alzheimer's disease, the method comprising administering to the subject a therapeutically effective amount of soft gelatin capsules disclosed herein.

[0102] In some embodiments, the method includes administering to a subject a total daily dose of compound I of about 0.3 mg to about 1.5 mg. In some embodiments, the method includes administering to a subject a total daily dose of compound I of about 0.6 mg to about 1.5 mg. In some embodiments, the method includes administering to a subject a total daily dose of compound I of about 0.9 mg to about 1.2 mg. In some embodiments, the method includes administering to a subject a total daily dose of compound I of about 1.2 mg. In some embodiments, the method includes administering to a subject a total daily dose of compound I of 1.2 mg. In some embodiments, the method includes administering to a subject a total daily dose of compound I of about 0.9 mg. In some embodiments, the method includes administering to a subject a total daily dose of compound I of 0.9 mg. In some embodiments, the method includes administering to a subject a total daily dose of compound I of 0.9 mg. In some embodiments, the method includes administering to a subject a total daily dose of compound I of about 0.9 mg. In some embodiments, the method includes administering to a subject a total daily dose of compound I of about 0.6 mg. In some embodiments, the method includes administering to a subject a total daily dose of compound I of 0.6 mg. In some embodiments, the method includes administering to a subject a total daily dose of compound I of about 0.3 mg. In some embodiments, the method includes administering to a subject a total daily dose of compound I of 0.3 mg.

[0103] In some embodiments, a dose of compound I is administered to the subject once, twice, three or four times daily.

[0104] In some embodiments, the method includes administering at least one loading dose to a subject; and at least one maintenance dose. In some embodiments, the method includes administering a loading dose to a subject daily. In some embodiments, the method includes administering a loading dose to a subject daily for at least 2, 4, 6, 8, or 10 weeks. In some embodiments, the method includes administering a loading dose to a subject daily for at least 2 weeks. In some embodiments, the method includes administering a loading dose to a subject daily for at least 4 weeks. In some embodiments, the method includes administering a loading dose to a subject daily for at least 6 weeks. In some embodiments, the method includes administering a loading dose to a subject daily for at least 8 weeks. In some embodiments, the method includes administering a loading dose to a subject daily for at least 10 weeks. In some embodiments, the loading dose is about 1.2 mg of compound I daily. In some embodiments, the loading dose is 1.2 mg of compound I daily. In some embodiments, a maintenance dose is administered daily. In some embodiments, the maintenance dose is about 0.9 mg of compound I daily. In some embodiments, the maintenance dose is 0.9 mg of compound I daily. In some embodiments, the maintenance dose is about 0.6 mg of compound I daily. In some embodiments, the maintenance dose is 0.6 mg of compound I daily.

[0105] On the one hand, this disclosure provides a pharmaceutical composition as disclosed herein for treating a subject with Huntington's disease.

[0106] On the one hand, this disclosure provides a pharmaceutical composition as disclosed herein for treating cognitive impairment in subjects with Huntington's disease.

[0107] On the one hand, this disclosure provides a pharmaceutical composition as disclosed herein for treating mild cognitive impairment (MCI) associated with Huntington's disease in a subject.

[0108] On the one hand, this disclosure provides a pharmaceutical composition as disclosed herein for improving executive function in subjects with mild cognitive impairment (MCI) associated with Huntington's disease.

[0109] On the one hand, this disclosure provides a pharmaceutical composition as disclosed herein for improving working memory in subjects with mild cognitive impairment (MCI) associated with Huntington's disease.

[0110] On the one hand, this disclosure provides a pharmaceutical composition as disclosed herein for improving learning in subjects with mild cognitive impairment (MCI) associated with Huntington's disease.

[0111] On the one hand, this disclosure provides a pharmaceutical composition as disclosed herein for improving learning and working memory in subjects with mild cognitive impairment (MCI) associated with Huntington's disease.

[0112] On the one hand, this disclosure provides a pharmaceutical composition as disclosed herein for improving cognition in subjects with Huntington's disease.

[0113] On the one hand, this disclosure provides a pharmaceutical composition as disclosed herein for slowing cognitive decline in subjects with Huntington's disease.

[0114] On the one hand, this disclosure provides a pharmaceutical composition as disclosed herein for treating a subject with Parkinson's disease.

[0115] On the one hand, this disclosure provides a pharmaceutical composition as disclosed herein for treating cognitive impairment in subjects with Parkinson's disease.

[0116] On the one hand, this disclosure provides a pharmaceutical composition as disclosed herein for treating mild cognitive impairment (MCI) associated with Parkinson's disease in a subject.

[0117] On the one hand, this disclosure provides a pharmaceutical composition as disclosed herein for improving executive function in subjects with mild cognitive impairment (MCI) associated with Parkinson's disease.

[0118] On the one hand, this disclosure provides a pharmaceutical composition as disclosed herein for improving working memory in subjects with mild cognitive impairment (MCI) associated with Parkinson's disease.

[0119] On the one hand, this disclosure provides a pharmaceutical composition as disclosed herein for improving learning in subjects with mild cognitive impairment (MCI) associated with Parkinson's disease.

[0120] On the one hand, this disclosure provides a pharmaceutical composition as disclosed herein for improving learning and working memory in subjects with mild cognitive impairment (MCI) associated with Parkinson's disease.

[0121] On the one hand, this disclosure provides a pharmaceutical composition as disclosed herein for improving cognition in subjects with Parkinson's disease.

[0122] On the one hand, this disclosure provides a pharmaceutical composition as disclosed herein for slowing cognitive decline in subjects with Parkinson's disease.

[0123] On the one hand, this disclosure provides a pharmaceutical composition as disclosed herein for treating Alzheimer's disease in a subject.

[0124] On the one hand, this disclosure provides a pharmaceutical composition as disclosed herein for treating cognitive impairment in subjects with Alzheimer's disease.

[0125] On the one hand, this disclosure provides a pharmaceutical composition as disclosed herein for treating mild cognitive impairment (MCI) associated with Alzheimer's disease in a subject.

[0126] On the one hand, this disclosure provides a pharmaceutical composition as disclosed herein for improving executive function in subjects with mild cognitive impairment (MCI) associated with Alzheimer's disease.

[0127] On the one hand, this disclosure provides a pharmaceutical composition as disclosed herein for improving working memory in subjects with mild cognitive impairment (MCI) associated with Alzheimer's disease.

[0128] On the one hand, this disclosure provides a pharmaceutical composition as disclosed herein for improving learning in subjects with mild cognitive impairment (MCI) associated with Alzheimer's disease.

[0129] On the one hand, this disclosure provides a pharmaceutical composition as disclosed herein for improving learning and working memory in subjects with mild cognitive impairment (MCI) associated with Alzheimer's disease.

[0130] On the one hand, this disclosure provides a pharmaceutical composition as disclosed herein for improving cognition in subjects suffering from Alzheimer's disease.

[0131] On the one hand, this disclosure provides a pharmaceutical composition as disclosed herein for slowing cognitive decline in subjects with Alzheimer's disease.

[0132] On the one hand, this disclosure provides a pharmaceutical composition as disclosed herein for the treatment of mild dementia associated with Alzheimer's disease.

[0133] On the one hand, this disclosure provides a pharmaceutical composition as disclosed herein for improving executive function in subjects suffering from mild dementia associated with Alzheimer's disease.

[0134] On the one hand, this disclosure provides a pharmaceutical composition as disclosed herein for improving working memory in subjects suffering from mild dementia associated with Alzheimer's disease.

[0135] On the one hand, this disclosure provides a pharmaceutical composition as disclosed herein for improving learning in subjects with mild dementia associated with Alzheimer's disease.

[0136] On the one hand, this disclosure provides a pharmaceutical composition as disclosed herein for improving learning and working memory in subjects with mild dementia associated with Alzheimer's disease.

[0137] In some embodiments, the composition is formulated for administering a total daily dose of about 0.3 mg to about 1.5 mg of compound I. In some embodiments, the composition is formulated for administering a total daily dose of about 1.2 mg of compound I. In some embodiments, the composition is formulated for administering a total daily dose of 1.2 mg of compound I. In some embodiments, the composition is formulated for administering a total daily dose of about 0.9 mg of compound I. In some embodiments, the composition is formulated for administering a total daily dose of 0.9 mg of compound I. In some embodiments, the composition is formulated for administering a total daily dose of about 0.6 mg of compound I. In some embodiments, the composition is formulated for administering a total daily dose of 0.6 mg of compound I. In some embodiments, the composition is formulated for administering a total daily dose of 0.6 mg of compound I. In some embodiments, the composition is formulated for administering a total daily dose of about 0.3 mg of compound I. In some embodiments, the composition is formulated for administering a total daily dose of 0.3 mg of compound I. In some embodiments, the treatment includes administering at least one loading dose and at least one maintenance dose.

[0138] In some embodiments, the treatment includes daily administration of a loading dose for at least 2, 4, 6, 8, or 10 weeks.

[0139] In some embodiments, the treatment includes administering a loading dose daily for at least 2 weeks. In some embodiments, the treatment includes administering a loading dose daily for at least 4 weeks. In some embodiments, the treatment includes administering a loading dose daily for at least 6 weeks. In some embodiments, the treatment includes administering a loading dose daily for at least 8 weeks. In some embodiments, the treatment includes administering a loading dose daily for at least 10 weeks. In some embodiments, the loading dose is about 1.2 mg of compound I daily. In some embodiments, the loading dose is 1.2 mg of compound I daily. In some embodiments, the maintenance dose is about 0.9 mg of compound I daily. In some embodiments, a maintenance dose is administered daily. In some embodiments, the maintenance dose is 0.9 mg of compound I daily. In some embodiments, the maintenance dose is about 0.6 mg of compound I daily. In some embodiments, the maintenance dose is 0.6 mg of compound I daily.

[0140] On the one hand, this disclosure provides the use of the pharmaceutical composition disclosed herein for manufacturing a medicament for treating a subject with Huntington's disease.

[0141] On the one hand, this disclosure provides the use of a pharmaceutical composition as disclosed herein for manufacturing a medicament for treating cognitive impairment in a subject suffering from Huntington's disease.

[0142] On the one hand, this disclosure provides the use of a pharmaceutical composition as disclosed herein for manufacturing a medicament for treating mild cognitive impairment (MCI) associated with Huntington's disease in a subject.

[0143] On the one hand, this disclosure provides the use of a pharmaceutical composition as disclosed herein for manufacturing a medicament for improving executive function in a subject suffering from mild cognitive impairment (MCI) associated with Huntington's disease.

[0144] On one hand, this disclosure provides the use of a pharmaceutical composition as disclosed herein for manufacturing a medicament for improving working memory in a subject suffering from mild cognitive impairment (MCI) associated with Huntington's disease.

[0145] On the one hand, this disclosure provides the use of a pharmaceutical composition as disclosed herein for manufacturing a medicament for improving learning in a subject suffering from mild cognitive impairment (MCI) associated with Huntington's disease.

[0146] On the one hand, this disclosure provides the use of a pharmaceutical composition as disclosed herein for manufacturing a medicament for improving learning and working memory in subjects with mild cognitive impairment (MCI) associated with Huntington's disease.

[0147] On the one hand, this disclosure provides the use of a pharmaceutical composition as disclosed herein for manufacturing a medicament for improving cognition in a subject suffering from Huntington's disease.

[0148] On the one hand, this disclosure provides the use of a pharmaceutical composition as disclosed herein for manufacturing a medicament for slowing cognitive decline in subjects with Huntington's disease.

[0149] On the one hand, this disclosure provides the use of the pharmaceutical composition disclosed herein for manufacturing a medicament for treating a subject with Parkinson's disease.

[0150] On the one hand, this disclosure provides the use of the pharmaceutical composition disclosed herein for manufacturing a medicament for treating cognitive impairment in a subject suffering from Parkinson's disease.

[0151] On the one hand, this disclosure provides the use of a pharmaceutical composition as disclosed herein for manufacturing a medicament for treating mild cognitive impairment (MCI) associated with Parkinson's disease in a subject.

[0152] On the one hand, this disclosure provides the use of a pharmaceutical composition as disclosed herein for manufacturing a medicament for improving executive function in a subject suffering from mild cognitive impairment (MCI) associated with Parkinson's disease.

[0153] On one hand, this disclosure provides the use of a pharmaceutical composition as disclosed herein for manufacturing a medicament for improving working memory in a subject suffering from mild cognitive impairment (MCI) associated with Parkinson's disease.

[0154] On the one hand, this disclosure provides the use of a pharmaceutical composition as disclosed herein for manufacturing a medicament for improving learning in a subject suffering from mild cognitive impairment (MCI) associated with Parkinson's disease.

[0155] On the one hand, this disclosure provides the use of a pharmaceutical composition as disclosed herein for manufacturing a medicament for improving learning and working memory in subjects with mild cognitive impairment (MCI) associated with Parkinson's disease.

[0156] On the one hand, this disclosure provides the use of the pharmaceutical composition disclosed herein for manufacturing a medicament for improving cognition in a subject suffering from Parkinson's disease.

[0157] On the one hand, this disclosure provides the use of a pharmaceutical composition as disclosed herein for manufacturing a medicament for slowing cognitive decline in a subject with Parkinson's disease.

[0158] On the one hand, this disclosure provides the use of a pharmaceutical composition as disclosed herein for manufacturing a medicament for treating a subject with Alzheimer's disease.

[0159] On the one hand, this disclosure provides the use of the pharmaceutical composition disclosed herein for manufacturing a medicament for treating cognitive impairment in a subject suffering from Alzheimer's disease.

[0160] On the one hand, this disclosure provides the use of a pharmaceutical composition as disclosed herein for manufacturing a medicament for treating mild cognitive impairment (MCI) associated with Alzheimer's disease in a subject.

[0161] On the one hand, this disclosure provides the use of a pharmaceutical composition as disclosed herein for manufacturing a medicament for improving executive function in a subject suffering from mild cognitive impairment (MCI) associated with Alzheimer's disease.

[0162] On the one hand, this disclosure provides the use of a pharmaceutical composition as disclosed herein for manufacturing a medicament for improving working memory in subjects suffering from mild cognitive impairment (MCI) associated with Alzheimer's disease.

[0163] On the one hand, this disclosure provides the use of a pharmaceutical composition as disclosed herein for manufacturing a medicament for improving learning in subjects suffering from mild cognitive impairment (MCI) associated with Alzheimer's disease.

[0164] On the one hand, this disclosure provides the use of a pharmaceutical composition as disclosed herein for manufacturing a medicament for improving learning and working memory in subjects with mild cognitive impairment (MCI) associated with Alzheimer's disease.

[0165] On the one hand, this disclosure provides the use of a pharmaceutical composition as disclosed herein for manufacturing a medicament for improving cognition in a subject suffering from Alzheimer's disease.

[0166] On the one hand, this disclosure provides the use of a pharmaceutical composition as disclosed herein for manufacturing a medicament for slowing cognitive decline in subjects with Alzheimer's disease.

[0167] On the one hand, this disclosure provides the use of a pharmaceutical composition as disclosed herein for manufacturing a medicament for treating mild dementia associated with Alzheimer's disease.

[0168] On the one hand, this disclosure provides the use of a pharmaceutical composition as disclosed herein for manufacturing a medicament for improving executive function in a subject suffering from mild dementia associated with Alzheimer's disease.

[0169] On the one hand, this disclosure provides the use of a pharmaceutical composition as disclosed herein for manufacturing a medicament for improving working memory in a subject suffering from mild dementia associated with Alzheimer's disease.

[0170] On the one hand, this disclosure provides the use of a pharmaceutical composition as disclosed herein for manufacturing a medicament for improving learning in a subject suffering from mild dementia associated with Alzheimer's disease.

[0171] On the one hand, this disclosure provides the use of the pharmaceutical composition disclosed herein for manufacturing a medicament for improving learning and working memory in subjects with mild dementia associated with Alzheimer's disease.

[0172] In some embodiments, the total daily dose of compound I is from about 0.3 mg to about 1.5 mg. In some embodiments, the total daily dose of compound I is about 1.2 mg. In some embodiments, the total daily dose of compound I is 1.2 mg. In some embodiments, the total daily dose of compound I is about 0.9 mg. In some embodiments, the total daily dose of compound I is 0.9 mg. In some embodiments, the total daily dose of compound I is about 0.6 mg. In some embodiments, the total daily dose of compound I is 0.6 mg. In some embodiments, the total daily dose of compound I is about 0.3 mg. In some embodiments, the total daily dose of compound I is 0.3 mg. In some embodiments, the treatment includes administering at least one loading dose and at least one maintenance dose. In some embodiments, the treatment includes administering a loading dose daily for at least 2, 4, 6, 8, or 10 weeks. In some embodiments, the treatment includes administering a loading dose daily for at least 2 weeks. In some embodiments, the treatment includes administering a loading dose daily for at least 4 weeks. In some embodiments, the treatment includes administering a loading dose daily for at least 6 weeks. In some embodiments, the treatment includes administering a loading dose daily for at least 8 weeks. In some embodiments, the treatment comprises administering a loading dose daily for at least 10 weeks. In some embodiments, the loading dose is approximately 1.2 mg of compound I daily. In some embodiments, the loading dose is 1.2 mg of compound I daily. In some embodiments, a maintenance dose is administered daily. In some embodiments, the maintenance dose is approximately 0.9 mg of compound I daily. In some embodiments, the maintenance dose is 0.9 mg of compound I daily. In some embodiments, the maintenance dose is approximately 0.6 mg of compound I daily. In some embodiments, the maintenance dose is 0.6 mg of compound I daily.

[0173] On one hand, this disclosure provides a dosing regimen for administering a therapeutically effective amount of a pharmaceutical composition as disclosed herein to a subject in need, the dosing regimen comprising administering at least one loading dose to the subject; and at least one maintenance dose. In some embodiments, the loading dose is administered daily for at least 2, 4, 6, 8, or 10 weeks. In some embodiments, the loading dose is administered daily for at least 2 weeks. In some embodiments, the loading dose is administered daily for at least 4 weeks. In some embodiments, the loading dose is administered daily for at least 6 weeks. In some embodiments, the loading dose is administered daily for at least 8 weeks. In some embodiments, the loading dose is administered daily for at least 10 weeks. In some embodiments, the loading dose is about 1.2 mg of compound I daily. In some embodiments, the loading dose is 1.2 mg of compound I daily. In some embodiments, the maintenance dose is about 0.9 mg of compound I daily. In some embodiments, the maintenance dose is 0.9 mg of compound I daily. In some embodiments, the maintenance dose is about 0.6 mg of compound I daily. In some embodiments, the maintenance dose is 0.6 mg of compound I daily. Attached Figure Description

[0174] Figure 1A An exemplary XRPD pattern of crystal form A is depicted.

[0175] Figure 1B Exemplary TGA (top) and DSC (bottom) thermograms of crystal form A are depicted.

[0176] Figure 2A An exemplary XRPD pattern of crystal form B is depicted.

[0177] Figure 2B Exemplary TGA (top) and DSC (bottom) thermograms of crystal form B are depicted.

[0178] Figure 3A An exemplary XRPD pattern of crystal form C is depicted.

[0179] Figure 3B Exemplary TGA (top) and DSC (bottom) thermograms of crystal form C are depicted.

[0180] Figure 4A An exemplary XRPD pattern of crystal form D is depicted.

[0181] Figure 4B Exemplary TGA (top) and DSC (bottom) thermograms of crystal form D are depicted.

[0182] Figure 5A An exemplary XRPD pattern of crystal form E is depicted.

[0183] Figure 5BExemplary TGA (top) and DSC (bottom) thermograms of crystal form E are depicted. Detailed Implementation

[0184] General definition

[0185] The term "this paper" refers to the entire application.

[0186] Unless otherwise defined herein, the scientific and technical terms used in this application shall have the meanings commonly understood by one of ordinary skill in the art to which this disclosure pertains. Generally, the nomenclature used in connection with the compounds, compositions, and methods described herein is that which is well known and commonly used in the art.

[0187] It should be understood that any embodiment described herein, including those described in different embodiments of this disclosure and in different parts of the specification (including embodiments described only in the examples), can be combined with one or more other embodiments of this disclosure, unless expressly denied or undue. Combinations of embodiments are not limited to those specific combinations claimed by the multiple dependent claims. For example, any claim relying on another claim may be modified to include one or more limitations found in any other claim relying on the same basic claim. Where elements are presented in a list format such as a Markush group format, each subgroup of the elements is also disclosed, and any one or more elements may be removed from the group.

[0188] Throughout this specification, the word “comprise” or variations such as “comprises” or “comprising” should be understood to imply inclusion of the stated integer (or component) or group of integers (or components), but not to exclude any other integer (or component) or group of integers (or components).

[0189] Throughout this specification, when a composition or apparatus is described as having, including, or comprising (or variations thereof) specific components, it is contemplated that the composition may also substantially consist of or be composed of said components. Similarly, when a method or process is described as having, including, or comprising specific method steps, the method may also substantially consist of or be composed of said processing steps. Furthermore, it should be understood that the order of steps or the sequence of actions is irrelevant as long as the compositions and methods described herein remain operable. Moreover, two or more steps or actions may be performed simultaneously.

[0190] As used herein, the term “comprising” means “including, but not limited to”. “Comprising” and “including, but not limited to” are used interchangeably. Therefore, these terms are to be understood as implying the inclusion of the stated integers (or components) or groups of integers (or components), but not excluding any other integers (or components) or groups of integers (or components).

[0191] As used herein, “about” or “approximately” means within an acceptable margin of error for a particular value as determined by a person of ordinary skill in the art, which will depend in part on how the value was measured or determined, i.e., the limitations of the measurement system.

[0192] In the context of describing elements (especially in the context of the following claims), the use of the terms “an”, “a”, “the”, and similar designations should be interpreted to cover both the singular and the plural, unless otherwise indicated herein or explicitly contradicted by the context.

[0193] Unless the context clearly indicates otherwise, the term “or” as used herein should be understood to mean “and / or”.

[0194] Unless otherwise indicated herein, the description of ranges of values ​​herein is intended only as a shorthand method for individually referring to each individual value falling within that range and including its endpoints, and each individual value is incorporated into this specification as if individually described herein. All methods described herein may be performed in any suitable order unless otherwise stated herein or clearly contradicted by the context. Unless otherwise stated, the use of any and all instances or exemplary language (e.g., “such as”) provided herein is intended only to better illustrate the embodiments and does not constitute a limitation on the scope of the claims. None of the language in this specification should be construed as indicating that any unclaimed element is essential.

[0195] All publications, patents, and published patent applications mentioned in this application are specifically incorporated herein by reference. In the event of any conflict, this specification (including its specific definitions) shall prevail. Furthermore, any particular embodiment of this disclosure falling within the prior art may be expressly excluded from any one or more of the claims. Since such embodiments are considered to be known to those skilled in the art, they may be excluded even if not expressly stated herein. Any particular embodiment of this disclosure may be excluded from any claim for any reason, whether or not related to the existence of prior art.

[0196] The terms “active ingredient,” “active agent,” and “active substance” refer to a compound, alone or in combination with one or more pharmaceutically acceptable excipients, administered to a subject for the treatment, prevention, or improvement of one or more symptoms of a condition, disorder, or disease. As used herein, “active ingredient,” “active agent,” and “active substance” can be optically active isomers of the compounds described herein.

[0197] The terms “drug” and “therapeutic agent” refer to a compound or pharmaceutical composition thereof administered to a subject for the treatment, prevention or improvement of one or more symptoms of a condition, disorder or disease.

[0198] As used herein, the term "polymorph" refers to a crystalline form of a compound or its salts, hydrates, or solvates that are in a particular crystalline packing. The term "polymorph" includes pseudopolymorphs, which are typically different solvates of a material and therefore have different properties from one another. Thus, each different polymorph and pseudopolymorph disclosed herein is considered a different single-crystal form herein.

[0199] As used herein, the term “crystal” refers to a solid form composed of an ordered arrangement of structural units. Different crystalline forms of the same compound or its salts, hydrates, or solvates arise from different packings of solid molecules, resulting in different crystal symmetries and / or unit cell parameters. Different crystalline forms typically have different X-ray diffraction patterns, infrared spectra, melting points, densities, hardness, crystal shapes, optical and electrical properties, stability, and solubility. See, for example, Remington's Pharmaceutical Sciences, 18th edition, Mack Publishing, Easton Pa., 173 (1990); United States Pharmacopeia, 23rd edition, 1843-1844 (1995) (incorporated herein by reference). As used herein, the terms “crystalline form,” “single crystal form,” “crystalline solid form,” and “polymorph” are used interchangeably; these terms distinguish crystals that have different properties (e.g., different XRPD patterns and / or different DSC scan results).

[0200] The term "fundamentally pure" refers to the composition of a specific crystalline solid form of Compound I, which may be free of impurities and / or other solid forms of Compound I, at least within a specific weight percentage. The specific weight percentage is 70%, 75%, 80%, 85%, 90%, 95%, 99%, or any percentage between 70% and 100%. In some embodiments, Compound I may be a substantially pure sample of any crystalline solid form described herein. In some embodiments, Compound I may be substantially pure crystal form A. In some embodiments, Compound I may be substantially pure crystal form B. In some embodiments, Compound I may be substantially pure crystal form D.

[0201] Crystalline forms are typically characterized by X-ray powder diffraction (XRPD). XRPD reflectance patterns (peaks, typically expressed in 2θ degrees) are generally considered the fingerprint of a specific crystalline form. The relative intensities of XRPD peaks can vary, particularly depending on sample preparation techniques, crystal size distribution, filters, sample setup procedures, and the specific instrument used. In some cases, there may be more (i.e., new peaks) or fewer (i.e., peaks may disappear) peaks in an XRPD pattern, depending on the instrument type or setup. In some cases, any particular peak in an XRPD pattern may appear as a singlet, doublet, triplet, quartet, or multiplet, depending on the instrument type or setup, instrument sensitivity, measurement conditions, and / or the purity of the crystalline form. In some cases, any particular peak in an XRPD may appear in a symmetrical or asymmetrical shape, such as having shoulders. Furthermore, instrument variations and other factors can also affect the 2θ values. Those skilled in the art who understand these variations are able to use XRPD, as well as other known physicochemical techniques, to identify or determine the defining characteristics or properties of a particular crystalline form.

[0202] When referring to peaks in the XRPD spectrum of the crystalline form of compound I, the term "characteristic peak" refers to a set of peaks whose 2θ values ​​in the range of 0° to 40° are uniquely attributed to one of the crystalline forms of compound I.

[0203] The term "amorphous," applied to compounds, refers to a material that lacks a long-range order at the molecular level and, depending on temperature, can exhibit solid or liquid physical properties. Typically, such materials do not give distinctive X-ray diffraction patterns and, while exhibiting solid properties, are more formally described as liquids. Upon heating, a change in properties from solid to liquid occurs, characterized by a change in state, typically second-order ("glass transition").

[0204] The terms "anhydrous" or "waterless" are used interchangeably, and when used for compounds, they refer to solid states in which the compound's crystal lattice does not contain structural water or other solvent molecules.

[0205] The term "solvent" refers to a compound or its salt provided herein, which further includes stoichiometric or non-stoichiometric amounts of solvent bound by non-covalent intermolecular forces (e.g., hydrogen bonds). When the solvent is water, the solvate is a hydrate. When the solvent includes ethanol, the compound can be an ethanol solvate.

[0206] In the context of the polymorphic forms disclosed herein, the term "stability" refers to the stability of the polymorphic form relative to heat and / or humidity.

[0207] The term "pharmaceutically acceptable" refers to materials, compositions, and / or dosage forms that have been approved or are permitted for use in animals (especially humans) by U.S. federal or state regulatory agencies or by the appropriate agency in other countries outside the United States, or that are listed in the United States Pharmacopeia or other recognized pharmacopoeias. This term also refers to compounds, materials, compositions, and / or dosage forms that, to a reasonable medical judgment, are suitable for use in contact with tissues in humans and animals without causing excessive toxicity, irritation, allergic reactions, or other problems or complications, and that are proportionate to a reasonable benefit / risk ratio.

[0208] "Pharmaceutically acceptable salt" means a salt of the compound disclosed herein that is pharmaceutically acceptable and has the desired pharmacological activity of the parent compound. Specifically, such salts are non-toxic and can be addition salts of inorganic or organic acids, as well as addition salts of bases. Specifically, such salts include: (1) acid addition salts formed from inorganic acids (such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, etc.); or formed from organic acids such as acetic acid, propionic acid, hexanoic acid, cyclopentanepropionic acid, glycolic acid, pyruvic acid, lactic acid, malonic acid, succinic acid, malic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, 3-(4-hydroxybenzoyl)benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, 1,2-ethane-disulfonic acid, 2-hydroxyethylsulfonic acid, benzenesulfonic acid, 4-chlorobenzenesulfonic acid, 2-naphthalenesulfonic acid, 4-Toluenesulfonic acid, camphorsulfonic acid, 4-methylbicyclo[2.2.2]-oct-2-en-1-carboxylic acid, glucoheponic acid, 3-phenylpropionic acid, trimethylacetic acid, tert-butylacetic acid, dodecyl sulfate, gluconic acid, glutamic acid, hydroxynaphthenic acid, salicylic acid, stearic acid, mucoconic acid, etc.; or (2) salts formed when the acidic protons present in the parent compound are replaced by metal ions (e.g., alkali metal ions, alkaline earth metal ions, or aluminum ions); or salts formed when coordinated with organic bases (e.g., ethanolamine, diethanolamine, triethanolamine, N-methylglucosamine, etc.). Salts also include (by way of example) sodium, potassium, calcium, magnesium, ammonium, tetraalkylammonium, etc.; and when the compound contains a basic functional group, it also includes salts of non-toxic organic or inorganic acids, such as hydrochloride, hydrobromide, tartrate, methanesulfonate, acetate, maleate, oxalate, etc. The term "pharmaceutically acceptable cation" refers to an acceptable cation counterion of an acidic functional group. Examples of such cations include sodium, potassium, calcium, magnesium, ammonium, tetraalkylammonium cations, etc. See, for example, Berge et al., J. Pharm. Sci. (1977) 66(1):1–79.

[0209] Bioavailability (%F) refers to the percentage of administered compound I that enters the systemic circulation of a test animal or human. AUC (from zero to infinity) represents the total exposure of the drug over time. Total exposure (AUC) after intravenous drug administration. Inf Or AUC ∞ It is usually defined as 100% bioavailability (F%).

[0210] "Oral bioavailability" refers to the extent to which compound I is absorbed into the systemic circulation when the drug composition is orally administered, compared to intravenous injection.

[0211] The term "geometric mean" refers to the average or mean value that represents the central tendency of a set of values ​​by calculating the product of these values. The formula for calculating the geometric mean is: .

