Neuroactive steroids and their methods of use

Abstract

This disclosure relates to compound 1, its pharmaceutically acceptable salts or pharmaceutically acceptable compositions, for the treatment of CNS-related conditions, such as tremor, such as spontaneous tremor; depression; and anxiety disorders; and methods for improving the efficacy of compound 1 in treating these CNS-related conditions. This disclosure also relates to methods for improving the bioavailability of compound 1 or its pharmaceutically acceptable salts or pharmaceutically acceptable compositions.

Description

Neuroactive steroids and their usage GABA (gamma-aminobutyric acid) has a profound impact on overall brain excitability because up to 40% of neurons in the brain use GABA as a neurotransmitter. GABA interacts with its recognition site on the GRC (GABA receptor complex) to promote the downward flow of chloride ions into the cell along the electrochemical gradient of the GRC. This increase in intracellular chloride content causes hyperpolarization of the transmembrane potential, thereby making neurons less sensitive to excitatory input (i.e., reducing neuronal excitability). In other words, the higher the chloride ion concentration in neurons, the lower the brain excitability (arousal level). There is ample evidence that the GRC is responsible for regulating anxiety, seizures, and sedation. Therefore, GABA and drugs that act like GABA (e.g., therapeutically useful barbiturates and benzodiazepines (BZ), such as Valium®) produce their therapeutically useful effects by interacting with specific regulatory sites on the GRC. Accumulated evidence has indicated that GRC contains unique sites for neuroactive steroids (Lan, NC et al., Neuwchem. Res. 16:347-356 (1991)). Neuroactive steroids can be produced endogenously. The most potent endogenous neuroactive steroids are 3α-hydroxy-5-reductodrine-20-one and 3cc-21-dihydroxy-5-reductodrine-20-one, metabolites of the hormonal steroids progesterone and deoxycorticosterone, respectively. In 1986, the ability of these steroid metabolites to alter brain excitability was recognized (Majewska, MD et al., Science 232: 1004-1007 (1986); Harrison, NL et al., J Pharmacol. Exp. Ther. 241:346-353 (1987)). Compound 1 (the neuroactive steroid described herein) has been shown to be GABA. A Positive ectopic regulators of receptors target synaptic and extrasynaptic GABA. A Receptor. As a GABA receptor. ACompound 1 is a positive ectopic modulator of the receptor and is intended as a therapeutic agent for CNS-related conditions, such as tremor (e.g., spontaneous tremor), depression (e.g., postpartum depression), and anxiety disorders. While various routes of administration are available, the oral route is preferred due to its convenience. However, many therapeutic agents experience low bioavailability after oral administration due to numerous problems, including poor absorption or easy first-pass metabolism. Furthermore, solid dosage forms (e.g., tablets and capsules) are superior to other dosage forms because they can be taken orally by the patient (a convenient and safe method of drug administration) and are more stable (physical and chemically stable) than liquids. However, oral administration of solid dosage forms also suffers from low bioavailability. For Compound 1 to be used as a therapeutic agent for CNS-related conditions, especially via oral administration in solid dosage forms, an acceptable bioavailability must be achieved. This disclosure provides a method for treating CNS-related conditions by administering to an individual in need a therapeutically effective amount of compound 1 or 1-(2-((3R,5R,8R,9R,10S,13S,14S,17S)-3-hydroxy-3,13-dimethylhexadecylhydro-1H-cyclopentan[a]phenanthrene-17-yl)-2-sideoxyethyl)-1H-pyrazole-4-carboxynitrile having the following formula (Compound 1). Compound 1 is also known as compound SAGE-217. In some embodiments, compound 1 is not administered with food or is administered substantially simultaneously with food. In some embodiments, compound 1 is administered substantially simultaneously with food. In some embodiments, the method includes treating CNS-related conditions by administering a therapeutically effective amount of compound 1 or its pharmaceutically acceptable salt to an individual, wherein the therapeutically effective amount of compound 1 is substantially administered simultaneously with food. In some embodiments, the therapeutically effective dose is in the form of a solid dosage form. Examples of solid dosage forms include tablets, capsules, granules, powders, small capsules, reconfigurable powders, dry powder inhalers, and chewable tablets. In the present disclosure, compared with the administration of compound 1 without food, the administration of a therapeutically effective amount of compound 1 substantially simultaneously with food increases the bioavailability of compound 1. The bioavailability of compound 1 can be determined from plasma concentration-time curves, specifically the area under the curve (AUC). For example, bioavailability, or its increase, can be measured by comparing the AUC of formulations containing compound 1 administered with food. 0-t (AUC from the time of drug administration to the final quantifiable concentration) and the AUC of the formulation containing compound 1 not administered with food. 0-t To measure. In some embodiments, a therapeutically effective amount of compound 1 (or a pharmaceutically acceptable salt thereof) is substantially administered simultaneously with food to increase the bioavailability of compound 1 for the treatment of CNS-related conditions, and the therapeutically effective amount of compound 1 is in a solid dosage form (e.g., tablets or capsules). In some embodiments, the therapeutically effective amount of compound 1 is substantially administered simultaneously with food, and the bioavailability is increased by about 10% or more; about 20% or more; about 30% or more; about 40% or more; about 50% or more; or about 55% or more compared to the bioavailability when compound 1 is not administered with food. In some embodiments, a therapeutically effective amount of compound 1 is administered once daily, substantially simultaneously with food. In other embodiments, a therapeutically effective amount of compound 1 is administered twice daily, substantially simultaneously with food. In some embodiments, a therapeutically effective amount of compound 1 is administered once daily, substantially simultaneously with food, as a capsule. In some embodiments, a therapeutically effective amount of compound 1 is administered once daily, substantially simultaneously with food, as two capsules. In some embodiments, a therapeutically effective amount of compound 1 is about 20 mg to about 60 mg, and is administered substantially simultaneously with food. In other embodiments, a therapeutically effective amount of compound 1 is about 25 mg to about 50 mg, and is administered substantially simultaneously with food. In other embodiments, a therapeutically effective amount of compound 1 is about 25 mg to about 35 mg, and is administered substantially simultaneously with food. In other embodiments, a therapeutically effective amount of compound 1 is about 30 mg, for example, 30 mg, and is administered substantially simultaneously with food. In some embodiments of this disclosure, a therapeutically effective amount of compound 1 is administered substantially simultaneously with food, for example, within approximately 60 minutes before or after food intake. In some embodiments, a therapeutically effective amount of compound 1 is administered substantially simultaneously with food, for example, within approximately 45 minutes, 30 minutes, 15 minutes, or 5 minutes before or after food intake. In some embodiments, the food is a high-fat diet as defined herein, or a regular diet as discussed herein. In other embodiments, the food contains at least 50 calories, at least 100 calories, at least 200 calories, or at least 300 calories. This disclosure is particularly characterized by a method comprising administering to an individual a therapeutically effective amount of Compound 1 as described below to treat a CNS-related condition (e.g., mood disorder or movement disorder). This disclosure is characterized by a method of treating an individual with a CNS-related condition using a composition comprising Compound 1 as described herein, such as tremor, e.g., spontaneous tremor; depression, e.g., postpartum depression; and anxiety disorder. In some embodiments, Compound 1 is administered substantially simultaneously with food or not. In some embodiments of either of the above, Compound 1 is administered substantially simultaneously with food. This disclosure is also particularly characterized by, for example, GABA-related diseases or conditions, such as mood disorders, movement disorders, postpartum depression, major depressive disorder, spontaneous tremor, or Parkinson's disease. In some embodiments, the CNS-related condition is a depressive condition, such as major depressive disorder. In some embodiments, the individual has a mild depressive condition, such as mild major depressive disorder. In some embodiments, the individual has a moderate depressive condition, such as moderate major depressive disorder. In some embodiments, the individual has a severe depressive condition, such as severe major depressive disorder. In some embodiments, the individual has an extremely severe depressive condition, such as extremely severe major depressive disorder. In some embodiments, the individual's baseline HAM-D total score (i.e., prior to treatment with compound 1) is at least 24. In some embodiments, the individual's baseline HAM-D total score is at least 18. In some embodiments, the individual's baseline HAM-D total score is between 14 and 18, including 14 and 18. In some embodiments, the individual's baseline HAM-D total score is between 19 and 22, including 19 and 22. In some embodiments, the individual's HAM-D total score is greater than or equal to 23 prior to treatment with compound 1. In some embodiments, the baseline score is at least 10, 15, or 20. In some embodiments, after treatment with compound 1, an individual's total HAM-D score is approximately 0 to 10 (e.g., less than 10; 0 to 10, 0 to 6, 0 to 4, 0 to 3, 0 to 2, or 1.8). In some embodiments, after treatment with compound 1, the total HAM-D score is less than 10, 7, 5, or 3. In some embodiments, the reduction in the total HAM-D score is from a baseline score of approximately 20 to 30 (e.g., 22 to 28, 23 to 27, 24 to 27, 25 to 27, 26 to 27) to a total HAM-D score of approximately 0 to 10 (e.g., less than 10; 0 to 10, 0 to 6, 0 to 4, 0 to 3, 0 to 2, or 1.8) after treatment with compound 1. In some embodiments, the reduction in the baseline total HAM-D score to the total HAM-D score after treatment with compound 1 is at least 1, 2, 3, 4, 5, 7, 10, 25, 40, 50, or 100 times. In some embodiments, the percentage reduction in the baseline total HAM-D score to the total HAM-D score after treatment with compound 1 is at least 50% (e.g., 60%, 70%, 80%, or 90%). In some embodiments, the therapeutic effect is measured as the reduction in the total HAM-D score relative to the baseline total HAM-D score after treatment with compound 1 (e.g., at 12, 24, or 48 hours post-administration; or 24, 48, 72, or 96 hours or longer; or 1, 2, or 14 days or longer), which is at least 10, 15, or 20 points. In some embodiments, the method of treating a depressive disorder (e.g., major depressive disorder) provides a therapeutic effect within 14 days, 10 days, 4 days, 3 days, 2 days, or 1 day, or within 24 hours, 20 hours, 16 hours, 12 hours, 10 hours, or 8 hours or less (e.g., as measured by a reduction in the Hamilton Depression Rating Scale (HAM-D)). In some embodiments, the method of treating a depressive disorder (e.g., major depressive disorder) provides a therapeutic effect within the first or second day of treatment with compound 1 (e.g., as measured by a statistically significant reduction in the total HAM-D score). In some embodiments, the method of treating a depressive disorder (e.g., major depressive disorder) provides a therapeutic effect within 14 days or less from the start of treatment with compound 1 (e.g., as measured by a statistically significant reduction in the total HAM-D score). In some embodiments, the method of treating a depressive disorder (e.g., major depressive disorder) provides a therapeutic effect within 21 days or less from the start of treatment with compound 1 (e.g., as measured by a statistically significant reduction in the total HAM-D score). In some embodiments, the method of treating depressive disorders (e.g., major depressive disorder) provides a therapeutic effect (e.g., as measured by a statistically significant reduction in the total HAM-D score) within 28 days or less from the start of treatment with Compound 1. In some embodiments, the therapeutic effect is a reduction in the total HAM-D score from baseline after treatment with Compound 1 (e.g., once daily for 14 days). In some embodiments, an individual's total HAM-D score was at least 24 before treatment with Compound 1. In some embodiments, an individual's total HAM-D score was at least 18 before treatment with Compound 1. In some embodiments, an individual's total HAM-D score was between and including 14 and 18 before treatment with Compound 1. In some embodiments, after treatment with Compound 1, the individual's total HAM-D score decreased by at least 10 relative to the baseline total HAM-D score. In some embodiments, after treatment with Compound 1, the individual's total HAM-D score decreased by at least 15 (e.g., at least 17) relative to the baseline total HAM-D score. In some embodiments, the total HAM-D score associated with an individual treated with compound 1 is not greater than a value in the range of 6 to 8. In some embodiments, the total HAM-D score associated with an individual treated with compound 1 is not greater than 7. In some embodiments, the method provides a therapeutic effect within 14 days, 10 days, 4 days, 3 days, 2 days, or 1 day, or 24 hours, 20 hours, 16 hours, 12 hours, 10 hours, or 8 hours or less (e.g., as measured by a reduction in the Clinical Global Impression-Improvement Scale (CGI)). In some embodiments, the CNS condition is a depressive condition, such as major depressive disorder. In some embodiments, the method for treating a depressive condition (e.g., major depressive disorder) provides a therapeutic effect within the second day of the treatment period. In some embodiments, the therapeutic effect is a reduction in the CGI score from baseline at the end of the treatment period (e.g., 14 days after administration). In some embodiments, the method provides a therapeutic effect within 14 days, 10 days, 4 days, 3 days, 2 days, or 1 day, or within 24 hours, 20 hours, 16 hours, 12 hours, 10 hours, or 8 hours or less (e.g., as measured by a reduction in the Montgomery-Asberg Depression Rating Scale (MADRS)). In some embodiments, the CNS condition is a depressive condition, such as major depressive disorder. In some embodiments, the method for treating a depressive condition (e.g., major depressive disorder) provides a therapeutic effect within the second day of the treatment period. In some embodiments, the therapeutic effect is a reduction in the MADRS score from baseline at the end of the treatment period (e.g., 14 days after administration). The features of this disclosure are particularly those concerning an article comprising a therapeutically effective amount of compound 1, packaging material, and a label affixed to the packaging material indicating that the therapeutically effective amount of compound 1 should be taken with food, or a packaging insert contained in the packaging material indicating that the therapeutically effective amount of compound 1 should be taken with food. In some embodiments, the therapeutically effective amount of compound 1 is in a solid dosage form, such as tablets or capsules. In some embodiments, the label or packaging insert further indicates that the therapeutically effective amount of compound 1 is taken once daily. In some embodiments, the label or packaging insert further indicates that the therapeutically effective amount of compound 1 is about 20 mg to about 60 mg; about 25 mg to about 50 mg; or about 25 mg to about 35 mg; or about 30 mg, for example, 30 mg. In some embodiments, the label or packaging insert further indicates that the therapeutically effective amount of compound 1 should be taken with food that is part of a high-fat diet or a regular diet. In some embodiments, the label or packaging insert further indicates that the therapeutically effective amount of compound 1 should be taken with food to increase the bioavailability of compound 1. In some embodiments, the label or packaging insert further indicates that the therapeutically effective amount of compound 1 is for the treatment of CNS-related conditions. In some embodiments, the method includes a method of treating CNS-related conditions by administering a therapeutically effective amount of compound 1, wherein the therapeutically effective amount of compound 1 is about 30 mg, for example 30 mg, and is administered substantially simultaneously with food. In particular, this disclosure provides a method for GABA administration in patients who require it. A A method for positive ectopic regulation of a receptor, wherein the method comprises administering a therapeutically effective amount of compound 1 substantially simultaneously with food to the patient. In some embodiments, the therapeutically effective amount is in the form of a solid dosage form, such as a tablet or capsule. In some embodiments, the therapeutically effective amount of compound 1 is administered once daily. In some embodiments, the therapeutically effective amount of compound 1 is about 20 mg to about 60 mg; about 25 mg to about 50 mg; or about 25 mg to about 35 mg; or about 30 mg, for example, 30 mg. In some embodiments, the therapeutically effective amount of compound 1 is substantially simultaneously with food, for example, within about 45 minutes, about 30 minutes, about 15 minutes, or about 5 minutes before or after food intake. In some embodiments, the food is a high-fat diet as defined herein, or a regular diet as discussed herein. In other embodiments, the food is at least 50 calories, at least 100 calories, at least 200 calories, or at least 300 calories. In some embodiments, administering a therapeutically effective amount of compound 1 simultaneously with food increases the bioavailability of the compound compared to not administering it with food. In some embodiments, the availability of organisms is based on a comparison of AUC values. In some embodiments, the availability of organisms is increased by about 10% or more; about 20% or more; about 30% or more; about 40% or more; about 50% or more; or about 55% or more. In particular, this disclosure provides a method for treating an individual with CNS-related conditions (e.g., GABA-related diseases or conditions such as mood disorders, movement disorders, postpartum depression, major depressive disorder, spontaneous tremor, or Parkinson's disease). This method comprises substantially simultaneously administering a therapeutically effective amount of compound 1 to the individual along with food, wherein such administration results in increased bioavailability of compound 1 compared to administration without food. In some embodiments, bioavailability is based on a comparison of AUC values. 0-t Value. In some embodiments, the bioavailability or AUC of compound 1 in the formulation is used. 0-t The value of AUC of compound 1 in another formulation 0-tThe values ​​are compared. In some embodiments, compound 1 is administered to the capsule along with food, and compound 1 is administered to the capsule without being administered to food. In some embodiments, the AUC values ​​are compared. 0-t The values ​​were compared, and the AUC of compound 1 formulation administered to the capsule along with food was also compared. 