[0212] "Plasma concentration" refers to the concentration of compound 1 in the plasma components of a subject's blood. It should be understood that the plasma concentration of compound 1 may vary significantly among different subjects due to metabolic differences and / or potential interactions with other therapeutic agents. According to one embodiment disclosed herein, the plasma concentration of compound 1 may vary from subject to subject. Similarly, values ​​such as maximum values ​​may also vary from subject to subject. Plasma concentration (C max ), time to reach maximum plasma concentration (t) max ) or the total area under the plasma concentration-time curve (AUC) ∞ (This may vary depending on the individual subject.)

[0213] The term "AUC" last "" refers to the time from 0 to t last The area under the plasma concentration-time curve.

[0214] The term "t" last "" refers to the time of the last measurable concentration.

[0215] The term "t" max "" refers to the time it takes to reach the maximum concentration.

[0216] Term "C" max "This refers to the maximum concentration of the drug in the blood plasma."

[0217] The term "CL" z " / F" refers to the apparent clearance of uncorrected bioavailability measured after extravascular administration.

[0218] The term "V" z " / F" refers to the apparent volume of distribution without adjusting for bioavailability.

[0219] As used herein, the term “modulation” means an interaction with a target, directly or indirectly, to alter the activity of the target, including by way of example only, enhancing the activity of the target, inhibiting the activity of the target, limiting the activity of the target, or prolonging the activity of the target.

[0220] As used herein, the term "modifier" refers to a compound that alters the activity of a molecule. For example, a modifier can increase or decrease the intensity of a certain activity of a molecule compared to the activity intensity without the modifier. In some embodiments, the modifier is an inhibitor that reduces the intensity of one or more activities of a molecule. In some embodiments, an inhibitor completely blocks one or more activities of a molecule. In some embodiments, the modifier is an activator that enhances the intensity of at least one activity of a molecule. In some embodiments, the presence of the modifier results in an activity that would not occur in the absence of the modifier.

[0221] The term "subject" to be administered includes, but is not limited to, human subjects (i.e., males or females of any age, such as pediatric subjects (e.g., infants, children, adolescents) or adult subjects (e.g., young adults, middle-aged, or elderly)) and / or non-human animals, such as mammals, like primates (e.g., cynomolgus monkeys, rhesus monkeys), cattle, pigs, horses, sheep, goats, rodents, cats, and / or dogs. In some embodiments, the subject is a human. In some embodiments, the subject is a non-human animal. The terms "human," "patient," and "subject" are used interchangeably herein.

[0222] In this article, "disease", "disorder" and "symptom" can be used interchangeably.

[0223] As used herein, the terms “treatment,” “being treated,” or “therapeutic approach” include improving or stabilizing a subject’s condition by reversing, alleviating, or blocking symptoms, clinical signs, and underlying pathology of a condition. As used herein and as is well known in the art, “treatment” is a method for achieving a beneficial or desired outcome, including clinical outcomes. Beneficial or desired clinical outcomes include, but are not limited to: relief, improvement, reduction of one or more symptoms or the severity of symptoms associated with a condition, slowing its progression, reducing the extent of the disease, stabilizing (i.e., not worsening) the disease state, slowing or decelerating disease progression, improving or alleviating the disease state, and relief (whether partial or complete), whether detectable or undetectable. “Treatment” can also refer to prolonged survival compared to expected survival without treatment. Exemplary beneficial clinical outcomes are described herein.

[0224] As used herein, unless otherwise stated, the terms “preventive,” “prevention,” and variations thereof refer to measures taken before a subject begins to suffer from a particular disease, disorder, or symptom.

[0225] Generally, the “effective amount” of a compound refers to the amount sufficient to elicit the desired biological response. Those skilled in the art will understand that the effective amount of the compounds disclosed herein may vary depending on a variety of factors, such as the desired biological endpoint, the pharmacokinetics of the compound, the disease being treated, the route of administration, and the age, weight, health status, and condition of the subject. Effective doses cover both therapeutic and prophylactic treatments.

[0226] The terms "pharmaceutical effective amount," "therapeutic effective amount," or "therapeutic dose" refer to a dose sufficient to treat a subject's disease, for example, to produce a beneficial and / or desired change in the health status of a subject with a disease, to treat, cure, suppress, or improve a physiological response or condition, or to delay or alleviate one or more symptoms associated with a disease, disorder, or symptom. A complete therapeutic effect may not be achieved with a single dose but may require multiple doses. Therefore, a therapeutic effective amount may be administered in one or more doses. The exact effective amount required by a subject depends on many factors, such as the subject's body type, health, and age, the nature and severity of the disease, the chosen therapeutic drug or combination therapy, and the route of administration. Technicians can readily determine the effective amount for a given situation through routine experiments. The terms "pharmaceutical effective amount," "therapeutic effective amount," or "therapeutic dose" also refer to a dose required to improve a patient's clinical symptoms. Therapeutic effective dose of a compound also refers to a therapeutic dose, whether used alone or in combination with other therapies, that produces a therapeutic effect on a disease, symptom, or condition. The term "therapeutic effective dose" can encompass a dose that improves overall efficacy, reduces or prevents symptoms or causes of a disease or condition, or enhances the efficacy of other therapeutic agents.

[0227] As used herein, and unless otherwise stated, a "preventively effective amount" of a compound is a dose sufficient to prevent a disease, condition, or illness, or to prevent one or more symptoms associated with a disease, condition, or illness, or to prevent its recurrence. A preventively effective amount of a compound means the amount of a therapeutic agent, alone or in combination with other agents, that provides a preventive benefit in preventing a disease, condition, or illness. The term "preventively effective amount" may also encompass amounts that improve overall prevention or enhance the preventive efficacy of another preventive agent.

[0228] A "loading dose" refers to a higher initial dose given at the start of treatment to rapidly reach therapeutic concentrations in the body before decreasing to a lower maintenance dose.

[0229] The term "maintenance dose" as used in this article refers to a lower dose given after the loading dose.

[0230] As used herein, unless otherwise stated, "pharmacokinetics" can be defined as the study of the absorption, distribution, metabolism, and excretion of drugs in the body. "Pharmacokinetics" can also be defined as the characteristic interactions between drugs and the human body in terms of absorption, distribution, metabolism, and excretion; or, a branch of pharmacology, the study of how drugs enter, are transported, and are excreted from the body.

[0231] A substance, compound, or pharmaceutical agent may be “administered” or “delivered” to a subject using one of a variety of methods known to those skilled in the art. For example, a compound or preparation may be administered in the form of soft gelatin capsules, hard-shell capsules, or oral solutions. Administration may also be performed, for example, once, multiple times, and / or over one or more extended time periods. In some embodiments, the route of administration includes direct administration (including self-administration by the subject) and indirect administration (including prescription). For example, as used herein, administration to a patient by instructing the patient to self-administer the drug or administration by another person, and / or prescription to a patient, are considered as administration to the patient. When a method is part of a treatment regimen that includes multiple drugs or modes of treatment, this disclosure considers that these drugs may be administered at the same or different times via the same or different routes of administration. The appropriate method of administering a substance, compound, or pharmaceutical agent to a subject also depends on, for example, the subject’s age, whether the subject is active at the time of administration, whether the subject has cognitive impairment at the time of administration, the degree of cognitive impairment, and the chemical and biological properties of the compound or pharmaceutical agent (e.g., solubility, digestibility, bioavailability, stability, and toxicity).

[0232] Pharmaceutical Composition

[0233] On the other hand, this article describes a lipid formulation comprising compound I or a pharmaceutically acceptable salt thereof, and a method thereof for treating diseases or disorders associated with NMDA receptor regulation. These lipid formulations have several advantages: a) consistent exposure levels under high-fat, low-fat / low-calorie, and fasting / postprandial states; b) low exposure variability; c) higher exposure levels and AUC in all postprandial states compared to tablets; d) lower C60% of the drug formulation in all postprandial states. max All are higher than tablets. The lipid formulation disclosed herein can self-emulsify upon contact with gastrointestinal fluids. This ensures uniform dispersion of compound I and the carrier, thereby guaranteeing stable absorption of compound I under various eating / fasting conditions.

[0234] Therefore, in one respect, this disclosure provides a pharmaceutical composition comprising compound I:

[0235]

[0236] Compound I;

[0237] Or a pharmaceutically acceptable salt thereof; and one or more glycerides, wherein the glycerides comprise about 30% to about 100% w / w monoglycerides.

[0238] The pharmaceutical compositions disclosed herein can be prepared using any form of compound I, including its free base, salt, or crystal form (e.g., hydrate, anhydrous, and solvated forms). For clarity, for example, when the pharmaceutical compositions disclosed herein are prepared using the crystal form of compound I, compound I is dissolved in the formulation such that no crystals of compound I are present in the pharmaceutical composition. Similarly, when the pharmaceutical compositions disclosed herein are prepared using a pharmaceutically acceptable salt of compound I, the salt form of compound I is completely dissolved in the pharmaceutical composition.

[0239] In some embodiments, this disclosure provides a pharmaceutical composition comprising compound I:

[0240]

[0241] Compound I;

[0242] And one or more glycerides, said glycerides comprising about 30% to about 100% w / w monoglycerides. In some embodiments, the pharmaceutical composition is prepared using compound I. In other embodiments, the pharmaceutical composition is prepared using a pharmaceutically acceptable salt of compound I. Compound I and its chemical synthesis methods are disclosed in U.S. Patent No. 10,227,375 and PCT Publication No. WO2014160480, the contents of which are incorporated herein by reference.

[0243] In some embodiments, the pharmaceutical composition is prepared using a crystal form of compound I. In some embodiments, the crystal form of compound I is an anhydrous form. In some embodiments, the crystal form of compound I is a solvate form. In some embodiments, the crystal form of compound I is a hydrate form. In some embodiments, the crystal form of compound I is a monohydrate form. In some embodiments, compound I used to prepare the pharmaceutical composition disclosed herein is a crystal form selected from crystal forms A, B, C, D, and E. In some embodiments, the crystal form is crystal form A. In some embodiments, the crystal form is crystal form B. In some embodiments, the crystal form is crystal form C. In some embodiments, the crystal form is crystal form D. In some embodiments, the crystal form is crystal form E. The preparation of crystal forms A, B, C, D, and E is disclosed in WO2023250185 and WO2024015201, the disclosures of which are incorporated herein by reference.

[0244] A. Crystal form A

[0245] In some embodiments, the crystal form of compound I used to prepare the pharmaceutical compositions disclosed herein is crystal form A of compound I. In some embodiments, the amorphous form of compound I is crystal form A. In some embodiments, crystal form A has one or more features selected from the group consisting of:

[0246] a) XRPD spectra containing peaks with 2θ values ​​of 15.3 ± 0.2, 16.6 ± 0.2, and 17.9 ± 0.2 degrees;

[0247] b) Basically as Figure 1A The XRPD map shown;

[0248] c) DSC thermal analysis curve containing the endothermic peak at approximately 203 °C;

[0249] d) Basically as Figure 1B The DSC thermal analysis curve shown below;

[0250] e) A TGA curve exhibiting a loss of at least approximately 0.04 wt% between approximately 25°C and approximately 190°C; and

[0251] f) Basically as Figure 1B The TGA curve shown.

[0252] In some embodiments, crystal form A is characterized by having an XRPD spectrum containing peaks with 2θ values ​​of 15.3 ± 0.2, 16.6 ± 0.2, and 17.9 ± 0.2 degrees. In some embodiments, crystal form A is characterized by having an XRPD spectrum containing peaks with 2θ values ​​of 15.3 ± 0.2, 16.6 ± 0.2, and 17.9 ± 0.2 degrees, and further containing at least one additional peak selected from the group consisting of 2θ angles of 11.3 ± 0.2, 14.5 ± 0.2, 17.7 ± 0.2, and 20.1 ± 0.2 degrees. In some embodiments, crystal form A is characterized by having an XRPD spectrum containing peaks with 2θ values ​​of 14.5 ± 0.2, 15.3 ± 0.2, 16.6 ± 0.2, 17.9 ± 0.2, and 20.1 ± 0.2 degrees. In some embodiments, crystal form A is characterized in that its XRPD spectrum contains peaks with 2θ values ​​of 11.3 ± 0.2, 14.5 ± 0.2, 15.3 ± 0.2, 16.6 ± 0.2, 17.7 ± 0.2, 17.9 ± 0.2, and 20.1 ± 0.2 degrees. In some embodiments, crystalline form A is characterized in that it is substantially as follows: Figure 1A The depicted XRPD map.

[0253] In some embodiments, crystal form A is characterized in that its thermogravimetric analysis (TGA) thermogram shows that crystal form A loses at least about 0.04 wt% between about 25°C and about 190°C. In some embodiments, crystal form A is characterized in that its thermogravimetric analysis (TGA) thermogram shows that crystal form A loses about 0.04 wt% between about 25°C and about 190°C. In some embodiments, crystal form A is characterized in that its thermogravimetric analysis (TGA) thermogram is substantially as shown in... Figure 1B As shown.

[0254] In some embodiments, crystal form A is characterized by being substantially as follows: Figure 1B The differential scanning calorimetry (DSC) thermogram depicted is shown in the figure. In some embodiments, crystal form A is characterized in that its DSC thermogram contains an endothermic peak at about 203°C. In some embodiments, crystal form A is characterized in that its DSC thermogram contains a melting endothermic peak at about 203°C.

[0255] In some embodiments, crystal form A is substantially free of other polymorphic forms. In some embodiments, crystal form A has a polymorphic purity of at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%. In some embodiments, crystal form A has a polymorphic purity of at least 90%. In some embodiments, crystal form A has a polymorphic purity of at least 92%. In some embodiments, crystal form A has a polymorphic purity of at least 94%. In some embodiments, crystal form A has a polymorphic purity of at least 96%. In some embodiments, crystal form A has a polymorphic purity of at least 98%. In some embodiments, crystal form A has a polymorphic purity of at least 99%.

[0256] B. Crystal form B

[0257] In some embodiments, the crystal form of compound I used to prepare the pharmaceutical composition disclosed herein is crystal form B of compound I. In some embodiments, the amorphous form of compound I is crystal form B. In some embodiments, crystal form B has one or more features selected from the group consisting of:

[0258] a) XRPD spectra containing peaks with 2θ values ​​of 14.4 ± 0.2, 16.8 ± 0.2, and 18.5 ± 0.2 degrees;

[0259] b) Basically as Figure 2A The XRPD map shown;

[0260] c) DSC thermal analysis curve containing the endothermic peak at approximately 204 °C;

[0261] d) Basically as Figure 2B The DSC thermal analysis curve shown below;

[0262] e) A TGA curve exhibiting a loss of at least approximately 0.2 wt% between approximately 70°C and approximately 150°C; and

[0263] f) Basically as Figure 2B The TGA curve shown.

[0264] In some embodiments, crystal form B is characterized in that its XRPD spectrum contains peaks with 2θ values ​​of 14.4 ± 0.2, 16.8 ± 0.2, and 18.5 ± 0.2 degrees. In some embodiments, crystal form B is characterized in that its XRPD spectrum contains peaks with 2θ values ​​of 14.4 ± 0.2, 16.8 ± 0.2, and 18.5 ± 0.2 degrees, and further contains at least one additional peak selected from the group consisting of 2θ values ​​of 10.9 ± 0.2, 15.4 ± 0.2, and 19.0 ± 0.2 degrees. In some embodiments, crystal form B is characterized in that its XRPD spectrum contains peaks with 2θ values ​​of 10.9 ± 0.2, 14.4 ± 0.2, 16.8 ± 0.2, 18.5 ± 0.2, and 19.0 ± 0.2 degrees. In some embodiments, crystal form B is characterized in that its XRPD spectrum contains peaks with 2θ values ​​of 10.9 ± 0.2, 14.4 ± 0.2, 15.4 ± 0.2, 16.8 ± 0.2, 18.5 ± 0.2, and 19.0 ± 0.2 degrees. In some embodiments, crystal form B is characterized in that its XRPD spectrum is substantially as follows: Figure 2A What is depicted.

[0265] In some embodiments, crystal form B is characterized in that its thermogravimetric analysis (TGA) chromatogram shows a loss of at least about 0.2 wt% between about 70°C and about 150°C. In some embodiments, crystal form B is characterized in that its thermogravimetric analysis (TGA) chromatogram is substantially as follows: Figure 2B As depicted in the text.

[0266] In some embodiments, crystal form B is characterized in that its differential scanning calorimetry (DSC) thermogram is substantially as follows: Figure 2B As depicted in [the text]. In some embodiments, crystal form B is characterized in that its DSC thermogram includes an endothermic peak at approximately 204°C. In some embodiments, crystal form B is characterized in that its DSC thermogram includes a melting endothermic peak at approximately 204°C.

[0267] In some embodiments, crystal form B is substantially free of other polymorphic forms. In some embodiments, crystal form B has a polymorphic purity of at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%. In some embodiments, crystal form B has a polymorphic purity of at least 90%. In some embodiments, crystal form B has a polymorphic purity of at least 92%. In some embodiments, crystal form B has a polymorphic purity of at least 94%. In some embodiments, crystal form B has a polymorphic purity of at least 96%. In some embodiments, crystal form B has a polymorphic purity of at least 98%. In some embodiments, crystal form B has a polymorphic purity of at least 99%.

[0268] C. Crystal form C

[0269] In some embodiments, the crystal form of compound I used to prepare the pharmaceutical composition disclosed herein is crystal form C of compound I. In some embodiments, the hydrate crystal form of compound I is crystal form C. In some embodiments, the monohydrate crystal form of compound I is crystal form C. In some embodiments, crystal form C has one or more features selected from the group consisting of:

[0270] a) XRPD spectra containing peaks with 2θ values ​​of 12.0 ± 0.2, 15.1 ± 0.2, and 21.3 ± 0.2 degrees;

[0271] b) Basically as Figure 3A The XRPD map shown;

[0272] c) DSC thermal analysis curve containing the endothermic peak at approximately 204 °C;

[0273] d) DSC thermogram containing the endothermic peak at approximately 120 °C;

[0274] e) Basically as Figure 3B The DSC thermal spectrum shown below;

[0275] f) A TGA curve exhibiting at least approximately 3 wt% loss between approximately 23°C and approximately 125°C; and

[0276] g) Basically as Figure 3B The TGA curve shown.

[0277] In some embodiments, crystal form C is characterized in that its XRPD spectrum contains peaks with 2θ values ​​of 12.0 ± 0.2, 15.1 ± 0.2, and 21.3 ± 0.2 degrees. In some embodiments, crystal form C is characterized in that its XRPD spectrum contains peaks with 2θ values ​​of 12.0 ± 0.2, 15.1 ± 0.2, and 21.3 ± 0.2 degrees, and further contains at least one additional peak selected from the group consisting of 2θ angles of 12.9 ± 0.2, 16.3 ± 0.2, 17.5 ± 0.2, 20.1 ± 0.2, and 25.8 ± 0.2 degrees. In some embodiments, crystal form C is characterized in that its XRPD spectrum contains peaks with 2θ angles of 12.0 ± 0.2, 15.1 ± 0.2, 16.3 ± 0.2, 17.5 ± 0.2, 20.1 ± 0.2, 21.3 ± 0.2, and 25.8 ± 0.2 degrees. In some embodiments, crystal form C is characterized in that its XRPD spectrum contains peaks with 2θ angles of 12.0 ± 0.2, 12.9 ± 0.2, 15.1 ± 0.2, 16.3 ± 0.2, 17.5 ± 0.2, 20.1 ± 0.2, 21.3 ± 0.2, and 25.8 ± 0.2 degrees. In some embodiments, crystal form C is characterized in that its XRPD spectrum is substantially as follows: Figure 3A What is depicted.

[0278] In some embodiments, crystalline form C is characterized in that its thermogravimetric analysis (TGA) thermogram shows a loss of at least about 3 wt% between about 23°C and about 125°C. In some embodiments, crystalline form C is characterized in that its thermogravimetric analysis (TGA) thermogram shows a loss of about 3-4 wt% between about 23°C and about 125°C. In some embodiments, crystalline form C is characterized in that its thermogravimetric analysis (TGA) thermogram is substantially as follows: Figure 3B As depicted in the text.

[0279] In some embodiments, crystal form C is characterized in that its differential scanning calorimetry (DSC) thermogram is substantially as follows: Figure 3B As depicted in [the text]. In some embodiments, crystal form C is characterized in that its DSC thermogram includes an endothermic peak at about 204°C. In some embodiments, crystal form C is characterized in that its DSC thermogram includes an endothermic peak at about 120°C. In some embodiments, crystal form C is characterized in that its DSC thermogram includes endothermic peaks at about 120°C and about 204°C. In some embodiments, crystal form C is characterized in that its DSC thermogram includes a dehydration endothermic peak at about 120°C. In some embodiments, crystal form C is characterized in that its DSC thermogram includes a melting endothermic peak at about 204°C.

[0280] In some embodiments, crystal form C is substantially free of other polymorphic forms. In some embodiments, crystal form C has a polymorphic purity of at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%. In some embodiments, crystal form C has a polymorphic purity of at least 90%. In some embodiments, crystal form C has a polymorphic purity of at least 92%. In some embodiments, crystal form C has a polymorphic purity of at least 94%. In some embodiments, crystal form C has a polymorphic purity of at least 96%. In some embodiments, crystal form C has a polymorphic purity of at least 98%. In some embodiments, crystal form C has a polymorphic purity of at least 99%.

[0281] D. Crystal form D

[0282] In some embodiments, the crystal form of compound I used to prepare the pharmaceutical compositions disclosed herein is crystal form D of compound I. In some embodiments, a crystal form of compound I is crystal form D. In some embodiments, crystal form D has one or more features selected from the group consisting of:

[0283] a) XRPD spectra containing peaks with 2θ values ​​of 15.2 ± 0.2, 17.4 ± 0.2, and 17.7 ± 0.2 degrees;

[0284] b) Basically as Figure 4A The XRPD map shown;

[0285] c) DSC thermal analysis curve containing the endothermic peak at approximately 204 °C;

[0286] d) DSC thermogram containing the endothermic peak at approximately 127 °C;

[0287] e) Basically as Figure 4B The DSC thermal spectrum shown below;

[0288] f) A TGA curve exhibiting at least approximately 14 wt% loss between approximately 60°C and approximately 150°C; and

[0289] g) Basically as Figure 4B The TGA curve shown.

[0290] In some embodiments, crystal form D is characterized in that its XRPD spectrum contains peaks with 2θ values ​​of 15.2 ± 0.2, 17.4 ± 0.2, and 17.7 ± 0.2 degrees. In some embodiments, crystal form D is characterized in that its XRPD spectrum contains peaks with 2θ values ​​of 15.2 ± 0.2, 17.4 ± 0.2, and 17.7 ± 0.2 degrees, and further contains at least one additional peak selected from the group consisting of 2θ values ​​of 9.1 ± 0.2, 16.4 ± 0.2, 18.3 ± 0.2, and 18.9 ± 0.2 degrees. In some embodiments, crystal form D is characterized in that its XRPD spectrum contains peaks with 2θ values ​​of 15.2 ± 0.2, 16.4 ± 0.2, 17.4 ± 0.2, 18.3 ± 0.2, and 18.9 ± 0.2 degrees. In some embodiments, crystal form D is characterized in that its XRPD spectrum contains peaks with 2θ values ​​of 9.1 ± 0.2, 15.2 ± 0.2, 16.4 ± 0.2, 17.4 ± 0.2, 17.7 ± 0.2, 18.3 ± 0.2, and 18.9 ± 0.2 degrees. In some embodiments, crystal form D is characterized in that its XRPD spectrum is substantially as follows: Figure 4A As depicted in the text.

[0291] In some embodiments, crystal form D is characterized in that its thermogravimetric analysis (TGA) thermogram shows that crystal form D loses at least about 14 wt% between about 60°C and about 150°C. In some embodiments, crystal form D is characterized in that its thermogravimetric analysis (TGA) thermogram shows that crystal form D loses about 14-15 wt% between about 60°C and about 150°C. In some embodiments, crystal form D is characterized in that its thermogravimetric analysis (TGA) thermogram shows that crystal form D loses about 14 wt% between about 60°C and about 150°C. In some embodiments, crystal form D is characterized in that its thermogravimetric analysis (TGA) thermogram is substantially as follows: Figure 4B As depicted in the text.

[0292] In some embodiments, crystal form D is characterized in that its differential scanning calorimetry (DSC) thermogram is substantially as follows: Figure 4B As depicted in [the text]. In some embodiments, crystal form D is characterized in that its DSC thermogram includes an endothermic peak at about 204°C. In some embodiments, crystal form D is characterized in that its DSC thermogram includes an endothermic peak at about 127°C. In some embodiments, crystal form D is characterized in that its DSC thermogram includes endothermic peaks at both about 127°C and about 204°C. In some embodiments, crystal form D is characterized in that its DSC thermogram includes an endothermic peak during melting at about 127°C. In some embodiments, crystal form D is characterized in that its DSC thermogram includes an endothermic peak during melting at about 204°C.

[0293] In some embodiments, crystal form D is substantially free of other polymorphic forms. In some embodiments, crystal form D has a polymorphic purity of at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%. In some embodiments, crystal form D has a polymorphic purity of at least 90%. In some embodiments, crystal form D has a polymorphic purity of at least 92%. In some embodiments, crystal form D has a polymorphic purity of at least 94%. In some embodiments, crystal form D has a polymorphic purity of at least 96%. In some embodiments, crystal form D has a polymorphic purity of at least 98%. In some embodiments, crystal form D has a polymorphic purity of at least 99%.

[0294] D. Crystal form E

[0295] In some embodiments, the crystal form is a n-butanol solvate. In some embodiments, the crystal form is crystal form E, characterized in that its XRPD spectrum contains peaks with 2θ values ​​of 4.9 ± 0.2, 12.0 ± 0.2, 12.2 ± 0.2, and 17.0 ± 0.2 degrees. In some embodiments, the XRPD spectrum of crystal form E further contains at least one additional peak, the position of which is selected from the group consisting of 2θ values ​​of 8.5 ± 0.2, 14.9 ± 0.2, 15.8 ± 0.2, 18.2 ± 0.2, and 21.4 ± 0.2 degrees. In some embodiments, the crystal form is crystal form E, characterized in that its XRPD spectrum has characteristic peaks located at 2θ values ​​of 4.9 ± 0.2, 12.0 ± 0.2, 12.2 ± 0.2, 17.0 ± 0.2, and 21.4 ± 0.2 degrees. In some embodiments, the crystal form is crystal form E, characterized in that its XRPD pattern is substantially as shown in the figure. Figure 5A As depicted in the text.

[0296] In some embodiments, crystal form E has substantially the following characteristics: Figure 5B The TGA thermogram depicted in the figure. In some embodiments, crystal form E has substantially the same properties as described above. Figure 5B The differential scanning calorimetry (DSC) thermogram depicted herein. In some embodiments, the thermogram includes an endothermic peak at approximately 203 °C. In some embodiments, the DSC thermogram includes an endothermic peak at approximately 87 °C.

[0297] In some embodiments, crystal form E is substantially free of other polymorphic forms. In some embodiments, crystal form E has a polymorphic purity of at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%. In some embodiments, crystal form E has a polymorphic purity of at least 90%. In some embodiments, crystal form E has a polymorphic purity of at least 92%. In some embodiments, crystal form D has a polymorphic purity of at least 94%. In some embodiments, crystal form E has a polymorphic purity of at least 96%. In some embodiments, crystal form E has a polymorphic purity of at least 98%. In some embodiments, crystal form E has a polymorphic purity of at least 99%.

[0298] In some embodiments, the pharmaceutical composition comprises about 0.05% to about 1.0% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.1% to about 1.0% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.15% to about 1.0% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.2% to about 1.0% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.25% to about 1.0% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.3% to about 1.0% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.35% to about 1.0% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.4% to about 1.0% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.45% to about 1.0% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.5% to about 1.0% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.55% to about 1.0% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.6% to about 1.0% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.65% to about 1.0% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.7% to about 1.0% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.75% to about 1.0% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.8% to about 1.0% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.85% to about 1.0% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.9% to about 1.0% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.95% to about 1.0% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.1% to about 0.9% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.1% to about 0.8% w / w of compound I or a pharmaceutically acceptable salt thereof.In some embodiments, the pharmaceutical composition comprises about 0.1% to about 0.7% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.1% to about 0.6% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.1% to about 0.5% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.1% to about 0.4% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.1% to about 0.3% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.1% to about 0.2% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.2% to about 0.4% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.25% to about 0.4% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.3% to about 0.4% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.3% to about 0.35% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.25% to about 0.35% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.25% to about 0.3% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.25% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.3% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.35% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.4% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 0.05%, about 0.1%, about 0.15%, about 0.2%, about 0.25%, about 0.3%, about 0.35%, about 0.4%, about 0.45%, about 0.5%, about 0.55%, about 0.6%, about 0.65%, about 0.7%, about 0.75%, about 0.8%, about 0.85%, about 0.9%, about 0.95%, or about 1% of compound I or a pharmaceutically acceptable salt thereof.

[0299] In some embodiments, the pharmaceutical composition comprises 0.05% to 1.0% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises 0.1% to 1.0% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises 0.15% to 1.0% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises 0.2% to 1.0% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises 0.25% to 1.0% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises 0.3% to 1.0% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises 0.35% to 1.0% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises 0.4% to 1.0% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises 0.45% to 1.0% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises 0.5% to 1.0% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises 0.55% to 1.0% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises 0.6% to 1.0% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises 0.65% to 1.0% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises 0.7% to 1.0% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises 0.75% to 1.0% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises 0.8% to 1.0% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises 0.85% to 1.0% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises 0.9% to 1.0% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises 0.95% to 1.0% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises 0.1% to 0.9% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises 0.1% to 0.8% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises 0.1% to 0.7% w / w of compound I or a pharmaceutically acceptable salt thereof.In some embodiments, the pharmaceutical composition comprises 0.1% to 0.6% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises 0.1% to 0.5% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises 0.1% to 0.4% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises 0.1% to 0.3% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises 0.1% to 0.2% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises 0.2% to 0.4% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises 0.25% to 0.4% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises 0.3% to 0.4% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises 0.3% to 0.35% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises 0.25% to 0.35% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises 0.25% to 0.3% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises 0.25% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises 0.3% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises 0.35% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises 0.4% w / w of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises 0.05%, 0.1%, 0.15%, 0.2%, 0.25%, 0.3%, 0.35%, 0.4%, 0.45%, 0.5%, 0.55%, 0.6%, 0.65%, 0.7%, 0.75%, 0.8%, 0.85%, 0.9%, 0.95%, or 1% of compound I or a pharmaceutically acceptable salt thereof.

[0300] In some embodiments, the pharmaceutical composition comprises about 0.05% to about 1.0% w / w of compound I. In some embodiments, the pharmaceutical composition comprises about 0.1% to about 1.0% w / w of compound I. In some embodiments, the pharmaceutical composition comprises about 0.15% to about 1.0% w / w of compound I. In some embodiments, the pharmaceutical composition comprises about 0.2% to about 1.0% w / w of compound I. In some embodiments, the pharmaceutical composition comprises about 0.25% to about 1.0% w / w of compound I. In some embodiments, the pharmaceutical composition comprises about 0.3% to about 1.0% w / w of compound I. In some embodiments, the pharmaceutical composition comprises about 0.35% to about 1.0% w / w of compound I. In some embodiments, the pharmaceutical composition comprises about 0.4% to about 1.0% w / w of compound I. In some embodiments, the pharmaceutical composition comprises about 0.45% to about 1.0% w / w of compound I. In some embodiments, the pharmaceutical composition comprises about 0.45% to about 1.0% w / w of compound I. In one embodiment, the pharmaceutical composition comprises about 0.5% to about 1.0% w / w of compound I. In some embodiments, the pharmaceutical composition comprises about 0.55% to about 1.0% w / w of compound I. In some embodiments, the pharmaceutical composition comprises about 0.6% to about 1.0% w / w of compound I. In some embodiments, the pharmaceutical composition comprises about 0.65% to about 1.0% w / w of compound I. In some embodiments, the pharmaceutical composition comprises about 0.7% to about 1.0% w / w of compound I. In some embodiments, the pharmaceutical composition comprises about 0.75% to about 1.0% w / w of compound I. In some embodiments, the pharmaceutical composition comprises about 0.8% to about 1.0% w / w of compound I. In some embodiments, the pharmaceutical composition comprises about 0.85% to about 1.0% w / w of compound I. In some embodiments, the pharmaceutical composition comprises about 0.9% to about 1.0% w / w of compound I. In some embodiments, the pharmaceutical composition comprises about 0.95% to about 1.0% w / w of compound I. In some embodiments, the pharmaceutical composition comprises about 0.1% to about 0.9% w / w of compound I. In some embodiments, the pharmaceutical composition comprises about 0.1% to about 0.8% w / w of compound I. In some embodiments, the pharmaceutical composition comprises about 0.1% to about 0.7% w / w of compound I. In some embodiments, the pharmaceutical composition comprises about 0.1% to about 0.6% w / w of compound I. In some embodiments, the pharmaceutical composition comprises about 0.1% to about 0.5% w / w of compound I. In some embodiments, the pharmaceutical composition comprises about 0.1% to about 0.4% w / w of compound I. In some embodiments, the pharmaceutical composition comprises about 0.1% to about 0.3% w / w of compound I.In some embodiments, the pharmaceutical composition comprises about 0.1% to about 0.2% w / w of compound I. In some embodiments, the pharmaceutical composition comprises about 0.2% to about 0.4% w / w of compound I. In some embodiments, the pharmaceutical composition comprises about 0.25% to about 0.4% w / w of compound I. In some embodiments, the pharmaceutical composition comprises about 0.3% to about 0.4% w / w of compound I. In some embodiments, the pharmaceutical composition comprises about 0.3% to about 0.35% w / w of compound I. In some embodiments, the pharmaceutical composition comprises about 0.25% to about 0.35% w / w of compound I. In some embodiments, the pharmaceutical composition comprises about 0.25% to about 0.35% w / w of compound I. In some embodiments, the pharmaceutical composition comprises about 0.25% w / w of compound I. In some embodiments, the pharmaceutical composition comprises about 0.3% w / w of compound I. In some embodiments, the pharmaceutical composition comprises about 0.35% w / w of compound I. In some embodiments, the pharmaceutical composition comprises about 0.4% w / w of compound I. In some embodiments, the pharmaceutical composition comprises about 0.05%, about 0.1%, about 0.15%, about 0.2%, about 0.25%, about 0.3%, about 0.35%, about 0.4%, about 0.45%, about 0.5%, about 0.55%, about 0.6%, about 0.65%, about 0.7%, about 0.75%, about 0.8%, about 0.85%, about 0.9%, about 0.95%, or about 1% of compound I.

[0301] In some embodiments, the pharmaceutical composition comprises 0.05% to 1.0% w / w of compound I. In some embodiments, the pharmaceutical composition comprises 0.1% to 1.0% w / w of compound I. In some embodiments, the pharmaceutical composition comprises 0.15% to 1.0% w / w of compound I. In some embodiments, the pharmaceutical composition comprises 0.2% to 1.0% w / w of compound I. In some embodiments, the pharmaceutical composition comprises 0.25% to 1.0% w / w of compound I. In some embodiments, the pharmaceutical composition comprises 0.3% to 1.0% w / w of compound I. In some embodiments, the pharmaceutical composition comprises 0.35% to 1.0% w / w of compound I. In some embodiments, the pharmaceutical composition comprises 0.4% to 1.0% w / w of compound I. In some embodiments, the pharmaceutical composition comprises 0.45% to 1.0% w / w of compound I. In some embodiments, the pharmaceutical composition comprises 0.45% to 1.0% of compound I. In one embodiment, the pharmaceutical composition comprises 0.5% to 1.0% w / w of compound I. In some embodiments, the pharmaceutical composition comprises 0.55% to 1.0% w / w of compound I. In some embodiments, the pharmaceutical composition comprises 0.6% to 1.0% w / w of compound I. In some embodiments, the pharmaceutical composition comprises 0.65% to 1.0% w / w of compound I. In some embodiments, the pharmaceutical composition comprises 0.7% to 1.0% w / w of compound I. In some embodiments, the pharmaceutical composition comprises 0.75% to 1.0% w / w of compound I. In some embodiments, the pharmaceutical composition comprises 0.8% to 1.0% w / w of compound I. In some embodiments, the pharmaceutical composition comprises 0.85% to 1.0% w / w of compound I. In some embodiments, the pharmaceutical composition comprises 0.9% to 1.0% w / w of compound I. In some embodiments, the pharmaceutical composition comprises 0.95% to 1.0% w / w of compound I. In some embodiments, the pharmaceutical composition comprises 0.1% to 0.9% w / w of compound I. In some embodiments, the pharmaceutical composition comprises 0.1% to 0.8% w / w of compound I. In some embodiments, the pharmaceutical composition comprises 0.1% to 0.7% w / w of compound I. In some embodiments, the pharmaceutical composition comprises 0.1% to 0.6% w / w of compound I. In some embodiments, the pharmaceutical composition comprises 0.1% to 0.5% w / w of compound I. In some embodiments, the pharmaceutical composition comprises 0.1% to 0.4% w / w of compound I. In some embodiments, the pharmaceutical composition comprises 0.1% to 0.3% w / w of compound I. In some embodiments, the pharmaceutical composition comprises 0.1% to 0.2% w / w of compound I.In some embodiments, the pharmaceutical composition comprises 0.2% to 0.4% w / w of compound I. In some embodiments, the pharmaceutical composition comprises 0.25% to 0.4% w / w of compound I. In some embodiments, the pharmaceutical composition comprises 0.3% to 0.4% w / w of compound I. In some embodiments, the pharmaceutical composition comprises 0.3% to 0.35% w / w of compound I. In some embodiments, the pharmaceutical composition comprises 0.25% to 0.35% w / w of compound I. In some embodiments, the pharmaceutical composition comprises 0.25% to 0.3% w / w of compound I. In some embodiments, the pharmaceutical composition comprises 0.25% w / w of compound I. In some embodiments, the pharmaceutical composition comprises 0.3% w / w of compound I. In some embodiments, the pharmaceutical composition comprises 0.35% w / w of compound I. In some embodiments, the pharmaceutical composition comprises 0.4% w / w of compound I. In some embodiments, the pharmaceutical composition comprises 0.05%, 0.1%, 0.15%, 0.2%, 0.25%, 0.3%, 0.35%, 0.4%, 0.45%, 0.5%, 0.55%, 0.6%, 0.65%, 0.7%, 0.75%, 0.8%, 0.85%, 0.9%, 0.95%, and 1% of compound I.

[0302] In some embodiments, the drug loading is equivalent to about 0.05 mg to about 1 mg of compound I or a pharmaceutically acceptable salt thereof per 1 gram of total weight of the pharmaceutical composition, for example, about 0.05 mg / g to about 1 mg / g.

[0303] In some embodiments, the amount of compound I or a pharmaceutically acceptable salt I thereof in the composition is from about 50 μg / g to about 3 mg / g. In some embodiments, the amount of compound I or a pharmaceutically acceptable salt I thereof in the composition is from about 100 μg / g to about 3 mg / g. In some embodiments, the amount of compound I or a pharmaceutically acceptable salt I thereof in the composition is from about 150 μg / g to about 3 mg / g. In some embodiments, the amount of compound I or a pharmaceutically acceptable salt I thereof in the composition is from about 500 μg / g to about 10 mg / g. In some embodiments, the amount of compound I or a pharmaceutically acceptable salt thereof in the composition is about 50 μg / g, about 75 μg / g, about 100 μg / g, about 110 μg / g, about 120 μg / g, about 130 μg / g, about 140 μg / g, about 150 μg / g, about 160 μg / g, about 170 μg / g, about 180 μg / g, about 190 μg / g, about 200 μg / g, about 210 μg / g, about 220 μg / g, about 240 μg / g, about 240 μg / g, about 250 μg / g, about 260 μg / g, about 270 μg / g, about 280 μg / g, about 290 μg / g, about 300 μg / g, about 310 μg / g, about 320 μg / g, about 330 μg / g. μg / g, approximately 340 μg / g, approximately 350 μg / g, approximately 360 μg / g, approximately 370 μg / g, approximately 380 μg / g, approximately 390 μg / g, approximately 400 μg / g, approximately 410 μg / g, approximately 420 μg / g, approximately 430 μg / g, approximately 440 μg / g, approximately 450 μg / g, approximately 460 μg / g, approximately 470 μg / g, approximately 480 μg / g, approximately 490 μg / g, approximately 500 μg / g, approximately 510 μg / g, approximately 520 μg / g, approximately 530 μg / g, approximately 540 μg / g, approximately 550 μg / g, approximately 560 μg / g, approximately 570 μg / g, approximately 580 μg / g, approximately 590 μg / g, approximately 600 μg / g μg / g, approximately 610 μg / g, approximately 620 μg / g, approximately 630 μg / g, approximately 640 μg / g, approximately 650 μg / g, approximately 650 μg / g, approximately 660 μg / g, approximately 670 μg / g, approximately 680 μg / g, approximately 690 μg / g, approximately 700 μg / g, approximately 710 μg / g, approximately 720 μg / g, approximately 730 μg / g, approximately 740 μg / g, approximately 750 μg / g, approximately 760 μg / g, approximately 770 μg / g, approximately 780 μg / g, approximately 790 μg / g, approximately 800 μg / g, approximately 810 μg / g, approximately 820 μg / g, approximately 830 μg / g, approximately 840 μg / gApproximately 850 μg / g, approximately 860 μg / g, approximately 870 μg / g, approximately 880 μg / g, approximately 890 μg / g, approximately 900 μg / g, approximately 910 μg / g, approximately 920 μg / g, approximately 930 μg / g, approximately 940 μg / g, approximately 950 μg / g, approximately 950 μg / g, approximately 960 μg / g, approximately 970 μg / g, approximately 980 μg / g, approximately 990 μg / g, approximately 1 mg / g, approximately 1.1 mg / g, approximately 1.2 mg / g, approximately 1.3 mg / g, approximately 1.4 mg / g, approximately 1.5 mg / g, approximately 1.6 mg / g, approximately 1.7 mg / g, approximately 1.8 mg / g, approximately 1.9 mg / g. mg / g, approximately 2 mg / g, approximately 2.1 mg / g, approximately 2.2 mg / g, approximately 2.3 mg / g, approximately 2.4 mg / g, approximately 2.5 mg / g, approximately 2.6 mg / g, approximately 2.7 mg / g, approximately 2.8 mg / g, approximately 2.9 mg / g, approximately 3 mg / g, 3.1 mg / g, approximately 3.2 mg / g, approximately 3.3 mg / g, approximately 3.4 mg / g, approximately 3.5 mg / g, approximately 3.6 mg / g, approximately 3.7 mg / g, approximately 3.8 mg / g, approximately 3.9 mg / g, approximately 4 mg / g, approximately 4.1 mg / g, approximately 4.2 mg / g, approximately 4.3 mg / g, approximately 4.4 mg / g, approximately 4.5 mg / g, approximately 4.6 mg / g, approximately 4.7 mg / g, approximately 4.8 mg / g, approximately 4.9 mg / g. mg / g, approximately 5 mg / g, approximately 5.1 mg / g, approximately 5.2 mg / g, approximately 5.3 mg / g, approximately 5.4 mg / g, approximately 5.5 mg / g, approximately 5.6 mg / g, approximately 5.7 mg / g, approximately 5.8 mg / g, approximately 5.9 mg / g, approximately 6 mg / g, approximately 6.1 mg / g, approximately 6.2 mg / g, approximately 6.3 mg / g, approximately 6.4 mg / g, approximately 6.5 mg / g, approximately 6.6 mg / g, approximately 6.7 mg / g, approximately 6.8 mg / g, approximately 6.9 mg / g, approximately 7 mg / g, approximately 7.1 mg / g, approximately 7.2 mg / g, approximately 7.3 mg / g, approximately 7.4 mg / g, approximately 7.5 mg / g, approximately 7.6 mg / g, approximately 7.7 mg / g, approximately 7.8 mg / g, approximately 7.9 mg / g, approximately 8 mg / g mg / g, approximately 8.1 mg / g, approximately 8.2 mg / g, approximately 8.3 mg / g, approximately 8.4 mg / g, approximately 8.5 mg / g, approximately 8.6 mg / g, approximately 8.7 mg / g, approximately 8.8 mg / g, approximately 8.9 mg / g, approximately 9 mg / g, approximately 9.1 mg / g, approximately 9.2 mg / g, approximately 9.3 mg / g, approximately 9.4 mg / g, approximately 9.5 mg / g, approximately 9.6 mg / g,Approximately 9.7 mg / g, approximately 9.8 mg / g, approximately 9.9 mg / g, or approximately 10 mg / g.

[0304] In some embodiments, the amount of compound I or a pharmaceutically acceptable salt I thereof in the composition is from 50 μg / g to 3 mg / g. In some embodiments, the amount of compound I or a pharmaceutically acceptable salt I thereof in the composition is from 100 μg / g to 3 mg / g. In some embodiments, the amount of compound I or a pharmaceutically acceptable salt I thereof in the composition is from 150 μg / g to 3 mg / g. In some embodiments, the amount of compound I or a pharmaceutically acceptable salt I thereof in the composition is from 500 μg / g to 10 mg / g. In some embodiments, the amount of compound I or a pharmaceutically acceptable salt thereof in the composition is 50 μg / g, 75 μg / g, 100 μg / g, 110 μg / g, 120 μg / g, 130 μg / g, 140 μg / g, 150 μg / g, 160 μg / g, 170 μg / g, 180 μg / g, 190 μg / g, 200 μg / g, 210 μg / g, 220 μg / g, 240 μg / g, 240 μg / g, 250 μg / g, 260 μg / g, 270 μg / g, 280 μg / g, 290 μg / g, 300 μg / g, 310 μg / g, 320 μg / g, 330 μg / g, 340 μg / g, 350 μg / g, 36 ...70 μg / g, 280 μg / g, 290 μg / g, 300 μg / g, 310 μg / g, 320 μg / g, 330 μg / g, 340 μg / g, 350 μg / g, 360 μg / g, 360 μg / g, 370 μg / g, 280 μg / g, 350 μg / g, 360 μg / g, 360 μg / g, 370 μg / μg / g, 370 μg / g, 380 μg / g, 390 μg / g, 400 μg / g, 410 μg / g, 420 μg / g, 430 μg / g, 440 μg / g, 450 μg / g, 460 μg / g, 470 μg / g, 480 μg / g, 490 μg / g, 500 μg / g, 510 μg / g, 520 μg / g, 530 μg / g, 540 μg / g, 550 μg / g, 560 μg / g, 570 μg / g, 580 μg / g, 590 μg / g, 600 μg / g, 610 μg / g, 620 μg / g, 630 μg / g, 640 μg / g, 650 μg / g, 650 μg / g, 660 μg / g, 670 μg / g, 680 μg / g, 690 μg / g, 700 μg / g, 710 μg / g, 720 μg / g, 730 μg / g, 740 μg / g, 750 μg / g, 760 μg / g, 770 μg / g, 780 μg / g, 790 μg / g, 800 μg / g, 810 μg / g, 820 μg / g, 830 μg / g, 840 μg / g, 850 μg / g, 860 μg / g, 870 μg / g, 880 μg / g, 890 μg / g, 900 μg / g, 910 μg / g, 920 μg / g, 930 μg / g, 940μg / g, 950 μg / g, 950 μg / g, 960 μg / g, 970 μg / g, 980 μg / g, 990 μg / g, 1 mg / g, 1.1 mg / g, 1.2 mg / g, 1.3 mg / g, 1.4 mg / g, 1.5 mg / g, 1.6 mg / g, 1.7 mg / g, 1.8 mg / g, 1.9 mg / g, 2 mg / g, 2.1 mg / g, 2.2 mg / g, 2.3 mg / g, 2.4 mg / g, 2.5 mg / g, 2.6 mg / g, 2.7 mg / g, 2.8 mg / g, 2.9 mg / g, 3 mg / g, 3.1 mg / g, 3.2 mg / g, 3.3 mg / g, 3.4 mg / g, 3.5 mg / g, 3.6 mg / g, 3.7 mg / g, 3.8 mg / g, 3.9 mg / g, 4 mg / g, 4.1 mg / g, 4.2 mg / g, 4.3 mg / g, 4.4 mg / g, 4.5 mg / g, 4.6 mg / g, 4.7 mg / g, 4.8 mg / g, 4.9 mg / g, 5 mg / g, 5.1 mg / g, 5.2 mg / g, 5.3 mg / g, 5.4 mg / g, 5.5 mg / g, 5.6 mg / g, 5.7 mg / g, 5.8 mg / g, 5.9 mg / g, 6 mg / g, 6.1 mg / g, 6.2 mg / g, 6.3 mg / g, 6.4 mg / g, 6.5 mg / g, 6.6 mg / g, 6.7 mg / g, 6.8 mg / g, 6.9 mg / g, 7 mg / g, 7.1 mg / g, 7.2 mg / g, 7.3 mg / g, 7.4 mg / g, 7.5 mg / g, 7.6 mg / g, 7.7 mg / g, 7.8 mg / g, 7.9 mg / g, 8 mg / g, 8.1 mg / g, 8.2 mg / g, 8.3 mg / g, 8.4 mg / g, 8.5 mg / g, 8.6 mg / g, 8.7 mg / g, 8.8 mg / g, 8.9 mg / g, 9 mg / g, 9.1 mg / g, 9.2 mg / g, 9.3 mg / g, 9.4 mg / g, 9.5 mg / g, 9.6 mg / g, 9.7 mg / g, 9.8 mg / g, 9.9 mg / g or 10 mg / g.

[0305] In some embodiments, the amount of compound I in the composition is from about 50 μg / g to about 3 mg / g. In some embodiments, the amount of compound I in the composition is from about 100 μg / g to about 3 mg / g. In some embodiments, the amount of compound I in the composition is from about 150 μg / g to about 3 mg / g. In some embodiments, the amount of compound I in the composition is from about 500 μg / g to about 10 mg / g. In some embodiments, compound I in the composition is approximately 50 μg / g, approximately 75 μg / g, approximately 100 μg / g, approximately 110 μg / g, approximately 120 μg / g, approximately 130 μg / g, approximately 140 μg / g, approximately 150 μg / g, approximately 160 μg / g, approximately 170 μg / g, approximately 180 μg / g, approximately 190 μg / g, approximately 200 μg / g, approximately 210 μg / g, approximately 220 μg / g, approximately 240 μg / g, approximately 240 μg / g, approximately 250 μg / g, approximately 260 μg / g, approximately 270 μg / g, approximately 280 μg / g, approximately 290 μg / g, approximately 300 μg / g, approximately 310 μg / g, approximately 320 μg / g, approximately 330 μg / g, approximately 340 μg / g, etc. μg / g, approximately 350 μg / g, approximately 360 μg / g, approximately 370 μg / g, approximately 380 μg / g, approximately 390 μg / g, approximately 400 μg / g, approximately 410 μg / g, approximately 420 μg / g, approximately 430 μg / g, approximately 440 μg / g, approximately 450 μg / g, approximately 460 μg / g, approximately 470 μg / g, approximately 480 μg / g, approximately 490 μg / g, approximately 500 μg / g, approximately 510 μg / g, approximately 520 μg / g, approximately 530 μg / g, approximately 540 μg / g, approximately 550 μg / g, approximately 560 μg / g, approximately 570 μg / g, approximately 580 μg / g, approximately 590 μg / g, approximately 600 μg / g, approximately 610 μg / g μg / g, approximately 620 μg / g, approximately 630 μg / g, approximately 640 μg / g, approximately 650 μg / g, approximately 650 μg / g, approximately 660 μg / g, approximately 670 μg / g, approximately 680 μg / g, approximately 690 μg / g, approximately 700 μg / g, approximately 710 μg / g, approximately 720 μg / g, approximately 730 μg / g, approximately 740 μg / g, approximately 750 μg / g, approximately 760 μg / g, approximately 770 μg / g, approximately 780 μg / g, approximately 790 μg / g, approximately 800 μg / g, approximately 810 μg / g, approximately 820 μg / g, approximately 830 μg / g, approximately 840 μg / g, approximately 850 μg / g, approximately 860 μg / g, approximately 870 μg / g μg / g, approximately 880 μg / g, approximately 890 μg / g, approximately 900 μg / gμg / g, approximately 910 μg / g, approximately 920 μg / g, approximately 930 μg / g, approximately 940 μg / g, approximately 950 μg / g, approximately 950 μg / g, approximately 960 μg / g, approximately 970 μg / g, approximately 980 μg / g, approximately 990 μg / g, approximately 1 mg / g, approximately 1.1 mg / g, approximately 1.2 mg / g, approximately 1.3 mg / g, approximately 1.4 mg / g, approximately 1.5 mg / g, approximately 1.6 mg / g, approximately 1.7 mg / g, approximately 1.8 mg / g, approximately 1.9 mg / g, approximately 2 mg / g, approximately 2.1 mg / g, approximately 2.2 mg / g, approximately 2.3 mg / g, approximately 2.4 mg / g, approximately 2.5 mg / g, approximately 2.6 mg / g, approximately 2.7 mg / g, approximately 2.8 mg / g. mg / g, approximately 2.9 mg / g, approximately 3 mg / g, 3.1 mg / g, approximately 3.2 mg / g, approximately 3.3 mg / g, approximately 3.4 mg / g, approximately 3.5 mg / g, approximately 3.6 mg / g, approximately 3.7 mg / g, approximately 3.8 mg / g, approximately 3.9 mg / g, approximately 4 mg / g, approximately 4.1 mg / g, approximately 4.2 mg / g, approximately 4.3 mg / g, approximately 4.4 mg / g, approximately 4.5 mg / g, approximately 4.6 mg / g, approximately 4.7 mg / g, approximately 4.8 mg / g, approximately 4.9 mg / g, approximately 5 mg / g, approximately 5.1 mg / g, approximately 5.2 mg / g, approximately 5.3 mg / g, approximately 5.4 mg / g, approximately 5.5 mg / g, approximately 5.6 mg / g, approximately 5.7 mg / g, approximately 5.8 mg / g, approximately 5.9 mg / g. mg / g, approximately 6 mg / g, approximately 6.1 mg / g, approximately 6.2 mg / g, approximately 6.3 mg / g, approximately 6.4 mg / g, approximately 6.5 mg / g, approximately 6.6 mg / g, approximately 6.7 mg / g, approximately 6.8 mg / g, approximately 6.9 mg / g, approximately 7 mg / g, approximately 7.1 mg / g, approximately 7.2 mg / g, approximately 7.3 mg / g, approximately 7.4 mg / g, approximately 7.5 mg / g, approximately 7.6 mg / g, approximately 7.7 mg / g, approximately 7.8 mg / g, approximately 7.9 mg / g, approximately 8 mg / g, approximately 8.1 mg / g, approximately 8.2 mg / g, approximately 8.3 mg / g, approximately 8.4 mg / g, approximately 8.5 mg / g, approximately 8.6 mg / g, approximately 8.7 mg / g, approximately 8.8 mg / g, approximately 8.9 mg / g, approximately 9 mg / g mg / g, approximately 9.1 mg / g, approximately 9.2 mg / g, approximately 9.3 mg / g, approximately 9.4 mg / g, approximately 9.5 mg / g, approximately 9.6 mg / g, approximately 9.7 mg / g, approximately 9.8 mg / g, approximately 9.9 mg / g, or approximately 10 mg / g.

[0306] In some embodiments, the amount of compound I in the composition is from 50 μg / g to 3 mg / g. In some embodiments, the amount of compound I in the composition is from 100 μg / g to 3 mg / g. In some embodiments, the amount of compound I in the composition is from 150 μg / g to 3 mg / g. In some embodiments, the amount of compound I in the composition is from 500 μg / g to 10 mg / g. In some embodiments, the amount of Compound I in the composition is 50 μg / g, 75 μg / g, 100 μg / g, 110 μg / g, 120 μg / g, 130 μg / g, 140 μg / g, 150 μg / g, 160 μg / g, 170 μg / g, 180 μg / g, 190 μg / g, 200 μg / g, 210 μg / g, 220 μg / g, 240 μg / g, 240 μg / g, 250 μg / g, 260 μg / g, 270 μg / g, 280 μg / g, 290 μg / g, 300 μg / g, 310 μg / g, 320 μg / g, 330 μg / g, 340 μg / g, 350 μg / g, 360 μg / g, 370 μg / g、380 μg / g、390 μg / g、400 μg / g、410 μg / g、420 μg / g、430 μg / g、440 μg / g、450 μg / g、460 μg / g、470 μg / g、480 μg / g、490 μg / g、500 μg / g、510 μg / g, 520 μg / g, 530 μg / g, 540 μg / g, 550 μg / g, 560 μg / g, 570 μg / g, 580 μg / g, 590 μg / g, 600 μg / g, 610 μg / g, 620 μg / g, 630 μg / g, 640 μg / g, 650 μg / g, 650 μg / g, 660 μg / g, 670 μg / g, 680 μg / g, 690 μg / g, 700 μg / g, 710 μg / g, 720 μg / g, 730 μg / g, 740 μg / g, 750 μg / g, 760 μg / g, 770 μg / g, 780 μg / g, 790 μg / g, 800 μg / g, 810 μg / g, 820 μg / g, 830 μg / g, 840 μg / g, 850 μg / g, 860 μg / g, 870 μg / g, 880 μg / g, 890 μg / g, 900 μg / g, 910 μg / g, 920 μg / g, 930 μg / g, 940 μg / g, 950 μg / g, 950 μg / g, 960 μg / g, 970 μg / g, 980 μg / g, 990μg / g, 1 mg / g, 1.1 mg / g, 1.2 mg / g, 1.3 mg / g, 1.4 mg / g, 1.5 mg / g, 1.6 mg / g, 1.7 mg / g, 1.8 mg / g, 1.9 mg / g, 2 mg / g, 2.1 mg / g, 2.2 mg / g, 2.3 mg / g, 2.4 mg / g, 2.5 mg / g, 2.6 mg / g, 2.7 mg / g, 2.8 mg / g, 2.9 mg / g, 3 mg / g, 3.1 mg / g, 3.2 mg / g, 3.3 mg / g, 3.4 mg / g, 3.5 mg / g, 3.6 mg / g, 3.7 mg / g, 3.8 mg / g, 3.9 mg / g, 4 mg / g, 4.1 mg / g, 4.2 mg / g, 4.3 mg / g, 4.4 mg / g, 4.5 mg / g, 4.6 mg / g, 4.7 mg / g, 4.8 mg / g, 4.9 mg / g, 5 mg / g, 5.1 mg / g, 5.2 mg / g, 5.3 mg / g, 5.4 mg / g, 5.5 mg / g, 5.6 mg / g, 5.7 mg / g, 5.8 mg / g, 5.9 mg / g, 6 mg / g, 6.1 mg / g, 6.2 mg / g, 6.3 mg / g, 6.4 mg / g, 6.5 mg / g, 6.6 mg / g, 6.7 mg / g, 6.8 mg / g, 6.9 mg / g, 7 mg / g, 7.1 mg / g, 7.2 mg / g, 7.3 mg / g, 7.4 mg / g, 7.5 mg / g, 7.6 mg / g, 7.7 mg / g, 7.8 mg / g, 7.9 mg / g, 8 mg / g, 8.1 mg / g, 8.2 mg / g, 8.3 mg / g, 8.4 mg / g, 8.5 mg / g, 8.6 mg / g, 8.7 mg / g, 8.8 mg / g, 8.9 mg / g, 9 mg / g, 9.1 mg / g, 9.2 mg / g, 9.3 mg / g, 9.4 mg / g, 9.5 mg / g, 9.6 mg / g, 9.7 mg / g, 9.8 mg / g, 9.9 mg / g or 10 mg / g.

[0307] In some embodiments, the pharmaceutical composition comprises about 50 μg, about 75 μg, about 100 μg, about 150 μg, about 200 μg, about 250 μg, about 300 μg, about 350 μg, about 400 μg, about 450 μg, about 500 μg, about 550 μg, about 600 μg, about 650 μg, about 700 μg, about 750 μg, about 800 μg, about 850 μg, about 900 μg, about 950 μg, or about 1000 μg of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 1 mg, about 1.2 mg, about 1.5 mg, about 2 mg, about 2.5 mg, about 3 mg, about 3.5 mg, about 4 mg, about 4.5 mg, about 5 mg, about 5.5 mg, about 6 mg, about 6.5 mg, about 7 mg, about 7.5 mg, about 8 mg, about 8.5 mg, about 9 mg, about 9.5 mg, or about 10 mg of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 150 μg of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 300 μg of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 500 μg of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 600 μg of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 900 μg of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 1.2 mg of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 3 mg of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 10 mg of compound I or a pharmaceutically acceptable salt thereof.

[0308] In some embodiments, the pharmaceutical composition comprises 50 μg, 75 μg, 100 μg, 150 μg, 200 μg, 250 μg, 300 μg, 350 μg, 400 μg, 450 μg, 500 μg, 550 μg, 600 μg, 650 μg, 700 μg, 750 μg, 800 μg, 850 μg, 900 μg, 950 μg, or 1000 μg of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises 1 mg, 1.2 mg, 1.5 mg, 2 mg, 2.5 mg, 3 mg, 3.5 mg, 4 mg, 4.5 mg, 5 mg, 5.5 mg, 6 mg, 6.5 mg, 7 mg, 7.5 mg, 8 mg, 8.5 mg, 9 mg, 9.5 mg, or 10 mg of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises 150 μg of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises 300 μg of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises 500 μg of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises 600 μg of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises 900 μg of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 1.2 mg of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 3 mg of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 10 mg of compound I or a pharmaceutically acceptable salt thereof.