0-t The value is higher than the AUC of compound 1 formulation which is not administered to the capsule with food. 0-t Value. In some embodiments, the AUC of compound 1 formulation, which is administered to the capsule without food, is... 0-t When compared, the AUC of compound 1 formulation administered to the capsule along with food. 0-t The value has an increase of at least 10% or more. In other embodiments, this increase percentage is at least 20% or more; at least 30% or more; at least 40% or more; at least 40% or more; or at least 55% or more. In some embodiments, the CNS-related condition is a depressive condition, such as major depressive disorder. In some embodiments, the method of treating a depressive condition (e.g., major depressive disorder) provides a therapeutic effect within 14 days, 10 days, 4 days, 3 days, 2 days, or 1 day, or 24 hours, 20 hours, 16 hours, 12 hours, 10 hours, or 8 hours or less (e.g., as measured by a reduction in the Hamilton Depression Rating Scale (HAM-D)). In some embodiments, the CNS-related condition is a depressive condition, such as major depressive disorder. In some embodiments, the individual has a mild depressive condition, such as mild major depressive disorder. In some embodiments, the individual has a moderate depressive condition, such as moderate major depressive disorder. In some embodiments, the individual has a severe depressive condition, such as severe major depressive disorder. In some embodiments, the individual has an extremely severe depressive condition, such as extremely severe major depressive disorder. In some embodiments, the individual's baseline HAM-D total score is at least 24. In some embodiments, the individual's baseline HAM-D total score is at least 18. In some embodiments, the individual's baseline HAM-D total score is between 14 and 18, including 14 and 18. In some embodiments, the individual's baseline HAM-D total score is between 19 and 22, including 19 and 22. In some embodiments, the individual's HAM-D total score is greater than or equal to 23 prior to treatment with compound 1. In some embodiments, the baseline score is at least 10, 15, or 20. In some embodiments, after treatment with compound 1, an individual's total HAM-D score is approximately 0 to 10 (e.g., less than 10; 0 to 10, 0 to 6, 0 to 4, 0 to 3, 0 to 2, or 1.8). In some embodiments, after treatment with compound 1, the total HAM-D score is less than 10, 7, 5, or 3. In some embodiments, the reduction in the total HAM-D score is from a baseline score of approximately 20 to 30 (e.g., 22 to 28, 23 to 27, 24 to 27, 25 to 27, 26 to 27) to a total HAM-D score of approximately 0 to 10 (e.g., less than 10; 0 to 10, 0 to 6, 0 to 4, 0 to 3, 0 to 2, or 1.8) after treatment with compound 1. In some embodiments, the reduction in the baseline total HAM-D score to the total HAM-D score after treatment with compound 1 is at least 1, 2, 3, 4, 5, 7, 10, 25, 40, 50, or 100 times. In some embodiments, the percentage reduction in the baseline total HAM-D score to the total HAM-D score after treatment with compound 1 is at least 50% (e.g., 60%, 70%, 80%, or 90%). In some embodiments, the therapeutic effect is measured as the reduction in the total HAM-D score relative to the baseline total HAM-D score after treatment with compound 1 (e.g., at 12, 24, or 48 hours post-administration; or 24, 48, 72, or 96 hours or longer; or 1, 2, or 14 days or longer), which is at least 10, 15, or 20 points. In some embodiments, the method of treating depressive disorders (e.g., major depressive disorder) provides a therapeutic effect within 14 days, 10 days, 4 days, 3 days, 2 days, or 1 day, or within 24 hours, 20 hours, 16 hours, 12 hours, 10 hours, or 8 hours or less (e.g., as measured by a reduction in the Hamilton Depression Rating Scale (HAM-D)). In some embodiments, the method of treating depressive disorders (e.g., major depressive disorder) provides a therapeutic effect within the first or second day of treatment with compound 1 (e.g., as measured by a statistically significant reduction in the total HAM-D score). In some embodiments, the method of treating depressive disorders (e.g., major depressive disorder) provides a therapeutic effect within 14 days or less from the start of treatment with compound 1 (e.g., as measured by a statistically significant reduction in the total HAM-D score). In some embodiments, the method of treating depressive disorders (e.g., major depressive disorder) provides a therapeutic effect within 21 days or less from the start of treatment with compound 1 (e.g., as measured by a statistically significant reduction in the total HAM-D score). In some embodiments, the method of treating depressive disorders (e.g., major depressive disorder) provides a therapeutic effect (e.g., as measured by a statistically significant reduction in the total HAM-D score) within 28 days or less from the start of treatment with Compound 1. In some embodiments, the therapeutic effect is a reduction in the total HAM-D score from baseline after treatment with Compound 1 (e.g., once daily for 14 days). In some embodiments, an individual's total HAM-D score was at least 24 before treatment with Compound 1. In some embodiments, an individual's total HAM-D score was at least 18 before treatment with Compound 1. In some embodiments, an individual's total HAM-D score was between and including 14 and 18 before treatment with Compound 1. In some embodiments, after treatment with Compound 1, the individual's total HAM-D score decreased by at least 10 relative to the baseline total HAM-D score. In some embodiments, after treatment with Compound 1, the individual's total HAM-D score decreased by at least 15 (e.g., at least 17) relative to the baseline total HAM-D score. In some embodiments, the total HAM-D score associated with an individual treated with compound 1 is not greater than a value in the range of 6 to 8. In some embodiments, the total HAM-D score associated with an individual treated with compound 1 is not greater than 7. In some embodiments, the method provides a therapeutic effect (e.g., as measured by a reduction in the Clinical Global Impression Index (CGI)) within 14 days, 10 days, 4 days, 3 days, 2 days, or 1 day, or 24 hours, 20 hours, 16 hours, 12 hours, 10 hours, or 8 hours or less. In some embodiments, the method for treating depressive disorders (e.g., major depressive disorder) provides a therapeutic effect within the second day of the treatment period. In some embodiments, the therapeutic effect is a reduction in the CGI score from baseline at the end of the treatment period (e.g., 14 days after administration). In some embodiments, the method provides a therapeutic effect (e.g., as measured by a reduction in the Montgomery-Asperger Depression Rating Scale (MADRS)) within 14 days, 10 days, 4 days, 3 days, 2 days, or 1 day, or 24 hours, 20 hours, 16 hours, 12 hours, 10 hours, or 8 hours or less. In some embodiments, the method for treating depressive disorders (e.g., major depressive disorder) provides a therapeutic effect within the second day of the treatment period. In some embodiments, the therapeutic effect is a reduction in the MADRS score from baseline at the end of the treatment period (e.g., 14 days after administration). In some of the foregoing embodiments, individual compound 1 (e.g., about 30 mg of compound 1) is administered once daily for less than 2 weeks. In some of the foregoing embodiments, individual compound 1 (e.g., about 30 mg of compound 1) is administered once daily for 1 day. In some of the foregoing embodiments, individual compound 1 (e.g., about 30 mg of compound 1) is administered once daily for 2 days. In some of the foregoing embodiments, individual compound 1 (e.g., about 30 mg of compound 1) is administered once daily for at least 14 days. In some embodiments, individual compound 1 (e.g., about 30 mg of compound 1) is administered once daily for at least 28 days. In some embodiments, individual compound 1 (e.g., about 30 mg of compound 1) is administered once daily for at least 6 months. In some embodiments, individual compound 1 is administered once daily (e.g., at a dose of about 30 mg) for at least one year. In some embodiments, individual compound 1 is administered once daily (e.g., at a dose of about 30 mg) for life. In some embodiments, individual compound 1 is administered at night. In some embodiments, individual compound 1 is administered no more than one hour before the individual falls asleep. In some embodiments, individual compound 1 is administered no more than 15 minutes before the individual falls asleep. In some embodiments, compound 1 is administered long-term. Cross-reference to related applications This application claims priority to USSN 62 / 555,404, filed September 7, 2017, and USSN 62 / 595,998, filed December 7, 2017, the contents of which are incorporated herein by reference in their entirety. This disclosure relates to compound 1 or 1-(2-((3R,5R,8R,9R,10S,13S,14S,17S)-3-hydroxy-3,13-dimethylhexadecylhydro-1H-cyclopentan[a]phenanthrene-17-yl)-2-sideoxyethyl)-1H-pyrazole-4-carboxynitrile, which has the formula (Compound 1), Methods for treating CNS-related conditions using Compound 1 and methods for improving the effectiveness of administering Compound 1 for treating such CNS-related conditions. In one instance, this disclosure relates to a method of administering compound 1 to individuals in a manner that can increase the therapeutic efficacy of compound 1. Advantageously, when administered orally with food, compound 1 exhibits an increased bioavailability in individuals. It should be understood that in some embodiments, the methods described (e.g., methods for improving the dosing efficacy of compound 1) may relate to a pharmaceutically acceptable salt of compound 1 for the treatment of CNS-related conditions, such as (but not limited to) depressive disorders, such as major depressive disorder. The term "AUC" is defined as the area under the time / plasma concentration curve after administration of a pharmaceutical composition. 0- 無限大 AUC represents the area under the curve of plasma concentration versus time from time 0 to infinity. 0-t AUC represents the area under the curve of plasma concentration versus time from time 0 to time t. As used in this paper, AUC 0-t The AUC is the area under the time curve from the time of drug administration to the final quantifiable plasma concentration. It should be understood that the AUC value can be determined using methods known in the industry. As used herein, the term "bioavailability" generally refers to the rate and extent to which an active ingredient or its active form is absorbed from a pharmaceutical product and becomes available at the site of action. See US Code of Federal Regulations, 21, Part 320.1 (2001 edition). For oral dosage forms, bioavailability refers to the process by which an active ingredient is released from an oral dosage form (e.g., tablets), converted to its active form (if the active ingredient is not yet in its active form), and moves to the site of action (e.g., absorbed into the systemic circulation). For example, bioavailability is based on the area under the plasma concentration-time curve (e.g., AUC). 0-t To compare the bioavailability among different formulations containing compound 1, the AUC of each formulation will be compared. 0-t Values ​​(e.g., a comparison between compound 1 formulations administered in capsules with food and compound 1 formulations administered in capsules without food). It should be understood that AUC values ​​can be compared as a percentage increase or decrease. It should be further understood that percentage increases or decreases are calculated as known in the art. The terms "not with food" or "fasting" are defined as the condition of not consuming food for a period of approximately 2 hours before and after administration of compound 1. As used herein, the term "unit dosage form" is defined as the form in which compound 1 is administered to an individual. Specifically, a unit dosage form may be, for example, a pill, capsule, or tablet. Preferably, the unit dosage form is a capsule. A typical amount of compound 1 in a unit dosage form used in this invention is from about 10 mg to about 100 mg, preferably from about 20 mg to about 50 mg (e.g., about 30 mg, for example, 30 mg). In a preferred embodiment of this invention, the unit dosage form contains about 30 mg (e.g., 30 mg) of compound 1 and is in capsule form. Preferably, a capsule containing about 30 mg (e.g., 30 mg) of compound 1 is administered to an individual once daily. In some embodiments, two capsules together contain 30 mg of compound 1. In some embodiments, one capsule contains 30 mg of compound 1. As used herein, "submitted substantially simultaneously with food" or "substantially simultaneously" means the intake (or introduction) of a food-containing substance (e.g., a high-fat diet, a standard diet or a regular diet, a food containing at least 50 calories, a food containing at least 100 calories, a food containing at least 200 calories or a food containing at least 300 calories) within 5 minutes, 10 minutes, 15 minutes, 30 minutes, 45 minutes, 60 minutes, 75 minutes or 90 minutes before or after the intake (or introduction) of the composition of the present invention (e.g., a therapeutically effective amount of compound 1). Term "C" max "" refers to the maximum concentration of the therapeutic agent (e.g., compound 1) in the blood (e.g., plasma) after administration of the pharmaceutical composition. Term "t" max "This refers to the achievement of C after administration of a pharmaceutical composition containing a therapeutic agent (e.g., compound 1)." max Time (in hours). As used herein, "solid dosage form" means one or more pharmaceutical dosages in solid form, such as tablets, capsules, granules, powders, small capsules, reconfigurable powders, dry powder inhalers, and chewable tablets. As used herein, a "high-fat diet" refers to a diet high in fat and calories, where approximately 50% of the total calories come from fat and the diet comprises approximately 800 to 1000 calories. A diet can also consist of approximately 150 calories from protein, 250 calories from carbohydrates, and 500-600 calories from fat. An illustrative high-fat diet includes the test diets described in the December 2002 document, *Guidance for Industry, Food-Effect Bioavailability and Fed Bioequivalence Studies*, published by the U.S. Department of Health and Human Services Food and Drug Administration, the Center for Drug Evaluation and Research (CDER), and the Center for Biologics Evaluation and Research (CBER). An illustrative high-fat diet contains approximately 50% of the total calories as fat and comprises approximately 800 to 1000 calories; 500-600 calories are derived from fat. As used in this article, the term "fat" is used in its conventional and industry-recognized meaning. As used in this article, "regular diet" or "standard diet" refers to a diet of approximately 300 to 800 calories. Unless otherwise expressly stated, the teachings of this invention include the specific quantitative value itself when the term "about" is used before a quantitative value. Unless otherwise indicated or speculated, as used herein, the term "about" means ±10% variation from the nominal value. As used herein, the baseline total score of the scales described herein for assessing an individual’s condition (e.g., the Hamilton Depression Rating Scale, the Montgomery-Asperger Depression Rating Scale, or the Modified Clinical Global Impression Scale) is the individual’s total score measured before treatment with a therapeutic agent (e.g., Compound 1). The chemical definitions, including specific functional groups and chemical terms, are elaborated in more detail below. Chemical elements are based on the periodic table (CAS version). The Handbook of Chemistry and Physics, 75th edition, is used for identification, and specific functional groups are usually defined as described therein. Furthermore, the general principles of organic chemistry, as well as specific functional groups and reactivity, are explained in the following literature: Thomas Sorrell, Organic Chemistry, University Science Books, Sausalito, 1999; Smith and March, March's Advanced Organic Chemistry, 5th Edition, John Wiley & Sons, Inc., New York, 2001; Larock, Comprehensive Organic Transformations, VCH Publishers, Inc., New York, 1989; and Carruthers, Some Modern Methods of Organic Synthesis, 3rd edition, Cambridge University Press, Cambridge, 1987. The compounds described herein may contain one or more asymmetric centers and therefore may exist in various isomeric forms (e.g., mirror-image isomers and / or non-mirror-image isomers). For example, the compounds described herein may exist as individual mirror-image isomers, non-mirror-image isomers, or geometric isomers, or as mixtures of stereoisomers, including racemic mixtures and mixtures rich in one or more stereoisomers. Isomers may be separated from mixtures by methods known to those skilled in the art, including chiral high-performance liquid chromatography (HPLC) and the formation and crystallization of chiral salts; or preferred isomers may be prepared by asymmetric synthesis. See, for example, Jacques et al. Enantiomers, Racemates and Resolutions (Wiley Interscience, New York, 1981); Wilen et al., Tetrahedron33:2725 (1977); Eliel, Stereochemistry of Carbon Compounds (McGraw-Hill, NY, 1962); and Wilen, Tables of Resolving Agents and Optical Resolutions, page 268 (edited by El Eliel, Univ. of Notre Dame Press, Notre Dame, IN, 1972). This invention further covers compounds described herein in either their individual isomer forms, substantially free of other isomers, or in mixtures of various isomers. The article “a (and an)” used in this article refers to one or more (i.e., at least one) grammatical objects of that article. For example, “analogy” means one or more analogies. As used herein, the term "modulation" refers to the inhibition or enhancement of GABA receptor function. A "modulator" (e.g., a modulatory compound) may be, for example, an agonist, partial agonist, antagonist, or partial antagonist of the GABA receptor. "Pharmaceutical acceptable" means that it has been approved by federal or state government regulatory agencies or the corresponding agencies in countries other than the United States, or can be approved or listed in the United States Pharmacopeia or other recognized pharmacopoeia for use in animals, and more specifically for use in humans. "Pharmaceutically acceptable salts" refers to salts of the compounds of the present invention that are pharmaceutically acceptable and possess the desired pharmacological activity of the parent compound. Specifically, such salts are non-toxic and may be inorganic or organic acid addition salts and base addition salts. Specifically, such salts include: (1) acid addition salts formed from inorganic acids, such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid and the like; 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. (1) Ethanesulfonic acid, 1,2-ethane-disulfonic acid, 2-hydroxyethanesulfonic acid, benzenesulfonic acid, 4-chlorobenzenesulfonic acid, 2-naphthalenesulfonic acid, 4-toluenesulfonic acid, camphorsulfonic acid, 4-methylbicyclo[2.2.2]-oct-2-ene-1-carboxylic acid, glucoheponic acid, 3-phenylpropionic acid, trimethylacetic acid, tributylacetic acid, lauryl sulfate, gluconic acid, glutamic acid, hydroxynaphthoic acid, salicylic acid, stearic acid, muconic acid and the like; or (2) a salt formed when an acidic proton present in the parent compound is substituted by a metal ion (e.g., an alkali metal ion, an alkaline earth metal ion or an aluminum ion) or coordinated with an organic base (e.g., ethanolamine, diethanolamine, triethanolamine, N-methylglucosamine and the like). Salts further include (by way of example only) sodium salts, potassium salts, calcium salts, magnesium salts, ammonium salts, tetraalkylammonium salts, and the like; and when the compound contains a basic functional group, it is a salt of a non-toxic organic or inorganic acid, such as hydrochloride, hydrobromide, tartrate, methanesulfonate, acetate, maleate, oxalate, and the like. The term "pharmaceutically acceptable cation" refers to an acceptable cation-relative ion with an acidic functional group. Examples of such cations include sodium, potassium, calcium, magnesium, ammonium, tetraalkylammonium cations, and the like. See, for example, Berge et al. J. Pharm. Sci. (1977) 66(1): 1-79. The intended recipient of this "individual" includes (but is not limited to) humans (i.e., males or females of any age, such as pediatric individuals (e.g., infants, children, adolescents) or adult individuals (e.g., young adults, middle-aged adults, or elderly adults)) and / or non-human animals (e.g., mammals, such as primates (e.g., cynomolgus monkeys, rhesus monkeys), cattle, pigs, horses, sheep, goats, rodents, cats, and / or dogs). In some embodiments, the individual is human. In some embodiments, the individual is a non-human animal. The terms "human," "patient," and "individual" are used interchangeably herein. Disease, symptoms, and condition can be used interchangeably in this article. As used herein and unless otherwise specified, the terms “treat, treating, and treatment” encompass actions taken to reduce the severity of a given disease, condition, or illness, or to delay or slow its progression (“therapeutic treatment”), while an individual has the given disease, condition, or illness, and also encompass actions taken before an individual begins to have the given disease, condition, or illness (“preventive treatment”). As used herein and unless otherwise specified, a “treatment cycle” includes a first dose of neuroactive steroids, a second dose of neuroactive steroids, and a third dose of neuroactive steroids, which are sufficient to treat the individual. Generally, the "effective amount" of a compound refers to an amount sufficient to elicit the desired biological response, such as for treating CNS-related conditions (e.g., conditions described herein, such as tremor (e.g., spontaneous tremor); depression (e.g., postpartum depression); or anxiety disorder)). As will be understood by those skilled in the art, the effective amount of the compounds of this invention can vary depending on factors such as the desired biological endpoint, the pharmacokinetics of the compound, the disease being treated, the mode of administration, and the individual's age, weight, health status, and condition. Effective amounts encompass both therapeutic and preventative treatment. As used herein and unless otherwise specified, a "therapeuticly effective amount" of a compound is an amount sufficient to provide therapeutic benefit in the treatment of a disease, symptom, or condition, or to delay or minimize one or more symptoms associated with that disease, symptom, or condition. A therapeutically effective amount of a compound means the amount by which a therapeutic agent, alone or in combination with other therapies, provides therapeutic benefit in the treatment of a disease, symptom, or condition. The term "therapeuticly effective amount" may also encompass amounts that improve overall therapy, reduce or prevent symptoms or causes of a disease or condition, or enhance the therapeutic efficacy of another therapeutic agent. As used herein and unless otherwise specified, a "preventively effective amount" of a compound is an amount sufficient to prevent a disease, condition, or illness, or one or more symptoms associated with that disease, condition, or illness, or to prevent its recurrence. A preventively effective amount of a compound means the amount by which a therapeutic agent, alone or in combination with other agents, provides a preventive benefit in the prevention of 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. As used herein, "crystal" refers to a solid with a highly regular chemical structure, i.e., a long-range structural order in a crystal lattice. Molecules are arranged