[0309] In some embodiments, the pharmaceutical composition comprises about 50 μg, about 75 μg, about 100 μg, about 150 μg, about 200 μg, about 250 μg, about 300 μg, about 350 μg, about 400 μg, about 450 μg, about 500 μg, about 550 μg, about 600 μg, about 650 μg, about 700 μg, about 750 μg, about 800 μg, about 850 μg, about 900 μg, about 950 μg, or about 1000 μg of compound I. In some embodiments, the pharmaceutical composition comprises about 1 mg, about 1.2 mg, about 1.5 mg, about 2 mg, about 2.5 mg, about 3 mg, about 3.5 mg, about 4 mg, about 4.5 mg, about 5 mg, about 5.5 mg, about 6 mg, about 6.5 mg, about 7 mg, about 7.5 mg, about 8 mg, about 8.5 mg, about 9 mg, about 9.5 mg, or about 10 mg of compound I. In some embodiments, the pharmaceutical composition comprises about 150 μg of compound I. In some embodiments, the pharmaceutical composition comprises about 300 μg of compound I. In some embodiments, the pharmaceutical composition comprises about 500 μg of compound I. In some embodiments, the pharmaceutical composition comprises about 600 μg of compound I. In some embodiments, the pharmaceutical composition comprises about 900 μg of compound I. In some embodiments, the pharmaceutical composition comprises about 1.2 mg of compound I. In some embodiments, the pharmaceutical composition comprises about 3 mg of compound I. In some embodiments, the pharmaceutical composition comprises about 10 mg of compound I.

[0310] In some embodiments, the pharmaceutical composition comprises 50 μg, 75 μg, 100 μg, 150 μg, 200 μg, 250 μg, 300 μg, 350 μg, 400 μg, 450 μg, 500 μg, 550 μg, 600 μg, 650 μg, 700 μg, 750 μg, 800 μg, 850 μg, 900 μg, 950 μg, or 1000 μg of compound I. In some embodiments, the pharmaceutical composition comprises 1 mg, 1.2 mg, 1.5 mg, 2 mg, 2.5 mg, 3 mg, 3.5 mg, 4 mg, 4.5 mg, 5 mg, 5.5 mg, 6 mg, 6.5 mg, 7 mg, 7.5 mg, 8 mg, 8.5 mg, 9 mg, 9.5 mg, or 10 mg of compound I. In some embodiments, the pharmaceutical composition comprises 150 μg of compound I. In some embodiments, the pharmaceutical composition comprises 300 μg of compound I. In some embodiments, the pharmaceutical composition comprises 500 μg of compound I. In some embodiments, the pharmaceutical composition comprises 600 μg of compound I. In some embodiments, the pharmaceutical composition comprises 900 μg of compound I. In some embodiments, the pharmaceutical composition comprises 1.2 mg of compound I. In some embodiments, the pharmaceutical composition comprises 3 mg of compound I. In some embodiments, the pharmaceutical composition comprises 10 mg of compound I.

[0311] In some embodiments, the amount of compound I or a pharmaceutically acceptable salt I thereof in the composition is from about 2 mg / g to about 4 mg / g. In some embodiments, the amount of compound I or a pharmaceutically acceptable salt I thereof in the composition is from about 2 mg / g to about 3 mg / g. In some embodiments, the amount of compound I or a pharmaceutically acceptable salt thereof in the composition is about 2 mg / g, about 2.1 mg / g, about 2.2 mg / g, about 2.3 mg / g, about 2.4 mg / g, about 2.5 mg / g, about 2.6 mg / g, about 2.7 mg / g, about 2.8 mg / g, about 2.9 mg / g, about 3 mg / g, about 3.1 mg / g, about 3.2 mg / g, about 3.3 mg / g, about 3.4 mg / g, about 3.5 mg / g, 3.6 mg / g, about 3.7 mg / g, about 3.8 mg / g, about 3.9 mg / g, or about 4 mg / g.

[0312] In some embodiments, the amount of compound I or a pharmaceutically acceptable salt I thereof in the composition is from 2 mg / g to 4 mg / g. In some embodiments, the amount of compound I or a pharmaceutically acceptable salt I thereof in the composition is from 2 mg / g to 3 mg / g. In some embodiments, the amount of compound I or a pharmaceutically acceptable salt thereof in the composition is 2 mg / g, 2.1 mg / g, 2.2 mg / g, 2.3 mg / g, 2.4 mg / g, 2.5 mg / g, 2.6 mg / g, 2.7 mg / g, 2.8 mg / g, 2.9 mg / g, 3 mg / g, 3.1 mg / g, 3.2 mg / g, 3.3 mg / g, 3.4 mg / g, 3.5 mg / g, 3.6 mg / g, 3.7 mg / g, 3.8 mg / g, 3.9 mg / g, or 4 mg / g.

[0313] In some embodiments, the amount of compound I in the composition is from about 2 mg / g to about 4 mg / g. In some embodiments, the amount of compound I in the composition is from about 2 mg / g to about 3 mg / g. In some embodiments, the amount of compound I in the composition is about 2 mg / g, about 2.1 mg / g, about 2.2 mg / g, about 2.3 mg / g, about 2.4 mg / g, about 2.5 mg / g, about 2.6 mg / g, about 2.7 mg / g, about 2.8 mg / g, about 2.9 mg / g, about 3 mg / g, about 3.1 mg / g, about 3.2 mg / g, about 3.3 mg / g, about 3.4 mg / g, about 3.5 mg / g, 3.6 mg / g, about 3.7 mg / g, about 3.8 mg / g, about 3.9 mg / g, or about 4 mg / g.

[0314] In some embodiments, the amount of compound I in the composition is from 2 mg / g to 4 mg / g. In some embodiments, the amount of compound I in the composition is from 2 mg / g to 3 mg / g. In some embodiments, the amount of compound I in the composition is 2 mg / g, 2.1 mg / g, 2.2 mg / g, 2.3 mg / g, 2.4 mg / g, 2.5 mg / g, 2.6 mg / g, 2.7 mg / g, 2.8 mg / g, 2.9 mg / g, 3 mg / g, 3.1 mg / g, 3.2 mg / g, 3.3 mg / g, 3.4 mg / g, 3.5 mg / g, 3.6 mg / g, 3.7 mg / g, 3.8 mg / g, 3.9 mg / g, or 4 mg / g.

[0315] In some embodiments, the pharmaceutical composition comprises about 150 μg, about 200 μg, about 250 μg, about 300 μg, about 350 μg, about 400 μg, about 450 μg, about 500 μg, about 550 μg, about 600 μg, about 650 μg, about 700 μg, about 750 μg, about 800 μg, about 850 μg, about 900 μg, about 950 μg, or about 1000 μg of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 1 mg, about 1.5 mg, about 2 mg, about 2.5 mg, or about 3 mg of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 150 μg of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 3 mg of compound I or a pharmaceutically acceptable salt thereof.

[0316] In some embodiments, the pharmaceutical composition comprises 150 μg, 200 μg, 250 μg, 300 μg, 350 μg, 400 μg, 450 μg, 500 μg, 550 μg, 600 μg, 650 μg, 700 μg, 750 μg, 800 μg, 850 μg, 900 μg, 950 μg, or 1000 μg of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises 1 mg, 1.5 mg, 2 mg, 2.5 mg, or 3 mg of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises 150 μg of compound I or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises about 3 mg of compound I or a pharmaceutically acceptable salt thereof.

[0317] In some embodiments, the pharmaceutical composition comprises about 150 μg, about 200 μg, about 250 μg, about 300 μg, about 350 μg, about 400 μg, about 450 μg, about 500 μg, about 550 μg, about 600 μg, about 650 μg, about 700 μg, about 750 μg, about 800 μg, about 850 μg, about 900 μg, about 950 μg, or about 1000 μg of compound I. In some embodiments, the pharmaceutical composition comprises about 1 mg, about 1.5 mg, about 2 mg, about 2.5 mg, or about 3 mg of compound I. In some embodiments, the pharmaceutical composition comprises about 150 μg of compound I. In some embodiments, the pharmaceutical composition comprises about 3 mg of compound I.

[0318] In some embodiments, the pharmaceutical composition comprises 150 μg, 200 μg, 250 μg, 300 μg, 350 μg, 400 μg, 450 μg, 500 μg, 550 μg, 600 μg, 650 μg, 700 μg, 750 μg, 800 μg, 850 μg, 900 μg, 950 μg, or 1000 μg of compound I. In some embodiments, the pharmaceutical composition comprises 1 mg, 1.5 mg, 2 mg, 2.5 mg, or 3 mg of compound I. In some embodiments, the pharmaceutical composition comprises 150 μg of compound I. In some embodiments, the pharmaceutical composition comprises 3 mg of compound I.

[0319] In some embodiments, the amount of monoglycerides in the glyceride is greater than about 30% w / w. In some embodiments, the amount of monoglycerides in the glyceride is about 30% to about 100% w / w. In some embodiments, the amount of monoglycerides in the glyceride is about 30% to about 90% w / w. In some embodiments, the amount of monoglycerides in the glyceride is about 30% to about 80% w / w. In some embodiments, the amount of monoglycerides in the glyceride is about 30% to about 70% w / w. In some embodiments, the amount of monoglycerides in the glyceride is about 30% to about 60% w / w. In some embodiments, the amount of monoglycerides in the glyceride is about 30% to about 50% w / w. In some embodiments, the amount of monoglycerides in the glyceride is about 30% to about 40% w / w. In some embodiments, the amount of monoglycerides in the glyceride is about 40% to about 100% w / w. In some embodiments, the amount of monoglycerides in the glyceride is about 40% to about 90% w / w. In some embodiments, the amount of monoglycerides in the glyceride is about 40% to about 80% w / w. In some embodiments, the amount of monoglycerides in the glyceride is about 40% to about 70% w / w. In some embodiments, the amount of monoglycerides in the glyceride is about 40% to about 60% w / w. In some embodiments, the amount of monoglycerides in the glyceride is about 40% to about 50% w / w. In some embodiments, the amount of monoglycerides in the glyceride is about 50% to about 100% w / w. In some embodiments, the amount of monoglycerides in the glyceride is about 50% to about 90% w / w. In some embodiments, the amount of monoglycerides in the glyceride is about 50% to about 80% w / w. In some embodiments, the amount of monoglycerides in the glyceride is about 50% to about 70% w / w. In some embodiments, the amount of monoglycerides in the glyceride is about 50% to about 60% w / w. In some embodiments, the amount of monoglycerides in the glyceride is about 60% to about 100% w / w. In some embodiments, the amount of monoglycerides in the glyceride is about 60% to about 90% w / w. In some embodiments, the amount of monoglycerides in the glyceride is about 60% to about 80% w / w. In some embodiments, the amount of monoglycerides in the glyceride is about 60% to about 70% w / w. In some embodiments, the amount of monoglycerides in the glyceride is about 70% to about 100% w / w. In some embodiments, the amount of monoglycerides in the glyceride is about 70% to about 90% w / w. In some embodiments, the amount of monoglycerides in the glyceride is about 70% to about 80% w / w. In some embodiments, the amount of monoglycerides in the glyceride is about 80% to about 100% w / w. In some embodiments, the amount of monoglycerides in the glyceride is about 80% to about 90% w / w.In some embodiments, the amount of monoglycerides in the glycerides is from about 90% to about 100% w / w. In some embodiments, the amount of monoglycerides in the glycerides is about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or about 100% w / w.

[0320] In some embodiments, the amount of monoglycerides in the glyceride is greater than 30% w / w. In some embodiments, the amount of monoglycerides in the glyceride is 30% to 100% w / w. In some embodiments, the amount of monoglycerides in the glyceride is 30% to 90% w / w. In some embodiments, the amount of monoglycerides in the glyceride is 30% to 80% w / w. In some embodiments, the amount of monoglycerides in the glyceride is 30% to 70% w / w. In some embodiments, the amount of monoglycerides in the glyceride is 30% to 60% w / w. In some embodiments, the amount of monoglycerides in the glyceride is 30% to 50% w / w. In some embodiments, the amount of monoglycerides in the glyceride is 30% to 40% w / w. In some embodiments, the amount of monoglycerides in the glyceride is 40% to 100% w / w. In some embodiments, the amount of monoglycerides in the glyceride is 40% to 90% w / w. In some embodiments, the amount of monoglycerides in the glyceride is 40% to 80% w / w. In some embodiments, the amount of monoglycerides in the glyceride is 40% to 70% w / w. In some embodiments, the amount of monoglycerides in the glyceride is 40% to 60% w / w. In some embodiments, the amount of monoglycerides in the glyceride is 40% to 50% w / w. In some embodiments, the amount of monoglycerides in the glyceride is 50% to 100% w / w. In some embodiments, the amount of monoglycerides in the glyceride is 50% to 90% w / w. In some embodiments, the amount of monoglycerides in the glyceride is 50% to 80% w / w. In some embodiments, the amount of monoglycerides in the glyceride is 50% to 70% w / w. In some embodiments, the amount of monoglycerides in the glyceride is 50% to 60% w / w. In some embodiments, the amount of monoglycerides in the glyceride is 60% to 100% w / w. In some embodiments, the amount of monoglycerides in the glyceride is 60% to 90% w / w. In some embodiments, the amount of monoglycerides in the glyceride is 60% to 80% w / w. In some embodiments, the amount of monoglycerides in the glyceride is 60% to 70% w / w. In some embodiments, the amount of monoglycerides in the glyceride is 70% to 100% w / w. In some embodiments, the amount of monoglycerides in the glyceride is 70% to 90% w / w. In some embodiments, the amount of monoglycerides in the glyceride is 70% to 80% w / w. In some embodiments, the amount of monoglycerides in the glyceride is 80% to 100% w / w. In some embodiments, the amount of monoglycerides in the glyceride is 80% to 90% w / w. In some embodiments, the amount of monoglycerides in the glyceride is 90% to 100% w / w.In some embodiments, the amount of monoglycerides in the glycerides is 30%, about 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% w / w, 95% w / w, or 100% w / w.

[0321] In some embodiments, one or more glycerides comprise one or more monoglycerides, diglycerides, or triglycerides, or combinations thereof. Exemplary glycerides include, but are not limited to, mono / dicaprylic / capric glyceride, mono / dicaprylic / capric glyceride, type I monocaprylic glyceride, type I monocaprylic glyceride, type I monocaprylic / capric glyceride, monolinoleic glyceride, and equivalents and combinations thereof. In some embodiments, one or more glycerides comprise monocaprylic glyceride. In some embodiments, one or more glycerides comprise monolinoleic glyceride. In some embodiments, one or more glycerides comprise both monocaprylic glyceride and monolinoleic glyceride.

[0322] In some embodiments, the pharmaceutical composition comprises one or more fatty acid monoesters, diesters, or triesters linked to glycerol moieties (glycerides) of different chain lengths, which may be used alone or in combination with fatty acid monoesters or diesters linked to propylene glycol moieties. In some embodiments, the pharmaceutical composition comprises one or more fatty acid monoesters, diesters, or triesters linked to glycerol moieties (glycerides) of different chain lengths. In some embodiments, the pharmaceutical composition comprises one or more fatty acid monoesters, diesters, or triesters linked to glycerol moieties (glycerides) of different chain lengths, which may be used in combination with fatty acid monoesters or diesters linked to propylene glycol moieties. In some embodiments, the pharmaceutical composition comprises one or more fatty acid monoesters linked to glycerol moieties (glycerides) of different chain lengths. In some embodiments, the pharmaceutical composition comprises one or more fatty acid diesters linked to glycerol moieties (glycerides) of different chain lengths. In some embodiments, the pharmaceutical composition comprises one or more fatty acid triesters linked to glycerol moieties (glycerides) of different chain lengths. In some embodiments, the pharmaceutical composition comprises one or more fatty acid monoesters linked to propylene glycol moieties. In some embodiments, the pharmaceutical composition comprises one or more fatty acid diesters linked to propylene glycol moieties.

[0323] Exemplary fatty acid monoesters and diesters linked to the glycerol moiety include, but are not limited to: mono / dicaprylic / capric glyceride, type I monocaprylic glyceride, type I monocaprylic glyceride, type I monocaprylic / capric glyceride, monolinoleic glyceride, or equivalents thereof. Exemplary fatty acid monoesters and diesters linked to the propylene glycol moiety (propylene glycol esters) include, but are not limited to: type II propylene glycol monocaprylate, propylene glycol monolaurate, and propylene glycol dicaprylate / dicaprylate.

[0324] In some embodiments, the pharmaceutical composition comprises one or more glycerides with different fatty acid chain length distributions. In some embodiments, the pharmaceutical composition comprises one or more medium-chain monoglycerides, diglycerides, or triglycerides (e.g., hexanoic acid (C6), caprylic acid (C8), capric acid (C10), lauric acid (C12)). In some embodiments, the pharmaceutical composition comprises one or more long-chain triglycerides (e.g., myristic acid (C14), palmitic acid (C16), stearic acid (C18), oleic acid (C18), linoleic acid (C18)). In some embodiments, the pharmaceutical composition comprises a combination of medium-chain monoglycerides, diglycerides, or triglycerides and long-chain triglycerides.

[0325] In some embodiments, one or more glycerides in the pharmaceutical composition are selected from glyceryl monocaprylate, glyceryl monolinoleate, and combinations thereof. In some embodiments, the glyceride is glyceryl monocaprylate. In some embodiments, the glyceride is glyceryl monolinoleate. In some embodiments, the pharmaceutical composition comprises glyceryl monocaprylate and glyceryl monolinoleate.

[0326] In some embodiments, the amount of caprylic / caprylic acid glyceride is about 20% to about 80% w / w. In some embodiments, the amount of caprylic / caprylic acid glyceride is about 20% to about 70% w / w. In some embodiments, the amount of caprylic / caprylic acid glyceride is about 20% to about 60% w / w. In some embodiments, the amount of caprylic / caprylic acid glyceride is about 20% to about 50% w / w. In some embodiments, the amount of caprylic / caprylic acid glyceride is about 20% to about 40% w / w. In some embodiments, the amount of caprylic / caprylic acid glyceride is about 20% to about 30% w / w. In some embodiments, the amount of caprylic / caprylic acid glyceride is about 30% to about 80% w / w. In some embodiments, the amount of caprylic / caprylic acid glyceride is about 30% to about 70% w / w. In some embodiments, the amount of caprylic / caprylic acid glyceride is about 30% to about 60% w / w. In some embodiments, the amount of caprylic / caprylic acid glyceride is about 30% to about 50% w / w. In some embodiments, the amount of caprylic / caprylic acid glyceride is about 30% to about 40% w / w. In some embodiments, the amount of caprylic / caprylic acid glyceride is about 40% to about 80% w / w. In some embodiments, the amount of caprylic / caprylic acid glyceride is about 40% to about 70% w / w. In some embodiments, the amount of caprylic / caprylic acid glyceride is about 40% to about 60% w / w. In some embodiments, the amount of caprylic / caprylic acid glyceride is about 40% to about 50% w / w. In some embodiments, the amount of caprylic / caprylic acid glyceride is about 50% to about 80% w / w. In some embodiments, the amount of caprylic / caprylic acid glyceride is about 50% to about 70% w / w. In some embodiments, the amount of caprylic / caprylic acid glyceride is about 50% to about 60% w / w. In some embodiments, the amount of caprylic / caprylic acid glyceride is about 60% to about 80% w / w. In some embodiments, the amount of caprylic / caprylic acid glyceride is about 60% to about 70% w / w. In some embodiments, the amount of caprylic / caprylic acid glyceride is about 70% to about 80% w / w. In some embodiments, the amount of caprylic / caprylic acid glyceride is about 20%, about 30%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, or about 80% w / w. In some embodiments, the amount of caprylic / caprylic acid glyceride is about 46%, about 47%, about 48%, about 49%, about 50%, about 51%, about 52%, about 53%, about 54%, about 56%, about 57%, about 58%, about 59%, about 61%, about 62%, about 63%, or about 64% w / w. In some embodiments, the amount of caprylic / caprylic acid glyceride is about 49% w / w. In some embodiments, the amount of caprylic / caprylic acid glyceride is about 50% w / w. In some embodiments, the amount of caprylic / caprylic acid glyceride is about 51% w / w.In some embodiments, the amount of caprylic / caprylic acid glyceride is about 49.5%, about 49.6%, about 49.7%, about 49.8%, about 49.9%, about 50.0%, about 50.1%, about 50.2%, about 50.3%, about 50.4%, or about 50.5% w / w. In some embodiments, the amount of caprylic / caprylic acid glyceride is about 49.8% w / w. In some embodiments, the amount of caprylic / caprylic acid glyceride is about 59% w / w. In some embodiments, the amount of caprylic / caprylic acid glyceride is about 60%. In some embodiments, the amount of caprylic / caprylic acid glyceride is about 61% w / w. In some embodiments, the amount of caprylic / caprylic acid glyceride is about 59.5%, about 59.6%, 59.7%, about 59.8%, about 59.9%, about 60.0%, about 60.1%, about 60.2%, or about 60.3% w / w. In some embodiments, the amount of caprylic / caprylic acid glyceride is about 59.8% w / w.

[0327] In some embodiments, the amount of caprylic / caprylic acid glyceride is 20% to 80% w / w. In some embodiments, the amount of caprylic / caprylic acid glyceride is 20% to 70% w / w. In some embodiments, the amount of caprylic / caprylic acid glyceride is 20% to 60% w / w. In some embodiments, the amount of caprylic / caprylic acid glyceride is 20% to 50% w / w. In some embodiments, the amount of caprylic / caprylic acid glyceride is 20% to 40% w / w. In some embodiments, the amount of caprylic / caprylic acid glyceride is 20% to 30% w / w. In some embodiments, the amount of caprylic / caprylic acid glyceride is 30% to 80% w / w. In some embodiments, the amount of caprylic / caprylic acid glyceride is 30% to 70% w / w. In some embodiments, the amount of caprylic / caprylic acid glyceride is 30% to 60% w / w. In some embodiments, the amount of caprylic / caprylic acid glyceride is 30% to 50% w / w. In some embodiments, the amount of caprylic / caprylic acid glyceride is 30% to 40% w / w. In some embodiments, the amount of caprylic / caprylic acid glyceride is 40% to 80% w / w. In some embodiments, the amount of caprylic / caprylic acid glyceride is 40% to 70% w / w. In some embodiments, the amount of caprylic / caprylic acid glyceride is 40% to 60% w / w. In some embodiments, the amount of caprylic / caprylic acid glyceride is 40% to 50% w / w. In some embodiments, the amount of caprylic / caprylic acid glyceride is 50% to 80% w / w. In some embodiments, the amount of caprylic / caprylic acid glyceride is 50% to 70% w / w. In some embodiments, the amount of caprylic / caprylic acid glyceride is 50% to 60% w / w. In some embodiments, the amount of caprylic / caprylic acid glyceride is 60% to 80% w / w. In some embodiments, the amount of caprylic / caprylic acid glyceride is 60% to 70% w / w. In some embodiments, the amount of caprylic / caprylic acid glyceride is 70% to 80% w / w. In some embodiments, the amount of caprylic / caprylic acid glyceride is 20%, 30%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, or 80% w / w. In some embodiments, the amount of caprylic / caprylic acid glyceride is 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 56%, 57%, 58%, 59%, 61%, 62%, 63%, or 64% w / w. In some embodiments, the amount of caprylic / caprylic acid glyceride is 49% w / w. In some embodiments, the amount of caprylic / caprylic acid glyceride is 50% w / w. In some embodiments, the amount of caprylic / caprylic acid glyceride is 51% w / w. In some embodiments, the amount of caprylic / caprylic acid glyceride is 49.5%, 49.6%, 49.7%, 49.8%, 49.9%, 50.0%, 50.1%, 50.2%, 50.3%, 50.4%, or 50.5% w / w. In some embodiments, the amount of caprylic / caprylic acid glyceride is 49.8% w / w. In some embodiments, the amount of caprylic / caprylic acid glyceride is 59% w / w. In some embodiments, the amount of caprylic / caprylic acid glyceride is 60%.In some embodiments, the amount of caprylic / caprylic acid glyceride is 61% w / w. In some embodiments, the amount of caprylic / caprylic acid glyceride is 59.5%, 59.6%, 59.7%, 59.8%, 59.9%, 60.0%, 60.1%, 60.2%, or 60.3% w / w. In some embodiments, the amount of caprylic / caprylic acid glyceride is 59.8% w / w.

[0328] In some embodiments, the amount of monolinoleic acid glyceride is about 10% to about 30% w / w. In some embodiments, the amount of monolinoleic acid glyceride is about 15% to about 30% w / w. In some embodiments, the amount of monolinoleic acid glyceride is about 15% to about 25% w / w. In some embodiments, the amount of monolinoleic acid glyceride is about 15% to about 20% w / w. In some embodiments, the amount of monolinoleic acid glyceride is about 20% to about 30% w / w. In some embodiments, the amount of monolinoleic acid glyceride is about 25% to about 30% w / w. In some embodiments, the amount of monolinoleic acid glyceride is about 10%, 15%, 20%, 25%, 30% w / w. In some embodiments, the amount of monolinoleic acid glyceride is about 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25% w / w. In some embodiments, the amount of monolinoleic acid glyceride is about 19%. In some embodiments, the amount of monolinoleic acid glyceride is about 20% w / w. In some embodiments, the amount of monolinoleic acid glyceride is about 21% w / w. In some embodiments, the amount of monolinoleic acid glyceride is about 19.5%, about 19.6%, about 19.7%, about 19.8%, about 19.9%, about 20.1%, about 20.2%, about 20.3%, about 20.4%, or about 20.5% w / w. In some embodiments, the amount of monolinoleic acid glyceride is about 19.8% w / w. In some embodiments, the amount of monolinoleic acid glyceride is about 19.9% ​​w / w. In some embodiments, the amount of monolinoleic acid glyceride is about 20% w / w. In some embodiments, the amount of monolinoleic acid glyceride is about 22.0%, about 22.1%, about 22.2%, about 22.3%, about 22.4%, about 22.5%, about 22.6%, about 22.7%, about 22.8%, or about 22.9% w / w. In some embodiments, the amount of monolinoleic acid glyceride is about 22.3% w / w. In some embodiments, the amount of monolinoleic acid glyceride is about 22.4% w / w. In some embodiments, the amount of monolinoleic acid glyceride is about 22.5% w / w.

[0329] In some embodiments, the amount of monolinoleic acid glyceride is 10% to 30% w / w. In some embodiments, the amount of monolinoleic acid glyceride is 15% to 30% w / w. In some embodiments, the amount of monolinoleic acid glyceride is 15% to 25% w / w. In some embodiments, the amount of monolinoleic acid glyceride is 15% to 20% w / w. In some embodiments, the amount of monolinoleic acid glyceride is 20% to 30% w / w. In some embodiments, the amount of monolinoleic acid glyceride is 25% to 30% w / w. In some embodiments, the amount of monolinoleic acid glyceride is 10%, 15%, 20%, 25%, 30% w / w. In some embodiments, the amount of monolinoleic acid glyceride is 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25% w / w. In some embodiments, the amount of monolinoleic acid glyceride is 19%. In some embodiments, the amount of monolinoleic acid glyceride is 20% w / w. In some embodiments, the amount of monolinoleic acid glyceride is 21% w / w. In some embodiments, the amount of monolinoleic acid glyceride is 19.5%, 19.6%, 19.7%, 19.8%, 19.9%, 20.1%, 20.2%, 20.3%, 20.4%, or 20.5% w / w. In some embodiments, the amount of monolinoleic acid glyceride is 19.8% w / w. In some embodiments, the amount of monolinoleic acid glyceride is 19.9% ​​w / w. In some embodiments, the amount of monolinoleic acid glyceride is 20% w / w. In some embodiments, the amount of monolinoleic acid glyceride is 22.0%, 22.1%, 22.2%, 22.3%, 22.4%, 22.5%, 22.6%, 22.7%, 22.8%, or 22.9% w / w. In some embodiments, the amount of monolinoleic acid glyceride is 22.3% w / w. In some embodiments, the amount of monolinoleic acid glyceride is 22.4% w / w. In some embodiments, the amount of monolinoleic acid glyceride is 22.5% w / w.

[0330] In some embodiments, the composition further comprises a surfactant. In some embodiments, the surfactant is stearoyl polyoxyethylene-32 glycerol ester. In some embodiments, the surfactant is lauroyl polyoxyethylene-32 glycerol ester.

[0331] In some embodiments, the amount of stearoyl polyoxyethylene-32 glycerol is about 5.0% to about 20% w / w. In some embodiments, the amount of stearoyl polyoxyethylene-32 glycerol is about 5.0% to about 15% w / w. In some embodiments, the amount of stearoyl polyoxyethylene-32 glycerol is about 5.0% to about 10% w / w. In some embodiments, the amount of stearoyl polyoxyethylene-32 glycerol is about 5.0% to about 9.0% w / w. In some embodiments, the amount of stearoyl polyoxyethylene-32 glycerol is about 5.0% to about 8.0% w / w. In some embodiments, the amount of stearoyl polyoxyethylene-32 glycerol is about 5.0% to about 7.5% w / w. In some embodiments, the amount of stearoyl polyoxyethylene-32 glycerol is about 6.0% to about 10% w / w. In some embodiments, the amount of stearoyl polyoxyethylene-32 glycerol is about 6.0% to about 9.0% w / w. In some embodiments, the amount of stearoyl polyoxyethylene-32 glycerol is about 6.0% to about 8.0% w / w. In some embodiments, the amount of stearoyl polyoxyethylene-32 glycerol is about 6.0% to about 7.5% w / w. In some embodiments, the amount of stearoyl polyoxyethylene-32 glycerol is about 7.0% to about 10.0% w / w. In some embodiments, the amount of stearoyl polyoxyethylene-32 glycerol is about 7.0% to about 9.0% w / w. In some embodiments, the amount of stearoyl polyoxyethylene-32 glycerol is about 7.0% to about 8.0% w / w. In some embodiments, the amount of stearoyl polyoxyethylene-32 glycerol is about 7.0% to about 7.5% w / w. In some embodiments, the amount of stearoyl polyoxyethylene-32 glycerol is about 7.0%, about 7.1%, about 7.2%, about 7.3%, about 7.4%, about 7.5%, about 7.6%, about 7.7%, about 7.8%, about 7.9%, or about 8.0% w / w. In some embodiments, the amount of stearoyl polyoxyethylene-32 glycerol is about 7.4% w / w. In some embodiments, the amount of stearoyl polyoxyethylene-32 glycerol is about 7.5% w / w. In some embodiments, the amount of stearoyl polyoxyethylene-32 glycerol is about 10% w / w. In some embodiments, the amount of stearoyl polyoxyethylene-32 glycerol is about 15% w / w. In some embodiments, the amount of stearoyl polyoxyethylene-32 glycerol is about 20% w / w.