in a regular, periodic manner in the three-dimensional space of the crystal lattice. Specifically, a crystal form can be produced as one or more single crystal forms. For the purposes of this application, the terms "crystal form," "single crystal form," "crystalline solid form," "solid form," and "polymorph" are synonyms and are used interchangeably; these terms distinguish crystals with different properties (e.g., different XRPD patterns and / or different DSC scan results). The term "substantially crystalline" refers to a form that can crystallize at least a specific weight percentage. A specific weight percentage is 70%, 75%, 80%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9%, or any percentage between 70% and 100%. In some embodiments, the specific weight percentage of crystallinity is at least 90%. In some other embodiments, the specific weight percentage of crystallinity is at least 95%. In some embodiments, Compound 1 may be a substantially crystalline sample of any crystalline solid form described herein (e.g., form A, C, or K). The term "substantially pure" refers to the composition of a particular crystalline solid form of Compound 1 that is free from impurities and / or other solid forms of Compound 1 by at least 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 1 may be a substantially pure sample of any crystalline solid form (e.g., form A, C, or K) described herein. In some embodiments, Compound 1 may be substantially pure form A. In some embodiments, Compound 1 may be substantially pure form C. As used herein, the terms "anhydrous" or "anhydrous form," when referring to the crystalline form of Compound 1, mean that no solvent molecules (including water molecules) form a portion of the unit cell of the crystalline form. However, an anhydrous crystalline sample may contain solvent molecules that do not form a portion of the unit cell of the anhydrous crystalline form, such as residual solvent molecules left over from the formation of the crystalline form. In a preferred embodiment, the solvent may constitute 0.5% by weight of the total composition of the anhydrous form of the sample. In a more preferred embodiment, the solvent may constitute 0.2% by weight of the total composition of the anhydrous form of the sample. In some embodiments, an anhydrous crystalline sample of Compound 1 contains no solvent molecules, such as no detectable amount of solvent. The term "solvent compound," when referring to the crystalline form of Compound 1, means that solvent molecules (e.g., organic solvents and water) form a portion of the unit cell of the crystalline form. Solvent compounds containing water as a solvent are also referred to herein as "hydrates." The term "isomorphic," when referring to the crystalline form of Compound 1, means that the form may contain different chemical compositions in the unit cell, such as different solvent molecules, but have the same XRPD pattern. The isomorphic crystal form is sometimes referred to as "isomorphic body" in this article. The term "characteristic peak" in the context of the XRPD pattern of the crystalline form of compound 1 refers to a set of 2θ values ​​spanning the range of 0°–40° that are assigned as a whole to certain peaks of only one crystalline form of compound 1. Bioavailability and Food: Food can alter the bioavailability of drugs or compounds and can have clinically significant consequences. Food can alter bioavailability in unpredictable ways through various mechanisms, including delaying gastric emptying, stimulating bile flow, altering gastrointestinal (GI) pH, increasing visceral blood flow, altering the luminal metabolism of active pharmaceutical ingredients (APIs), and / or physically and chemically interacting with the dosage form or API. The nutrient and calorie content, volume, and temperature of the diet can influence physiological changes in the GI pathway by affecting drug transit time, luminal dissolution, drug permeability, and systemic bioavailability. Administering drugs or compounds with food can alter bioavailability by affecting the API or drug product. The mechanisms by which food alters the bioavailability of drugs or compounds are difficult to determine. This disclosure provides a method for increasing the extent of absorption of compound 1, which is measured by the concentration obtained over time in the bloodstream in an individual requiring its therapeutic effect. This method involves orally administering a therapeutically effective amount of compound 1 and food to the individual. The concentration in the bloodstream is measured as the plasma concentration of compound 1 (e.g., ng / mL). Pharmacokinetic parameters involved in determining plasma concentration include the maximum observed plasma concentration (C0). max From time zero to the final quantifiable concentration (AUC) 0-t The area under the plasma concentration-time curve (AUC) and the area from zero to infinity (AUC) of plasma concentration. 0- ∞ The AUC of compound 1 administered with food. The increase in biological availability of compound 1 administered with food compared to administration under fasting (or without food) conditions is measured by the increase in one or more of the aforementioned pharmacokinetic parameters. In some embodiments, the AUC of compound 1 formulation administered in capsules without food is... 0-t When compared, the AUC of compound 1 formulation administered to the capsule along with food. 0-t The value has an increase of at least 10% or more. In other embodiments, this increase percentage is at least 20% or more; at least 30% or more; at least 40% or more; at least 40% or more; or at least 55% or more. Individuals may ingest the compound or drug in a fasting or eating state, with or without food. In a fasting state, an individual may fast (e.g.) overnight for at least ten (10) hours. The individual may then ingest the drug or compound, wherein the individual has not consumed food for at least four hours after administration. Alternatively, an individual may fast (e.g.) for two hours and then ingest the drug or compound, wherein the individual has not consumed food for at least two hours after administration. In a eating state or with food, an individual may begin a meal (high-fat or regular) thirty (30) minutes before administration of the drug or compound. The individual may then consume this meal for 30 minutes or less; however, the drug or compound may be administered thirty (30) minutes after the start of the meal. Therefore, it is desirable to administer the compound (e.g., compound 1) in a manner that maximizes bioavailability. One aspect of this disclosure is a method for increasing the bioavailability of compound 1 in an individual by administering compound 1 in a therapeutically effective amount along with food. In one aspect of this disclosure, a therapeutically effective amount of compound 1 is substantially administered to the individual simultaneously with food. The food may be a high-fat diet or a regular diet. A high-fat diet may contain approximately 50% of the total dietary calories as fat and approximately 800 to 1000 calories. An illustrative high-fat diet includes the test diet disclosed in the document Guidance for Industry, Food-Effect Bioavailability and Fed Bioequivalence Studies published in December 2002 by the U.S. Food and Drug Administration's Department of Health and Human Services, Center for Drug Evaluation and Research (CDER), and Center for Biologics Evaluation and Research (CBER). An illustrative high-fat diet contains approximately 50% of the total dietary calories as fat and approximately 800 to 1000 calories; 500-600 calories are from fat. As used herein, the term "fat" is used in its conventional and industry-accepted sense. For example, a high-fat diet could consist of two fried eggs in butter, two strips of bacon, two slices of toast with butter, 4 oz. of hash browns, and 8 oz. of whole milk. A regular or standard diet could consist of meals such as breakfast, lunch, or dinner with 300 to 800 calories. For example, an individual could eat dinner, finish it within 30 minutes, and then immediately after finishing dinner, ingest a therapeutically effective amount of compound 1. The method disclosed herein involves substantially simultaneously administering a therapeutically effective amount of Compound 1 with a food, which may be a snack or less than a meal. For example, Compound 1 may be substantially simultaneously administered with a food containing approximately 50 calories. Alternatively, Compound 1 may be substantially simultaneously administered with a food containing approximately 100 calories. Compound 1 may be substantially simultaneously administered with a food containing approximately 200 or approximately 300 calories. For example, an individual may consume a food (e.g., a snack), such as fruit, granola, crackers, cheese, etc., and then the individual will ingest (take) a therapeutically effective amount of Compound 1. In another embodiment of this disclosure, a therapeutically effective amount of compound 1 is substantially administered to the individual simultaneously with a food (e.g., a high-fat, regular diet, or a food containing approximately 50 to approximately 300 calories, as discussed herein), wherein substantially simultaneous administration with food means administering the therapeutically effective amount of compound 1 within 5, 10, 15, 30, 45, 60, 75, or 90 minutes before or after ingestion or consumption of the food. For example, the therapeutically effective amount of compound 1 is administered approximately 90 minutes before or after ingestion or consumption of the food (e.g., a high-fat, regular diet, or a food containing approximately 50 to approximately 300 calories, as discussed herein). For example, the therapeutically effective amount of compound 1 is administered approximately 75 minutes before or after ingestion or consumption of the food (e.g., a high-fat, regular diet, or a food containing approximately 50 to approximately 300 calories, as discussed herein). For example, a therapeutically effective amount of compound 1 may be administered approximately 60 minutes before or after consuming food (e.g., high-fat, regular, or foods containing approximately 50 to approximately 300 calories, as discussed herein). For example, a therapeutically effective amount of compound 1 may be administered approximately 45 minutes before or after consuming food (e.g., high-fat, regular, or foods containing approximately 50 to approximately 300 calories, as discussed herein). For example, a therapeutically effective amount of compound 1 may be administered approximately 30 minutes before or after consuming food (e.g., high-fat, regular, or foods containing approximately 50 to approximately 300 calories, as discussed herein). For example, a therapeutically effective amount of compound 1 may be administered approximately 15 minutes before or after consuming food (e.g., high-fat, regular, or foods containing approximately 50 to approximately 300 calories, as discussed herein). For example, a therapeutically effective amount of compound 1 may be administered approximately 10 minutes before or after consuming food (e.g., a high-fat, regular diet, or food containing approximately 50 to approximately 300 calories, as discussed herein). Alternatively, a therapeutically effective amount of compound 1 may be administered approximately 5 minutes before or after consuming food (e.g., a high-fat, regular diet, or food containing approximately 50 to approximately 300 calories, as discussed herein). Compound 1 can be administered with food at any time of day, for example, substantially simultaneously with food (e.g., high-fat, regular meals, or foods containing approximately 50 to approximately 300 calories, as discussed herein) at any time of day. For example, a therapeutically effective amount of Compound 1 can be administered (or self-administered) substantially simultaneously with breakfast. For example, a therapeutically effective amount of Compound 1 can be administered (or self-administered) substantially simultaneously with lunch. For example, a therapeutically effective amount of Compound 1 can be administered (or self-administered) substantially simultaneously with dinner. The increased bioavailability of Compound 1 in individuals receiving Compound 1 can be demonstrated by any suitable means. Desirably, oral administration of Compound 1 with food increases its bioavailability, such as through the AUC of Compound 1. 0-t Value and AUC of compound 1 given with or without food 0-t The increase in value is evidenced by this. The compositions disclosed herein may also be packaged as articles containing a therapeutically effective amount of compound 1. Any of the various methods known to those skilled in the art for packaging tablets, capsules, or other solid dosage forms suitable for oral administration without degrading the components of this disclosure are suitable for packaging. In some forms, the product contains a therapeutically effective amount of compound 1, packaging material, and labels affixed to the packaging material or packaging inserts contained within the packaging material. In some embodiments, the packaging material includes at least one container. In some embodiments, the packaging material includes multiple containers. As used herein, a container is an object that contains a therapeutically effective amount of compound 1. For example, a container may be a bottle, blister pack, box, carton, narrow strip package, carton, or single-dose container. In some embodiments, a container is a bottle containing a therapeutically effective amount of compound 1. In some embodiments, a box contains a bottle containing a therapeutically effective amount of compound 1. In some embodiments, a container is a blister pack containing a therapeutically effective amount of compound 1. It should be understood that packaging materials may comprise a single material or a variety of materials. For example, packaging materials may comprise glass, paper, plastic, or metal. In some embodiments, the packaging material is composed of glass, plastic, and metal. In some embodiments, the packaging material is composed of glass and plastic. In some embodiments, the packaging material is composed of glass and metal. In some embodiments, the packaging material is composed of plastic and metal. In some embodiments, the packaging material is composed of glass. For example, the packaging material is a glass bottle. In some embodiments, the packaging material is composed of plastic. For example, the packaging material is a plastic bottle or a plastic blister pack. In some embodiments, the packaging material is composed of metal. For example, the packaging material is a metal (e.g., aluminum) blister pack. In some embodiments, the container has a closure. After the drug container is filled with a solid dosage form containing compound 1, the closure is used to cover the container. Depending on the type of container, the closure may have different shapes and sizes. The closure may be made of rubber, a cap or top seal, a vandal-resistant closure, a child-proof closure, etc. The packaging material disclosed herein may have one, two, three, four, or five types of closures. For example, if the container is a glass bottle, the glass bottle may have a rubber seal and a plastic cap. Packaging materials may also have labels and printed information related to the pharmaceutical composition. Additionally, the product may contain manuals, reports, notices, brochures, or leaflets containing product information. This form of pharmaceutical information is known in the pharmaceutical industry as a "packaging insert." Packaging inserts may be attached to or included in the product. Packaging inserts and any product label provide information related to a therapeutically effective amount of compound 1. This information and labeling provide various forms of information used by healthcare professionals and patients, describing a therapeutically effective amount of compound 1, its dosage, and various other parameters required by regulatory agencies such as the United States Food and Drug Administration (FDA). The desired outcome is to provide compound 1 to the individual in the form of a prepared preparation, which is associated with the prescription information recommending that the individual administer compound 1 orally with food. The preparation also suggests that this will increase the bioavailability of compound 1. It is preferable to provide compound 1 to the individual in the form of a prepared preparation, which, along with the recommended dosage of compound 1 administered with food, increases the extent of compound 1 absorption (e.g., by comparing the AUC of compound 1 with administration under fasting conditions). 0-t The value reflects the prescription information. In some embodiments, compound 1 is in packaging material having a label affixed to the packaging material indicating that a therapeutically effective amount of compound 1 should be taken with food, or a packaging insert containing an indication that a therapeutically effective amount of compound 1 should be taken with food within the packaging material. The labeling instructions will be consistent with the treatment methods described herein. The label may be associated with the container in any way that maintains physical proximity to both, and as a non-limiting example, it may be contained in packaging material such as a box or plastic shrink wrap or may be associated with instructions adhered to the container (e.g., using adhesive or other adhesive or holding devices that do not obscure the labeling instructions). In one embodiment, this disclosure provides a pharmaceutical composition comprising a compound of the present invention (also referred to as the "active ingredient"), such as compound 1, and a pharmaceutically acceptable excipient. In some embodiments, the pharmaceutical composition comprises an effective amount of the active ingredient. In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of the active ingredient. In some embodiments, the pharmaceutical composition comprises a preventatively effective amount of the active ingredient. The pharmaceutical compositions provided herein can be administered via a variety of routes, including (but not limited to) oral (enteral), non-enteral (by injection), rectal, percutaneous, intradermal, intrathecal, subcutaneous (SC), intravenous (IV), intramuscular (IM), and intranasal administration. In a preferred embodiment, compound 1 is administered orally to an individual. Generally, the compounds described herein are administered in an effective amount. The actual amount of the compound administered will usually be determined by the physician based on factors including: the condition to be treated, the route of administration, the compound to be administered, the individual patient's age, weight and response, the severity of the patient's symptoms, and so on. When used to prevent the onset of CNS symptoms, the compounds described herein are typically administered to individuals at risk of developing the condition, as advised and under the supervision of a physician, at the dosages described above. Individuals at risk of developing a particular condition typically include those with a family history of the condition or those identified through genetic testing or screening as particularly susceptible to the condition. The pharmaceutical compositions described herein can also be administered over a long period (“chronic administration”). Chronic administration refers to administration of the compound or a pharmaceutical composition thereof over an extended period (e.g., over 3 months, 6 months, 1 year, 2 years, 3 years, 5 years, etc.), or indefinitely, for example, for the remainder of an individual’s life. In some embodiments, chronic administration is intended, for example, to provide a constant level of the compound in the blood within a therapeutic window of the extended period. The pharmaceutical compositions of the present invention can be further delivered using a variety of administration methods. For example, in some embodiments, the pharmaceutical composition can be administered in a concentrated form to, for example, increase the concentration of the compound in the blood to an effective amount. The formulation of the concentrated dose depends on the total amount of the desired active ingredient in the whole body; for example, intramuscular or subcutaneous concentrated doses allow for slow release of the active ingredient, while direct intravenous delivery (e.g., via an IV drip bag) allows for faster delivery, which rapidly increases the concentration of the active ingredient in the blood to an effective amount. In other embodiments, the pharmaceutical composition can be administered, for example, via an IV drip bag in a continuous infusion form to provide maintenance of a steady-state concentration of the active ingredient in the individual body. Furthermore, in other embodiments, the pharmaceutical composition can be administered first as a concentrated dose, followed by continuous infusion. Compositions intended for oral administration may be in the form of bulk liquid solutions, suspensions, or bulk powders. However, more commonly, these compositions are provided in unit dosage forms to facilitate precise drug delivery. The term "unit dosage form" refers to a physically discrete unit suitable for single-dose administration to an individual human or other mammals, each unit containing a predetermined amount of active material calculated to produce the desired therapeutic effect, and suitable pharmaceutical excipients. Typical unit dosage forms include pre-filled, pre-measured ampoules or syringes of liquid compositions, or, in the case of solid compositions, pills, tablets, capsules, or the like. In these compositions, the compound is typically a minor component (about 0.1% by weight to about 50% by weight, or preferably about 1% by weight to about 40% by weight), and the remainder