[0332] In some embodiments, the amount of stearoyl polyoxyethylene-32 glycerol is 5.0% to 20% w / w. In some embodiments, the amount of stearoyl polyoxyethylene-32 glycerol is 5.0% to 15% w / w. In some embodiments, the amount of stearoyl polyoxyethylene-32 glycerol is 5.0% to 10% w / w. In some embodiments, the amount of stearoyl polyoxyethylene-32 glycerol is 5.0% to 9.0% w / w. In some embodiments, the amount of stearoyl polyoxyethylene-32 glycerol is 5.0% to 8.0% w / w. In some embodiments, the amount of stearoyl polyoxyethylene-32 glycerol is 5.0% to 7.5% w / w. In some embodiments, the amount of stearoyl polyoxyethylene-32 glycerol is 6.0% to 10% w / w. In some embodiments, the amount of stearoyl polyoxyethylene-32 glycerol is 6.0% to 9.0% w / w. In some embodiments, the amount of stearoyl polyoxyethylene-32 glycerol is 6.0% to 8.0% w / w. In some embodiments, the amount of stearoyl polyoxyethylene-32 glycerol is 6.0% to 7.5% w / w. In some embodiments, the amount of stearoyl polyoxyethylene-32 glycerol is 7.0% to 10.0% w / w. In some embodiments, the amount of stearoyl polyoxyethylene-32 glycerol is 7.0% to 9.0% w / w. In some embodiments, the amount of stearoyl polyoxyethylene-32 glycerol is 7.0% to 8.0% w / w. In some embodiments, the amount of stearoyl polyoxyethylene-32 glycerol is 7.0% to 7.5% w / w. In some embodiments, the amount of stearoyl polyoxyethylene-32 glycerol is 7.0%, 7.1%, 7.2%, 7.3%, 7.4%, 7.5%, 7.6%, 7.7%, 7.8%, 7.9%, or 8.0% w / w. In some embodiments, the amount of stearoyl polyoxyethylene-32 glycerol is 7.4% w / w. In some embodiments, the amount of stearoyl polyoxyethylene-32 glycerol is 7.5% w / w. In some embodiments, the amount of stearoyl polyoxyethylene-32 glycerol is 10% w / w. In some embodiments, the amount of stearoyl polyoxyethylene-32 glycerol is 15% w / w. In some embodiments, the amount of stearoyl polyoxyethylene-32 glycerol is 20% w / w.

[0333] In some embodiments, the amount of lauroyl polyoxyethylene-32 glycerol is about 5.0% to about 20% w / w. In some embodiments, the amount of lauroyl polyoxyethylene-32 glycerol is about 5.0% to about 15% w / w. In some embodiments, the amount of lauroyl polyoxyethylene-32 glycerol is about 5.0% to about 10% w / w. In some embodiments, the amount of lauroyl polyoxyethylene-32 glycerol is about 5.0% to about 9.0% w / w. In some embodiments, the amount of lauroyl polyoxyethylene-32 glycerol is about 5.0% to about 8.0% w / w. In some embodiments, the amount of lauroyl polyoxyethylene-32 glycerol is about 5.0% to about 7.5% w / w. In some embodiments, the amount of lauroyl polyoxyethylene-32 glycerol is about 6.0% to about 10% w / w. In some embodiments, the amount of lauroyl polyoxyethylene-32 glycerol is about 6.0% to about 9.0% w / w. In some embodiments, the amount of lauroyl polyoxyethylene-32 glycerol is about 6.0% to about 8.0% w / w. In some embodiments, the amount of lauroyl polyoxyethylene-32 glycerol is about 6.0% to about 7.5% w / w. In some embodiments, the amount of lauroyl polyoxyethylene-32 glycerol is about 7.0% to about 10.0% w / w. In some embodiments, the amount of lauroyl polyoxyethylene-32 glycerol is about 7.0% to about 9.0% w / w. In some embodiments, the amount of lauroyl polyoxyethylene-32 glycerol is about 7.0% to about 8.0% w / w. In some embodiments, the amount of lauroyl polyoxyethylene-32 glycerol is about 7.0% to about 7.5% w / w. In some embodiments, the amount of lauroyl polyoxyethylene-32 glycerol ester is about 7.0%, about 7.1%, about 7.2%, about 7.3%, about 7.4%, about 7.5%, about 7.6%, about 7.7%, about 7.8%, about 7.9%, or about 8.0% w / w. In some embodiments, the amount of lauroyl polyoxyethylene-32 glycerol ester is about 7.4% w / w. In some embodiments, the amount of lauroyl polyoxyethylene-32 glycerol ester is about 7.5% w / w. In some embodiments, the amount of lauroyl polyoxyethylene-32 glycerol ester is about 10% w / w. In some embodiments, the amount of lauroyl polyoxyethylene-32 glycerol ester is about 15% w / w. In some embodiments, the amount of lauroyl polyoxyethylene-32 glycerol ester is about 20% w / w.

[0334] In some embodiments, the amount of lauroyl polyoxyethylene-32 glycerol ester is 5.0% to 20% w / w. In some embodiments, the amount of lauroyl polyoxyethylene-32 glycerol ester is 5.0% to 15% w / w. In some embodiments, the amount of lauroyl polyoxyethylene-32 glycerol ester is 5.0% to 10% w / w. In some embodiments, the amount of lauroyl polyoxyethylene-32 glycerol ester is 5.0% to 9.0% w / w. In some embodiments, the amount of lauroyl polyoxyethylene-32 glycerol ester is 5.0% to 8.0% w / w. In some embodiments, the amount of lauroyl polyoxyethylene-32 glycerol ester is 5.0% to 7.5% w / w. In some embodiments, the amount of lauroyl polyoxyethylene-32 glycerol ester is 6.0% to 10% w / w. In some embodiments, the amount of lauroyl polyoxyethylene-32 glycerol ester is 6.0% to 9.0% w / w. In some embodiments, the amount of lauroyl polyoxyethylene-32 glycerol ester is 6.0% to 8.0% w / w. In some embodiments, the amount of lauroyl polyoxyethylene-32 glycerol ester is 6.0% to 7.5% w / w. In some embodiments, the amount of lauroyl polyoxyethylene-32 glycerol ester is 7.0% to 10.0% w / w. In some embodiments, the amount of lauroyl polyoxyethylene-32 glycerol ester is 7.0% to 9.0% w / w. In some embodiments, the amount of lauroyl polyoxyethylene-32 glycerol ester is 7.0% to 8.0% w / w. In some embodiments, the amount of lauroyl polyoxyethylene-32 glycerol ester is 7.0% to 7.5% w / w. In some embodiments, the amount of lauroyl polyoxyethylene-32 glycerol ester is 7.0%, 7.1%, 7.2%, 7.3%, 7.4%, 7.5%, 7.6%, 7.7%, 7.8%, 7.9%, or 8.0% w / w. In some embodiments, the amount of lauroyl polyoxyethylene-32 glycerol is 7.4% w / w. In some embodiments, the amount of lauroyl polyoxyethylene-32 glycerol is 7.5% w / w. In some embodiments, the amount of lauroyl polyoxyethylene-32 glycerol is 10% w / w. In some embodiments, the amount of lauroyl polyoxyethylene-32 glycerol is 15% w / w. In some embodiments, the amount of lauroyl polyoxyethylene-32 glycerol is 20% w / w.

[0335] In some embodiments, the pharmaceutical composition further comprises a surfactant (e.g., vitamin E TPGS). In some embodiments, the amount of surfactant is from about 10% to about 30% w / w. In some embodiments, the amount of surfactant is from 10% to about 25% w / w. In some embodiments, the amount of surfactant is from about 10% to about 20% w / w. In some embodiments, the amount of surfactant is from about 15% to about 30% w / w. In some embodiments, the amount of surfactant is from about 15% to about 25% w / w. In some embodiments, the amount of surfactant is from about 15% to about 20% w / w. In some embodiments, the amount of surfactant is from about 10%, about 11%, about 12%, about 13%, about 14%, about 15%, about 16%, about 17%, about 18%, about 19%, about 20%, about 21%, about 22%, about 23%, about 24%, about 25%, about 26%, about 27%, about 28%, about 29%, or about 30% w / w. In some embodiments, the amount of surfactant is about 19.5%, about 19.6%, about 19.7%, about 19.8%, about 19.9%, about 20.1%, about 20.2%, about 20.3%, about 20.4%, or about 20.5% w / w. In some embodiments, the amount of surfactant is about 19.9% ​​w / w. In some embodiments, the amount of surfactant is about 20.0% w / w. In some embodiments, the amount of surfactant is about 20.1% w / w.

[0336] In some embodiments, the pharmaceutical composition further comprises a surfactant (e.g., vitamin E TPGS). In some embodiments, the amount of surfactant is 10% to 30% w / w. In some embodiments, the amount of surfactant is 10% to 25% w / w. In some embodiments, the amount of surfactant is 10% to 20% w / w. In some embodiments, the amount of surfactant is 15% to 30% w / w. In some embodiments, the amount of surfactant is 15% to 25% w / w. In some embodiments, the amount of surfactant is 15% to 20% w / w. In some embodiments, the amount of surfactant is 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, or 30% w / w. In some embodiments, the amount of surfactant is 19.5%, 19.6%, 19.7%, 19.8%, 19.9%, 20.1%, 20.2%, 20.3%, 20.4%, or 20.5% w / w. In some embodiments, the amount of surfactant is 19.9% ​​w / w. In some embodiments, the amount of surfactant is 20.0% w / w. In some embodiments, the amount of surfactant is 20.1% w / w.

[0337] In some embodiments, the pharmaceutical composition further comprises vitamin E TPGS. In some embodiments, the amount of vitamin E TPGS is from about 10% to about 30% w / w. In some embodiments, the amount of vitamin E TPGS is from 10% to about 25% w / w. In some embodiments, the amount of vitamin E TPGS is from about 10% to about 20% w / w. In some embodiments, the amount of vitamin E TPGS is from about 15% to about 30% w / w. In some embodiments, the amount of vitamin E TPGS is from about 15% to about 25% w / w. In some embodiments, the amount of vitamin E TPGS is from about 15% to about 20% w / w. In some embodiments, the amount of vitamin E TPGS is from about 10%, about 11%, about 12%, about 13%, about 14%, about 15%, about 16%, about 17%, about 18%, about 19%, about 20%, about 21%, about 22%, about 23%, about 24%, about 25%, about 26%, about 27%, about 28%, about 29%, or 30% w / w. In some embodiments, the amount of vitamin ETPGS is about 19.5%, about 19.6%, about 19.7%, about 19.8%, about 19.9%, about 20.1%, about 20.2%, about 20.3%, about 20.4%, or about 20.5% w / w. In some embodiments, the amount of vitamin ETPGS is about 19.9% ​​w / w. In some embodiments, the amount of vitamin ETPGS is about 20.0% w / w. In some embodiments, the amount of vitamin ETPGS is about 20.1% w / w.

[0338] In some embodiments, the amount of vitamin E TPGS is 10% to 30% w / w. In some embodiments, the amount of vitamin E TPGS is 10% to 25% w / w. In some embodiments, the amount of vitamin E TPGS is 10% to 20% w / w. In some embodiments, the amount of vitamin E TPGS is 15% to 30% w / w. In some embodiments, the amount of vitamin E TPGS is 15% to 25% w / w. In some embodiments, the amount of vitamin E TPGS is 15% to 20% w / w. In some embodiments, the amount of vitamin E TPGS is 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, or 30% w / w. In some embodiments, the amount of vitamin E TPGS is 19.5%, 19.6%, 19.7%, 19.8%, 19.9%, 20.1%, 20.2%, 20.3%, 20.4%, or 20.5% w / w. In some embodiments, the amount of vitamin E TPGS is 19.9% ​​w / w. In some embodiments, the amount of vitamin E TPGS is 20.0% w / w. In some embodiments, the amount of vitamin E ETPGS is 20.1% w / w.

[0339] In some embodiments, the pharmaceutical composition further comprises an antioxidant (e.g., butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), tocopherol, tocopheryl acetate, etc.).

[0340] In some embodiments, the amount of antioxidant is about 0.005% to about 0.015% w / w. In some embodiments, the amount of antioxidant is about 0.005% to about 0.010% w / w. In some embodiments, the amount of antioxidant is about 0.010% to about 0.015% w / w. In some embodiments, the amount of antioxidant is about 0.008% to about 0.012% w / w. In some embodiments, the amount of antioxidant is about 0.005%, about 0.006%, about 0.007%, about 0.008%, about 0.009%, about 0.010%, about 0.011%, about 0.012%, about 0.013%, about 0.014%, or about 0.015% w / w. In some embodiments, the amount of antioxidant is about 0.008% w / w. In some embodiments, the amount of antioxidant is about 0.009% w / w. In some embodiments, the amount of antioxidant is about 0.010% w / w. In some embodiments, the amount of antioxidant is about 0.011% w / w. In some embodiments, the amount of antioxidant is about 0.012% to about 0.015% w / w.

[0341] In some embodiments, the pharmaceutical composition further comprises an antioxidant, such as butylated hydroxyanisole (BHA). In some embodiments, the amount of the antioxidant is 0.005% to 0.015% w / w. In some embodiments, the amount of the antioxidant is 0.005% to 0.010% w / w. In some embodiments, the amount of the antioxidant is 0.010% to 0.015% w / w. In some embodiments, the amount of the antioxidant is 0.008% to 0.012% w / w. In some embodiments, the amount of the antioxidant is 0.005%, 0.006%, 0.007%, 0.008%, 0.009%, 0.010%, 0.011%, 0.012%, 0.013%, 0.014%, or 0.015% w / w. In some embodiments, the amount of the antioxidant is 0.008% w / w. In some embodiments, the amount of the antioxidant is 0.009% w / w. In some embodiments, the amount of antioxidant is 0.010% w / w. In some embodiments, the amount of antioxidant is 0.011% w / w. In some embodiments, the amount of antioxidant is 0.012% to 0.015% w / w.

[0342] In some embodiments, the amount of butylated hydroxyanisole (BHA) is from about 0.005% to about 0.015% w / w. In some embodiments, the amount of butylated hydroxyanisole (BHA) is from about 0.005% to about 0.010% w / w. In some embodiments, the amount of butylated hydroxyanisole (BHA) is from about 0.010% to about 0.015% w / w. In some embodiments, the amount of butylated hydroxyanisole (BHA) is from about 0.008% to about 0.012% w / w. In some embodiments, the amount of butylated hydroxyanisole (BHA) is about 0.005%, about 0.006%, about 0.007%, about 0.008%, about 0.009%, about 0.010%, about 0.011%, about 0.012%, about 0.013%, about 0.014%, or about 0.015% w / w. In some embodiments, the amount of butylated hydroxyanisole (BHA) is about 0.008% w / w. In some embodiments, the amount of butylated hydroxyanisole (BHA) is about 0.009% w / w. In some embodiments, the amount of butylated hydroxyanisole (BHA) is about 0.010% w / w. In some embodiments, the amount of butylated hydroxyanisole (BHA) is about 0.011% w / w. In some embodiments, the amount of butylated hydroxyanisole (BHA) is from about 0.012% to about 0.015% w / w.

[0343] In some embodiments, the pharmaceutical composition further comprises an antioxidant, such as butylated hydroxyanisole (BHA). In some embodiments, the amount of butylated hydroxyanisole (BHA) is 0.005% to 0.015% w / w. In some embodiments, the amount of butylated hydroxyanisole (BHA) is 0.005% to 0.010% w / w. In some embodiments, the amount of butylated hydroxyanisole (BHA) is 0.010% to 0.015% w / w. In some embodiments, the amount of butylated hydroxyanisole (BHA) is 0.008% to 0.012% w / w. In some embodiments, the amount of butylated hydroxyanisole (BHA) is 0.005%, 0.006%, 0.007%, 0.008%, 0.009%, 0.010%, 0.011%, 0.012%, 0.013%, 0.014%, or 0.015% w / w. In some embodiments, the amount of butylated hydroxyanisole (BHA) is 0.008% w / w. In some embodiments, the amount of butylated hydroxyanisole (BHA) is 0.009% w / w. In some embodiments, the amount of butylated hydroxyanisole (BHA) is 0.010% w / w. In some embodiments, the amount of butylated hydroxyanisole (BHA) is 0.011% w / w. In some embodiments, the amount of butylated hydroxyanisole (BHA) is from 0.012% to 0.015% w / w.

[0344] In some embodiments, the pharmaceutical composition comprises about 0.3% w / w of Compound I, about 60% w / w of caprylic acid glyceride, about 20% w / w of linoleic acid glyceride, about 20% w / w of vitamin E TPGS, and about 0.01% w / w of butylated hydroxyanisole. In some embodiments, the pharmaceutical composition comprises 0.3% w / w of Compound I, 60% w / w of caprylic acid glyceride, 20% w / w of linoleic acid glyceride, 20% w / w of vitamin E TPGS, and 0.01% w / w of butylated hydroxyanisole. In some embodiments, the pharmaceutical composition comprises 0.3% of Compound I, 59.8% of caprylic acid glyceride, 19.9% ​​of linoleic acid glyceride, 19.9% ​​of vitamin E TPGS, and 0.01% of butylated hydroxyanisole.

[0345] In some embodiments, the pharmaceutical composition comprises about 0.3% w / w of Compound I, about 50% w / w of glyceryl monocaprylate, about 22.5% w / w of glyceryl monolinoleate, about 20% w / w of vitamin E TPGS, about 7.5% w / w of stearoyl polyoxyethylene-32 glyceride, and about 0.01% w / w of butylated hydroxyanisole. In some embodiments, the pharmaceutical composition comprises 0.3% w / w of Compound I, 50% w / w of glyceryl monocaprylate, 22.5% w / w of glyceryl monolinoleate, 20% w / w of vitamin E TPGS, 7.5% w / w of stearoyl polyoxyethylene-32 glyceride, and 0.01% w / w of butylated hydroxyanisole. In some embodiments, the pharmaceutical composition comprises about 0.3% w / w of compound I, 49.8% w / w of caprylic acid glyceride, 22.4% w / w of linoleic acid glyceride, 19.9% ​​w / w of vitamin E TPGS, 7.5% w / w of stearoyl polyoxyethylene-32 glyceride, and 0.01% w / w of butylated hydroxyanisole.

[0346] In some embodiments, the pharmaceutical composition is an oral dosage form. In some embodiments, the pharmaceutical composition is a lipid formulation. In some embodiments, the oral dosage form is a soft gelatin capsule, a hard-shell capsule, or an oral liquid. In some embodiments, the oral dosage form is a soft gelatin capsule. In some embodiments, the oral dosage form is a hard-shell capsule. In some embodiments, the oral dosage form is an oral liquid.

[0347] On the one hand, this disclosure provides a pharmaceutical composition comprising a therapeutically effective amount of compound I.

[0348] (Compound I)

[0349] Or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier thereof;

[0350] When administered to a subject, the drug composition provides one or more of the following pharmacokinetic parameters:

[0351] a) C between approximately 8 and approximately 25 ng / mL max ;

[0352] b) AUC between approximately 100 and approximately 450 ng*h / mL last ;

[0353] c) AUC between approximately 100 and approximately 500 ng*h / mL inf ;

[0354] d) t between approximately 2 and approximately 8 hours max ;or

[0355] e) Bioavailability between approximately 70% and approximately 100%.

[0356] In some embodiments, the pharmaceutical composition provides a Cg concentration between about 8 and about 25 ng / mL. max In some embodiments, the pharmaceutical composition provides a Cg concentration between about 9 and about 25 ng / mL. max In some embodiments, the pharmaceutical composition provides a Cg concentration between about 10 and about 25 ng / mL. max In some embodiments, the pharmaceutical composition provides a Cg concentration between about 11 and about 25 ng / mL. max In some embodiments, the pharmaceutical composition provides a Cg concentration between about 12 and about 25 ng / mL. max In some embodiments, the pharmaceutical composition provides a Cg concentration between about 13 and about 25 ng / mL. max In some embodiments, the pharmaceutical composition provides a Cg concentration between about 14 and about 25 ng / mL. max In some embodiments, the pharmaceutical composition provides a Cg concentration between about 15 and about 25 ng / mL. max .

[0357] In some embodiments, the pharmaceutical composition provides about 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, 12, 12.5, 13, 13.5, 14, 14.5, 15, 15.5, 16, 16.5, 17, 17.5, 18, 18.5, 19, 19.5, 20, 20.5, 21, 21.5, 22, 22.5, 23.0, 23.5, 24, 24.5, or 25 ng / mL of C max In some embodiments, the pharmaceutical composition provides about 12, 12.1, 12.2, 12.3, 12.4, 12.6, 12.7, 12.8, 12.9, 13.0 ng / mL, 15.1, 15.2, 15.3, 15.4, 15.6, 15.7, 15.8, 15.9, or 16 ng / mL of C. max In some embodiments, the pharmaceutical composition provides about 12 ng / mL of C. max In some embodiments, the pharmaceutical composition provides approximately 12.1 ng / mL of C. max In some embodiments, the pharmaceutical composition provides approximately 12.2 ng / mL of C. max In some embodiments, the pharmaceutical composition provides approximately 12.3 ng / mL of C. max In some embodiments, the pharmaceutical composition provides approximately 12.4 ng / mL of C. max In some embodiments, the pharmaceutical composition provides approximately 12.5 ng / mL of C.max In some embodiments, the pharmaceutical composition provides approximately 12.6 ng / mL of C. max In some embodiments, the pharmaceutical composition provides approximately 12.7 ng / mL of C. max In some embodiments, the pharmaceutical composition provides approximately 12.8 ng / mL of C. max In some embodiments, the pharmaceutical composition provides approximately 12.9 ng / mL of C. max In some embodiments, the pharmaceutical composition provides approximately 13 ng / mL of C. max In some embodiments, the pharmaceutical composition provides about 15 ng / mL of C. max In some embodiments, the pharmaceutical composition provides approximately 15.1 ng / mL of C. max In some embodiments, the pharmaceutical composition provides approximately 15.2 ng / mL of C. max In some embodiments, the pharmaceutical composition provides approximately 15.3 ng / mL of C. max In some embodiments, the pharmaceutical composition provides approximately 15.4 ng / mL of C. max In some embodiments, the pharmaceutical composition provides approximately 15.5 ng / mL of C. max In some embodiments, the pharmaceutical composition provides approximately 15.6 ng / mL of C. max In some embodiments, the pharmaceutical composition provides approximately 15.7 ng / mL of C. max In some embodiments, the pharmaceutical composition provides approximately 15.8 ng / mL of C. max In some embodiments, the pharmaceutical composition provides approximately 15.9 ng / mL of C. max In some embodiments, the pharmaceutical composition provides approximately 16 ng / mL of C. max .

[0358] In some embodiments, the pharmaceutical composition provides a C concentration between 8 and 25 ng / mL. max In some embodiments, the pharmaceutical composition provides a C0 concentration between 9 and 25 ng / mL. max In some embodiments, the pharmaceutical composition provides a C10 concentration between 10 and 25 ng / mL. max In some embodiments, the pharmaceutical composition provides a C10 concentration between 11 and 25 ng / mL. max In some embodiments, the pharmaceutical composition provides a C10 concentration between 12 and 25 ng / mL. max In some embodiments, the pharmaceutical composition provides a C10 concentration between 13 and 25 ng / mL. max In some embodiments, the pharmaceutical composition provides a C10 concentration between 14 and 25 ng / mL.max In some embodiments, the pharmaceutical composition provides a C15 to 25 ng / mL. max .

[0359] In some embodiments, the pharmaceutical composition provides a C2 concentration of 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, 12, 12.5, 13, 13.5, 14, 14.5, 15, 15.5, 16, 16.5, 17, 17.5, 18, 18.5, 19, 19.5, 20, 20.5, 21, 21.5, 22, 22.5, 23.0, 23.5, 24, 24.5, or 25 ng / mL. max In some embodiments, the pharmaceutical composition provides 12, 12.1, 12.2, 12.3, 12.4, 12.6, 12.7, 12.8, 12.9, or 13.0 ng / mL of C. max In some embodiments, the pharmaceutical composition provides a C15.1, 15.2, 15.3, 15.4, 15.6, 15.7, 15.8, 15.9, or 16 ng / mL. max In some embodiments, the pharmaceutical composition provides 12 ng / mL of C max In some embodiments, the pharmaceutical composition provides 12.1 ng / mL of C max In some embodiments, the pharmaceutical composition provides 12.2 ng / mL of C max In some embodiments, the pharmaceutical composition provides 12.3 ng / mL of C max In some embodiments, the pharmaceutical composition provides 12.4 ng / mL of C max In some embodiments, the pharmaceutical composition provides 12.5 ng / mL of C max In some embodiments, the pharmaceutical composition provides 12.6 ng / mL of C max In some embodiments, the pharmaceutical composition provides 12.7 ng / mL of C max In some embodiments, the pharmaceutical composition provides 12.8 ng / mL of C max In some embodiments, the pharmaceutical composition provides 12.9 ng / mL of C max In some embodiments, the pharmaceutical composition provides 13 ng / mL of C max In some embodiments, the pharmaceutical composition provides 15 ng / mL of C max In some embodiments, the pharmaceutical composition provides 15.1 ng / mL of C max In some embodiments, the pharmaceutical composition provides 15.2 ng / mL of C maxIn some embodiments, the pharmaceutical composition provides 15.3 ng / mL of C max In some embodiments, the pharmaceutical composition provides 15.4 ng / mL of C. max In some embodiments, the pharmaceutical composition provides 15.5 ng / mL of C max In some embodiments, the pharmaceutical composition provides 15.6 ng / mL of C max In some embodiments, the pharmaceutical composition provides 15.7 ng / mL of C max In some embodiments, the pharmaceutical composition provides 15.8 ng / mL of C max In some embodiments, the pharmaceutical composition provides 15.9 ng / mL of C max In some embodiments, the pharmaceutical composition provides 16 ng / mL of C max .

[0360] In some embodiments, C max The geometric mean C max .

[0361] In some embodiments, C max The range is the geometric mean C max The range.

[0362] In some embodiments, the pharmaceutical composition provides t for about 2 to about 8 hours. max In some embodiments, the pharmaceutical composition provides a duration of about 3 to about 8 hours. max In some embodiments, the pharmaceutical composition provides a dose of approximately 4 to approximately 8 hours. max In some embodiments, the pharmaceutical composition provides a dose of approximately 5 to approximately 8 hours. max In some embodiments, the pharmaceutical composition provides a dose of approximately 6 to approximately 8 hours. max In some embodiments, the pharmaceutical composition provides t for about 7 to about 8 hours. max In some embodiments, the pharmaceutical composition provides a duration of about 3 to about 6 hours. max In some embodiments, the pharmaceutical composition provides approximately 2 hours of t max In some embodiments, the pharmaceutical composition provides approximately 2.5 hours of t max In some embodiments, the pharmaceutical composition provides approximately 3 hours of t max In some embodiments, the pharmaceutical composition provides approximately 3.5 hours of t max In some embodiments, the pharmaceutical composition provides approximately 4 hours of t max In some embodiments, the pharmaceutical composition provides approximately 4.5 hours of t maxIn some embodiments, the pharmaceutical composition provides approximately 5 hours of t max In some embodiments, the pharmaceutical composition provides approximately 5.5 hours of t max In some embodiments, the pharmaceutical composition provides approximately 6 hours of t max In some embodiments, the pharmaceutical composition provides approximately 6.5 hours of t max In some embodiments, the pharmaceutical composition provides approximately 7 hours of t max In some embodiments, the pharmaceutical composition provides approximately 7.5 hours of t max In some embodiments, the pharmaceutical composition provides approximately 8 hours of t max .

[0363] In some embodiments, the pharmaceutical composition provides t for 2 to 8 hours. max In some embodiments, the pharmaceutical composition provides t for 3 to 8 hours. max In some embodiments, the pharmaceutical composition provides t for 4 to 8 hours. max In some embodiments, the pharmaceutical composition provides t for 5 to 8 hours. max In some embodiments, the pharmaceutical composition provides t for 6 to 8 hours. max In some embodiments, the pharmaceutical composition provides t for 7 to 8 hours. max In some embodiments, the pharmaceutical composition provides t for 3 to 6 hours. max In some embodiments, the pharmaceutical composition provides 2 hours of t max In some embodiments, the pharmaceutical composition provides 2.5 hours of treatment. max In some embodiments, the pharmaceutical composition provides 3 hours of t max In some embodiments, the pharmaceutical composition provides 3.5 hours of treatment. max In some embodiments, the pharmaceutical composition provides 4 hours of t max In some embodiments, the pharmaceutical composition provides 4.5 hours of treatment. max In some embodiments, the pharmaceutical composition provides 5 hours of t max In some embodiments, the pharmaceutical composition provides 5.5 hours of treatment. max In some embodiments, the pharmaceutical composition provides 6 hours of t max In some embodiments, the pharmaceutical composition provides 6.5 hours of treatment. max In some embodiments, the pharmaceutical composition provides 7 hours of t max In some embodiments, the pharmaceutical composition provides 7.5 hours of treatment. max In some embodiments, the pharmaceutical composition provides 8 hours of t max .

[0364] In some embodiments, t max Geometric mean t max .

[0365] In some embodiments, t max The range is the geometric mean t max The range.

[0366] In some embodiments, the pharmaceutical composition provides t for about 20 to about 200 hours. last In some embodiments, the pharmaceutical composition is provided for about 20, about 24, about 28, about 32, about 36, about 40, about 44, about 48, about 52, about 56, about 60, about 64, about 68, about 72, about 76, about 80, about 84, about 88, about 92, about 96, about 100, about 104, about 108, about 112, about 116, about 120, about 124, about 128, about 132, about 136, about 140, about 144, about 148, about 152, about 156, about 160, about 164, about 168, about 172, about 176, about 180, about 184, about 188, about 192, about 196, or about 200 hours. last .

[0367] In some embodiments, the pharmaceutical composition provides t for 20 to 200 hours. last In some embodiments, the pharmaceutical composition is provided for t-hours between 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, 104, 108, 112, 116, 120, 124, 128, 132, 136, 140, 144, 148, 152, 156, 160, 164, 168, 172, 176, 180, 184, 188, 192, 196, or 200 hours. last .

[0368] In some embodiments, t last Geometric mean t last .

[0369] In some embodiments, t last The range is the geometric mean t last The range.

[0370] In some embodiments, the pharmaceutical composition provides an AUC between about 100 and about 450 ng*h / mL. last In some embodiments, the pharmaceutical composition provides an AUC of about 125 and about 400 ng*h / mL. lastIn some embodiments, the pharmaceutical composition provides an AUC of about 150 and about 350 ng*h / mL. last In some embodiments, the pharmaceutical composition provides an AUC of about 175 and about 300 ng*h / mL. last In some embodiments, the pharmaceutical composition provides an AUC of about 200 and about 275 ng*h / mL. last In some embodiments, the pharmaceutical composition provides an AUC of about 225 and about 250 ng*h / mL. last .

[0371] In some embodiments, the pharmaceutical composition provides an AUC of about 225, about 226, about 227, about 228, about 229, about 230, about 231, about 232, about 233, about 234, about 235, about 236, about 237, about 238, about 239, about 240, about 241, about 242, about 243, about 245, about 246, about 247, about 248, about 249, or about 250 ng*h / mL. last In some embodiments, the pharmaceutical composition provides an AUC of approximately 225 ng*h / mL. last In some embodiments, the pharmaceutical composition provides an AUC of approximately 226 ng*h / mL. last In some embodiments, the pharmaceutical composition provides an AUC of approximately 227 ng*h / mL. last In some embodiments, the pharmaceutical composition provides an AUC of approximately 228 ng*h / mL. last In some embodiments, the pharmaceutical composition provides an AUC of approximately 229 ng*h / mL. last In some embodiments, the pharmaceutical composition provides an AUC of approximately 230 ng*h / mL. last In some embodiments, the pharmaceutical composition provides an AUC of approximately 231 ng*h / mL. last In some embodiments, the pharmaceutical composition provides an AUC of approximately 232 ng*h / mL. last In some embodiments, the pharmaceutical composition provides an AUC of approximately 233 ng*h / mL. last In some embodiments, the pharmaceutical composition provides an AUC of approximately 234 ng*h / mL. last In some embodiments, the pharmaceutical composition provides an AUC of approximately 235 ng*h / mL. last In some embodiments, the pharmaceutical composition provides an AUC of approximately 236 ng*h / mL. last In some embodiments, the pharmaceutical composition provides an AUC of approximately 237 ng*h / mL. lastIn some embodiments, the pharmaceutical composition provides an AUC of approximately 238 ng*h / mL. last In some embodiments, the pharmaceutical composition provides an AUC of approximately 239 ng*h / mL. last In some embodiments, the pharmaceutical composition provides an AUC of approximately ng*h / mL. last In some embodiments, the pharmaceutical composition provides an AUC of approximately 241 ng*h / mL. last In some embodiments, the pharmaceutical composition provides an AUC of approximately 242 ng*h / mL. last In some embodiments, the pharmaceutical composition provides an AUC of approximately 243 ng*h / mL. last In some embodiments, the pharmaceutical composition provides an AUC of approximately 244 ng*h / mL. last In some embodiments, the pharmaceutical composition provides an AUC of approximately 245 ng*h / mL. last In some embodiments, the pharmaceutical composition provides an AUC of approximately 246 ng*h / mL. last In some embodiments, the pharmaceutical composition provides an AUC of approximately 247 ng*h / mL. last In some embodiments, the pharmaceutical composition provides an AUC of approximately 248 ng*h / mL. last In some embodiments, the pharmaceutical composition provides an AUC of approximately 249 ng*h / mL. last In some embodiments, the pharmaceutical composition provides an AUC of about 250 ng*h / mL. last .

[0372] In some embodiments, the pharmaceutical composition provides an AUC between 100 and 450 ng*h / mL. last In some embodiments, the pharmaceutical composition provides an AUC between 125 and 400 ng*h / mL. last In some embodiments, the pharmaceutical composition provides an AUC between 150 and 350 ng*h / mL. last In some embodiments, the pharmaceutical composition provides an AUC between 175 and 300 ng*h / mL. last In some embodiments, the pharmaceutical composition provides an AUC between 200 and 275 ng*h / mL. last In some embodiments, the pharmaceutical composition provides an AUC between 225 and 250 ng*h / mL. last .

[0373] In some embodiments, the pharmaceutical composition provides an AUC of 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 245, 246, 247, 248, 249, or 250 ng*h / mL. last In some embodiments, the pharmaceutical composition provides an AUC of 225 ng*h / mL. last In some embodiments, the pharmaceutical composition provides an AUC of 226 ng*h / mL. last In some embodiments, the pharmaceutical composition provides an AUC of 227 ng*h / mL. last In some embodiments, the pharmaceutical composition provides an AUC of 228 ng*h / mL. last In some embodiments, the pharmaceutical composition provides an AUC of 229 ng*h / mL. last In some embodiments, the pharmaceutical composition provides an AUC of 230 ng*h / mL. last In some embodiments, the pharmaceutical composition provides an AUC of 231 ng*h / mL. last In some embodiments, the pharmaceutical composition provides an AUC of 232 ng*h / mL. last In some embodiments, the pharmaceutical composition provides an AUC of 233 ng*h / mL. last In some embodiments, the pharmaceutical composition provides an AUC of 234 ng*h / mL. last In some embodiments, the pharmaceutical composition provides an AUC of 235 ng*h / mL. last In some embodiments, the pharmaceutical composition provides an AUC of 236 ng*h / mL. last In some embodiments, the pharmaceutical composition provides an AUC of 237 ng*h / mL. last In some embodiments, the pharmaceutical composition provides an AUC of 238 ng*h / mL. last In some embodiments, the pharmaceutical composition provides an AUC of 239 ng*h / mL. last In some embodiments, the pharmaceutical composition provides an AUC of 240 ng*h / mL. last In some embodiments, the pharmaceutical composition provides an AUC of 241 ng*h / mL. last In some embodiments, the pharmaceutical composition provides an AUC of 242 ng*h / mL. last In some embodiments, the pharmaceutical composition provides an AUC of 243 ng*h / mL. lastIn some embodiments, the pharmaceutical composition provides an AUC of 244 ng*h / mL. last In some embodiments, the pharmaceutical composition provides an AUC of 245 ng*h / mL. last In some embodiments, the pharmaceutical composition provides an AUC of 246 ng*h / mL. last In some embodiments, the pharmaceutical composition provides an AUC of 247 ng*h / mL. last In some embodiments, the pharmaceutical composition provides an AUC of 248 ng*h / mL. last In some embodiments, the pharmaceutical composition provides an AUC of 249 ng*h / mL. last In some embodiments, the pharmaceutical composition provides an AUC of 250 ng*h / mL. last .

[0374] In some embodiments, AUC last Geometric mean AUC last .

[0375] In some embodiments, AUC last The range is the geometric mean AUC last The range.

[0376] In some embodiments, the pharmaceutical composition provides an AUC between about 100 and about 500 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC between about 125 and about 400 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC between about 150 and about 350 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC between about 175 and about 300 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC between about 200 and about 275 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC between about 225 and about 275 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC between about 250 and about 275 ng*h / mL. Inf .

[0377] In some embodiments, the pharmaceutical composition provides about 225, about 226, about 227, about 228, about 229, about 230, about 231, about 232, about 233, about 234, about 235, about 236, about 237, about 238, about 239, about 240, about 241, about 242, about 243, about 245, about 246, about 247, about 248, about 249, or about 250, about 251, about 252, about 253, about 254, about 255, about 256, about 257, about 258, about 259, about 260, about 261, about 262, about 263, about 265, about 266, about 267, about 268, about 269, about 270, about 271, about 272, about 273, or about 265. AUC of ng*h / mL Inf In some embodiments, the pharmaceutical composition provides an AUC of approximately 225 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of approximately 226 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of approximately 227 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of approximately 228 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of approximately 229 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of approximately 230 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of approximately 231 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of approximately 232 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of approximately 233 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of approximately 234 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of approximately 235 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of approximately 236 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of approximately 237 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of approximately 238 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of approximately 239 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of approximately ng*h / mL. InfIn some embodiments, the pharmaceutical composition provides an AUC of approximately 241 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of approximately 242 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of approximately 243 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of approximately 244 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of approximately 245 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of approximately 246 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of approximately 247 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of approximately 248 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of approximately 249 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of about 250 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of approximately 251 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of approximately 252 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of approximately 253 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of approximately 254 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of approximately 255 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of approximately 256 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of approximately 257 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of approximately 258 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of approximately 259 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of approximately 260 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of approximately 261 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of approximately 262 ng*h / mL. InfIn some embodiments, the pharmaceutical composition provides an AUC of approximately 263 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of approximately 264 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of approximately 265 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of approximately 266 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of approximately 267 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of approximately 268 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of approximately 269 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of approximately 270 ng*h / mL. Inf .

[0378] In some embodiments, the pharmaceutical composition provides an AUC between 100 and 500 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC between 125 and 400 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC between 150 and 350 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC between 175 and 300 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC between 200 and 275 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC between 225 and 275 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC between 250 and 275 ng*h / mL. Inf .

[0379] In some embodiments, the pharmaceutical composition provides an AUC of 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 265, 266, 267, 268, 269, 270, 271, 272, 273, or 265 ng*h / mL. InfIn some embodiments, the pharmaceutical composition provides an AUC of 225 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of 226 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of 227 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of 228 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of 229 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of 230 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of 231 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of 232 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of 233 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of 234 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of 235 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of 236 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of 237 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of 238 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of 239 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of 240 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of 241 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of 242 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of 243 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of 244 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of 245 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of 246 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of 247 ng*h / mL.Inf In some embodiments, the pharmaceutical composition provides an AUC of 248 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of 249 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of 250 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of 251 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of 252 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of 253 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of 254 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of 255 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of 256 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of 257 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of 258 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of 259 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of 260 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of 261 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of 262 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of 263 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of 264 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of 265 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of 266 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of 267 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of 268 ng*h / mL. Inf In some embodiments, the pharmaceutical composition provides an AUC of 269 ng*h / mL. InfIn some embodiments, the pharmaceutical composition provides an AUC of 270 ng*h / mL. Inf .

[0380] In some embodiments, AUC Inf Geometric mean AUC Inf .

[0381] In some embodiments, AUC Inf The range is the geometric mean AUC Inf The range.

[0382] In some embodiments, the pharmaceutical composition provides a CL between about 2 and about 12 L / h. z / F. In some embodiments, the pharmaceutical composition provides a CL between about 3 and about 12 L / h. z / F. In some embodiments, the pharmaceutical composition provides a CL between about 4 and about 12 L / h. z / F. In some embodiments, the pharmaceutical composition provides a CL between about 5 and about 12 L / h. z / F. In some embodiments, the pharmaceutical composition provides a CL between about 6 and about 12 L / h. z / F. In some embodiments, the pharmaceutical composition provides a CL between about 7 and about 12 L / h. z / F. In some embodiments, the pharmaceutical composition provides a CL between about 8 and about 12 L / h. z / F. In some embodiments, the pharmaceutical composition provides a CL between about 9 and about 12 L / h. z / F. In some embodiments, the pharmaceutical composition provides a CL between about 10 and about 12 L / h. z / F. In some embodiments, the pharmaceutical composition provides a CL between about 11 and about 12 L / h. z / F. In some embodiments, the pharmaceutical composition provides a CL between about 3 and about 7 L / h. z / F. In some embodiments, the pharmaceutical composition provides a CL between about 4 and about 5 L / h. z / F.

[0383] In some embodiments, the pharmaceutical composition provides about 2, about 2.5, about 3, about 3.5, about 4, about 4.5, about 5, about 5.5, about 6, about 6.5, about 7, about 7.5, about 8, about 8.5, about 9, about 9.5, about 10, about 10.5, about 11, about 11.5, or about 12 L / h of CL. z / F. In some embodiments, the pharmaceutical composition provides about 2 L / h of CL. z / F. In some embodiments, the pharmaceutical composition provides about 2.5 L / h of CL.z / F. In some embodiments, the pharmaceutical composition provides about 3 L / h of CL. z / F. In some embodiments, the pharmaceutical composition provides approximately 3.5 L / h of CL. z / F. In some embodiments, the pharmaceutical composition provides about 4 L / h of CL. z / F. In some embodiments, the pharmaceutical composition provides approximately 4.5 L / h of CL. z / F. In some embodiments, the pharmaceutical composition provides about 5 L / h of CL. z / F. In some embodiments, the pharmaceutical composition provides approximately 5.5 L / h of CL. z / F. In some embodiments, the pharmaceutical composition provides about 6 L / h of CL. z / F. In some embodiments, the pharmaceutical composition provides approximately 6.5 L / h of CL. z / F. In some embodiments, the pharmaceutical composition provides about 7 L / h of CL. z / F. In some embodiments, the pharmaceutical composition provides approximately 7.5 L / h of CL. z / F. In some embodiments, the pharmaceutical composition provides about 8 L / h of CL. z / F. In some embodiments, the pharmaceutical composition provides approximately 8.5 L / h of CL. z / F. In some embodiments, the pharmaceutical composition provides approximately 9 L / h of CL. z / F. In some embodiments, the pharmaceutical composition provides approximately 9.5 L / h of CL. z / F. In some embodiments, the pharmaceutical composition provides about 10 L / h of CL. z / F. In some embodiments, the pharmaceutical composition provides about 10.5 L / h of CL. z / F. In some embodiments, the pharmaceutical composition provides about 11 L / h of CL. z / F. In some embodiments, the pharmaceutical composition provides approximately 11.5 L / h of CL. z / F. In some embodiments, the pharmaceutical composition provides about 12 L / h of CL. z / F.

[0384] In some embodiments, the pharmaceutical composition provides a CL between 2 and 12 L / h. z / F. In some embodiments, the pharmaceutical composition provides a CL between 3 and 12 L / h. z / F. In some embodiments, the pharmaceutical composition provides a CL between 4 and 12 L / h. z / F. In some embodiments, the pharmaceutical composition provides a CL between 5 and 12 L / h. z / F. In some embodiments, the pharmaceutical composition provides a CL between 6 and 12 L / h. z / F. In some embodiments, the pharmaceutical composition provides a CL between 7 and 12 L / h. z / F. In some embodiments, the pharmaceutical composition provides a CL between 8 and 12 L / h. z / F. In some embodiments, the pharmaceutical composition provides a CL between 9 and 12 L / h. z / F. In some embodiments, the pharmaceutical composition provides a CL between 10 and 12 L / h. z / F. In some embodiments, the pharmaceutical composition provides a CL between 11 and 12 L / h. z / F. In some embodiments, the pharmaceutical composition provides a CL between 3 and 7 L / h. z / F. In some embodiments, the pharmaceutical composition provides a CL between 4 and 5 L / h. z / F.

[0385] In some embodiments, the pharmaceutical composition provides a CL of 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, or 12 L / h. z / F. In some embodiments, the pharmaceutical composition provides 2 L / h of CL. z / F. In some embodiments, the pharmaceutical composition provides 2.5 L / h of CL. z / F. In some embodiments, the pharmaceutical composition provides 3 L / h of CL. z / F. In some embodiments, the pharmaceutical composition provides 3.5 L / h of CL. z / F. In some embodiments, the pharmaceutical composition provides 4 L / h of CL. z / F. In some embodiments, the pharmaceutical composition provides 4.5 L / h of CL. z / F. In some embodiments, the pharmaceutical composition provides 5 L / h of CL. z / F. In some embodiments, the pharmaceutical composition provides 5.5 L / h of CL. z / F. In some embodiments, the pharmaceutical composition provides 6 L / h of CL. z / F. In some embodiments, the pharmaceutical composition provides 6.5 L / h of CL. z / F. In some embodiments, the pharmaceutical composition provides 7 L / h of CL. z / F. In some embodiments, the pharmaceutical composition provides 7.5 L / h of CL. z / F. In some embodiments, the pharmaceutical composition provides 8 L / h of CL. z / F. In some embodiments, the pharmaceutical composition provides 8.5 L / h of CL. z / F. In some embodiments, the pharmaceutical composition provides 9 L / h of CL. z / F. In some embodiments, the pharmaceutical composition provides 9.5 L / h of CL. z / F. In some embodiments, the pharmaceutical composition provides 10 L / h of CL. z / F. In some embodiments, the pharmaceutical composition provides 10.5 L / h of CL. z / F. In some embodiments, the pharmaceutical composition provides 11 L / h of CL. z / F. In some embodiments, the pharmaceutical composition provides 11.5 L / h of CL. z / F. In some embodiments, the pharmaceutical composition provides 12 L / h of CL. z / F.

[0386] In some embodiments, CL z / F CL is the geometric mean z / F.

[0387] In some embodiments, CL z The range of / F is the geometric mean CL z The range of / F.

[0388] In some embodiments, the pharmaceutical composition provides a volume of about 100 to about 250 L. z / F. In some embodiments, the pharmaceutical composition provides a volume between about 125 and about 250 L. z / F. In some embodiments, the pharmaceutical composition provides a volume between about 150 and about 250 L. z / F. In some embodiments, the pharmaceutical composition provides a volume between about 175 and about 250 L. z / F. In some embodiments, the pharmaceutical composition provides a volume between about 200 and about 250 L. z / F. In some embodiments, the pharmaceutical composition provides a volume between about 130 and about 160 L. z / F. In some embodiments, the pharmaceutical composition provides a volume between about 140 and about 150 L. z / F.

[0389] In some embodiments, the pharmaceutical composition provides a volume of about 100, about 110, about 120, about 130, about 140, about 150, about 160, about 170, about 180, about 190, about 200, about 210, about 220, about 230, about 240, or about 250 L. z / F. In some embodiments, the pharmaceutical composition provides about 100 L of V. z / F. In some embodiments, the pharmaceutical composition provides about 110 L of V. z / F. In some embodiments, the pharmaceutical composition provides about 120 L of V. z / F. In some embodiments, the pharmaceutical composition provides about 130 L of V. z / F. In some embodiments, the pharmaceutical composition provides about 140 L of V. z / F. In some embodiments, the pharmaceutical composition provides about 150 L of V. z / F. In some embodiments, the pharmaceutical composition provides about 160 L of V. z / F. In some embodiments, the pharmaceutical composition provides approximately 170 L of V. z / F. In some embodiments, the pharmaceutical composition provides about 180 L of V. z / F. In some embodiments, the pharmaceutical composition provides approximately 190 L of V. z / F. In some embodiments, the pharmaceutical composition provides about 200 L of V. z / F. In some embodiments, the pharmaceutical composition provides about 210 L of V. z / F. In some embodiments, the pharmaceutical composition provides about 220 L of V. z / F. In some embodiments, the pharmaceutical composition provides about 230 L of V. z / F. In some embodiments, the pharmaceutical composition provides about 240 L of V. z / F. In some embodiments, the pharmaceutical composition provides about 250 L of V. z / F.

[0390] In some embodiments, the pharmaceutical composition provides a volume between 100 and 250 L. z / F. In some embodiments, the pharmaceutical composition provides a volume between 125 and 250 L. z / F. In some embodiments, the pharmaceutical composition provides a volume between 150 and 250 L. z / F. In some embodiments, the pharmaceutical composition provides a volume between 175 and 250 L. z / F. In some embodiments, the pharmaceutical composition provides a volume between 200 and 250 L. z / F. In some embodiments, the pharmaceutical composition provides a volume between 130 and 160 L. z / F. In some embodiments, the pharmaceutical composition provides a volume between 140 and 150 L. z / F.

[0391] In some embodiments, the pharmaceutical composition provides a volume of 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 L. z / F. In some embodiments, the pharmaceutical composition provides 100 L of V. z / F. In some embodiments, the pharmaceutical composition provides 110 L of V. z / F. In some embodiments, the pharmaceutical composition provides 120 L of V. z / F. In some embodiments, the pharmaceutical composition provides 130 L of V. z / F. In some embodiments, the pharmaceutical composition provides 140 L of V. z / F. In some embodiments, the pharmaceutical composition provides 150 L of V. z / F. In some embodiments, the pharmaceutical composition provides 160L of V. z / F. In some embodiments, the pharmaceutical composition provides 170 L of V. z / F. In some embodiments, the pharmaceutical composition provides 180 L of V. z / F. In some embodiments, the pharmaceutical composition provides 190 L of V. z / F. In some embodiments, the pharmaceutical composition provides 200 L of V. z / F. In some embodiments, the pharmaceutical composition provides 210 L of V. z / F. In some embodiments, the pharmaceutical composition provides 220 L of v z / F. In some embodiments, the pharmaceutical composition provides 230 L of V. z / F. In some embodiments, the pharmaceutical composition provides 240 L of V. z / F. In some embodiments, the pharmaceutical composition provides 250 L of V. z / F.

[0392] In some embodiments, V z / F is the geometric mean CL z / F.

[0393] In some embodiments, V z The range of / F is the geometric mean V z The range of / F.

[0394] In some embodiments, the pharmaceutical composition provides about 70% to about 100% bioavailability. In some embodiments, the pharmaceutical composition provides about 80% to about 100% bioavailability. In some embodiments, the pharmaceutical composition provides about 70%, about 71%, about 72%, about 73%, about 74%, about 75%, about 76%, about 77%, about 78%, about 79%, about 80%, about 81%, about 82%, about 83%, about 84%, about 85%, about 86%, about 87%, about 88%, about 89%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, or about 100% bioavailability. In some embodiments, the pharmaceutical composition provides about 85% to about 100% bioavailability. In some embodiments, the pharmaceutical composition provides about 90% to about 100% bioavailability. In some embodiments, the pharmaceutical composition provides about 95% to about 100% bioavailability. In some embodiments, the pharmaceutical composition provides about 100% bioavailability.

[0395] In some embodiments, the pharmaceutical composition provides 70 to 100% bioavailability. In some embodiments, the pharmaceutical composition provides 80 to 100% bioavailability. In some embodiments, the pharmaceutical composition provides 90 to 100% bioavailability. In some embodiments, the pharmaceutical composition provides 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% bioavailability. In some embodiments, the pharmaceutical composition provides 85 to 100% bioavailability. In some embodiments, the pharmaceutical composition provides 90 to 100% bioavailability. In some embodiments, the pharmaceutical composition provides 95 to 100% bioavailability. In some embodiments, the pharmaceutical composition provides 100% bioavailability.

[0396] In some embodiments, the pharmaceutical composition provides a Cg concentration between about 8 and about 25 ng / mL. max AUC between approximately 100 and approximately 450 ng*h / mL last ; and t between 20 and 200 hours last .

[0397] In some embodiments, the pharmaceutical composition provides a Cg concentration between about 8 and about 25 ng / mL. max AUC between approximately 100 and approximately 450 ng*h / mL last ; t between 20 and 200 hours last ; and between approximately 2 and approximately 8 hours t max .

[0398] In some embodiments, the pharmaceutical composition provides a Cg concentration between about 8 and about 25 ng / mL. max AUC between approximately 100 and approximately 450 ng*h / mL last ; t between 20 and 200 hours last ; and V between approximately 100 and approximately 250 L z / F.

[0399] In some embodiments, the pharmaceutical composition provides a Cg concentration between about 8 and about 25 ng / mL. max AUC between approximately 100 and approximately 450 ng*h / mL last ; t between 20 and 200 hours last ; and CL between approximately 2 and approximately 12 L / h z / F.

[0400] In some embodiments, the pharmaceutical composition provides a Cg concentration between about 8 and about 25 ng / mL. max AUC between approximately 100 and approximately 450 ng*h / mL last ; t between 20 and 200 hours last ; and bioavailability between approximately 70% and approximately 100%.

[0401] In some embodiments, the pharmaceutical composition provides a Cg concentration between about 8 and about 25 ng / mL. max AUC between approximately 100 and approximately 450 ng*h / mL last ; t between 20 and 200 hours last Between approximately 2 and approximately 8 hours max ; and V between approximately 100 and approximately 250 L z / F.

[0402] In some embodiments, the pharmaceutical composition provides a Cg concentration between about 8 and about 25 ng / mL. max AUC between approximately 100 and approximately 450 ng*h / mL last ; t between 20 and 200 hours last Between approximately 2 and approximately 8 hours max CL between approximately 2 and approximately 12 L / h z / F.

[0403] In some embodiments, the pharmaceutical composition provides a Cg concentration between about 8 and about 25 ng / mL. max AUC between approximately 100 and approximately 450 ng*h / mL last ; t between 20 and 200 hours last Between approximately 2 and approximately 8 hours maxV between approximately 100 and approximately 250 L z / F; and CL between approximately 2 and approximately 12 L / h z / F.

[0404] In some embodiments, the pharmaceutical composition provides a Cg between about 10 and about 18 ng / mL. max AUC between approximately 150 and approximately 250 ng*h / mL last ; and t between 50 and 70 hours last .

[0405] In some embodiments, the pharmaceutical composition provides a Cg between about 10 and about 18 ng / mL. max AUC between approximately 150 and approximately 250 ng*h / mL last ; t between 50 and 70 hours last ; and between approximately 3 and 5 hours t max .

[0406] In some embodiments, the pharmaceutical composition provides a Cg between about 10 and about 18 ng / mL. max AUC between approximately 150 and approximately 250 ng*h / mL last ; t between 50 and 70 hours last ; and V between approximately 140 and approximately 160 L z / F.

[0407] In some embodiments, the pharmaceutical composition provides a Cg between about 10 and about 18 ng / mL. max AUC between approximately 150 and approximately 250 ng*h / mL last ; t between 50 and 70 hours last ; and CL between approximately 3 and approximately 6 L / h z / F.

[0408] In some embodiments, the pharmaceutical composition provides a Cg between about 10 and about 18 ng / mL. max AUC between approximately 150 and approximately 250 ng*h / mL last ; t between 50 and 70 hours last ; and bioavailability between approximately 70% and approximately 100%.

[0409] In some embodiments, the pharmaceutical composition provides a Cg between about 10 and about 18 ng / mL. max AUC between approximately 150 and approximately 250 ng*h / mL last ; t between 50 and 70 hours last Between approximately 2 and approximately 8 hours max; and V between approximately 140 and approximately 160 L z / F.

[0410] In some embodiments, the pharmaceutical composition provides a Cg between about 10 and about 18 ng / mL. max AUC between approximately 150 and approximately 250 ng*h / mL last ; t between 70 and 700 hours last Between approximately 2 and approximately 8 hours max CL between approximately 3 and approximately 5 L / h z / F.

[0411] In some embodiments, the pharmaceutical composition provides a Cg between about 10 and about 18 ng / mL. max AUC between approximately 150 and approximately 250 ng*h / mL last ; t between 50 and 70 hours last Between approximately 2 and approximately 8 hours max V between approximately 140 and approximately 160 L z / F; and CL between approximately 3 and approximately 5 L / h z / F.

[0412] In some embodiments, the pharmaceutical composition provides a Cg between about 15 and about 18 ng / mL. max AUC between approximately 200 and approximately 250 ng*h / mL last ; and t between 50 and 70 hours last .

[0413] In some embodiments, the pharmaceutical composition provides a Cg between about 15 and about 18 ng / mL. max AUC between approximately 200 and approximately 250 ng*h / mL last ; t between 50 and 70 hours last ; and between approximately 3 and 5 hours t max .

[0414] In some embodiments, the pharmaceutical composition provides a Cg between about 15 and about 18 ng / mL. max AUC between approximately 200 and approximately 250 ng*h / mL last ; t between 50 and 70 hours last ; and V between approximately 140 and approximately 160 L z / F.

[0415] In some embodiments, the pharmaceutical composition provides a Cg between about 15 and about 18 ng / mL. max AUC between approximately 200 and approximately 250 ng*h / mLlast ; t between 50 and 70 hours last ; and CL between approximately 3 and approximately 6 L / h z / F.

[0416] In some embodiments, the pharmaceutical composition provides a Cg between about 15 and about 18 ng / mL. max AUC between approximately 200 and approximately 250 ng*h / mL last ; t between 50 and 70 hours last ; and bioavailability between approximately 70% and approximately 100%.

[0417] In some embodiments, the pharmaceutical composition provides a Cg between about 15 and about 18 ng / mL. max AUC between approximately 200 and approximately 250 ng*h / mL last ; t between 50 and 70 hours last Between approximately 2 and approximately 8 hours max ; and V between approximately 140 and approximately 160 L z / F.

[0418] In some embodiments, the pharmaceutical composition provides a Cg between about 15 and about 18 ng / mL. max AUC between approximately 200 and approximately 250 ng*h / mL last ; t between 70 and 700 hours last Between approximately 2 and approximately 8 hours max CL between approximately 3 and approximately 5 L / h z / F.

[0419] In some embodiments, the pharmaceutical composition provides a Cg between about 15 and about 18 ng / mL. max AUC between approximately 200 and approximately 250 ng*h / mL last ; t between 50 and 70 hours last Between approximately 2 and approximately 8 hours max V between approximately 140 and approximately 160 L z / F; and CL between approximately 3 and approximately 5 L / h z / F.

[0420] In some embodiments, the pharmaceutical composition provides a Cg concentration between about 8 and about 25 ng / mL. max ; and AUC between approximately 100 and approximately 500 ng*h / mL inf .

[0421] In some embodiments, the pharmaceutical composition provides a Cg concentration between about 8 and about 25 ng / mL. maxAUC between approximately 100 and approximately 500 ng*h / mL inf ; and between approximately 2 and approximately 8 hours t max .

[0422] In some embodiments, the pharmaceutical composition provides a Cg concentration between about 8 and about 25 ng / mL. max AUC between approximately 100 and approximately 500 ng*h / mL inf ; and V between approximately 100 and approximately 250 L z / F.

[0423] In some embodiments, the pharmaceutical composition provides a Cg concentration between about 8 and about 25 ng / mL. max AUC between approximately 100 and approximately 500 ng*h / mL inf ; and CL between approximately 2 and approximately 12 L / h z / F.

[0424] In some embodiments, the pharmaceutical composition provides a Cg concentration between about 8 and about 25 ng / mL. max AUC between approximately 100 and approximately 500 ng*h / mL inf ; and bioavailability between approximately 70% and approximately 100%.

[0425] In some embodiments, the pharmaceutical composition provides a Cg concentration between about 8 and about 25 ng / mL. max AUC between approximately 100 and approximately 500 ng*h / mL inf Between approximately 2 and approximately 8 hours max ; and V between approximately 100 and approximately 250 L z / F.

[0426] In some embodiments, the pharmaceutical composition provides a Cg concentration between about 8 and about 25 ng / mL. max AUC between approximately 100 and approximately 500 ng*h / mL inf Between approximately 2 and approximately 8 hours max CL between approximately 2 and approximately 12 L / h z / F.

[0427] In some embodiments, the pharmaceutical composition provides a Cg concentration between about 8 and about 25 ng / mL. max AUC between approximately 100 and approximately 500 ng*h / mL inf Between approximately 2 and approximately 8 hours max V between approximately 100 and approximately 250 L z / F; and CL between approximately 2 and approximately 12 L / h z / F.

[0428] In some embodiments, the pharmaceutical composition provides a Cg between about 10 and about 18 ng / mL. max AUC between approximately 150 and approximately 300 ng*h / mL inf ; and t between 50 and 70 hours last .