consists of various mediators or excipients and processing aids that contribute to the formation of the desired delivery form. The components described above, which can be administered orally, injected, or topically, are merely representative. Other materials, processing techniques, and similar descriptions are available in [the relevant section]. The text is incorporated herein by reference in Part 8 of Remington's Pharmaceutical Sciences, 17th edition, 1985, Mack Publishing Company, Easton, Pennsylvania. The compounds of this invention can also be administered in a sustained-release form or via a sustained-release drug delivery system. For a description of representative sustained-release materials, please refer to [link to relevant documentation]. Remington's Pharmaceutical Sciences. This invention also relates to pharmaceutically acceptable acid addition salts of the compounds of this invention. The acids used to prepare pharmaceutically acceptable salts are acids that form non-toxic acid addition salts (i.e., salts containing pharmacologically acceptable anions), such as hydrochlorides, hydroiodides, hydrobromates, nitrates, sulfates, hydrogen sulfates, phosphates, acetates, lactates, citrates, tartrates, succinates, maleates, fumarates, benzoates, p-toluenesulfonates, and the like. In some embodiments, compound 1 is in solid form or crystalline form. For example, compound 1 may be in form A (as discussed herein), form C (as discussed herein), or form K (as discussed herein). Form A can be prepared by: stirring crude compound 1 as a slurry in ethyl acetate below 10°C, then filtering and drying under vacuum; or dissolving crude compound 1 in dichloromethane and then concentrating the solution twice under vacuum with ethyl acetate until dry. Form A can be determined by XRPD to be the crystalline form of compound 1. TGA, together with the single-crystal structure of form A, can be used to infer that form A is anhydrous. DSC can be used to indicate the presence of two endothermic events occurring at temperatures below 300°C: the first endothermic event, T, begins at 157.2°C, indicating the transformation of form A to form K, and the second endothermic event, T, begins at 203.8°C, indicating the melting point of form K. DVS can be used to show that form A exhibits a water uptake of less than 0.30% by weight at a relative humidity (RH) of less than or equal to 95%. In some embodiments, the XRPD pattern of Form A can be substantially as depicted in Figure 3A. Additionally, the representative peaks of the XRPD pattern of Form A can be indicated by their values ​​of 2θ, d-spacing, and relative intensity, as shown, for example, in Table 1 below: Table 1. Selected experimental XRPD pattern data for Form A. 2θ (degrees) d-distance (Å) Relative intensity (%) 9.494611 9.31518 40.49 10.78823 8.20093 46.5 13.22776 6.69345 37.69 14.89123 5.94927 10.18 15.99324 5.54174 15.09 18.28113 4.85302 31.96 18.93233 4.68754 100 21.05207 4.2201 10.38 21.64548 4.10573 24.16 23.50505 3.78495 15.37 In some embodiments, form A has an XRPD pattern with characteristic peaks between and including the following 2θ (degree) values: 9.3 to 9.7 (e.g., 9.5), 10.6 to 11.0 (e.g., 10.8), 13.0 to 13.4 (e.g., 13.2), 14.7 to 15.1 (e.g., 14.9), 15.8 to 16.2 (e.g., 16.0), 18.1 to 18.5 (e.g., 18.3), 18.7 to 19.1 (e.g., 18.9), 20.9 to 21.3 (e.g., 21.1), 21.4 to 21.8 (e.g., 21.6), and 23.3 to 23.7 (e.g., 23.5). In some embodiments, form A has an XRPD pattern with characteristic peaks between and including the following 2θ (degree) values: 9.3 to 9.7 (e.g., 9.5), 10.6 to 11.0 (e.g., 10.8), 13.0 to 13.4 (e.g., 13.2), 18.7 to 19.1 (e.g., 18.9), and 21.4 to 21.8 (e.g., 21.6). In some embodiments, form A has an XRPD pattern with characteristic peaks at the following 2θ (degree) values: 9.5, 10.8, 13.2, 14.9, 16.0, 18.3, 18.9, 21.1, 21.6, and 23.5. In some embodiments, form A has an XRPD pattern with characteristic peaks at the following 2θ (degree) values: 9.5, 10.8, 13.2, 18.9, and 21.6. The calculated XRPD data for the selected peaks can be obtained from the X-ray diffraction data of the single crystal of Form A, as shown in Table 2 below, which supplements the experimental data in Table 1. Table 2. Calculated XRPD pattern data for Form A. 2θ (degrees) d-distance (Å) Relative intensity (%) 10.9265 8.09076 21.14 13.32097 6.64132 48.56 14.11329 6.27021 20.36 14.94619 5.92262 24.95 16.05232 5.5169 49.72 17.42404 5.08555 48.28 18.40825 4.81581 100 19.2493 4.60725 18.47 24.23572 3.66943 19.02 24.3725 3.64915 19.56 Form C is the anhydrous crystalline form of compound 1 as determined by XRPD, and can be prepared from form A in isopropanol and isopropyl acetate using slurry conversion crystallization at 50°C. TGA and single-crystal X-ray crystallography can be used to confirm the absence of solvent in form C. DSC can be used to indicate two endothermic events below 300°C: a broad peak with a T starting at 183.8°C corresponds to the transformation of form C to form K, and a sharp peak with a T starting at 211.0°C corresponds to the melting of form K. DVS can be used to show that form C exhibits a water uptake of less than 0.32% by weight at RH less than or equal to 95%. In some embodiments, form C may have a substantially similar XRPD pattern as illustrated in Figure 4A. Additionally, the representative peaks of the XRPD pattern from form C can be indicated by their values ​​for 2θ, d-spacing, and relative intensity, as shown, for example, in Table 3 below: Table 3. Selected experimental XRPD pattern data for form C. 2θ (degrees) d-distance (Å) Relative Intensity (%) 22.60955 3.93279 26.76 20.65623 4.30006 27.84 13.36358 6.62573 28.42 14.81188 5.98097 33.78 21.50066 4.12963 36.7 21.54634 4.12439 36.94 9.889125 8.94443 41.85 11.79075 7.50579 65.73 14.41313 6.14552 65.89 16.99542 5.21715 100 In some embodiments, form C may have an XRPD pattern with characteristic peaks between and including the following 2θ (degree) values: 9.7 to 10.1 (e.g., 9.9), 11.6 to 12.0 (e.g., 11.8), 13.2 to 13.6 (e.g., 13.4), 14.2 to 14.6 (e.g., 14.4), 14.6 to 15.0 (e.g., 14.8), 16.8 to 17.2 (e.g., 17.0), 20.5 to 20.9 (e.g., 20.7), 21.3 to 21.7 (e.g., 21.5), 21.4 to 21.8 (e.g., 21.6), and 22.4 to 22.8 (e.g., 22.6). In some embodiments, form C may have an XRPD pattern with characteristic peaks between and including the following 2θ (degree) values: 9.7 to 10.1 (e.g., 9.9), 14.6 to 15.0 (e.g., 14.8), 16.8 to 17.2 (e.g., 17.0), 20.5 to 20.9 (e.g., 20.7), and 21.3 to 21.7 (e.g., 21.5). In some embodiments, form C may have an XRPD pattern with characteristic peaks at the following 2θ (degree) values: 9.9, 11.8, 13.4, 14.4, 14.8, 17.0, 20.7, 21.5, 21.6, and 22.6. In some embodiments, form C may have an XRPD pattern with characteristic peaks at the following 2θ (degree) values: 9.9, 14.8, 17.0, 20.7, and 21.5. The calculated XRPD data for the selected peaks can be obtained using X-ray diffraction data from the single crystal of Form C, as provided in Table 4 below. These simulated peaks supplement the experimental data in Table 3. Table 4. Calculated XRPD pattern data for Form C. 2θ (degrees) d-distance (Å) Relative intensity (%) 9.861923 8.96162 19.41 11.75959 7.51938 37.75 13.33554 6.6341 31.9 14.38478 6.15248 43.36 14.79021 5.98473 26.68 16.96659 5.22162 100 19.61234 4.52277 17.69 20.60123 4.30785 30.39 21.48653 4.13232 25.6 22.57956 3.93469 27.32 Form K can be prepared by heating various forms of compound 1 (e.g., form A or form C) to an elevated temperature. The sample analyzed in this form can be determined to be crystalline by XRPD analysis. TGA can be used to indicate no weight loss before the decomposition temperature and to demonstrate that form K is anhydrous. DSC can be used to demonstrate that form K exhibits a single endothermic reaction, with a T starting at 211.6 °C, corresponding to the melting point of the analyzed sample. DVS measurements are performed to demonstrate that form K exhibits less than 0.35% by weight water uptake at RH less than or equal to 95%. In some embodiments, form K may have a substantially similar XRPD pattern as illustrated in Figure 5. Additionally, representative peaks of the XRPD pattern from form K can be indicated by their 2θ and relative intensity values, as shown, for example, in Table 5 below: Table 5. Selected experimental XRPD pattern data for form K. 2θ (degrees) d-distance (Å) Relative intensity (%) 13.9471 6.3498 19.12 20.09767 4.41829 20.68 23.20826 3.83268 23.69 22.05504 4.0304 24.27 19.10905 4.64459 24.93 21.32362 4.16697 26.68 19.33614 4.59055 28.07 14.16125 6.25426 47 16.84678 5.26284 61.56 11.75077 7.53124 100 In some embodiments, form K may have an XRPD pattern with characteristic peaks between and including the following 2θ (degree) values: 11.6 to 12.0 (e.g., 11.8), 13.7 to 14.1 (e.g., 13.9), 14.0 to 14.4 (e.g., 14.2), 16.6 to 17.0 (e.g., 16.8), 18.9 to 19.3 (e.g., 19.1), 19.1 to 19.5 (e.g., 19.3), 19.9 to 20.3 (e.g., 20.1), 21.1 to 21.5 (e.g., 21.3), 21.9 to 22.3 (e.g., 22.1), and 23.0 to 23.4 (e.g., 23.2). In some embodiments, form K may have an XRPD pattern with characteristic peaks between and including the following 2θ (degree) values: 11.6 to 12.0 (e.g., 11.8), 16.6 to 17.0 (e.g., 16.8), 18.9 to 19.3 (e.g., 19.1), 19.9 to 20.3 (e.g., 20.1), and 23.0 to 23.4 (e.g., 23.2). In some embodiments, form K may have an XRPD pattern with characteristic peaks at the following 2θ (degree) values: 11.8, 13.9, 14.2, 16.8, 19.1, 19.3, 20.1, 21.3, 22.1, and 23.2. In some embodiments, form K may have an XRPD pattern with characteristic peaks at the following 2θ (degree) values: 11.8, 16.8, 19.1, 20.1, and 23.2. Solid compositions (e.g., solid dosage forms) may include, for example, any of the following components, or a solid form of a compound 1 with similar properties: binder, surfactant, diluent or filler, buffer, anti-adhesion agent, flow aid, hydrophilic or hydrophobic polymer, retardant, stabilizer or stabilizer, disintegrant or hyperdistegrant, dispersant, antioxidant, defoamer, filler, flavoring agent, colorant, lubricant, adsorbent, preservative, plasticizer, coating or sweetener, or mixtures thereof. For example, one or more excipients may be adhesives, such as microcrystalline cellulose, polyvinylpyrrolidone, hydroxypropyl cellulose, low-viscosity hydroxypropyl methylcellulose, tragacanth gum, or gelatin; diluents, such as mannitol, microcrystalline cellulose, maltodextrin, starch, or lactose; disintegrants, such as alginate, Primogel, sodium starch glycolate, crospovidone, or corn starch; lubricants, such as magnesium stearate, sodium stearyl fumarate, or glyceryl betaine; flow aids, such as colloidal silica; preservatives, such as potassium sorbate or methylparaben; and surfactants, such as sodium lauryl sulfate, sodium docusate, polysorbate 20, polysorbate 80, hexadecyl triethylammonium bromide, polyethylene oxide-polypropylene oxide copolymer, or Cremophor EL. EL); antioxidants, such as butylated hydroxytoluene, butylated hydroxyanisole, propyl gallate, ascorbic acid, tocopherol or tocopheryl acetate, sodium sulfite or sodium metabisulfite; coatings containing one or more of the following: hydroxypropyl methylcellulose, polyvinyl alcohol, methacrylate copolymers, cellulose acetate, hydroxypropyl methylcellulose acetate succinate, shellac and others; sweeteners, such as sucrose, sucralose, acesulfame K, sodium aspartame or saccharin; or flavoring agents, such as peppermint, methyl salicylate or orange flavoring. Any well-known pharmaceutical excipient may be incorporated into the dosage form, and see the FDA's Inactive Ingredients Guide; Remington: The Science and Practice of Pharmacy, 21st edition (Pharmaceutical Press, 2005); Handbook of Pharmaceutical Excipients, 6th edition (Pharmacrutical Press, 2009), all of which are incorporated herein by reference. Transdermal compositions are typically formulated as topical ointments or creams containing one or more active ingredients. When formulated as an ointment, the active ingredient is usually combined with a paraffin or water-miscible ointment base. Alternatively, the active ingredient may be formulated into a cream using, for example, an oil-in-water cream base. These transdermal formulations are well known in the art and typically include other ingredients that enhance the dermal permeability and stability of the active ingredient or formulation. All such known transdermal formulations and ingredients are included within the scope provided herein. Topical delivery compositions of interest include liquid formulations, such as lotions (liquids containing insoluble materials in the form of suspensions or emulsions intended for external application, including spray lotions) and aqueous solutions; semi-solid formulations, such as gels (colloids in which the dispersed phase has been combined with a dispersion medium to produce a semi-solid material, such as a jelly), creams (soft solids or thick liquids), and ointments (soft oily preparations); and solid formulations, such as topical patches. Therefore, the delivery media components of interest include (but are not limited to): oil-in-water (O / W) and water-in-oil (W / O) emulsions, emulsions, lotions, creams, ointments, gels, slurries, powders, masks, coatings, sprays, aerosols, sticks and patches. Compound 1 described herein can also be administered via a transdermal device. Therefore, transdermal administration can be accomplished using reservoir-type or film-type patches, adhesive-based patches, or patches of other matrix types. Delivery compositions of interest include liquid formulations, such as lotions (liquids containing insoluble materials in the form of suspensions or emulsions intended for external application, including spray lotions) and aqueous solutions; semi-solid formulations, such as gels (colloids, where the dispersed phase has been combined with a dispersion medium to produce a semi-solid substance, such as a jelly), creams (soft solids or thick liquids), and ointments (soft oily preparations); and solid formulations, such as topical patches. Therefore, delivery media components of interest include (but are not limited to): oil-in-water (O / W) and water-in-oil (W / O) emulsions, emulsions, lotions, creams, ointments, gels, slurries, powders, masks, coatings, sprays, aerosols, sticks, and patches. For transdermal patches, the active agent layer includes one or more active agents, one of which is compound I. In some embodiments, the matrix is ​​an adhesive matrix. The matrix may include polymeric materials. Suitable polymers for adhesive matrices include (but are not limited to): polyurethanes, acrylates, styrene block copolymers, polysiloxanes, and the like. For example, the adhesive matrix may include (but is not limited to) acrylate polymers, polysiloxanes, polyisobutylene (PIB), polyisoprene, polybutadiene, styrene block polymers, combinations thereof, and the like. Other examples of adhesives are described in Satas, "Acrylic Adhesives," Handbook of Pressure-Sensitive Adhesive Technology, 2nd edition, pp. 396-456 (edited by D. Satas), Van Nostrand Reinhold, New York (1989), the disclosure of which is incorporated herein by reference. In some embodiments, the surfactant layer includes a penetration enhancer. The penetration enhancer may include (but is not limited to) the following: aliphatic alcohols, such as (but not limited to) saturated or unsaturated high carbon number alcohols having 12 to 22 carbon atoms, such as oleyl alcohol and lauryl alcohol; fatty acids, such as (but not limited to) linoleic acid, oleic acid, linolenic acid, stearic acid, isostearic acid, and palmitic acid; fatty acid esters, such as (but not limited to) isopropyl myristate, diisopropyl adipate, and isopropyl palmitate; alkanolamines, such as (but not limited to) triethanolamine, triethanolamine hydrochloride, and diisopropyl alcohol; polyol alkyl groups. Ethers, such as (but not limited to) alkyl ethers of the following polyols: for example, glycerol, ethylene glycol, propylene glycol, 1,3-butanediol, diglycerol, polyglycerol, diethylene glycol, polyethylene glycol, dipropylene glycol, polypropylene glycol, dehydrated sorbitol, sorbitol, isosorbide, methyl glucoside, oligosaccharides and reducing oligosaccharides, wherein the alkyl portion of the polyol alkyl ether preferably has 6 to 20 carbon atoms; polyoxyethylene alkyl ethers, such as (but not limited to) wherein the alkyl portion has 6 to 20 carbon atoms and the repeating unit of the polyoxyethylene chain (e.g., -OCH) 2CH 2-) Polyoxyethylene alkyl ethers of number 1 to 9, such as (but not limited to) polyoxyethylene lauryl ether, polyoxyethylene hexadecyl ether, polyoxyethylene stearyl ether, and polyoxyethylene oil ether; glycerides (i.e., fatty acid esters of glycerol), such as (but not limited to) glycerides, diglycerides, triglycerides, or combinations thereof of fatty acids having 6 to 18 carbon atoms. In some embodiments, the polymer matrix comprises polyvinylpyrrolidone. The composition may further comprise one or more fillers or one or more antioxidants. In some embodiments, the described dermal formulation may have a multilayer structure. For example, the dermal formulation may have an adhesive matrix and a backing. The above-described components, which can be administered orally, injected, or topically, are representative only. Other materials, processing techniques, and similar descriptions are described in Part 8 of Remington's Pharmaceutical Sciences, 17th Edition, 1985, Mack Publishing Company, Easton, Pennsylvania, which are incorporated herein by reference. The solid form of compound 1 of this invention can also be administered in a sustained-release form or via a sustained-release drug delivery system. For a description of representative sustained-release materials, please refer to Remington's Pharmaceutical Sciences. Generally, the compounds described herein are administered in an effective amount. The actual amount of the compound administered will usually be determined by the physician based on factors including: the condition to be treated, the route of administration, the compound to be administered, the individual patient's age, weight, response, severity of symptoms, and so on. The compounds provided herein can be administered as the sole active agent, or in combination with other active agents. In one embodiment, the present invention provides a combination of the compounds of the present invention with another pharmacologically active agent. Combination administration can be performed by any technique known to those skilled in the art, including, for example, administration alone, sequentially, simultaneously, and alternately. Although the description of pharmaceutical compositions provided herein is primarily concerned with those suitable for human administration, those skilled in the art will understand that such compositions are generally suitable for administration to all species of animals. Modifications made to these compositions to make them suitable for human administration to various animals are well known in the art, and generally, skilled veterinary pharmacologists can use common experimental designs and / or perform these modifications. General considerations in the formulation and / or manufacture of pharmaceutical compositions can be found in (for example) Remington: The Science and Practice of Pharmacy, 21st Edition, Lippincott Williams & Wilkins, 2005. Used for throwing ( For example, oral administration ) This document provides methods for treating or preventing the conditions described herein, comprising orally administering to an individual in need a total daily dose of compound 1 of about 10 mg to about 100 mg. (Compound 1) or its pharmaceutically acceptable salt or isotope or pharmaceutical composition thereof. This article also provides methods for treating or preventing the conditions described herein, which involve orally administering to an individual in need a total daily dose of about 30 mg (e.g., 30 mg) of compound 1 or a pharmaceutically acceptable salt or isotope thereof or a pharmaceutical composition thereof. This article also provides methods for treating or preventing the conditions described herein, which involve administering a total daily dose of compound 1 orally to an individual in need of about 30 mg (e.g., 30 mg). Compound 1, or a pharmaceutically acceptable salt or isotope thereof, or a pharmaceutical composition thereof, may be formulated for oral administration. In some embodiments of this disclosure, the pharmaceutical composition is formulated into an oral administration form (e.g., via oral (oral (PO)) administration). Oral administration may take the form of tablets, capsules, chewable capsules, delayed-release or sustained-release tablets and capsules and / or powders or granules. Oral administration typically involves swallowing, thereby allowing the compound to enter the gastrointestinal tract (GIT). Other dosage forms or administration units for oral administration include solid formulations such as tablets, capsules containing microparticles or powders, sacs, vials, powders, granules, rhomboid tablets, reconfigurable powders, and liquid formulations (e.g., suspensions, emulsions, and elixirs). Oral dosage forms may contain other excipients, such as binders (e.g., syrups, gum arabic, gelatin, sorbitol, starch, PVP, HPMC, and tragacanth gum); fillers (e.g., lactose, sugar, corn starch, calcium phosphate, sorbitol, and glycine); ingot lubricants (e.g., magnesium stearate); flow aids (e.g., magnesium trisilicate, powdered cellulose, starch, talc, and tricalcium phosphate); and disintegrants (e.g., starch, sodium glycolate, and microcrystalline cellulose). Additionally, oral dosage forms may contain preservatives, antioxidants, flavoring agents, granulating binders, wetting agents, and colorants. The amount of each type of additive used (e.g., gliding agents, binders, disintegrants, fillers or diluents, and lubricants) can vary within the range commonly used in the industry. Thus, for example, the amount of gliding agent can vary from 0.1 wt% to 10 wt%, particularly from 0.1 wt% to 5 wt% (e.g., 0.1 wt% to 0.5 