[0429] In some embodiments, the pharmaceutical composition provides a Cg between about 10 and about 18 ng / mL. max AUC between approximately 150 and approximately 300 ng*h / mL inf ; and between approximately 3 and 5 hours t max .

[0430] In some embodiments, the pharmaceutical composition provides a Cg between about 10 and about 18 ng / mL. max AUC between approximately 150 and approximately 300 ng*h / mL inf ; and V between approximately 140 and approximately 160 L z / F.

[0431] In some embodiments, the pharmaceutical composition provides a Cg between about 10 and about 18 ng / mL. max AUC between approximately 150 and approximately 300 ng*h / mL inf ; and CL between approximately 3 and approximately 6 L / h z / F.

[0432] In some embodiments, the pharmaceutical composition provides a Cg between about 10 and about 18 ng / mL. max AUC between approximately 150 and approximately 300 ng*h / mL inf ; and bioavailability between approximately 70% and approximately 100%.

[0433] In some embodiments, the pharmaceutical composition provides a Cg between about 10 and about 18 ng / mL. max AUC between approximately 150 and approximately 300 ng*h / mL inf Between approximately 3 and 5 hours max ; and V between approximately 140 and approximately 160 L z / F.

[0434] In some embodiments, the pharmaceutical composition provides a Cg between about 10 and about 18 ng / mL. max AUC between approximately 150 and approximately 300 ng*h / mL inf Between approximately 3 and 5 hours max CL between approximately 3 and approximately 6 L / h z / F.

[0435] In some embodiments, the pharmaceutical composition provides a Cg between about 10 and about 18 ng / mL. max AUC between approximately 150 and approximately 300 ng*h / mL inf Between approximately 3 and 5 hours max V between approximately 140 and approximately 160 L z / F; and CL between approximately 3 and approximately 6 L / h z / F.

[0436] In some embodiments, the pharmaceutical composition provides a Cg between about 15 and about 18 ng / mL. max AUC between approximately 200 and 300 ng*h / mL inf ; and t between 50 and 70 hours last .

[0437] In some embodiments, the pharmaceutical composition provides a Cg between about 15 and about 18 ng / mL. max AUC between approximately 200 and 300 ng*h / mL inf ; and between approximately 3 and 5 hours t max .

[0438] In some embodiments, the pharmaceutical composition provides a Cg between about 15 and about 18 ng / mL. max AUC between approximately 200 and 300 ng*h / mL inf ; and V between approximately 140 and approximately 160 L z / F.

[0439] In some embodiments, the pharmaceutical composition provides a Cg between about 15 and about 18 ng / mL. max AUC between approximately 200 and 300 ng*h / mL inf ; and CL between approximately 3 and approximately 6 L / h z / F.

[0440] In some embodiments, the pharmaceutical composition provides a Cg between about 15 and about 18 ng / mL. max AUC between approximately 200 and 300 ng*h / mL inf ; and bioavailability between approximately 70% and approximately 100%.

[0441] In some embodiments, the pharmaceutical composition provides a Cg between about 15 and about 18 ng / mL. max AUC between approximately 200 and 300 ng*h / mL inf Between approximately 3 and 5 hoursmax ; and V between approximately 140 and approximately 160 L z / F.

[0442] In some embodiments, the pharmaceutical composition provides a Cg between about 15 and about 18 ng / mL. max AUC between approximately 200 and 300 ng*h / mL inf Between approximately 3 and 5 hours max CL between approximately 3 and approximately 6 L / h z / F.

[0443] In some embodiments, the pharmaceutical composition provides a Cg between about 15 and about 18 ng / mL. max AUC between approximately 200 and 300 ng*h / mL inf Between approximately 3 and 5 hours max V between approximately 140 and approximately 160 L z / F; and CL between approximately 3 and approximately 6 L / h z / F.

[0444] In some embodiments, the pharmaceutical composition provides a C concentration between 8 and 25 ng / mL. max AUC between 100 and 450 ng*h / mL last ; and t between 20 and 200 hours last .

[0445] In some embodiments, the pharmaceutical composition provides a C concentration between 8 and 25 ng / mL. max AUC between 100 and 450 ng*h / mL last ; t between 20 and 200 hours last ; and t between 2 and 8 hours max .

[0446] In some embodiments, the pharmaceutical composition provides a C concentration between 8 and 25 ng / mL. max AUC between 100 and 450 ng*h / mL last ; t between 20 and 200 hours last ; and V between 100 and 250L z / F.

[0447] In some embodiments, the pharmaceutical composition provides a C concentration between 8 and 25 ng / mL. max AUC between 100 and 450 ng*h / mL last ; t between 20 and 200 hours last ; and CL between 2 and 12 L / hz / F.

[0448] In some embodiments, the pharmaceutical composition provides a C concentration between 8 and 25 ng / mL. max AUC between 100 and 450 ng*h / mL last ; t between 20 and 200 hours last ; and bioavailability between 70% and 100%.

[0449] In some embodiments, the pharmaceutical composition provides a C concentration between 8 and 25 ng / mL. max AUC between 100 and 450 ng*h / mL last ; t between 20 and 200 hours last ; t between 2 and 8 hours max ; and V between 100 and 250L z / F.

[0450] In some embodiments, the pharmaceutical composition provides a C concentration between 8 and 25 ng / mL. max AUC between 100 and 450 ng*h / mL last ; t between 20 and 200 hours last ; t between 2 and 8 hours max CL between 2 and 12 L / h z / F.

[0451] In some embodiments, the pharmaceutical composition provides a C concentration between 8 and 25 ng / mL. max AUC between 100 and 450 ng*h / mL last ; t between 20 and 200 hours last ; t between 2 and 8 hours max V between 100 and 250L z / F; and CL between 2 and 12 L / h z / F.

[0452] In some embodiments, the pharmaceutical composition provides a C10 to 18 ng / mL. max AUC between 150 and 250 ng*h / mL last ; and t between 50 and 70 hours last .

[0453] In some embodiments, the pharmaceutical composition provides a C10 to 18 ng / mL. max AUC between 150 and 250 ng*h / mL last ; t between 50 and 70 hours last; and t between 3 and 5 hours max .

[0454] In some embodiments, the pharmaceutical composition provides a C10 to 18 ng / mL. max AUC between 150 and 250 ng*h / mL last ; t between 50 and 70 hours last ; and V between 140 and 160 L z / F.

[0455] In some embodiments, the pharmaceutical composition provides a C10 to 18 ng / mL. max AUC between 150 and 250 ng*h / mL last ; t between 50 and 70 hours last ; and CL between 3 and 6 L / h z / F.

[0456] In some embodiments, the pharmaceutical composition provides a C10 to 18 ng / mL. max AUC between 150 and 250 ng*h / mL last ; t between 50 and 70 hours last ; and bioavailability between 70% and 100%.

[0457] In some embodiments, the pharmaceutical composition provides a C10 to 18 ng / mL. max AUC between 150 and 250 ng*h / mL last ; t between 50 and 70 hours last ; t between 2 and 8 hours max ; and V between 140 and 160 L z / F.

[0458] In some embodiments, the pharmaceutical composition provides a C10 to 18 ng / mL. max AUC between 150 and 250 ng*h / mL last ; t between 70 and 700 hours last ; t between 2 and 8 hours max CL between 3 and 5 L / h z / F.

[0459] In some embodiments, the pharmaceutical composition provides a C10 to 18 ng / mL. max AUC between 150 and 250 ng*h / mL last ; t between 50 and 70 hours last ; t between 2 and 8 hoursmax V between 140 and 160 L z / F; and CL between 3 and 5 L / h z / F.

[0460] In some embodiments, the pharmaceutical composition provides a C15 to 18 ng / mL. max AUC between 200 and 250 ng*h / mL last ; and t between 50 and 70 hours last .

[0461] In some embodiments, the pharmaceutical composition provides a C15 to 18 ng / mL. max AUC between 200 and 250 ng*h / mL last ; t between 50 and 70 hours last ; and t between 3 and 5 hours max .

[0462] In some embodiments, the pharmaceutical composition provides a C15 to 18 ng / mL. max AUC between 200 and 250 ng*h / mL last ; t between 50 and 70 hours last ; and V between 140 and 160 L z / F.

[0463] In some embodiments, the pharmaceutical composition provides a C15 to 18 ng / mL. max AUC between 200 and 250 ng*h / mL last ; t between 50 and 70 hours last ; and CL between 3 and 6 L / h z / F.

[0464] In some embodiments, the pharmaceutical composition provides a C15 to 18 ng / mL. max AUC between 200 and 250 ng*h / mL last ; t between 50 and 70 hours last ; and bioavailability between 70% and 100%.

[0465] In some embodiments, the pharmaceutical composition provides a C15 to 18 ng / mL. max AUC between 200 and 250 ng*h / mL last ; t between 50 and 70 hours last ; t between 2 and 8 hours max ; and V between 140 and 160 Lz / F.

[0466] In some embodiments, the pharmaceutical composition provides a C15 to 18 ng / mL. max AUC between 200 and 250 ng*h / mL last ; t between 70 and 700 hours last ; t between 2 and 8 hours max CL between 3 and 5 L / h z / F.

[0467] In some embodiments, the pharmaceutical composition provides a C15 to 18 ng / mL. max AUC between 200 and 250 ng*h / mL last ; t between 50 and 70 hours last ; t between 2 and 8 hours max V between 140 and 160 L z / F; and CL between 3 and 5 L / h z / F.

[0468] In some embodiments, the pharmaceutical composition provides a C concentration between 8 and 25 ng / mL. max ; and the AUC between 100 and 500 ng*h / mL inf .

[0469] In some embodiments, the pharmaceutical composition provides a C concentration between 8 and 25 ng / mL. max AUC between 100 and 500 ng*h / mL inf ; and t between 2 and 8 hours max .

[0470] In some embodiments, the pharmaceutical composition provides a C concentration between 8 and 25 ng / mL. max AUC between 100 and 500 ng*h / mL inf ; and V between 100 and 250L z / F.

[0471] In some embodiments, the pharmaceutical composition provides a C concentration between 8 and 25 ng / mL. max AUC between 100 and 500 ng*h / mL inf ; and CL between 2 and 12 L / h z / F.

[0472] In some embodiments, the pharmaceutical composition provides a C concentration between 8 and 25 ng / mL. maxAUC between 100 and 500 ng*h / mL inf ; and bioavailability between 70% and 100%.

[0473] In some embodiments, the pharmaceutical composition provides a C concentration between 8 and 25 ng / mL. max AUC between 100 and 500 ng*h / mL inf ; t between 2 and 8 hours max ; and V between 100 and 250L z / F.

[0474] In some embodiments, the pharmaceutical composition provides a C concentration between 8 and 25 ng / mL. max AUC between 100 and 500 ng*h / mL inf ; t between 2 and 8 hours max CL between 2 and 12 L / h z / F.

[0475] In some embodiments, the pharmaceutical composition provides a C concentration between 8 and 25 ng / mL. max AUC between 100 and 500 ng*h / mL inf ; t between 2 and 8 hours max V between 100 and 250L z / F; and CL between 2 and 12 L / h z / F.

[0476] In some embodiments, the pharmaceutical composition provides a C10 to 18 ng / mL. max AUC between 150 and 300 ng*h / mL inf ; and t between 50 and 70 hours last .

[0477] In some embodiments, the pharmaceutical composition provides a C10 to 18 ng / mL. max AUC between 150 and 300 ng*h / mL inf ; and t between 3 and 5 hours max .

[0478] In some embodiments, the pharmaceutical composition provides a C10 to 18 ng / mL. max AUC between 150 and 300 ng*h / mL inf ; and V between 140 and 160 L z / F.

[0479] In some embodiments, the pharmaceutical composition provides a C10 to 18 ng / mL. max AUC between 150 and 300 ng*h / mL inf ; and CL between 3 and 6 L / h z / F.

[0480] In some embodiments, the pharmaceutical composition provides a C10 to 18 ng / mL. max AUC between 150 and 300 ng*h / mL inf ; and bioavailability between 70% and 100%.

[0481] In some embodiments, the pharmaceutical composition provides a C10 to 18 ng / mL. max AUC between 150 and 300 ng*h / mL inf ; t between 3 and 5 hours max ; and V between 140 and 160 L z / F.

[0482] In some embodiments, the pharmaceutical composition provides a C10 to 18 ng / mL. max AUC between 150 and 300 ng*h / mL inf ; t between 3 and 5 hours max CL between 3 and 6 L / h z / F.

[0483] In some embodiments, the pharmaceutical composition provides a C10 to 18 ng / mL. max AUC between 150 and 300 ng*h / mL inf ; t between 3 and 5 hours max V between 140 and 160 L z / F; and CL between 3 and 6 L / h z / F.

[0484] In some embodiments, the pharmaceutical composition provides a C15 to 18 ng / mL. max AUC between 200 and 300 ng*h / mL inf ; and t between 50 and 70 hours last .

[0485] In some embodiments, the pharmaceutical composition provides a C15 to 18 ng / mL. max AUC between 200 and 300 ng*h / mL inf ; and t between 3 and 5 hours max .

[0486] In some embodiments, the pharmaceutical composition provides a C15 to 18 ng / mL. max AUC between 200 and 300 ng*h / mL inf ; and V between 140 and 160 L z / F.

[0487] In some embodiments, the pharmaceutical composition provides a C15 to 18 ng / mL. max AUC between 200 and 300 ng*h / mL inf ; and CL between 3 and 6 L / h z / F.

[0488] In some embodiments, the pharmaceutical composition provides a C15 to 18 ng / mL. max AUC between 200 and 300 ng*h / mL inf ; and bioavailability between 70% and 100%.

[0489] In some embodiments, the pharmaceutical composition provides a C15 to 18 ng / mL. max AUC between 200 and 300 ng*h / mL inf ; t between 3 and 5 hours max ; and V between 140 and 160 L z / F.

[0490] In some embodiments, the pharmaceutical composition provides a C15 to 18 ng / mL. max AUC between 200 and 300 ng*h / mL inf ; t between 3 and 5 hours max CL between 3 and 6 L / h z / F.

[0491] In some embodiments, the pharmaceutical composition provides a C15 to 18 ng / mL. max AUC between 200 and 300 ng*h / mL inf ; t between 3 and 5 hours max V between 140 and 160 L z / F; and CLz / F between 3 and 6 L / h.

[0492] In some embodiments, the pharmaceutical compositions of this disclosure exhibit PK characteristics substantially similar when administered on an empty stomach to those when administered after a meal / food. In some embodiments, the pharmaceutical compositions of this disclosure may exhibit PK characteristics consistent with those expected for once-daily administration. In some embodiments, the PK characteristics exhibited by the pharmaceutical compositions are consistent with those expected for administration of a daily maintenance dose following a loading dose.

[0493] In some embodiments, the pharmaceutical compositions providing the PK parameters disclosed herein can be administered via a variety of routes, including oral, parenteral, rectal, transdermal, intradermal, intrathecal, subcutaneous, intravenous, intramuscular, and intranasal administration. In some embodiments, the pharmaceutical compositions providing the PK parameters disclosed herein can be in any dosage form (e.g., solids (such as pills, tablets, capsules, etc.), liquids, liposomes (such as gelatin capsules), prefilled liquid compositions, ampoules of a predetermined amount, or syringes).

[0494] In some embodiments, the pharmaceutical composition providing PK parameters comprises compound I or a pharmaceutically acceptable salt thereof; and one or more glycerides, wherein the glycerides comprise about 30% to about 100% w / w monoglycerides.

[0495] How to use

[0496] Compound I, as described herein, is a positive allosteric modulator of NMDA receptor function and is therefore useful for the treatment and prevention of, for example, identified CNS-related conditions in subjects.

[0497] On the one hand, this disclosure provides a method for treating a subject with a disease, disorder, or condition requiring positive allosteric NMDA receptor modulation, the method comprising administering to the subject an effective amount of a pharmaceutical composition as disclosed herein.

[0498] In some embodiments, this disclosure provides a method for treating a subject with CNS-related conditions, the method comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition as disclosed herein.

[0499] In some embodiments, this disclosure provides a method for preventing a disease, disorder, or condition in a subject that requires positive allosteric NMDA receptor modulation, the method comprising administering to the subject an effective amount of a pharmaceutical composition as disclosed herein.

[0500] In some embodiments, this disclosure provides a pharmaceutical composition as disclosed herein for treating a subject with a disease, disorder, or condition requiring positive allosteric NMDA receptor modulation.

[0501] In some embodiments, this disclosure provides a pharmaceutical composition as disclosed herein for the prevention of diseases, disorders, or conditions in subjects that require positive NMDA receptor regulation.

[0502] In some embodiments, this disclosure provides the use of a pharmaceutical composition as disclosed herein for manufacturing a medicament for treating a disease, disorder, or condition in a subject that requires positive allosteric NMDA receptor modulation.

[0503] In some embodiments, this disclosure provides the use of a pharmaceutical composition as disclosed herein for the manufacture of a medicament for the prevention of diseases, disorders, or conditions in subjects that require positive allosteric NMDA receptor modulation.

[0504] In some embodiments, this disclosure provides a method for treating a disease, disorder, or condition in a subject that requires positive allosteric NMDA receptor modulation, wherein, after administration of the pharmaceutical composition to the subject, the pharmaceutical composition provides one or more of the following pharmacokinetic parameters: a) Cg between about 8 and about 25 ng / mL max b) AUC between approximately 100 and approximately 450 ng*h / mL last c) AUC between approximately 100 and approximately 500 ng*h / mL inf ;d) t between approximately 2 and approximately 8 hours max e) V between approximately 100 and approximately 250 L z / F;f) CL between approximately 2 and approximately 12 L / h z / F; or g) bioavailability between approximately 70 and approximately 100%.

[0505] In some embodiments, CNS-related diseases are selected from the group consisting of Huntington's disease, Parkinson's disease, and Alzheimer's disease.

[0506] Parkinson's disease

[0507] Parkinson's disease affects the dopamine-producing nerve cells in the brain. Symptoms include rigidity, tremor, and changes in speech and gait. Parkinson's syndrome is characterized by tremor, bradykinesia, rigidity, and postural instability. Parkinson's syndrome has the same symptoms as Parkinson's disease, but it is a symptom complex rather than a progressive neurodegenerative disease.

[0508] On the one hand, this disclosure provides a method for treating or preventing Parkinson's disease in a subject, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition described herein.

[0509] In some embodiments, this disclosure provides a method for treating Parkinson's disease in a subject, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition described herein. In some embodiments, this disclosure provides a method for preventing Parkinson's disease in a subject, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition described herein.

[0510] In some embodiments, this disclosure provides a method for treating cognitive impairment in a subject with Parkinson's disease, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition described herein.

[0511] In some embodiments, this disclosure provides a method for treating mild cognitive impairment (MCI) associated with Parkinson's disease in a subject, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition described herein.

[0512] In some embodiments, this disclosure provides a method for improving executive function in a subject suffering from mild cognitive impairment (MCI) associated with Parkinson's disease, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition described herein.

[0513] In some embodiments, this disclosure provides a method for improving the working memory of a subject suffering from mild cognitive impairment (MCI) associated with Parkinson's disease, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition described herein.

[0514] In some embodiments, this disclosure provides a method for improving learning in a subject suffering from mild cognitive impairment (MCI) associated with Parkinson's disease, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition described herein.

[0515] In some embodiments, this disclosure provides a method for improving the learning and working memory of a subject suffering from mild cognitive impairment (MCI) associated with Parkinson's disease, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition described herein.

[0516] In some embodiments, this disclosure provides a method for improving cognition in a subject suffering from Parkinson's disease, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition described herein.

[0517] In some embodiments, this disclosure provides a method for slowing cognitive decline in a subject suffering from Parkinson's disease, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition described herein.

[0518] On one hand, this disclosure provides a pharmaceutical composition as described herein for treating or preventing Parkinson's disease in a subject. In some embodiments, this disclosure provides a pharmaceutical composition as described herein for treating Parkinson's disease in a subject. In some embodiments, this disclosure provides a pharmaceutical composition as described herein for preventing Parkinson's disease in a subject.

[0519] In some embodiments, this disclosure provides a pharmaceutical composition as disclosed herein for treating cognitive impairment in a subject with Parkinson's disease.

[0520] In some embodiments, this disclosure provides a pharmaceutical composition as disclosed herein for treating mild cognitive impairment (MCI) associated with Parkinson's disease in a subject.

[0521] In some embodiments, this disclosure provides a pharmaceutical composition as disclosed herein for improving executive function in a subject with mild cognitive impairment (MCI) associated with Parkinson's disease.

[0522] In some embodiments, this disclosure provides a pharmaceutical composition as disclosed herein for improving working memory in subjects with mild cognitive impairment (MCI) associated with Parkinson's disease.

[0523] In some embodiments, this disclosure provides a pharmaceutical composition as disclosed herein for improving learning in subjects with mild cognitive impairment (MCI) associated with Parkinson's disease.

[0524] In some embodiments, this disclosure provides a pharmaceutical composition as disclosed herein for improving learning and working memory in subjects with mild cognitive impairment (MCI) associated with Parkinson's disease.

[0525] In some embodiments, this disclosure provides a pharmaceutical composition as disclosed herein for improving cognition in a subject with Parkinson's disease.

[0526] In some embodiments, this disclosure provides a pharmaceutical composition as disclosed herein for slowing cognitive decline in a subject with Parkinson's disease.

[0527] On one hand, this disclosure provides the use of a pharmaceutical composition as disclosed herein in the manufacture of a medicament for treating or preventing Parkinson's disease in a subject. In some embodiments, this disclosure provides the use of a pharmaceutical composition as disclosed herein in the manufacture of a medicament for treating Parkinson's disease in a subject. In some embodiments, this disclosure provides the use of a pharmaceutical composition as disclosed herein in the manufacture of a medicament for preventing Parkinson's disease in a subject.

[0528] In some embodiments, this disclosure provides a use of the pharmaceutical composition disclosed herein for manufacturing a medicament for treating cognitive impairment in a subject with Parkinson's disease.

[0529] In some embodiments, this disclosure provides the use of a pharmaceutical composition as disclosed herein for manufacturing a medicament for treating mild cognitive impairment (MCI) associated with Parkinson's disease in a subject.

[0530] In some embodiments, this disclosure provides a use of a pharmaceutical composition as disclosed herein for manufacturing a medicament for improving executive function in a subject suffering from mild cognitive impairment (MCI) associated with Parkinson's disease.

[0531] In some embodiments, this disclosure provides a use of a pharmaceutical composition as disclosed herein for manufacturing a medicament for improving working memory in a subject suffering from mild cognitive impairment (MCI) associated with Parkinson's disease.

[0532] In some embodiments, this disclosure provides a use of a pharmaceutical composition as disclosed herein for manufacturing a medicament for improving learning in a subject suffering from mild cognitive impairment (MCI) associated with Parkinson's disease.

[0533] In some embodiments, this disclosure provides the use of a pharmaceutical composition as disclosed herein for manufacturing a medicament for improving learning and working memory in a subject suffering from mild cognitive impairment (MCI) associated with Parkinson's disease.

[0534] In some embodiments, this disclosure provides a use of a pharmaceutical composition as disclosed herein for manufacturing a medicament for improving cognition in a subject suffering from Parkinson's disease.

[0535] In some embodiments, this disclosure provides a use of a pharmaceutical composition as disclosed herein for manufacturing a medicament for slowing cognitive decline in a subject with Parkinson's disease.

[0536] In some embodiments, the methods disclosed herein include administering the pharmaceutical composition described herein in combination with other therapeutic agents for the treatment of Parkinson's disease.

[0537] Huntington's disease

[0538] Huntington's disease is a genetic disorder that causes nerve cells in the brain to atrophy. Symptoms include uncontrolled movement, clumsiness, and balance problems. Huntington's disease can also impair walking, speaking, and swallowing.

[0539] On the one hand, this disclosure provides a method for treating or preventing Huntington's disease in a subject, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition described herein.

[0540] In some embodiments, this disclosure provides a method for treating Huntington's disease in a subject, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition described herein. In some embodiments, this disclosure provides a method for preventing Huntington's disease in a subject, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition described herein.

[0541] In some embodiments, this disclosure provides a method for treating cognitive impairment in a subject suffering from Huntington's disease, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition described herein.

[0542] In some embodiments, this disclosure provides a method for treating mild cognitive impairment (MCI) associated with Huntington's disease in a subject, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition described herein.

[0543] In some embodiments, this disclosure provides a method for improving executive function in a subject suffering from mild cognitive impairment (MCI) associated with Huntington's disease, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition described herein.

[0544] In some embodiments, this disclosure provides a method for improving the working memory of a subject suffering from mild cognitive impairment (MCI) associated with Huntington's disease, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition described herein.

[0545] In some embodiments, this disclosure provides a method for improving learning in a subject suffering from mild cognitive impairment (MCI) associated with Huntington's disease, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition described herein.

[0546] In some embodiments, this disclosure provides a method for improving learning and working memory in a subject suffering from mild cognitive impairment (MCI) associated with Huntington's disease, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition described herein.

[0547] In some embodiments, this disclosure provides a method for improving cognition in a subject suffering from Huntington's disease, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition described herein.

[0548] On one hand, this disclosure provides a pharmaceutical composition as described herein for treating or preventing Huntington's disease in a subject. In some embodiments, this disclosure provides a pharmaceutical composition as described herein for treating Huntington's disease in a subject. In some embodiments, this disclosure provides a pharmaceutical composition as described herein for preventing Huntington's disease in a subject.

[0549] In some embodiments, this disclosure provides a pharmaceutical composition as disclosed herein for treating cognitive impairment in a subject with Huntington's disease.

[0550] In some embodiments, this disclosure provides a pharmaceutical composition as disclosed herein for treating mild cognitive impairment (MCI) associated with Huntington's disease in a subject.

[0551] In some embodiments, this disclosure provides a pharmaceutical composition as disclosed herein for improving executive function in a subject with mild cognitive impairment (MCI) associated with Huntington's disease.

[0552] In some embodiments, this disclosure provides a pharmaceutical composition as disclosed herein for improving working memory in subjects with mild cognitive impairment (MCI) associated with Huntington's disease.

[0553] In some embodiments, this disclosure provides a pharmaceutical composition as disclosed herein for improving learning in subjects with mild cognitive impairment (MCI) associated with Huntington's disease.

[0554] In some embodiments, this disclosure provides a pharmaceutical composition as disclosed herein for improving learning and working memory in subjects with mild cognitive impairment (MCI) associated with Huntington's disease.

[0555] In some embodiments, this disclosure provides a pharmaceutical composition as disclosed herein for improving cognition in a subject with Huntington's disease.

[0556] In some embodiments, this disclosure provides a pharmaceutical composition as disclosed herein for slowing cognitive decline in a subject with Huntington's disease.

[0557] In some embodiments, this disclosure provides a method for slowing cognitive decline in a subject suffering from Huntington's disease, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition described herein.

[0558] On one hand, this disclosure provides the use of a pharmaceutical composition as disclosed herein for manufacturing a medicament for treating or preventing Huntington's disease in a subject. In some embodiments, this disclosure provides the use of a pharmaceutical composition as disclosed herein for manufacturing a medicament for treating Huntington's disease in a subject. In some embodiments, this disclosure provides the use of a pharmaceutical composition as disclosed herein for manufacturing a medicament for preventing Huntington's disease in a subject.

[0559] In some embodiments, this disclosure provides a use of the pharmaceutical composition disclosed herein for manufacturing a medicament for treating cognitive impairment in a subject with Huntington's disease.

[0560] In some embodiments, this disclosure provides a use of a pharmaceutical composition as disclosed herein for manufacturing a medicament for treating mild cognitive impairment (MCI) associated with Huntington's disease in a subject.

[0561] In some embodiments, this disclosure provides the use of a pharmaceutical composition as disclosed herein for manufacturing a medicament for improving executive function in a subject suffering from mild cognitive impairment (MCI) associated with Huntington's disease.

[0562] In some embodiments, this disclosure provides the use of a pharmaceutical composition as disclosed herein for manufacturing a medicament for improving working memory in a subject suffering from mild cognitive impairment (MCI) associated with Huntington's disease.

[0563] In some embodiments, this disclosure provides a use of a pharmaceutical composition as disclosed herein for manufacturing a medicament for improving learning in a subject suffering from mild cognitive impairment (MCI) associated with Huntington's disease.

[0564] In some embodiments, this disclosure provides the use of a pharmaceutical composition as disclosed herein for manufacturing a medicament for improving learning and working memory in a subject suffering from mild cognitive impairment (MCI) associated with Huntington's disease.

[0565] In some embodiments, this disclosure provides a use of a pharmaceutical composition as disclosed herein for manufacturing a medicament for improving cognition in a subject suffering from Huntington's disease.

[0566] In some embodiments, this disclosure provides a use of a pharmaceutical composition as disclosed herein for manufacturing a medicament for slowing cognitive decline in a subject with Huntington's disease.

[0567] In some embodiments, the methods disclosed herein include administering the pharmaceutical composition described herein in combination with other therapeutic agents for the treatment of Huntington's disease. Examples of such other therapeutic agents include, but are not limited to, chorea medications (e.g., bubenazine (TBZ), deuterated bubenazine (DBZ)), antipsychotics (e.g., olanzapine, risperidone), antidepressants (citalopram, fluoxetine, sertraline), and mood stabilizers (e.g., lamotrigine, carbamazepine).

[0568] Alzheimer's disease

[0569] Alzheimer's disease (AD) is an age-related neurodegenerative disease. Clinically, it is characterized by overall cognitive impairment, particularly memory loss, behavioral and personality changes. The progression of AD is associated with the gradual damage to the function and structure of the hippocampus and neocortex, two vulnerable brain regions responsible for memory and cognition.

[0570] On the one hand, this disclosure provides a method for treating or preventing Alzheimer's disease in a subject, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition described herein.

[0571] In some embodiments, this disclosure provides a method for treating Alzheimer's disease in a subject, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition described herein. In some embodiments, this disclosure provides a method for preventing Alzheimer's disease in a subject, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition described herein.

[0572] In some embodiments, this disclosure provides a method for treating cognitive impairment in a subject with Alzheimer's disease, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition described herein.

[0573] In some embodiments, this disclosure provides a method for treating mild cognitive impairment (MCI) associated with Alzheimer's disease in a subject, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition described herein.

[0574] In some embodiments, this disclosure provides a method for improving executive function in a subject suffering from mild cognitive impairment (MCI) associated with Alzheimer's disease, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition described herein.

[0575] In some embodiments, this disclosure provides a method for improving the working memory of a subject suffering from mild cognitive impairment (MCI) associated with Alzheimer's disease, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition described herein.

[0576] In some embodiments, this disclosure provides a method for improving learning in a subject suffering from mild cognitive impairment (MCI) associated with Alzheimer's disease, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition described herein.

[0577] In some embodiments, this disclosure provides a method for improving learning and working memory in a subject suffering from mild cognitive impairment (MCI) associated with Alzheimer's disease, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition described herein.

[0578] In some embodiments, this disclosure provides a method for improving cognition in a subject suffering from Alzheimer's disease, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition described herein.

[0579] In some embodiments, this disclosure provides a method for slowing cognitive decline in a subject suffering from Alzheimer's disease, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition described herein.

[0580] In some embodiments, this disclosure provides a method for treating mild dementia associated with Alzheimer's disease in a subject, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition disclosed herein.

[0581] In some embodiments, this disclosure provides a method for improving executive function in a subject suffering from mild dementia associated with Alzheimer's disease, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition described herein.

[0582] In some embodiments, this disclosure provides a method for improving working memory in a subject suffering from mild dementia associated with Alzheimer's disease, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition described herein.

[0583] In some embodiments, this disclosure provides a method for improving learning in a subject suffering from dementia associated with Alzheimer's disease, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition described herein.

[0584] In some embodiments, this disclosure provides a method for improving the learning and working memory of a subject suffering from mild dementia associated with Alzheimer's disease, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition disclosed herein.

[0585] On one hand, this disclosure provides a pharmaceutical composition as described herein for treating or preventing Alzheimer's disease in a subject. In some embodiments, this disclosure provides a pharmaceutical composition as described herein for treating Alzheimer's disease in a subject. In some embodiments, this disclosure provides a pharmaceutical composition as described herein for preventing Alzheimer's disease in a subject.

[0586] In some embodiments, this disclosure provides a pharmaceutical composition as disclosed herein for treating cognitive impairment in a subject with Alzheimer's disease.

[0587] In some embodiments, this disclosure provides a pharmaceutical composition as disclosed herein for treating mild cognitive impairment (MCI) associated with Alzheimer's disease in a subject.

[0588] In some embodiments, this disclosure provides a pharmaceutical composition as disclosed herein for improving executive function in subjects with mild cognitive impairment (MCI) associated with Alzheimer's disease.

[0589] In some embodiments, this disclosure provides a pharmaceutical composition as disclosed herein for improving working memory in subjects with mild cognitive impairment (MCI) associated with Alzheimer's disease.

[0590] In some embodiments, this disclosure provides a pharmaceutical composition as disclosed herein for improving learning in subjects with mild cognitive impairment (MCI) associated with Alzheimer's disease.

[0591] In some embodiments, this disclosure provides a pharmaceutical composition as disclosed herein for improving learning and working memory in subjects with mild cognitive impairment (MCI) associated with Alzheimer's disease.

[0592] In some embodiments, this disclosure provides a pharmaceutical composition as disclosed herein for improving cognition in a subject with Alzheimer's disease.

[0593] In some embodiments, this disclosure provides a pharmaceutical composition as disclosed herein for slowing cognitive decline in subjects with Alzheimer's disease.

[0594] In some embodiments, this disclosure provides a pharmaceutical composition as disclosed herein for the treatment of mild dementia associated with Alzheimer's disease.

[0595] In some embodiments, this disclosure provides a pharmaceutical composition as disclosed herein for improving executive function in a subject suffering from mild dementia associated with Alzheimer's disease.

[0596] In some embodiments, this disclosure provides a pharmaceutical composition as disclosed herein for improving working memory in subjects with mild dementia associated with Alzheimer's disease.

[0597] In some embodiments, this disclosure provides a pharmaceutical composition as disclosed herein for improving learning in subjects with mild dementia associated with Alzheimer's disease.

[0598] In some embodiments, this disclosure provides a pharmaceutical composition as disclosed herein for improving learning and working memory in subjects with mild dementia associated with Alzheimer's disease.

[0599] On one hand, this disclosure provides the use of a pharmaceutical composition as disclosed herein for manufacturing a medicament for treating or preventing Alzheimer's disease in a subject. In some embodiments, this disclosure provides the use of a pharmaceutical composition as disclosed herein for manufacturing a medicament for treating Alzheimer's disease in a subject. In some embodiments, this disclosure provides the use of a pharmaceutical composition as disclosed herein for manufacturing a medicament for preventing Alzheimer's disease in a subject.

[0600] In some embodiments, this disclosure provides a use of the pharmaceutical composition disclosed herein for manufacturing a medicament for treating cognitive impairment in a subject with Alzheimer's disease.

[0601] In some embodiments, this disclosure provides a use of a pharmaceutical composition as disclosed herein for manufacturing a medicament for treating mild cognitive impairment (MCI) associated with Alzheimer's disease in a subject.

[0602] In some embodiments, this disclosure provides a use of a pharmaceutical composition as disclosed herein for manufacturing a medicament for improving executive function in a subject suffering from mild cognitive impairment (MCI) associated with Alzheimer's disease.

[0603] In some embodiments, this disclosure provides a use of a pharmaceutical composition as disclosed herein for manufacturing a medicament for improving working memory in a subject suffering from mild cognitive impairment (MCI) associated with Alzheimer's disease.

[0604] In some embodiments, this disclosure provides a use of a pharmaceutical composition as disclosed herein for manufacturing a medicament for improving learning in subjects with mild cognitive impairment (MCI) associated with Alzheimer's disease.

[0605] In some embodiments, this disclosure provides a use of a pharmaceutical composition as disclosed herein for manufacturing a medicament for improving learning and working memory in a subject suffering from mild cognitive impairment (MCI) associated with Alzheimer's disease.

[0606] In some embodiments, this disclosure provides a use of a pharmaceutical composition as disclosed herein for manufacturing a medicament for improving cognition in a subject suffering from Alzheimer's disease.

[0607] In some embodiments, this disclosure provides a use of a pharmaceutical composition as disclosed herein for manufacturing a medicament for slowing cognitive decline in a subject with Alzheimer's disease.

[0608] In some embodiments, this disclosure provides a use of a pharmaceutical composition as disclosed herein for manufacturing a medicament for treating mild dementia associated with Alzheimer's disease.

[0609] In some embodiments, this disclosure provides a use of a pharmaceutical composition as disclosed herein for manufacturing a medicament for improving executive function in a subject suffering from mild dementia associated with Alzheimer's disease.

[0610] In some embodiments, this disclosure provides the use of a pharmaceutical composition as disclosed herein for manufacturing a medicament for improving working memory in a subject suffering from mild dementia associated with Alzheimer's disease.

[0611] In some embodiments, this disclosure provides a use of a pharmaceutical composition as disclosed herein for manufacturing a medicament for improving learning in a subject suffering from mild dementia associated with Alzheimer's disease.

[0612] In some embodiments, this disclosure provides a use of a pharmaceutical composition as disclosed herein for manufacturing a medicament for improving learning and working memory in a subject suffering from mild dementia associated with Alzheimer's disease.

[0613] In some embodiments, the methods disclosed herein include administering the pharmaceutical composition described herein in combination with other therapeutic agents for the treatment of Alzheimer's disease.

[0614] In some embodiments, an adjunctive therapeutic agent for treating Alzheimer's disease is an anti-β-amyloid antibody or antigen-binding fragment thereof that can be used in the compositions, kits, and methods disclosed herein, and is an antibody. Any anti-β-amyloid antibody or antigen-binding fragment thereof, including the antibodies or antigen-binding fragments disclosed in U.S. Patents 10,842,871, 10,131,708, 9,828,420, and 8,906,367 and U.S. Patent Publication No. 2015 / 013155267 (the disclosures of all these patents are incorporated herein by reference), can be used in the pharmaceutical compositions, kits, and methods disclosed herein.

[0615] More specifically, adjunctive therapies for treating Alzheimer's disease include anti-β-amyloid antibodies, their antigen-binding fragments (or portions thereof), the light chains of the antibody, the heavy chains of the antibody, and fragments of these light chains or heavy chains. The anti-β-amyloid antibodies and their antigen-binding fragments disclosed herein also include antibodies lacking heavy chain and / or light chain signal sequences, as well as glycosylated antibodies. The anti-β-amyloid antibodies and their antigen-binding fragments disclosed herein also include precursor antibodies, non-glycosylated antibodies, and antibodies whose heavy chains and / or light chains contain signal sequences.

[0616] The antibodies and their antigen-binding fragments described herein can be purified and / or isolated using known techniques. “Purified” or “isolated” antibodies or portions thereof have been at least partially separated from molecules (e.g., peptides) of their source (e.g., cell supernatants; antibody mixtures such as those in an antibody library; etc.) and include antibodies obtained by any other suitable method. Isolated antibodies include substantially pure (e.g., substantially clean) antibodies, as well as antibodies produced through chemical synthesis, recombinant techniques, and combinations thereof.

[0617] Anti-β-amyloid antibodies or antigen-binding fragments thereof may be human. In some embodiments, the anti-amyloid β antibodies or antigen-binding fragments thereof disclosed herein are chimeric. In some embodiments, chimeric anti-amyloid β antibodies or antigen-binding fragments thereof comprise a chimeric IgH chain and a human Igκ chain. In some embodiments, chimeric anti-amyloid β antibodies or antigen-binding fragments thereof comprise a chimeric IgH chain and a human Igλ chain. In some embodiments, chimeric anti-S1 antibodies comprise a human sequence and a mouse sequence.

[0618] In some embodiments, the anti-amyloid β antibody or its antigen-binding fragment includes one to six complementarity-determining regions (CDRs) disclosed herein.

[0619] In some embodiments, the anti-β-amyloid antibody or its antigen-binding fragment is selected from the group consisting of barbiturumab, soranelizumab, gantrup, crimetuzumab, bonnetuzumab, lecanemab (BAN2401), aducanumab, and their antigen-binding fragments. In some embodiments, the anti-β-amyloid antibody or its antigen-binding fragment is barbiturumab or its antigen-binding fragment. In some embodiments, the anti-β-amyloid antibody or its antigen-binding fragment is soranelizumab or its antigen-binding fragment. In some embodiments, the anti-β-amyloid antibody or its antigen-binding fragment is gantrup or its antigen-binding fragment. In some embodiments, the anti-β-amyloid antibody or its antigen-binding fragment is crimetuzumab or its antigen-binding fragment. In some embodiments, the anti-β-amyloid antibody or its antigen-binding fragment is bonnetuzumab or its antigen-binding fragment. In some embodiments, the anti-β-amyloid antibody or its antigen-binding fragment is lecanemab (BAN2401) or its antigen-binding fragment. In some embodiments, the anti-β-amyloid antibody or its antigen-binding fragment is aducanumab or its antigen-binding fragment.

[0620] In some embodiments, an anti-β-amyloid antibody or its antigen-binding fragment binds to the same conformational epitope of β-amyloid as any of barbiturumab, soranelizumab, gantrupab, clindamycin, bonnetuzumab, lecanemab (BAN2401), aducanumab, and their antigen-binding fragments. In some embodiments, an anti-β-amyloid antibody or its antigen-binding fragment binds to the same conformational epitope of β-amyloid as barbiturumab. In some embodiments, an anti-β-amyloid antibody or its antigen-binding fragment binds to the same conformational epitope of β-amyloid as soranelizumab. In some embodiments, an anti-β-amyloid antibody or its antigen-binding fragment binds to the same conformational epitope of β-amyloid as gantrupab. In some embodiments, an anti-β-amyloid antibody or its antigen-binding fragment binds to the same conformational epitope of β-amyloid as clindamycin. In some embodiments, an anti-β-amyloid antibody or its antigen-binding fragment binds to the same conformational epitope of β-amyloid as bonnetuzumab. In some embodiments, an anti-β-amyloid antibody or its antigen-binding fragment binds to the same conformational epitope of β-amyloid as lecanumab (BAN2401). In some embodiments, an anti-β-amyloid antibody or its antigen-binding fragment binds to the same conformational epitope of β-amyloid as aducanumab (BAN2401).

[0621] In some embodiments, anti-β-amyloid antibodies or their antigen-binding fragments competitively inhibit the binding of barbiturumab, soranelizumab, gantrupab, cresolizumab, bonnetuzumab, lecanemab (BAN2401), and aducanumab to β-amyloid. In some embodiments, anti-β-amyloid antibodies or their antigen-binding fragments competitively inhibit the binding of barbiturumab to β-amyloid. In some embodiments, anti-β-amyloid antibodies or their antigen-binding fragments competitively inhibit the binding of soranelizumab to β-amyloid. In some embodiments, anti-β-amyloid antibodies or their antigen-binding fragments competitively inhibit the binding of gantrupab to β-amyloid. In some embodiments, anti-β-amyloid antibodies or their antigen-binding fragments competitively inhibit the binding of bonnetuzumab to β-amyloid. In some embodiments, anti-β-amyloid antibodies or their antigen-binding fragments competitively inhibit the binding of lecanemab (BAN2401) to β-amyloid. In some embodiments, the anti-β-amyloid antibody or its antigen-binding fragment competitively inhibits the binding of aducanumab to β-amyloid.

[0622] In some embodiments, the anti-β-amyloid antibody or its antigen-binding fragment comprises six complementarity-determining regions (CDRs) of any of the anti-β-amyloid antibodies disclosed herein, identified according to the Kabat, Chothia, or IMTG nomenclature. In some embodiments, the anti-β-amyloid antibody or its antigen-binding fragment comprises six complementarity-determining regions (CDRs) of any of the following antibodies: barbiturumab, soranelizumab, gantrupumab, krillizumab, lecanemab (BAN2401), and aducanumab. In some embodiments, the anti-β-amyloid antibody or its antigen-binding fragment comprises six complementarity-determining regions (CDRs) of barbiturumab. In some embodiments, the anti-amyloid β antibody or its antigen-binding fragment comprises six complementarity-determining regions (CDRs) of soranelizumab. In some embodiments, the anti-amyloid β antibody or its antigen-binding fragment comprises six complementarity-determining regions (CDRs) of gantrupumab. In some embodiments, the anti-amyloid β antibody or its antigen-binding fragment comprises six complementarity-determining regions (CDRs) of krillizumab. In some embodiments, the anti-amyloid β antibody or its antigen-binding fragment comprises six complementarity-determining regions (CDRs) of ponezilumab. In some embodiments, the anti-amyloid β antibody or its antigen-binding fragment comprises six complementarity-determining regions (CDRs) of lecanemumab (BAN2401). In some embodiments, the anti-amyloid β antibody or its antigen-binding fragment comprises six complementarity-determining regions (CDRs) of aducanumab.

[0623] Dosing regimen

[0624] In some embodiments, a subject is administered a total daily dose of about 0.3 mg to about 2.1 mg of Compound I or a pharmaceutically acceptable salt thereof. In some embodiments, a subject is administered a total daily dose of about 0.3 mg to about 1.8 mg of Compound I or a pharmaceutically acceptable salt thereof. In some embodiments, a subject is administered a total daily dose of about 0.3 mg to about 1.5 mg of Compound I or a pharmaceutically acceptable salt thereof. In some embodiments,...

Claims

1. A pharmaceutical composition comprising... a) Compound I: (Compound I); or a pharmaceutically acceptable salt thereof; and b) One or more glycerides, wherein the glycerides comprise monoglycerides between about 30% w / w and about 100% w / w.

2. The pharmaceutical composition according to claim 1, wherein the pharmaceutical composition comprises compound I.

3. The pharmaceutical composition according to any one of claims 1 to 2, wherein the pharmaceutical composition comprises a pharmaceutically acceptable salt of compound I.

4. The pharmaceutical composition according to any one of claims 1 to 3, wherein the pharmaceutical composition comprises about 0.2% w / w to about 0.4% w / w of compound I.

5. The pharmaceutical composition according to any one of claims 1 to 3, wherein the pharmaceutical composition comprises about 3 mg / g of compound I.

6. The pharmaceutical composition according to any one of claims 1 to 5, wherein the one or more glycerides are selected from the group consisting of mono / dicaprylic / capric glyceride, mono / dicaprylic / capric glyceride, type I monocaprylic glyceride, type I monocaprylic glyceride, type I monocaprylic / capric glyceride, monolinoleic glyceride, and combinations thereof.

7. The pharmaceutical composition according to any one of claims 1 to 6, wherein the one or more glycerides are selected from the group consisting of glyceryl monocaprylate, glyceryl monolinoleate, and combinations thereof.

8. The pharmaceutical composition according to any one of claims 1 to 7, wherein the pharmaceutical composition comprises glyceryl monocaprylate.

9. The pharmaceutical composition according to any one of claims 1 to 7, wherein the pharmaceutical composition comprises monolinoleic glyceride.

10. The pharmaceutical composition according to any one of claims 1 to 7, wherein the pharmaceutical composition comprises glyceryl monocaprylate and glyceryl monolinoleate.

11. The pharmaceutical composition according to any one of claims 1 to 10, wherein the amount of the one or more glycerides is from about 20% w / w to about 80% w / w.

12. The pharmaceutical composition according to any one of claims 7, 9 or 10, wherein the amount of said monolinoleic glyceride is from about 20% w / w to about 30% w / w.

13. The pharmaceutical composition according to any one of claims 1 to 12, further comprising stearoyl polyoxyethylene-32 glyceride.

14. The pharmaceutical composition according to claim 13, wherein the amount of stearoyl polyoxyethylene-32 glyceride is from about 5% w / w to about 20% w / w.

15. The pharmaceutical composition according to any one of claims 1 to 14, wherein the composition further comprises a surfactant.

16. The pharmaceutical composition of claim 15, wherein the amount of surfactant is from about 10% w / w to about 25% w / w.

17. The pharmaceutical composition according to any one of claims 15 to 16, wherein the surfactant is vitamin ETPGS.

18. The pharmaceutical composition according to any one of claims 1 to 17, wherein the composition further comprises an antioxidant.

19. The pharmaceutical composition of claim 18, wherein the amount of antioxidant is from about 0.005% w / w to about 0.02% w / w.

20. The pharmaceutical composition according to any one of claims 18 to 19, wherein the antioxidant is butylated hydroxyanisole (BHA).

21. A pharmaceutical composition comprising: a) Compound I, approximately 0.3% w / w. b) Approximately 60% w / w caprylic / caprylic acid glyceride, c) Approximately 20% w / w glyceryl monolinoleate d) Approximately 20% w / w vitamin E TPGS, and e) Approximately 0.01% w / w butylated hydroxyanisole.

22. A pharmaceutical composition comprising: a) Compound I, approximately 0.3% w / w. b) Approximately 50% w / w caprylic / caprylic acid glyceride c) Approximately 22.5% w / w monolinoleic acid glycerides, d) Approximately 20% w / w Vitamin E TPGS, e) Approximately 7.5% w / w stearoyl polyoxyethylene-32 glycerol ester, and f) Approximately 0.01% w / w butylated hydroxyanisole.

23. The pharmaceutical composition according to any one of claims 1 to 22, wherein the pharmaceutical composition is an oral dosage form.

24. The pharmaceutical composition according to any one of claims 1 to 23, wherein the pharmaceutical composition is a lipid formulation.

25. The pharmaceutical composition according to any one of claims 1 to 24, wherein the oral dosage form is a soft gelatin capsule, a hard-shell capsule, or an oral liquid.

26. The pharmaceutical composition according to any one of claims 1 to 25, wherein, after administration of the pharmaceutical composition to a subject, the pharmaceutical composition provides one or more of the following pharmacokinetic parameters: a) C between approximately 8 and approximately 25 ng / mL max ; b) AUC between approximately 100 and approximately 450 ng*h / mL last ; c) AUC between approximately 100 and approximately 500 ng*h / mL inf ; d) t between approximately 2 and approximately 8 hours max ;or e) Bioavailability between approximately 70% and approximately 100%.

27. A pharmaceutical composition comprising a therapeutically effective amount of compound I (Compound I), or a pharmaceutically acceptable salt thereof; and pharmaceutically acceptable carriers; When the pharmaceutical composition is administered to a subject, the pharmaceutical composition provides one or more of the following pharmacokinetic parameters: a) C between approximately 8 and approximately 25 ng / mL max ; b) AUC between approximately 100 and approximately 450 ng*h / mL last ; c) AUC between approximately 100 and approximately 500 ng*h / mL inf ; d) t between approximately 2 and approximately 8 hours max ;or e) Bioavailability between approximately 70% and approximately 100%.

28. The pharmaceutical composition of claim 27, wherein the pharmaceutical composition provides a Cg between about 8 and about 25 ng / mL. max .

29. The pharmaceutical composition according to any one of claims 27 to 28, wherein the pharmaceutical composition provides a time between about 2 and about 8 hours. max .

30. The pharmaceutical composition according to any one of claims 27 to 29, wherein the pharmaceutical composition provides an AUC between about 100 and about 450 ng*h / mL. last .

31. The pharmaceutical composition according to any one of claims 27 to 30, wherein the pharmaceutical composition provides an AUC between about 100 and about 500 ng*h / mL. inf .

32. The pharmaceutical composition according to any one of claims 27 to 31, wherein the pharmaceutical composition provides a bioavailability of about 70% to about 100%.

33. The pharmaceutical composition according to any one of claims 27 to 32, wherein the pharmacokinetic parameters are obtained after a single administration of the pharmaceutical composition.

34. The pharmaceutical composition according to any one of claims 27 to 32, wherein the pharmacokinetic parameters are obtained after 2 to 60 administrations of the pharmaceutical composition.

35. The pharmaceutical composition according to any one of claims 27 to 34, wherein the pharmacokinetic parameters are obtained under fasting conditions.

36. The pharmaceutical composition according to any one of claims 27 to 34, wherein the pharmacokinetic parameters are obtained under feeding conditions.

37. The pharmaceutical composition according to any one of claims 27 to 36, wherein the pharmaceutical composition is an oral dosage form.

38. A method for treating a subject with a CNS-related condition, wherein the CNS-related condition is selected from the group consisting of Huntington's disease, Parkinson's disease, and Alzheimer's disease, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition according to any one of claims 1 to 37.

39. A method for treating cognitive impairment in a subject suffering from a CNS-related condition, wherein the CNS-related condition is selected from the group consisting of Huntington's disease, Parkinson's disease, and Alzheimer's disease, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition according to any one of claims 1 to 37.

40. A method of treating a subject with mild cognitive impairment (MCI) associated with a CNS-related condition, wherein the CNS-related condition is selected from the group consisting of Huntington's disease, Parkinson's disease, and Alzheimer's disease, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition according to any one of claims 1 to 37.

41. A method for improving executive function in a subject suffering from mild cognitive impairment (MCI) associated with a CNS-related condition, wherein the CNS-related condition is selected from the group consisting of Huntington's disease, Parkinson's disease, and Alzheimer's disease, the method comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition according to any one of claims 1 to 37.

42. A method for improving working memory in a subject suffering from mild cognitive impairment (MCI) associated with a CNS-related condition, wherein the CNS-related condition is selected from the group consisting of Huntington's disease, Parkinson's disease, and Alzheimer's disease, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition according to any one of claims 1 to 37.

43. A method for improving learning in a subject suffering from mild cognitive impairment (MCI) associated with a CNS-related condition, wherein the CNS-related condition is selected from the group consisting of Huntington's disease, Parkinson's disease, and Alzheimer's disease, the method comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition according to any one of claims 1 to 37.

44. A method for improving learning and working memory in a subject suffering from mild cognitive impairment (MCI) associated with a CNS-related condition, wherein the CNS-related condition is selected from the group consisting of Huntington's disease, Parkinson's disease, and Alzheimer's disease, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition according to any one of claims 1 to 37.

45. A method for improving cognition in a subject suffering from a CNS-related condition, wherein the CNS-related condition is selected from the group consisting of Huntington's disease, Parkinson's disease, and Alzheimer's disease, the method comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition according to any one of claims 1 to 37.

46. ​​A method for slowing cognitive decline in a subject suffering from a CNS-related condition, wherein the CNS-related condition is selected from the group consisting of Huntington's disease, Parkinson's disease, and Alzheimer's disease, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition according to any one of claims 1 to 37.

47. The method according to any one of claims 38 to 46, comprising administering to the subject a total daily dose of compound I of about 0.3 mg to about 1.5 mg.

48. The method according to any one of claims 38 to 46, comprising administering to the subject a total daily dose of about 1.2 mg of compound I.

49. The method according to any one of claims 38 to 46, comprising administering to the subject a total daily dose of about 0.9 mg of compound I.

50. The method according to any one of claims 38 to 49, comprising administering at least one loading dose to the subject; and at least one maintenance dose.

51. The method of claim 50, wherein the loading dose is about 1.2 mg of compound I per day.

52. The method according to any one of claims 50 to 51, wherein the maintenance dose is about 0.9 mg of compound I daily.

53. The pharmaceutical composition according to any one of claims 1 to 37, for treating a subject with CNS-related conditions, wherein the CNS-related conditions are selected from the group consisting of Huntington's disease, Parkinson's disease and Alzheimer's disease.

54. The pharmaceutical composition according to any one of claims 1 to 37, for treating cognitive impairment in a subject suffering from CNS-related conditions, wherein the CNS-related conditions are selected from the group consisting of Huntington's disease, Parkinson's disease and Alzheimer's disease.

55. The pharmaceutical composition according to any one of claims 1 to 37, for treating a subject suffering from mild cognitive impairment (MCI) associated with a CNS-related condition, wherein the CNS-related condition is selected from the group consisting of Huntington's disease, Parkinson's disease, and Alzheimer's disease.

56. The pharmaceutical composition according to any one of claims 1 to 37, for improving executive function in a subject suffering from mild cognitive impairment (MCI) associated with CNS-related conditions, wherein the CNS-related conditions are selected from the group consisting of Huntington's disease, Parkinson's disease, and Alzheimer's disease.

57. The pharmaceutical composition according to any one of claims 1 to 37, for improving working memory in a subject suffering from mild cognitive impairment (MCI) associated with CNS-related conditions, wherein the CNS-related conditions are selected from the group consisting of Huntington's disease, Parkinson's disease, and Alzheimer's disease.

58. The pharmaceutical composition according to any one of claims 1 to 37, for improving learning in a subject suffering from mild cognitive impairment (MCI) associated with CNS-related conditions, wherein the CNS-related conditions are selected from the group consisting of Huntington's disease, Parkinson's disease, and Alzheimer's disease.

59. The pharmaceutical composition according to any one of claims 1 to 37, for improving learning and working memory in a subject suffering from mild cognitive impairment (MCI) associated with CNS-related conditions, wherein the CNS-related conditions are selected from the group consisting of Huntington's disease, Parkinson's disease, and Alzheimer's disease.

60. The pharmaceutical composition according to any one of claims 1 to 37, for improving cognition in a subject suffering from CNS-related disorders, wherein the CNS-related disorders are selected from the group consisting of Huntington's disease, Parkinson's disease and Alzheimer's disease.

61. The pharmaceutical composition according to any one of claims 1 to 37, for slowing cognitive decline in a subject suffering from CNS-related conditions, wherein the CNS-related conditions are selected from the group consisting of Huntington's disease, Parkinson's disease and Alzheimer's disease.

62. Use of the pharmaceutical composition according to any one of claims 1 to 37 for manufacturing a medicament for treating a subject with a CNS-related condition, wherein the CNS-related condition is selected from the group consisting of Huntington's disease, Parkinson's disease, and Alzheimer's disease.

63. Use of the pharmaceutical composition according to any one of claims 1 to 37 for manufacturing a medicament for treating cognitive impairment in a subject suffering from a CNS-related condition, wherein the CNS-related condition is selected from the group consisting of Huntington's disease, Parkinson's disease, and Alzheimer's disease.

64. Use of the pharmaceutical composition according to any one of claims 1 to 37 for manufacturing a medicament for treating a subject with mild cognitive impairment (MCI) associated with a CNS-related condition, wherein the CNS-related condition is selected from the group consisting of Huntington's disease, Parkinson's disease, and Alzheimer's disease.

65. The use of the pharmaceutical composition according to any one of claims 1 to 37 for manufacturing a medicament for improving executive function in a subject suffering from mild cognitive impairment (MCI) associated with CNS-related conditions, wherein the CNS-related conditions are selected from the group consisting of Huntington's disease, Parkinson's disease, and Alzheimer's disease.

66. The use of the pharmaceutical composition according to any one of claims 1 to 37 for manufacturing a medicament for improving the working memory of a subject suffering from mild cognitive impairment (MCI) associated with CNS-related conditions, wherein the CNS-related conditions are selected from the group consisting of Huntington's disease, Parkinson's disease, and Alzheimer's disease.

67. The use of the pharmaceutical composition according to any one of claims 1 to 37 for manufacturing a medicament for improving learning in a subject suffering from mild cognitive impairment (MCI) associated with a CNS-related condition, wherein the CNS-related condition is selected from the group consisting of Huntington's disease, Parkinson's disease, and Alzheimer's disease.

68. The use of the pharmaceutical composition according to any one of claims 1 to 37 for manufacturing a medicament for improving the learning and working memory of a subject suffering from mild cognitive impairment (MCI) associated with CNS-related conditions, wherein the CNS-related conditions are selected from the group consisting of Huntington's disease, Parkinson's disease, and Alzheimer's disease.

69. The use of the pharmaceutical composition according to any one of claims 1 to 37 for manufacturing a medicament for improving cognition in a subject suffering from a CNS-related condition, wherein the CNS-related condition is selected from the group consisting of Huntington's disease, Parkinson's disease, and Alzheimer's disease.

70. Use of the pharmaceutical composition of any one of claims 1 to 37 for manufacturing a medicament for slowing cognitive decline in a subject suffering from a CNS-related condition, wherein the CNS-related condition is selected from the group consisting of Huntington's disease, Parkinson's disease, and Alzheimer's disease.

71. A dosing regimen for administering a therapeutically effective amount of the pharmaceutical composition according to any one of claims 1 to 37 to a subject in need, said dosing regimen comprising administering at least one loading dose and at least one maintenance dose to said subject.

72. The dosing regimen of claim 71, wherein the loading dose is approximately 1.2 mg of compound I daily.

73. The dosing regimen according to any one of claims 71 to 72, wherein the maintenance dose is about 0.9 mg of compound I daily.

74. A method for treating a subject with a CNS-related condition, wherein the CNS-related condition is selected from the group consisting of Huntington's disease, Parkinson's disease, and Alzheimer's disease, the method comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition, the pharmaceutical composition comprising compound I or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier; wherein, after administration of the pharmaceutical composition to the subject, the pharmaceutical composition provides one or more of the following pharmacokinetic parameters: a) C between approximately 8 and approximately 25 ng / mL max ; b) AUC between approximately 100 and approximately 450 ng*h / mL last ; c) AUC between approximately 100 and approximately 500 ng*h / mL inf ; d) t between approximately 2 and approximately 8 hours max ;or e) Bioavailability between approximately 70% and approximately 100%.

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