wt%); the amount of binder can vary from about 10 wt% to 45 wt% (e.g., 20 wt% to 30 wt%); the amount of disintegrant can vary from 2 wt% to 20 wt% (e.g., 15 wt%); the amount of filler or diluent can vary from 15 wt% to 40 wt%; and the amount of lubricant can vary from 0.1 wt% to 5.0 wt%. It should be understood that oral dosage forms can be prepared using techniques known in the industry. The absolute amount of each additive and its amount relative to other additives similarly depend on the desired properties of the solid oral dosage form and can also be selected by someone skilled in this technique. In some embodiments, compound 1 is formulated into a solid dosage form, such as capsules or tablets. Capsules may be hard-shell or soft-shell capsules. Both types of capsules can be prepared from an aqueous solution of a gelling agent, such as animal protein (primarily gelatin) or plant polysaccharides or derivatives thereof (e.g., carrageenan and modified forms of starch and cellulose). Other ingredients may be added to the gelling agent solution, including plasticizers (e.g., glycerin or sorbitol) to reduce capsule stiffness, colorants, preservatives, disintegrants, lubricants, and surface treatments. Tablets can be defined as solid unit dosage forms containing or not containing one or more suitable excipients and prepared by molding or compression. They may comprise a mixture of active material and excipients, typically in powder form, compressed or compacted from powder into a solid dosage form. Excipients may include diluents, binders or granulators, flow aids, and lubricants to ensure efficient tablet formation; disintegrants to promote tablet breakdown in the digestive tract; sweeteners or flavoring agents to enhance taste; and pigments to make the tablets visually appealing or to aid in the visual identification of unknown tablets. Polymer coatings may be applied to make the tablets smoother and easier to swallow, control the release rate of the active ingredient, make them more environmentally resistant (extending their shelf life), or enhance the appearance of the tablets. In some embodiments, compound 1 is formulated into a solid unit dose or a solid dosage form. In some embodiments, the solid dosage form contains about 0.1 mg to about 10 mg of compound 1. In some embodiments, compound 1 is provided in a solid dosage form containing about 5 mg to about 50 mg. In some embodiments, compound 1 is provided in a solid dosage form containing about 10 mg to about 100 mg. In some embodiments, compound 1 is provided in a solid dosage form containing the following amounts of compound 1: about 0.5 mg, about 1 mg, about 3 mg, about 5 mg, about 10 mg, about 12 mg, about 15 mg, about 18 mg, about 20 mg, about 25 mg, about 28 mg, about 30 mg (e.g., 30 mg), about 33 mg, about 35 mg, about 40 mg, about 50 mg, about 55 mg, about 60 mg, about 65 mg, about 70 mg, about 75 mg, about 80 mg, about 85 mg, about 90 mg, about 95 mg, about 100 mg, about 105 mg, or about 110 mg. In some embodiments, the solid dosage form contains about 30 mg (e.g., 30 mg) of compound 1. Dosage and Pharmacokinetics The compositions described herein include therapeutically effective amounts of neuroactive steroids (e.g., compound 1) provided in dosage forms suitable for oral administration. In some embodiments, the compositions described herein include therapeutically effective amounts of neuroactive steroids (e.g., compound 1) provided in solid dosage forms suitable for oral administration. In some embodiments, the compositions described herein include a therapeutically effective amount of a neuroactive steroid (e.g., compound 1) provided in a solid dosage form suitable for oral administration, as described herein, and administered substantially simultaneously with food. The area under the curve (AUC) refers to the area under the curve that tracks the serum concentration (e.g., ngl / mL) of a neuroactive steroid over a given time period following oral administration of a control neuroactive steroid standard. "Control neuroactive steroid" is intended to refer to a formulation of neuroactive steroids used to determine the basis for determining the total hourly dose of neuroactive steroids to be administered to human individuals with tremors (e.g., spontaneous tremors), depression (e.g., postpartum depression), or anxiety disorders to achieve the desired positive effect (i.e., a modified positive therapeutic response relative to the response observed without neuroactive steroid administration). In one embodiment, the intended dose of neuroactive steroids provides the following final serum levels of neuroactive steroids: about 100 ng / mL to about 1000 ng / mL, about 1100 ng / mL to about 1450 ng / mL, 100 ng / mL to about 250 ng / mL, about 200 ng / mL to about 350 ng / mL, about 300 ng / mL to about 450 ng / mL, about 350 ng / mL to about 450 ng / mL, about 400 ng / mL to about 550 ng / mL, about 500 ng / mL to about 650 ng / mL, about 600 ng / mL to about 750 ng / mL, about 700 ng / mL to about 850 ng / mL, about 800 ng / mL to about 950 ng / mL, about 900 ng / mL to about 1050 ng / mL, about 1000 ng / mL to about 14 ... ng / mL to about 1150 ng / mL, about 100 ng / mL to about 1250 ng / mL, about 1200 ng / mL to about 1350 ng / mL, about 1300 ng / mL to about 1500 ng / mL. In specific embodiments, the serum concentrations of neuroactive steroids are approximately 100 ng / mL, 250 ng / mL, 300 ng / mL, 350 ng / mL, 360 ng / mL, 370 ng / mL, 380 ng / mL, 390 ng / mL, 400 ng / mL, 410 ng / mL, 420 ng / mL, 430 ng / mL, 440 ng / mL, 450 ng / mL, 500 ng / mL, 750 ng / mL, 900 ng / mL, 1200 ng / mL, 1400 ng / mL, or 1600 ng / mL. In one embodiment, the dose of neuroactive steroid to be administered provides the following final serum levels of neuroactive steroid: about 100 naphthol / L to about 5000 naphthol / L, about 100 naphthol / L to about 2500 naphthol / L, about 100 naphthol / L to about 1000 naphthol / L, 100 naphthol / L to about 500 naphthol / L, about 100 naphthol / L to about 250 naphthol / L, about 100 naphthol / L to about 200 naphthol / L, about 125 naphthol / L to about 175 naphthol / L, or about 140 naphthol / L to about 160 naphthol / L. In specific embodiments, the serum concentration of neuroactive steroids is approximately 100 naphthol / L, 125 naphthol / L, 150 naphthol / L, 175 naphthol / L, 200 naphthol / L, 250 naphthol / L, 300 naphthol / L, 350 naphthol / L, 500 naphthol / L, 750 naphthol / L, 1000 naphthol / L, 1500 naphthol / L, 2000 naphthol / L, 2500 naphthol / L, or 5000 naphthol / L. Method of Use This document provides a method for treating a condition (e.g., a CNS-related condition) for an individual in need, comprising administering to the individual an effective amount of Compound 1 or a pharmaceutically acceptable salt or composition thereof. In some embodiments, the condition is a CNS-related condition selected from the group consisting of: sleep disorders, mood disorders, schizophrenia spectrum disorders, seizure disorders, memory and / or cognitive impairments, motor disorders, personality disorders, autism spectrum disorders, pain, traumatic brain injury, vascular disease, substance abuse disorders and / or withdrawal syndromes, and tinnitus. In some embodiments, the condition is depression, such as major depressive disorder. In some embodiments, the condition is a comorbid condition (e.g., depression comorbid with a personality disorder or sleep disorders comorbid with a personality disorder). In some embodiments, the condition is a neurological condition as described herein. In some embodiments, the condition is a mental disorder as described herein. In some embodiments, the condition is a seizure as described herein. In some embodiments, the condition is a neuroinflammatory condition as described herein. In some embodiments, the condition is glaucoma or a metabolic disorder as described herein. In some embodiments, the condition is a sensory deficit condition as described herein. This document also provides methods for using compound 1 or its pharmaceutically acceptable salts or pharmaceutical compositions as neuroprotective agents. This document also provides methods for using compound 1 or its pharmaceutically acceptable salts or pharmaceutical compositions as analgesics or other agents for pain control. The neuropathic compound 1, or a pharmaceutically acceptable salt or composition thereof, can be used in the methods described herein, for example, to treat the conditions described herein (e.g., neuropathic disorders). Exemplary neuropathic disorders include (but are not limited to) neurodegenerative disorders, neurodevelopmental disorders, neuroendocrine disorders and functional disorders, motor disorders, and sleep disorders as described herein. The neurodegenerative compound 1 or a pharmaceutically acceptable salt or composition thereof may be used in the methods described herein, for example, for the treatment of neurodegenerative diseases. The term "neurodegenerative disease" includes diseases and conditions associated with progressive loss of neuronal structure or function or neuronal death. Neurodegenerative diseases and conditions include (but are not limited to) Alzheimer's disease (including symptoms associated with mild, moderate, or severe cognitive impairment); amyotrophic lateral sclerosis (ALS); hypoxic and ischemic injury; benign amnesia; cerebral edema; cerebellar ataxia, including McLeod's neuroacanthocytosis syndrome (MLS); intracranial injury; coma; contusions (e.g., spinal cord injury and head injury); dementia, including multiple infarction dementia and Alzheimer's disease; altered consciousness; Down syndrome; X-chromosome splitting syndrome; Gilles de la Tourette's syndrome; head trauma; hearing loss; Huntington's disease; Lennox syndrome. Neurodegenerative diseases include (but are not limited to) stroke, thromboembolic stroke, hemorrhagic stroke, cerebral ischemia, cerebral vasospasm, hypoglycemia, amnesia, hypoxia, hypoxia, perinatal asphyxia, and neurotoxic damage following cardiac arrest; Parkinson's disease; stroke; tinnitus; arteriosclerosis and viral infections that induce neurodegeneration (e.g., those caused by acquired immunodeficiency syndrome (AIDS) and encephalopathy). Treatment or prevention of neurodegenerative diseases also includes treating or preventing the loss of neuronal function characteristic of neurodegenerative symptoms. The neurodevelopmental disorder compound 1, or a pharmaceutically acceptable salt or composition thereof, can be used in the methods described herein, for example, to treat the disorder described herein, such as a neurodevelopmental disorder. In some embodiments, the neurodevelopmental disorder is an autism spectrum disorder. In some embodiments, the neurodevelopmental disorder is Smith-Lemli-Opitz syndrome. Neuroendocrine Disorders This article provides methods for treating neuroendocrine disorders and dysfunctions. As used herein, "neuroendocrine disorder" or "neuroendocrine dysfunction" refers to a variety of conditions caused by imbalances in the production of hormones directly related to the brain. Neuroendocrine disorders involve the interaction between the nervous and endocrine systems. Because the hypothalamus and pituitary gland are two regions in the brain that regulate hormone production, traumatic brain injury, for example, can damage the hypothalamus or pituitary gland, affecting hormone production and other neuroendocrine functions in the brain. In some embodiments, neuroendocrine disorders or dysfunctions are associated with women's health conditions or disorders (e.g., women's health conditions or disorders described herein). In some embodiments, the neuroendocrine disorder or dysfunction associated with a women's health condition or disorder is polycystic ovary syndrome. Symptoms of neuroendocrine disorders include (but are not limited to) behavioral, mood and sleep-related symptoms, reproductive function-related symptoms and physical symptoms; including (but not limited to) fatigue, poor memory, anxiety, depression, weight gain or loss, mood instability, lack of concentration, difficulty concentrating, lack of libido, infertility, amenorrhea, muscle loss, increased abdominal fat, low blood pressure, low heart rate, hair loss, anemia, constipation, poor cold tolerance and dry skin. The movement disorder compound 1, or a pharmaceutically acceptable salt or composition thereof, can be used in the methods described herein, for example, for the treatment of movement disorders. In some embodiments, the movement disorder is spontaneous tremor; rigid person syndrome; spastic state; Freidrich's ataxia; cerebellar ataxia; dystonia; Tourette syndrome; X-chromosome splitting-related tremor or ataxia syndrome; drug-induced or pharmacologically induced Parkinsonism (e.g., antipsychotic-induced acute akathisia, acute dystonia, Parkinson's disease or tardive dyskinesia, antipsychotic malignant syndrome or pharmacologically induced postural tremor), ataxia; cerebellar ataxia, including McLeod neuroacanthocytosis syndrome (MLS); levodopa-induced dyskinesia; Movement disorders, including akinesia and akinesia (rigidity) syndrome (including basal ganglia calcification, corticobasal ganglia degeneration, multiple system atrophy, Parkinson's disease-ALS dementia syndrome, Parkinson's disease, post-encephalitis Parkinson's disease, and progressive supranuclear palsy); muscle spasms and conditions related to muscle spasms or weakness, including chorea (e.g., benign hereditary chorea, drug-induced chorea, hemiparesis, Huntington's disease, neuroacanthocytosis, Sydenham's chorea). Chorea and symptomatic chorea), motor difficulties (including tics, such as complex tics, simple tics and symptomatic tics), myoclonus (including generalized myoclonus and focal myoclonus), tremor (such as resting tremor, postural tremor and intention tremor) or dystonia (including axial dystonia, dystonia of the fingers, hemiplegic dystonia, paroxysmal dystonia and focal dystonia, such as blepharospasm, oromandibular dystonia and spasmodic dysarthria and torticollis). As used herein, "movement disorder" refers to a variety of diseases and conditions associated with hyperactivity and related abnormalities in muscle control. Exemplary movement disorders include (but are not limited to) Parkinson's disease and Parkinson's syndrome (specifically defined as bradykinesia), dystonia, chorea and Huntington's disease, ataxia, tremor (e.g., spontaneous tremor), myoclonus and startle reflex, tic and Tourette syndrome, restless legs syndrome, stiff-person syndrome, and gait disorders. The methods described in this article can be used to treat tremor, for example, compound 1 or its pharmaceutically acceptable salt or pharmaceutically acceptable composition can be used to treat cerebellar tremor or intention tremor, dystonic tremor, spontaneous tremor, orthostatic tremor, Parkinsonian tremor, physiological tremor, psychogenic tremor or red nucleus tremor. Tremors can be induced by hereditary, degenerative, and idiopathic conditions, such as Wilson's disease, Parkinson's disease, and spontaneous tremor; metabolic disorders (e.g., thyroid-parathyroid disease, liver disease, and hypoglycemia); peripheral neuropathy (associated with Charcot-Marie-Tooth disease, Roussy-Levy disease, diabetes, and complex regional pain syndrome); toxins (nicotine, mercury, lead, CO, manganese, arsenic, toluene); drugs (narcolepsy drugs, tricyclic antidepressants, lithium, cocaine, alcohol, adrenaline, bronchodilators, theophylline, caffeine, steroids, valproate, amiodarone, thyroid hormones, and vincristine); and psychogenic conditions. Clinical tremor can be classified into physiological tremor, enhanced physiological tremor, spontaneous tremor syndrome (including classic spontaneous tremor, essential orthostatic tremor, and task and position-specific tremor), dystonic tremor, Parkinson's disease tremor, cerebellar tremor, Holmes' tremor (i.e., red nucleus tremor), palatal tremor, neuropathic tremor, toxic or drug-induced tremor, and psychogenic tremor. Tremor is an involuntary, sometimes rhythmic, muscle contraction and relaxation that may involve one or more body parts (e.g., hands, arms, eyes, face, head, vocal cords, trunk, and legs). Cerebellar tremor, or intention tremor, is a slow, broad tremor of the limbs that occurs after purposeful movement. Cerebellar tremor is caused by lesions or damage in the cerebellum originating from, for example, tumors, strokes, or diseases (e.g., multiple sclerosis, hereditary degenerative disorders). Dystonic tremor occurs in individuals affected by dystonia and is a motor disorder characterized by persistent, involuntary muscle contractions that result in twisting and repetitive movements and / or pain and abnormal posture or position. Dystonic tremor can affect any muscle in the body. It occurs irregularly and is usually relieved by rest. Spontaneous tremor or benign spontaneous tremor is the most common type of tremor. Some spontaneous tremors can be mild and non-progressive, and can be slowly progressive, starting on one side of the body but affecting both sides within 3 years. It most commonly affects the hands, but can also involve the head, voice, tongue, legs, and trunk. The frequency of tremor may decrease with age, but its severity can increase. Highly emotional stress, fever, physical exhaustion, or hypoglycemia can trigger tremors and / or increase their severity. Symptoms usually evolve over time and can be visible and persistent after an attack. Orthostatic tremor is characterized by rapid (e.g., greater than 12 Hz) rhythmic muscle contractions of the legs and trunk that occur immediately after standing. Cramps are felt in the thighs and legs, and the patient may uncontrollably shake when asked to stand in one place. Orthostatic tremor can occur in patients with spontaneous tremor. Parkinson's tremor is caused by damage to the structures in the brain that control movement. It is often a precursor to Parkinson's disease and is typically described as a "rolling" motion of the hands; it can also affect the jaw, lips, legs, and trunk. Onset of Parkinson's tremor usually begins after age 60. The movement begins in one limb or on one side of the body and can progress to the other side. Physiological tremor can occur in normal individuals and is not clinically significant. It can be seen in all voluntary muscle groups. Physiological tremor can be caused by certain medications, alcohol withdrawal, or medical conditions (including hyperactive thyroid and hypoglycemia). The frequency of the tremor is usually about 10 Hz. Psychogenic tremor, or hysterical tremor, can occur at rest or during postural or kinetic movement. Patients with psychogenic tremor may also have conversion disorder or another psychiatric disorder. Red nucleus tremor is characterized by coarse, slow tremors that can occur at rest, in a specific posture, and intentionally. The tremor is associated with conditions affecting the red nucleus of the midbrain, a classic example of an unusual stroke. Parkinson's disease affects the nerve cells in the brain that produce dopamine. Symptoms include muscle rigidity, tremor, and changes in speech and gait. Parkinson's disease is characterized by tremor, bradykinesia, rigidity, and postural instability. While Parkinson's disease shares the symptoms found in other Parkinson's diseases, it is a complex of symptoms rather than a progressive neurodegenerative disease. Dystonia is characterized by movement disorders that cause abnormal, usually repetitive, sustained or intermittent muscle contractions or postures. Dystonic movements can be patterned, torsional, or tremor-like. Dystonia usually begins or is exacerbated by voluntary movements and is associated with overflow muscle activation. Chorea is a neurological disorder characterized by rapid, involuntary movements, typically affecting the shoulders, hips, and face. Huntington's disease is a hereditary disorder that causes progressive weakening of nerve cells in the brain. Symptoms include uncontrolled movements, clumsiness, and balance problems. Huntington's disease can impair walking, speaking, and swallowing. Ataxia refers to the loss of complete control over bodily movements, and can affect the movements of the fingers, hands, arms, legs, body, speech, and eyes. Myoclonus and fright are responses to sudden and unexpected stimuli, which can be auditory, tactile, visual, or vestibular. A tic is a sudden, brief, repetitive, but non-rhythmic involuntary movement that typically mimics normal behavior and usually occurs outside the context of normal activity. Tics can be classified as motor tics or vocal tics; motor tics are related to movement, while vocal tics are related to sound. Tics can be characterized as simple or complex. For example, a simple motor tic involves only a few muscles limited to a specific part of the body. Tourette syndrome is a hereditary neuropsychiatric disorder that occurs in childhood, characterized by multiple types of motor tics and at least one vocal tic. Restless legs syndrome is characterized by a neurosensory-motor disorder in which the legs move uncontrollably even at rest. Stiff-person syndrome is characterized by involuntary painful spasms and muscle rigidity, typically involving progressive movement disorders in the lower back and legs. It usually results in a straight-leg gait with excessive lumbar lordosis. Characteristic abnormalities in EMG recordings and continuous motor unit activity of paravertebral muscles are typically observed. Variants include "stiff limb syndrome," which produces focal stiffness typically affecting the distal leg and foot. Gait disorders refer to abnormalities in walking patterns or styles caused by neuromuscular, arthritis, or other bodily changes. Gait is classified according to the system responsible for abnormal movement and includes hemiplegic gait, diplegic gait, neuropathic gait, myopathic gait, Parkinson's gait, chorea-like gait, ataxia gait, and sensorimotor gait. The sleep disorder compound 1, or a pharmaceutically acceptable salt or composition thereof, can be used in the methods described herein, for example, for treating sleep disorders. In some embodiments, the sleep disorder is comorbid with another condition (e.g., a sleep disorder comorbid with a personality disorder). The psychotropic compound 1, or a pharmaceutically acceptable salt or composition thereof, may be used in the methods described herein, for example, to treat the conditions described herein (e.g., psychotropic disorders). Exemplary psychotropic disorders include (but are not limited to) mood disorders, anxiety disorders, psychotic disorders, and impulse control disorders as described herein. This document also provides methods for treating mood disorders, such as clinical depression, postnatal or birth depression, perinatal depression, atypical depression, melancholic depression, psychotic major depressive disorder, rigid depression, seasonal affective disorder, dysphoric mood, dual depression, depressive personality disorder, recurrent transient depression, mild depressive disorder, bipolar disorder or bipolar disorder, depression caused by a chronic medical condition, comorbid depression, treatment-resistant depression, refractory depression, suicidal ideation or suicidal behavior. In some embodiments, the methods described herein provide a therapeutic effect on individuals suffering from depression (e.g., moderate or severe depression). In some embodiments, the mood disorder is associated with diseases or conditions described herein (e.g., neuroendocrine disorders and conditions, neurodegenerative diseases and conditions (e.g., epilepsy), movement disorders, tremors (e.g., Parkinson's disease), women's health conditions or disorders). Clinical depression, also known as major depressive disorder, severe depressive illness (MDD), unipolar depression, unipolar disorder, and recurrent depression, is a mental disorder characterized by a deep and persistent low mood accompanied by low self-esteem and loss of interest or enjoyment in normally pleasurable activities. Some individuals with clinical depression experience difficulty falling asleep, weight loss, and often feel irritable and easily angered. Clinical depression affects an individual's feelings, thoughts, and behaviors and can lead to a variety of emotional and physical problems. Individuals with clinical depression may find it difficult to perform daily activities and may feel as if life is meaningless. Perinatal depression refers to depression during pregnancy. Symptoms include irritability, crying, restlessness, difficulty falling asleep, exhaustion (emotional and / or physical), changes in appetite, difficulty concentrating, increased anxiety and / or distress, disconnection from the baby and / or fetus, and loss of interest in activities that were previously enjoyable. Postnatal depression (PND), also known as postpartum depression (PPD), refers to a group of clinical depressions affecting women after childbirth. Symptoms may include sadness, fatigue, changes in sleep and eating habits, decreased libido, crying episodes, anxiety, and irritability. In some embodiments, PND is treatment-resistant depression (e.g., as described herein). In some embodiments, PND is intractable depression (e.g., as described herein). In some embodiments, individuals with perinatal depression (PND) also experience depression or symptoms of depression during pregnancy. This depression is referred to herein as perinatal depression. In one embodiment, individuals experiencing perinatal depression have an increased risk of experiencing PND. Atypical depression (AD) is characterized by mood responsiveness (e.g., paranoid euphoria) and positivity, significant weight gain, or increased appetite. Patients with AD may also experience excessive sleep or hypersomnia (excessive sleep), heaviness in the limbs, and significant social deficits due to hypersensitivity to perceived social rejection. Melancholic depression is characterized by loss of pleasure in most or all activities (amortia), unresponsiveness to interesting stimuli, depressive mood that is more severe than sadness or loss, excessive weight loss, or excessive guilt. Major psychotic depression (PMD) or psychotic depression refers to a severe depressive episode that is particularly melancholic in nature, in which the individual experiences psychotic symptoms such as delusions and hallucinations. Kititary-associated depression refers to major depressive disorder involving motor and behavioral disturbances as well as other symptoms. Individuals may become taciturn and catatonic, and remain motionless or exhibit aimless or bizarre movements. Seasonal affective disorder (SAD) refers to a type of seasonal depression in which individuals exhibit a seasonal pattern of depressive episodes that occur at the beginning of autumn or winter. Dysphoric mood refers to a condition associated with one-dimensional depression, in which the same physical and cognitive problems are present. It is less severe than one-dimensional depression and often lasts longer (e.g., at least 2 years). Dual depression refers to a very depressive mood (dysphoric state of mind) that lasts for at least two years and is interspersed with periods of major depressive disorder. Depressive personality disorder (DPD) refers to a personality disorder characterized by depressive traits. Recurrent transient depression (RBD) refers to a condition in which an individual experiences approximately one depressive episode per month, each lasting two weeks or less and usually less than two to three days. Mild depressive disorder or mild depression refers to depression in which at least two of the symptoms are present for two weeks. Depression caused by chronic medical conditions refers to depression caused by chronic medical conditions such as cancer or chronic pain, chemotherapy, and chronic stress. Treatment-resistant depression refers to a condition in which an individual has received treatment for depression, but whose symptoms have not improved. For example, antidepressants or psychotherapy do not alleviate the depressive symptoms of an individual with treatment-resistant depression. In some cases, an individual with treatment-resistant depression may experience symptom improvement, but then relapse. Intractable depression occurs in patients with depression who are resistant to standard pharmacological treatments (including tricyclic antidepressants, MAOIs, SSRIs, and dual and triple uptake inhibitors and / or anxiolytics) and non-pharmacological treatments (e.g., psychotherapy, electroconvulsive therapy, vagus nerve stimulation, and / or transcranial magnetic stimulation). Postoperative depression refers to feelings of depression following a surgical procedure (e.g., due to the need to confront the death of someone). For example, an individual may experience persistent sadness or emptiness, loss of enjoyment or interest in hobbies and normally cherished activities, or a persistent sense of worthlessness or despair. Mood disorders related to women’s health conditions or illnesses refer to mood disorders (e.g., depression) that are related to (e.g., caused by) a woman’s health condition or illness (e.g., as described herein). Suicidal ideation, suicidal thought, and suicidal behavior refer to an individual's tendency to end their life. Suicidal ideation refers to thoughts about suicide or an unusual focus on suicide. The range of suicidal ideation varies greatly, from momentary thoughts to extended thoughts, detailed plans, role-playing, and attempted suicide. Symptoms include talking about suicide, acquiring suicide tools, avoiding social contact, focusing on death, feeling trapped or hopeless about the situation, increased alcohol or drug use, engaging in dangerous or self-destructive activities, and saying goodbye to people as if it were a final farewell. Depression or personality disorders can also co-occur with another condition. For example, depression can co-occur with personality disorders. In another instance, personality disorders can co-occur with sleep disorders. Symptoms of depression include persistent feelings of anxiety or sadness, helplessness, hopelessness, pessimism, worthlessness, lethargy, restlessness, difficulty sleeping, insomnia, irritability, fatigue, physical challenge, loss of interest in pleasurable activities or hobbies, loss of concentration, loss of energy, low self-esteem, lack of positive thoughts or plans, excessive sleep, overeating, loss of appetite, insomnia, self-harm, suicidal thoughts and intentions. The presence, severity, frequency, and duration of symptoms can vary from case to case. The symptoms of depression and their remission can be determined by a physician or psychologist (e.g., through a mental status examination). This article provides methods for treating anxiety disorders (e.g., generalized anxiety disorder, panic disorder, obsessive-compulsive disorder, phobias, post-traumatic stress disorder). Anxiety disorder is a general term encompassing several different forms of abnormal and pathological fear and anxiety. Current psychiatric diagnostic criteria identify numerous types of anxiety disorders. Generalized anxiety disorder (GAD) is a common chronic condition characterized by persistent anxiety that is not focused on any particular object or situation. Those with GAD experience nonspecific, persistent fear and worry and become overly concerned with daily affairs. GAD is the most common anxiety disorder affecting older adults. In panic disorder, an individual experiences brief, intense shock and anxiety, typically marked by trembling, shaking, panic, dizziness, nausea, and difficulty breathing. Panic attacks, defined by the APA as sudden onset of fear or discomfort peaking within less than 10 minutes, can last for several hours and can be triggered by stress, fear, or even physical activity; however, the specific cause is not always obvious. In addition to recurrent, unexpected panic attacks, a diagnosis of panic disorder requires that these attacks have chronic consequences: worry about the potential impact of the attack, persistent fear of future attacks, or significant changes in behavior associated with the attack. Therefore, those suffering from panic disorder experience symptoms even outside of specific panic attacks. Typically, panic sufferers notice normal changes in their heart rate, leading them to wonder if there is a problem with their heart or if another panic attack is imminent. In some cases, a heightened awareness of bodily functions (hypervigilance) occurs during a panic attack, where any perceived physiological changes are interpreted as a potentially life-threatening illness (i.e., extreme hypochondria). Obsessive-compulsive disorder (OCD) is a type of anxiety disorder characterized by recurring obsessive thoughts (depressing, persistent, and intrusive thoughts or images) and compulsive behaviors (impulses to perform specific actions or rituals). In terms of its belief in causal relationships that do not actually exist, OCD thinking patterns can resemble superstition. Often, the process is completely illogical; for example, a compulsive behavior of walking in a certain pattern may be used to alleviate obsessive thoughts of impending harm. In many cases, the compulsive behaviors are completely inexplicable, merely impulses to complete neurotic-triggered rituals. In rare cases, OCD sufferers may experience only obsessive thoughts without overt compulsive behaviors; significantly fewer sufferers experience only compulsive behaviors. One of the largest categories of anxiety disorders is phobias, which include all situations in which fear and anxiety are triggered by specific stimuli or situations. Victims typically anticipate frightening consequences upon encountering the object of their fear, which can be anything from animals to places to bodily fluids. Post-traumatic stress disorder (PTSD) is an anxiety disorder stemming from a traumatic experience. PTSD can arise from extreme situations such as combat, rape, hostage situations, or major accidents. It can also result from prolonged (chronic) exposure to severe stressors, such as a soldier who can tolerate individual combat but cannot cope with continuous combat. Common symptoms include flashbacks, avoidance behaviors, and depression. The psychotropic compound 1, or a pharmaceutically acceptable salt or composition thereof, can be used in the methods described herein, for example, for treating a psychotropic disorder. In some embodiments, the psychotropic disorder is schizophrenia or bipolar disorder. In some embodiments, the psychotropic disorder is schizophrenia. In some embodiments, the psychotropic disorder is bipolar disorder. Bipolar disorder or bipolar disorder causes extreme mood swings, including euphoria (mania or hypomania) and depression (depression). The impulse control disorder compound 1, or a pharmaceutically acceptable salt or composition thereof, can be used in the methods described herein, for example, for treating impulse control disorders. In some embodiments, the impulse control disorder is anorexia nervosa or alcohol withdrawal. In some embodiments, the impulse control disorder is anorexia nervosa. In some embodiments, the impulse control disorder is anorexia nervosa. The seizure-inducing compound 1, or a pharmaceutically acceptable salt or composition thereof, can be used in the methods described herein, for example, for treating seizures. In some embodiments, a seizure is epilepsy. In some embodiments, a seizure is a status epilepticus, such as a convulsive status epilepticus, such as an early status epilepticus, an established status epilepticus, a refractory status epilepticus, or a super-refractory status epilepticus. In some embodiments, the seizures are focal seizures with motor (automatisms, atonia, clonic, epileptic spasms, hyperkinesia, myoclonus, and tonic) or non-motor (spontaneous, cessation of activity, cognitive, emotional, and sensory) seizures; generalized seizures with motor (tonic-clonic, clonic, myoclonic, myoclonic-tonic-clonic, myoclonic-atonia, atonia, epileptic spasms) or non-motor (absence) seizures; seizures with unknown motor (tonic-clonic, epileptic spasms) or non-motor (cessation of activity) seizures; and seizures associated with clinical syndromes (e.g., Dravet syndrome, Rett syndrome, Lennox-Gasteau syndrome, tuberous sclerosis, Angelmans syndrome, menstrual epilepsy). In some embodiments, the seizures are caused by affective schizophrenia or by medications used to treat schizophrenia. Epilepsy is a brain disorder characterized by recurrent epileptic seizures over time. Types of epilepsy may include (but are not limited to) generalized epilepsy (e.g., childhood absence epilepsy, juvenile myoclonic epilepsy, epilepsy with grand mal seizures during wakefulness, West syndrome, Regger syndrome) and partial epilepsy (e.g., temporal lobe epilepsy, frontal lobe epilepsy, benign focal epilepsy in childhood). Status epilepticus (SE) Status epilepticus (SE) can include, for example, convulsive status epilepticus, such as early status epilepticus, established status epilepticus, refractory status epilepticus, or ultra-refractory status epilepticus; nonconvulsive status epilepticus, such as generalized status epilepticus, complex focal status epilepticus; generalized periodic epileptiform discharges; and periodic unilateral epileptiform discharges. Convulsive status epilepticus is characterized by the presence of convulsive status epileptic seizures and can include early status epilepticus, established status epilepticus, refractory status epilepticus, and ultra-refractory status epilepticus. Early status epilepticus is treated with first-line therapy. Established status epilepticus is characterized by persistent status epileptic seizures despite first-line therapy and the administration of second-line therapy. Refractory status epilepticus is characterized by persistent status epileptic seizures despite both first-line and second-line therapy and is usually treated with general anesthetics. The characteristic of super-refractory status epilepticus is that the epileptic seizures continue for 24 hours or longer despite first-line therapy, second-line therapy and general anesthetic treatment. Nonconvulsive status epilepticus may include, for example, focal nonconvulsive status epilepticus, such as complex focal nonconvulsive status epilepticus, simple focal nonconvulsive status epilepticus, and minimal nonconvulsive status epilepticus; and generalized nonconvulsive status epilepticus, such as delayed absence nonconvulsive status epilepticus, atypical absence nonconvulsive status epilepticus, or typical absence nonconvulsive status epilepticus. An epileptic seizure is a physical finding or change in behavior that occurs following an abnormal electrical activity in the brain. The term "epileptic seizure" is often used interchangeably with "convulsion." A convulsion is a rapid and uncontrollable shaking of the body. During a convulsion, the body's muscles repeatedly contract and relax. Based on the type of behavior and brain activity, epileptic seizures are divided into two main categories: generalized and focal (also known as localized or focal seizures). Classifying the type of epileptic seizure helps physicians diagnose whether a patient has epilepsy. Generalized seizures are caused by electrical impulses that spread throughout the entire brain, while focal seizures are (at least initially) caused by electrical impulses in a relatively small part of the brain. The part of the brain that produces a seizure is sometimes called a lesion. There are six types of generalized seizures. The most common, notable, and therefore most well-known is the generalized tonic-clonic seizure, also known as a grand mal seizure. In this type of seizure, the patient loses consciousness and usually collapses. Following loss of consciousness is a generalized tonic-clonic phase (called the "tonic" phase of the seizure) lasting 30 to 60 seconds, followed by violent shaking (the "clonic" phase) lasting 30 to 60 seconds, after which the patient enters a deep sleep ("postictal" or late seizure). During a grand mal seizure, injuries and accidents can occur, such as tongue biting and urinary incontinence. Absence seizures cause brief loss of consciousness (lasting only a few seconds) and are rarely or never asymptomatic. Patients (most commonly children) typically stop their activity and stare blankly. These seizures begin and end suddenly and can occur several times a day. Patients are usually unaware that they are having a seizure; they are only aware of "losing time." Myoclonic seizures consist of sporadic, sudden movements, usually occurring on both sides of the body. Patients sometimes describe these sudden movements as brief electric shocks. In severe cases, these seizures can cause a limping gait or involuntary throwing of objects. Clonic seizures involve repetitive, rhythmic, rapid movements on both sides of the body simultaneously. Tonic seizures are characterized by muscle rigidity. Atonic seizures consist of a sudden and complete loss of muscle tone, specifically in the arms and legs, which usually leads to falls. The epileptic seizures described in this article may include: epileptic seizures; acute recurrent seizures; cluster seizures; continuous seizures; uninterrupted seizures; delayed seizures; recurrent seizures; status epilepticus, such as refractory convulsive status epilepticus and nonconvulsive status epilepticus; refractory seizures; myoclonic seizures; tonic seizures; tonic-clonic seizures; simple focal seizures; complex focal seizures; secondary generalized seizures; atypical absence seizures; absence seizures; atonic seizures; benign Rolandic seizures; febrile seizures; emotional seizures; focal seizures; laughing seizures; generalized tonic-clonic seizures; infantile spasms; Jacksonian seizures; massive bilateral myoclonic seizures; multifocal seizures; neonatal paroxysmal seizures; nocturnal seizures; occipital lobe seizures; post-traumatic seizures; minimal seizures; and Sylvanian seizures. Seizure; visual reflex seizure; or withdrawal seizure. In some embodiments, the seizure is a generalized seizure associated with Dravier syndrome, Legg syndrome, tuberous sclerosis complex, Rett syndrome, or PCDH19-associated epilepsy in female children. The neuroinflammatory compound 1, or a pharmaceutically acceptable salt or composition thereof, can be used in the methods described herein, for example, to treat the conditions described herein (e.g., neuroinflammatory conditions). In some embodiments, the neuroinflammatory condition is multiple sclerosis or pediatric autoimmune neuropsychiatric disorder (PANDAS) associated with streptococcal infection. Pain relief / The pain-controlling compound 1, or a pharmaceutically acceptable salt or composition thereof, can be used in the methods described herein, for example, as an analgesic or as other agents for pain control. In some embodiments, the solid form of compound 1 or a pharmaceutically acceptable composition thereof can be used as an analgesic or as other agents for pain control to treat inflammatory pain, neuropathic pain, fibromyalgia, or peripheral neuropathy. The sensory deficit compound 1, or a pharmaceutically acceptable salt or composition thereof, can be used in the methods described herein, for example, to treat the condition described herein (e.g., sensory deficit). In some embodiments, the sensory deficit is tinnitus or synesthesia. In some embodiments, the sensory deficit is hearing impairment and / or loss. Assessment for symptoms ( For example, major depressive disorder ) This document also provides methods for assessing individuals with depressive disorders (e.g., major depressive disorder) before and after treatment with a therapeutic agent (e.g., compound 1). In some embodiments, the method includes monitoring the individual using a known depression scale, such as the Hamilton Depression Rating Scale (HAM-D), the Modified Clinical Global Impression Scale (CGI), and the Montgomery-Asperger Depression Rating Scale (MADRS). In some embodiments, the treatment effect can be measured by a decrease in the individual's total Hamilton Depression Rating Scale (HAM-D). The decrease in the total HAM-D score can occur within 4 days, 3 days, 2 days, or 1 day; or within 96 hours, 84 hours, 72 hours, 60 hours, 48 ​​hours, 24 hours, 20 hours, 16 hours, 12 hours, 10 hours, 8 hours, or less. The treatment effect can be evaluated across a specified treatment period. For example, the therapeutic effect can be measured by the reduction in the total HAM-D score from baseline after administration of compound 1 (e.g., 12, 24, or 48 hours after administration; or 24, 48, 72, or 96 hours or longer; or 1 day, 2 days, 14 days, 21 days, or 28 days; or 1 week, 2 weeks, 3 weeks, or 4 weeks; or 1 month, 2 months, 6 months, or 10 months; or 1 year, 2 years, or lifetime). In some embodiments, the individual has a mild depressive disorder, such as mild major depressive disorder. In some embodiments, the individual has a moderate depressive disorder, such as moderate major depressive disorder. In some embodiments, the individual has a severe depressive disorder, such as severe major depressive disorder. In some embodiments, the individual has a very severe depressive disorder, such as very severe major depressive disorder. In some embodiments, the individual's baseline HAM-D total score (i.e., prior to treatment with compound 1) is at least 24. In some embodiments, the individual's baseline HAM-D total score is at least 18. In some embodiments, the individual's baseline HAM-D total score is between 14 and 18, including 14 and 18. In some embodiments, the individual's baseline HAM-D total score is between 19 and 22, including 19 and 22. In some embodiments, the individual's HAM-D total score is greater than or equal to 23 prior to treatment with compound 1. In some embodiments, the baseline score is at least 10, 15, or 20. In some embodiments, after treatment with compound 1, an individual's total HAM-D score is approximately 0 to 10 (e.g., less than 10; 0 to 10, 0 to 6, 0 to 4, 0 to 3, 0 to 2, or 1.8). In some embodiments, after treatment with compound 1, the total HAM-D score is less than 10, 7, 5, or 3. In some embodiments, the reduction in the total HAM-D score is from a baseline score of approximately 20 to 30 (e.g., 22 to 28, 23 to 27, 24 to 27, 25 to 27, 26 to 27) to a total HAM-D score of approximately 0 to 10 (e.g., less than 10; 0 to 10, 0 to 6, 0 to 4, 0 to 3, 0 to 2, or 1.8) after treatment with compound 1. In some embodiments, the baseline HAM-D total score is reduced by at least 1, 2, 3, 4, 5, 7, 10, 25, 40, 50, or 100 times to the HAM-D total score after treatment with compound 1. In some embodiments, the percentage reduction in the baseline HAM-D total score to the HAM-D total score after treatment with compound 1 is at least 50% (e.g., 60%, 70%, 80%, or 90%). In some embodiments, the therapeutic effect is measured as the reduction in the HAM-D total score relative to the baseline HAM-D total score after treatment with compound 1 (e.g., at 12, 24, or 48 hours post-administration; or 24, 48, 72, or 96 hours or longer; or 1, 2, or 14 days or longer), which is at least 10, 15, or 20 points. In some embodiments, the method of treating depressive disorders (e.g., major depressive disorder) provides a therapeutic effect within 14 days, 10 days, 4 days, 3 days, 2 days, or 1 day, or within 24 hours, 20 hours, 16 hours, 12 hours, 10 hours, or 8 hours or less (e.g., as measured by a reduction in the Hamilton Depression Rating Scale (HAM-D)). In some embodiments, the method of treating depressive disorders (e.g., major depressive disorder) provides a therapeutic effect within the first or second day of treatment with compound 1 (e.g., as measured by a statistically significant reduction in the total HAM-D score). In some embodiments, the method of treating depressive disorders (e.g., major depressive disorder) provides a therapeutic effect within 14 days or less from the start of treatment with compound 1 (e.g., as measured by a statistically significant reduction in the total HAM-D score). In some embodiments, the method of treating depressive disorders (e.g., major depressive disorder) provides a therapeutic effect within 21 days or less from the start of treatment with compound 1 (e.g., as measured by a statistically significant reduction in the total HAM-D score). In some embodiments, the method of treating depressive disorders (e.g., major depressive disorder) provides a therapeutic effect (e.g., as measured by a statistically significant reduction in the total HAM-D score) within 28 days or less from the start of treatment with Compound 1. In some embodiments, the therapeutic effect is a reduction in the total HAM-D score from baseline after treatment with Compound 1 (e.g., once daily for 14 days). In some embodiments, an individual's total HAM-D score was at least 24 before treatment with Compound 1. In some embodiments, an individual's total HAM-D score was at least 18 before treatment with Compound 1. In some embodiments, an individual's total HAM-D score was between and including 14 and 18 before treatment with Compound 1. In some embodiments, after treatment with Compound 1, the individual's total HAM-D score decreased by at least 10 relative to the baseline total HAM-D score. In some embodiments, after treatment with Compound 1, the individual's total HAM-D score decreased by at least 15 (e.g., at least 17) relative to the baseline total HAM-D score. In some embodiments, the total HAM-D score associated with an individual treated with compound 1 is not greater than a value in the range of 6 to 8. In some embodiments, the total HAM-D score associated with an individual treated with compound 1 is not greater than 7. In some embodiments, the method provides a therapeutic effect (e.g., as measured by a reduction in the Clinical Global Impression Index (CGI)) within 14 days, 10 days, 4 days, 3 days, 2 days, or 1 day, or 24 hours, 20 hours, 16 hours, 12 hours, 10 hours, or 8 hours or less. In some embodiments, the CNS condition is a depressive condition, such as major depressive disorder. In some embodiments, the method for treating a depressive condition (e.g., major depressive disorder) provides a therapeutic effect within the second day of the treatment period. In some embodiments, the therapeutic effect is a reduction in the CGI score from baseline at the end of the treatment period (e.g., 14 days after administration). In some embodiments, the method provides a therapeutic effect (e.g., as measured by a reduction in the Montgomery-Asperger Depression Rating Scale (MADRS)) within 14 days, 10 days, 4 days, 3 days, 2 days, or 1 day, or 24 hours, 20 hours, 16 hours, 12 hours, 10 hours, or 8 hours or less. In some embodiments, the CNS condition is a depressive condition, such as major depressive disorder. In some embodiments, the method for treating a depressive condition (e.g., major depressive disorder) provides a therapeutic effect within the second day of the treatment period. In some embodiments, the therapeutic effect is a reduction in the MADRS score from baseline at the end of the treatment period (e.g., 14 days after administration). The therapeutic effect of treatment for major depressive disorder can be measured by a decrease in an individual's Montgomery-Asperger's Depression Rating Scale (MADRS) score. For example, MADRS scores can decrease within 4 days, 3 days, 2 days, or 1 day; or within 96 hours, 84 hours, 72 hours, 60 hours, 48 ​​hours, 24 hours, 20 hours, 16 hours, 12 hours, 10 hours, 8 hours, or less. The Montgomery-Asperger's Depression Rating Scale (MADRS) is a ten-item diagnostic questionnaire used by psychiatrists to measure the severity of depressive episodes in patients with mood disorders (regarding apparent sadness, reported sadness, anxiety, decreased sleep, decreased appetite, difficulty concentrating, fatigue, feelings of weakness, pessimistic thoughts, and suicidal ideation). In some of the foregoing embodiments, individual compound 1 (e.g., about 30 mg of compound 1) is administered once daily for less than 2 weeks. In some of the foregoing embodiments, individual compound 1 (e.g., about 30 mg of compound 1) is administered once daily for 1 day. In some of the foregoing embodiments, individual compound 1 (e.g., about 30 mg of compound 1) is administered once daily for 2 days. In some of the foregoing embodiments, individual compound 1 (e.g., about 30 mg of compound 1) is administered once daily for at least 14 days. In some embodiments, individual compound 1 (e.g., about 30 mg of compound 1) is administered once daily for at least 28 days. In some embodiments, individual compound 1 (e.g., about 30 mg of compound 1) is administered once daily for at least 6 months. In some embodiments, individual compound 1 is administered once daily (e.g., at a dose of about 30 mg) for at least one year. In some embodiments, individual compound 1 is administered once daily (e.g., at a dose of about 30 mg) for life. In some embodiments, individual compound 1 is administered at night. In some embodiments, individual compound 1 is administered no more than one hour before the individual falls asleep. In some embodiments, individual compound 1 is administered no more than 15 minutes before the individual falls asleep. In some embodiments, compound 1 is administered long-term. Examples are provided to enable a more complete understanding of the invention set forth herein. The synthetic and biological examples described in this application are provided to illustrate the compounds, pharmaceutical compositions, and methods provided herein, and should not be construed as limiting their scope in any way. Example 1. The safety and tolerability of compound 1 were evaluated by administering compound 1 capsules to healthy individuals. The relative bioavailability of compound 1 capsules compared to oral solution of compound 1 was also evaluated. The safety, tolerability, and relative bioavailability of compound 1 capsules were evaluated in a phase 1, single-center, open-label, four-stage, two-order crossover study. Twelve (12) individuals completed all four stages of the study; individuals who replaced those who discontinued the study were assigned to the same randomization sequence as those who discontinued the study. A maximum of 24 individuals were recruited for the study. This study consisted of four phases: Phase 1: On day 1, individuals (N=20) were randomized 1:1 to receive a single 30-mg dose of Compound 1 capsule or a single 30-mg dose of Compound 1 oral solution. The study drug was administered while fasting. Individuals were confined to an inpatient facility from day -1 until their discharge on day 3. Phase 2: After the clearance period (which ended on day 7), the same individuals (N=20) from Phase 1 were crossovered to the dosage form they did not receive in Phase 1. On day 8, the study drug was administered while fasting. Individuals were confined to an inpatient facility from day 7 until their discharge on day 10. Phase 3: Food effect (high fat): On day 15, all individuals received a single 30 mg dose of Compound 1 capsule. The study drug was administered after a high-fat meal. Individuals were confined to an inpatient facility from day 14 until their discharge on day 17. Phase 4: Food Effect (Standard): On day 22, all individuals received a single 30 mg dose of compound 1 capsule. The study drug was administered after a standard diet. Individuals were confined to the hospital facility from day 21 until their discharge on day 24. Individuals were hospitalized one day prior to scheduled dosing (i.e., on day -1, day 7, day 14, and day 21) for pre-dosing evaluation. Individuals underwent a treatment end visit on day 28 and a follow-up evaluation 13 days after the final dose (day 35). The dosage of Compound 1 capsules was two capsules administered with 8 ounces (240 mL) of water; both capsules should be swallowed as soon as possible. An oral solution of Compound 1 was prepared to approximately 40 mL, all of which was swallowed in one gulp, followed by approximately 200 mL of water to rinse the vial approximately five times. The time taken to swallow the initial 40 mL solution or capsules was zero for all evaluations. Except for water consumed during medication administration, individuals are not permitted to drink water before and within one hour after medication administration. One hour after medication administration, individuals may drink water freely. Individuals are required to fast overnight (at least 10 hours) prior to scheduled medication administration. In Phases 1 and 2, individuals are given a standard diet four hours or longer after dose administration. In Phase 3 (food effect, high-fat diet), the individual was given a high-fat diet 30 minutes before administration of the compound 1 capsule. The individual should consume this diet within 30 minutes or less, and the compound 1 dose was administered 30 minutes after the start of the diet. No other food should be consumed for at least 4 hours after administration. In Phase 4 (Standard Diet for Food Effects), the individual's standard diet is administered 30 minutes prior to the administration of the Compound 1 capsule. The individual should consume this diet within 30 minutes or less, and the Compound 1 dose is administered 30 minutes after the start of the diet. No other food should be consumed for at least 4 hours after administration. Plasma samples were collected at the following sampling times relative to drug administration for PK analysis of compound 1 during each stage: before drug administration on day 1 and at 15 and 30 minutes after drug administration, and at 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24 (day 2) and 48 (day 3) hours after drug administration. Keep plasma samples frozen at approximately -70°C to -80°C until analysis. Pack them as instructed to prevent breakage during transport and use sufficient dry ice to prevent thawing for at least 72 hours. Complete the sample identification form or equivalent and send it to the laboratory along with each set of samples. Bioanalysis of plasma samples for the determination of compound 1 was performed at Agilux Laboratories, Worcester, MA using a validated LC-MS / MS method. For compound 1, if appropriate, follow these guidelines to calculate the following PK parameters from individual plasma concentrations using Phoenix® WinNonLin® 6.3 or later: • Use the actual sampling time relative to the administration time, rather than the nominal time, in the calculation of all derived PK parameters. • Imputation without missing data. • Include any individual with missing concentration data in the PK analysis set, provided that at least C... max and AUC 0-t Reliable calculation. • Calculate AUC 0-t At least three time points with measurable plasma concentrations are required, and at least three time points at t are needed to calculate λz. max Subsequent time points with measurable plasma concentrations are provided. • Sample values ​​below the limit of quantification (BLQ) during the absorption period, prior to the first reported concentration, are replaced with 0. BLQ values ​​between the measurable concentration and the final BLQ value are designated as "missing". These measures are taken to prevent overestimation of AUC. 0-t and AUC 0-inf • Post-dosage values ​​for "Unreceived Samples" (NS), "Insufficient Sample for Analysis" (IS), or "Not Reported" (NR) are omitted in PK analyses. If the reported values ​​are close to the estimated t... max If the NS, IS, or NR values ​​are not reported at any of the two consecutive time points, the individual may be unable to perform a pharmacokinetic assessment. If the NS, IS, or NR values ​​are reported at more than two consecutive time points, the individual may be considered unable to perform a pharmacokinetic assessment. Table 6 provides the definitions and units of pharmacokinetic parameters. surface 6 Pharmacokinetic parameters h, hour; mL, milliliter; ng, nanogram AUC applied to compound 1 parameter 0-inf AUC 0-t and C max A linear mixture model was used to test the effects of administration conditions on absorption rate and extent for fixed-effects items (fasting solution, fasting capsule, feeding capsule [high-fat diet], feeding capsule [standard diet]). Pharmacokinetic parameters were transformed using the natural logarithm prior to analysis. An unstructured covariance matrix was used to allow for unequal variances of administration conditions, and the correlation between each in vivo administration condition measurement was modeled using the REPEATED command in SAS PROC MIXED. The Kenward and Roger methods were used to calculate the denominator degrees of freedom (DDFM=KR) for fixed effects. For AUC and C max The treatment ratio "test / control" was calculated using the antinomial coefficient of the difference between treatment methods. In this analysis, the compound 1 fasting solution condition was considered the control group, and the compound 1 fasting capsule condition was considered the test treatment group. AUC and C0 were constructed. max The 90% confidence interval of the geometric mean ratio of the test group to the control group. If AUC and C... max If the 90% confidence interval falls within the range (0.80, 1.25), then the conclusion is that there is no evidence of a conditioned effect. For the food-effects analysis, the capsule-eating condition (standard diet, high-fat diet) was used as the treatment group, and the capsule-fasting condition was used as the control group. The mean plasma concentration (± SD) of compound 1 over time is shown in Figure 1 (linear scale) and Figure 2 (semi-logarithmic scale). The arithmetic mean C after a single oral dose of compound 1 solution under fasting conditions. max The CV% was 119.77 ng / mL (32.087%). The median t... max (Minimum to maximum value) is 1.00 hour (0.50 hours - 4.00 hours). Arithmetic mean AUC 0-t (CV%) and AUC 0-infThe CV% were 795.4 h*ng / mL (22.42%) and 798.4 h*ng / mL (28.60%), respectively. The arithmetic mean t... 1 / 2 (CV%) was 13.50 hours (21.713%). The arithmetic mean C after a single oral dose of compound 1 capsule in a fasting state max The CV% was 22.98 ng / mL (35.653%). The median t... max The time from minimum to maximum is 4.02 hours (1.50 hours - 24.28 hours). The arithmetic mean (AUC) is... 0-t (CV%) and AUC 0-inf The CV% were 543.7 h*ng / mL (22.03%) and 642.1 h*ng / mL (9.60%), respectively. The arithmetic mean t... 1 / 2 (CV%) was 15.60 hours (11.939%). The arithmetic mean C of a single oral dose of compound 1 capsule administered concurrently with a high-fat diet. max The CV% was 64.37 ng / mL (21.814%). The median t... max The time from minimum to maximum is 5.97 hours (2.00 hours - 10.00 hours). The arithmetic mean (AUC) is... 0-t (CV%) and AUC 0-inf The CV% were 846.5 h*ng / mL (17.51%) and 895.7 h*ng / mL (29.16%), respectively. The arithmetic mean t... 1 / 2 (CV%) was 12.94 hours (12.507%). The arithmetic mean C of a single oral dose of compound 1 capsule administered concurrently with a standard diet max The CV% was 65.16 ng / mL (25.715%). The median t... max (Minimum to maximum) is 4.00 hours (1.00 hour - 8.00 hours). Arithmetic mean AUC 0-t(CV%) and AUC 0-inf The CV% were 851.8 h*ng / mL (18.03%) and 1020 h*ng / mL (12.92%), respectively. The arithmetic mean t... 1 / 2 (CV%) was 14.90 hours (16.115%). The results are summarized in Table 8: surface 8 compound 1 Summary of plasma pharmacokinetic parameters ( Pharmacokinetic Analysis Set ) AUC = Area under the curve; C max =Maximum concentration; G. =Geometric; t max =Time to maximum concentration; t ½ = Half-life * Summarized by median, minimum, and maximum values Compared to capsules administered in a fasting state, statistical analysis of plasma pharmacokinetics of compound 1 (Table 9) indicates the C60 concentration of the capsules when administered as a solution in a fasting state. max Decreased; the geometric mean ratio (90% CI) was 0.191 (0.17, 0.22). Compound 1 AUC 0-t It also decreased; the geometric mean ratio (90% CI) was 0.682 (0.62, 0.75). It has accurate capture AUC. 0-inf The number of individuals is insufficient to represent the overall picture, so only the geometric mean ratio (0.830) is presented. Compared to capsules administered in a fasting state, statistical analysis of plasma pharmacokinetics of compound 1 (Table 10) indicated the C-value of the capsule in a fed state (high-fat diet). max Increased; the geometric mean ratio (90% CI) was 2.879 (2.56, 3.28). Compound 1 AUC 0-t It also increased; the geometric mean ratio (90% CI) was 1.575 (1.45, 1.69). It has accurate capture AUC. 0-inf The number of individuals is insufficient to represent the overall picture, so only the geometric mean ratio (1.355) is presented. Compared to capsules administered in a fasting state, statistical analysis of plasma pharmacokinetics of compound 1 (Table 11) indicated the C-value of the capsules administered in a fed state (standard diet). max Increased; the geometric mean ratio (90% CI) was 2.894 (2.64, 3.25). Compound 1 AUC 0-t It also increased; the geometric mean ratio (90% CI) was 1.581 (1.43, 1.72). It has accurate capture AUC. 0-inf The number of individuals is insufficient to represent the overall picture, so only the geometric mean ratio (1.584) is presented. Compared to the solution in a fasting state, the statistical analysis of plasma pharmacokinetics of compound 1 (Table 12) indicated the C-value in a fed state (high-fat diet) when administered as a capsule. max Decreased; the geometric mean ratio (90% CI) was 0.549 (0.48, 0.63). Compound 1 AUC 0-t The values ​​are comparable; the geometric mean ratio (90% CI) is 1.074 (1.02, 1.12). It has an accurate capture AUC. 0-inf The number of individuals is insufficient to represent the overall picture, so only the geometric mean ratio (1.125) is presented. Compared to the solution in a fasting state, the statistical analysis of plasma pharmacokinetics of compound 1 (Table 13) when administered as a capsule in a fed state (standard diet) indicates the C-value in a fed state. max Decreased; the geometric mean ratio (90% CI) was 0.552 (0.49, 0.64). Compound 1 AUC 0-t The values ​​are comparable; the geometric mean ratio (90% CI) is 1.079 (1.02, 1.13). It has an accurate capture AUC. 0-inf The number of individuals is insufficient to represent the overall picture, so only the geometric mean ratio (1.315) is presented. surface 9 cast Drug conditions on compounds 1 Plasma pharmacokinetic parameters ( Pharmacokinetic Analysis Set ) Statistical analysis of the effect In this analysis, the AUC parameter applied to compound 1 will be used. 0-inf AUC 0-t and C max A linear mixture model with a fixed-effects term and fasting status was used to test the effects of dosing form (solution and capsule) on absorption rate and extent. An unstructured covariance matrix was used. Compound 1 fasting in solution was considered the control, and Compound 1 fasting in capsule was considered the treatment. If AUC and C... max If the 90% CI falls within the interval (0.8, 1.25), then evidence of no drug-induced conditioned effects is obtained. [1] Shows the number of individuals exposed to each treatment condition used in the mixed model. GM = geometric mean, GMR = ratio of geometric means*: from AUC 0-inf The non-convergence caused by sparse data surface 10 High-fat diets for compounds 1 Plasma pharmacokinetic parameters ( Pharmacokinetic Analysis Set ) Statistical analysis of the effect In this analysis, the AUC parameter applied to compound 1 will be used. 0-inf AUC 0-t and C max A linear mixture model with a fixed-effects term and drug administration form (capsule) will be used to test the effect of a high-fat diet on the rate and extent of absorption. An unstructured covariance matrix will be used. The condition of fasting for compound 1 capsules will be considered the control, and the condition of ingesting compound 1 capsules [high-fat diet] will be considered the test treatment. If AUC and C... maxIf the 90% CI falls within the range (0.8, 1.25), then evidence of no high-fat diet effect is obtained. [1] Shows the number of individuals exposed to each treatment condition used in the mixed model. GM = geometric mean, GMR = ratio of geometric means*: from AUC 0-inf The non-convergence caused by sparse data surface 11 Standard diet for compounds 1 Plasma pharmacokinetic parameters ( Pharmacokinetic Analysis Set ) Statistical analysis of the effect In this analysis, the AUC parameter applied to compound 1 will be used. 0-inf AUC 0-t and C max A linear mixture model with a fixed-effects term and drug administration form (capsule) will be used to test the effect of a standard fat diet on the rate and extent of absorption. An unstructured covariance matrix will be used. The condition of fasting for compound 1 capsules will be considered the control, and the condition of ingesting compound 1 capsules [standard fat diet] will be considered the test treatment. If AUC and C... max If the 90% CI falls within the range (0.8, 1.25), then evidence of the absence of a standard fat diet effect is obtained. [1] Shows the number of individuals exposed to each treatment condition used in the mixed model. GM = geometric mean, GMR = ratio of geometric means, *: from AUC 0-inf The non-convergence caused by sparse data surface 12 cast Drug conditions and high-fat diets for compounds 1 Plasma pharmacokinetic parameters ( Pharmacokinetic Analysis Set ) Statistical analysis of the effect In this analysis, the AUC parameter applied to compound 1 will be used. 0-inf AUC 0-t and C max A linear mixture model was used to test the effects of a high-fat diet and drug administration conditions on the rate and extent of absorption. An unstructured covariance matrix was used. The fasting solution condition for compound 1 was considered the control, and the ingested capsule of compound 1 (high-fat diet) was considered the treatment. If AUC and C... max If the 90% CI is within the range (0.8, 1.25), then there will be evidence of the absence of drug administration conditions and the effects of a high-fat diet. [1] Shows the number of individuals exposed to each treatment condition used in the mixed model. GM = geometric mean, GMR = ratio of geometric means, *: from AUC 0-inf The non-convergence caused by sparse data surface 13 cast Drug conditions and standard diet for compounds 1 Plasma pharmacokinetic parameters ( Pharmacokinetic Analysis Set ) Statistical analysis of the effect In this analysis, the AUC parameter applied to compound 1 will be used. 0-inf AUC 0-t and C max A linear mixture model was used to test the effects of a standard fat diet and drug administration conditions on the rate and extent of absorption. An unstructured covariance matrix was used. The fasting solution condition for compound 1 was used as the control, and the oral capsule of compound 1 [standard fat diet] was used as the test treatment. If AUC and C... max If the 90% CI is within the range (0.8, 1.25), then there will be evidence of the absence of drug administration conditions and the effects of a high-fat diet. [1] Shows the number of individuals exposed to each treatment condition used in the mixed model. GM = geometric mean, GMR = ratio of geometric means, *: from AUC 0-inf The non-convergence caused by sparse data Under fasting conditions, the exposure rate and extent of compound 1 in solution were greater than that in capsules. max The geometric mean ratios of AUC (capsule / solution) were 0.191 and 0.682, respectively, with 90% CIs of (0.17, 0.22) and (0.62, 0.75). Compared to the solution under fasting conditions, the exposure rate of compound 1 in the capsules under fed conditions (high-fat diet) was lower. max The geometric mean ratio (90% CI) for (eaten / fasted) was 0.549 (0.48, 0.63). Exposure to the capsules in the eaten state (high-fat diet) was comparable to that to the solution in the fasted state. AUC 0-t The geometric mean ratio of (90% CI) is 1.074 (1.02, 1.12). Compared to the solution under fasting conditions, the exposure rate of compound 1 administered via capsule during a feeding state (standard diet) was lower. max The geometric mean ratio (90% CI) for (eaten / fasted) was 0.552 (0.49, 0.64). The exposure level of the capsule under the eating state (high-fat diet) was comparable to that of the solution under the fasting state. As shown in Figures 1 and 2, the AUC curves of Compound 1 capsules under a high-fat diet were nearly identical to those under a standard diet. This is further supported by the data presented in Table 8, which shows the average AUC of Compound 1 capsules under a high-fat diet. 0-t The average AUC of compound 1 capsules was 846.5 h*ng / mL under the condition of eating (standard diet). 0-t The value was 851.8 h*ng / mL. In comparison, the average AUC of compound 1 capsules under fasting conditions was... 0-t It is 543.7 h*ng / mL. Compared to the fasting state, the exposure rate and extent of compound 1 were greater in the fed state (high-fat diet) than in capsules. max The geometric mean ratios of AUC (feeding / fasting) were 2.879 and 1.575, respectively, with 90% CIs of (2.56, 3.28) and (1.45, 1.69). Compared to the fasting state, the exposure rate and extent of compound 1 were greater in the fed state (standard diet) than in capsules. maxThe geometric mean ratios of AUC (feeding / fasting) were 2.894 and 1.581, respectively, with 90% CIs of (2.64, 3.25) and (1.43, 1.72). Example 2: Preparation of solid form A. Form A was prepared by stirring crude compound 1 in ethyl acetate at below 10°C, followed by filtration and drying under vacuum. Form A was also prepared by dissolving crude compound 1 in dichloromethane and then concentrating the solution twice under vacuum with ethyl acetate until dry. Example 3: Various wet crystallization methods for obtaining other solid forms of the present invention. To identify new crystal forms, form A was used as the starting material to evaluate different crystallization methods. In addition to form A, these methods were also used to identify form C. Slow evaporation crystallization experiments were conducted across eight different solvent systems. In each experiment, approximately 10 mg of Form A was dissolved in 0.4 mL to 1.0 mL of solvent in a 1.5 mL glass vial. Parafilm® sealed glass vials with 3 to 5 holes to allow solvent evaporation were used. In each experiment, approximately 10 to 20 mg of form A was suspended in 0.5 mL of solvent or a mixture of solvents. After stirring at room temperature or 50°C for 48 hours, the solids were separated by centrifugation for analysis (wet sample). If the suspension became a clear solution, it was kept under ambient conditions for slow evaporation. In each experiment, an antisolvent was added by dissolving approximately 10 mg of Form A in 0.1 mL to 1 mL of solvent to obtain a clear solution. The antisolvent was added in increments of 50 µL until precipitation was observed, or until the total volume of the antisolvent reached 20 times the volume of the solvent. The precipitate was then separated by centrifugation for analysis (wet sample). A slow evaporation experiment was performed if a clear solution was observed. For each experiment, approximately 10 mg of Form A was suspended in 0.8 mL to 1.0 mL of each solvent mixture at 50 °C. The resulting suspension was immediately filtered through a 0.2 µm filter, and the filtrate was collected and cooled from 50 °C to 5 °C at a rate of 0.1 °C / min. The precipitate was then separated for analysis (wet sample) by centrifugation at 10,000 rpm for 3 to 5 minutes. In each experiment, approximately 10 mg of Form A was dissolved in a suitable solvent in a 3-mL glass vial to obtain a clear solution. The vial was then placed into a 20-mL glass vial containing 3 mL of antisolvent and sealed. The system was kept at room temperature for 7 days to allow sufficient time for the solid to precipitate. The solid was separated and analyzed (wet sample) by centrifugation at 10,000 rpm for 3 to 5 minutes. If no precipitation was observed, the sample was kept under ambient conditions for slow evaporation. For solid vapor diffusion, approximately 10 mg of Form A was placed in a 3-mL glass vial, which was then sealed in a 20-mL glass vial containing 3 mL of the specified solvent. The system was kept at room temperature for 7 days to allow sufficient time for the organic vapor to interact with the solid. The solid (wet sample) was then analyzed. In each experiment, approximately 10 mg of Form A was dissolved in 0.5 mL to 1.0 mL of solvent in a 1.5 mL glass vial. The visually clear solution was kept under ambient conditions, and the cap was removed for rapid evaporation. The solid obtained by evaporation (dry sample) was then analyzed. In each experiment, a reverse solvent was added, dissolving approximately 20 mg of Form A in 0.2 mL to 0.6 mL of each solvent to obtain a clear solution. This solution was added to a glass vial containing 2.0 mL of each reverse solvent at room temperature. The resulting precipitate was centrifuged at 10,000 rpm for 3 to 5 minutes for analysis (wet sample). If no precipitation was observed, a slow evaporation experiment was performed on the remaining solution. The water activity assay was performed using H₂O and acetonitrile in a 0.2 interval, ranging from 0 to 1 water activity (aw). Approximately 10 mg of Form A was weighed into a 1.5 mL vial, and 0.5 mL of the solvent mixture was added. The suspension was stirred at 1000 rpm at room temperature. Residual solvent was removed from the sample by centrifugation (10000 rpm, 3 min). Example 4. Preparation of solid form C. Form C is prepared from form A by slurry conversion crystallization in isopropanol (IPA) and isopropyl acetate (IPAc) at 50°C. Example 5. Preparation of K in solid form. Form K is prepared by heating forms A, B, C, E, or F to an elevated temperature. The sample of form K analyzed was prepared by heating form F to 100°C. Example 6. Characterizing solid forms A and C using XRPD. Throughout this study, an PANalytical Empyrean X-ray powder diffractometer with a 12-well automated sampling platform was used for analysis. The XRPD parameters used are listed in Table 14. Instrument resolution calibration was performed every 6 months, and sensitivity measurements were performed after changing the sample platform. Silicon (Si) pressed powder samples were used as control standards. Table 14. XRPD Parameters Reflection Mode Parameters X-ray Wavelength Cu, kα, Kα1 (Å): 1.540598, Kα2 (Å): 1.544426 Kα2 / Kα1 Intensity Ratio: 0.50 X-ray Tube Setting 45 kV, 40 mA Diverging Slit Automated Scanning Mode Continuous Scan Range (2θ degrees) 3º to 40º Step Size (2θ degrees) 0.017° Scanning Speed ​​(degrees / min) Approximately 10 Form A: Form A crystals were observed by XRPD, as shown in Figure 3A. Form C: The XRPD pattern in Figure 4A shows Form C crystals. Example 7. Methods for producing single crystals of form A and form C. Form A: A single crystal system suitable for structure determination is obtained by slowly cooling it from 50°C to 5°C in isopropanol. Form C: A single crystal system suitable for structure determination is obtained by slowly cooling from 25°C to 5°C at a rate of 0.01°C / min in a cosolvent of isopropyl acetate / acetone (6:1, v / v) containing Form C seed crystals. Example 8. Single-crystal X-ray diffraction data for forms A and C. X-ray intensity data for prismatic crystals of form A (Table 15) and form C (Table 16) were collected at 290(2) K using a Bruker D8 Venture diffractometer (Mo Kα radiation, λ = 0.71073 Å). The crystal structures of forms A and C were determined from the obtained data. Table 15. Crystal data and structural refinement empirical formula C for single crystals of form A. 25 H 35 N 3O Formula weight 409.56, temperature 100(2) K, wavelength 0.71073 Å, crystal system, space group monoclinic. P2 Unit cell size a = 9.379(3) Å b = 9.922(3) Å c = 12.092(4) Å α = 90° β = 101.606(9)° γ = 90° Volume 1102.2(6) Å 3Z, calculated density 2, 1.234 Mg / m 3 Absorption coefficient 0.079 mm⁻¹ F(000) 444 Crystal size 0.30 × 0.20 × 0.10 mm 3 Data collection θ range 2.22 - 27.56° Constraints: -12 ≤ h ≤ 12, -12 ≤ k ≤ 12, -15 ≤ l ≤ 15 Collected reflections / uniqueness 23466 / 5060 [R(int) = 0.0670] Completeness 99.9% Refinement method for F2: Least squares of the entire matrix Data / constraints / parameters 5060 / 1 / 274 for F 2 The goodness of fit is 1.071. The final R-index is [I>2σ(I)]. 1 = 0.0425 wR 2 = 0.0989. The peak and trough of the greatest difference are 0.309 and -0.368 e∙Å, respectively. -3 Absolute structural parameters 1.5(11) Table 16. Crystal data and structural refinement of single crystals of form C: Empirical formula C 25 H 35 N 3O Formula weight 409.56, temperature 290(2) K, wavelength 0.71073 Å, crystal system, space group orthorhombic. P2 12 12 Unit cell size a = 9.6642(8)Å b = 9.8676(8)Å c = 23.9408(19)Å α = 90º β = 90º γ = 90º Volume 2283.1(3)Å 3 Z, calculated density 4, 1.192 mg / m³ 3 Absorption coefficient 0.076 mm -1 F(000) 888 crystal size: 0.28 × 0.05 × 0.03 mm 3Data collection θ range 2.71 - 27.61º Limiting indices: -12 ≤ h ≤ 12, -12 ≤ k ≤ 12, -31 ≤ l ≤ 31 Collected reflections / uniqueness: 33905 / 5265 [R(int) = 0.0823] Completeness: 99.3% Refinement method for F 2 Least square data for the entire matrix / constraints / parameters 5265 / 7 / 272 for F 2 The goodness of fit is 1.042. The final R-index is [I>2σ(I)]. 1 = 0.0647 wR 2 = 0.1128. The peak and trough of the greatest difference are 0.248 and -0.335 e∙Å, respectively. -3 Absolute structural parameter 0.0(19) Example 9. Unit cells of single-crystal structures of form A and form C. Form A is shown as a unit cell along the b-axis in Figure 3B. Form C is shown as a unit cell along the b-axis in Figure 4B. Example 10. Solid forms A, C, and K were characterized by temperature-dependent instrumental methods (TGA, DSC, and VT-XRPD). Thermogravimetric analysis (TGA) data were collected using a TA Q500 / Q5000 TGA from TA Instruments, and differential scanning calorimetry (DSC) was performed using a TA Q200 / Q2000 DSC from TA Instruments. The instrument parameters used are provided in Table 17. Table 17. Parameters for TGA and DSC Tests | Parameter | TGA | DSC | Method | Incline | Sample Disk | Platinum, Opening | Aluminum, Flanged Edge | |---|---|---|---|---|---|---| | Temperature | Room temperature to 350°C | Room temperature to 300°C | | Heating Rate | 10°C / min | 10°C / min | | Purge Gas | N₂ 2N 2 To supplement the temperature-dependent study and confirm the dissolution state in solid form, solution NMR was collected using dimethyl sulfoxide (DMSO-d6) as a solvent on a Bruker 400 MHz NMR spectrometer. Form A: Thermogravimetric analysis (TGA) and DSC were performed, and details are provided in Figure 3C. Thermogravimetric analysis of Form A resulted in a 1.0% weight loss at a maximum of 200°C. An endothermic reaction was observed on the DSC curve at 157.2°C (starting temperature) (representing the transformation of Form A to Form K), followed by a sharp melting peak for Form K at 203.8°C (starting temperature). Verification of the transformation to Form K was performed using VT-XRPD, as shown in Figure 3D. Form C: TGA and DSC were performed, and their respective curves are provided in Figure 4C. The TGA curve shows a 4.3% weight loss below 50°C, which may be due to loosely held solvent or amorphous solvent present due to insufficient drying. The DSC curve shows two endothermic peaks at 183.8°C and 211.0°C (starting temperature). Further investigation was conducted on the endothermic reaction at 183.8°C by heating Form C to 185°C, which resulted in a transformation of Form C to Form K, as shown in Figure 4D. (The text then abruptly shifts to discussing the presence and absence of nitrogen (N) in Form C.) 2) The flow path was analyzed using VT-XRPD to investigate potential air rehydration. As shown in Figure 4E, the flow path was analyzed in the presence and absence of N... No difference was observed in step 2, indicating that form C is anhydrous. Example 11. The hygroscopicity of forms A, C, and K as measured by DVS. Dynamic vapor adsorption (DVS) was measured using the SMS (Surface Measurement System) and the DVS intrinsic system. This was applied to LiCl and Mg(NO₃) compounds. 3) 2. The deliquescence point of KCl was calibrated at 25°C and relative humidity. The instrument parameters of the DVS system used throughout this study are listed in Table 18. Table 18. Parameters for DVS Testing Parameter | DVS Temperature | 25°C | Sample Size | 10 mg to 20 mg | Gas and Flow Rate | N 2,200 mL / min dm / dt 0.002% / min Minimum dm / dt stability duration: 10 min Maximum equilibrium time: 180 min RH range: 0%RH to 95%RH RH step size (adsorption): 10%RH from 0%RH to 90%RH; 5%RH from 90%RH to 95%RH RH step size (desorption): 10%RH from 90%RH to 0%RH; 5%RH from 95%RH to 90%RH The hygroscopicity of forms A, C, and K was investigated using DVS at 25°C. The XRPD patterns of each sample before and after DVS were compared to investigate any potential form changes. The DVS isotherm plot of form A shown in Figure 3E shows a water uptake of 0.06 wt% at 80% RH and less than 0.12 wt% at 95% RH, indicating that form A is non-hygroscopic. The XRPD pattern in Figure 3F indicates that form A shows no change in form before and after DVS. Similarly, the DVS isotherm plot for form C shown in Figure 4F shows a water uptake of 0.12 wt% at 80% RH and less than 0.30 wt% at 95% RH, indicating that form C is non-hygroscopic. The XRPD pattern in Figure 4G shows no change in form C before and after DVS. Example 12. Interconversion of forms A, C and K via slurry transformation. In one embodiment, the interconversion between forms A, C, and K can be investigated in a series of slurry conversion experiments conducted in ethyl acetate, n-butanol, and methyl tributyl ether (MBTE) at both room temperature (RT) and 50°C. Compound 1 exhibits moderate solubility and produces a solvated form during these screening experiments. The results of the slurry conversion experiments are summarized in Table 19. The transition temperature between forms A and C is estimated to be about 17°C, and the transition temperature between forms K and C is above 100°C. Table 19. Summary of Slurry Conversion Experiments Solvent Conditions Initial Form Final Form Ethyl Acetate RT Form A and K (containing form C seed crystals) Form C 50°C Form A and K Form C n-Butanol RT Form A, C, and K Form C 50°C Form A, C, and K Form C MBTE RT Form A, C, and K Form C 50°C Form A, C, and K Form C Example 13. Using form C seed crystals to transform form A into form C. Compound 1 (initial form A), dissolved in ethyl acetate at approximately 200 g / L to 225 g / L, is heated to 65°C for 1 to 3 hours in the presence of 0.2%–1.0% seed crystals of form C. The batch is then slowly cooled to a temperature between 25°C and 30°C over less than 3 hours to obtain form C. Seed crystals of form C can be obtained using the procedure described in Example 4. XRPD was performed using a Rigaku MiniFlex 600 (Cu Kα radiation at a tube voltage of 40 kV and a tube current of 15 mA), with a 2θ scan range of 2° to 40°, a step size of 0.01°, and a scan rate of 1° / min or 2° / min. The transformation from form A to form C in ethyl acetate at 65°C with 1.0% form C seed crystals over time was monitored using XRPD, as indicated in Figure 6. Example 14. Rapid and sustained improvement of depressive symptoms in individuals with major depressive disorder in a phase 2 open-label study of compound 1 ("Part A"). In this multicenter, open-label, phase 2 clinical trial, individuals were administered 30 mg of compound 1 from day 1 to day 14, and evaluation continued until day 28. Reduction in depressive and anxiety symptoms was assessed using the Hamilton Depression Rating Scales (HAM-D and HAM-A) and the Montgomery-Asperger's Depression Rating Scale (MADRS). Safety and tolerability were evaluated using standard safety parameters. Pharmacokinetic parameters were also assessed. Methods and Materials Study Design and Participants: This multicenter, open-label component of the Phase 2 trial was conducted at two sites in the United States, each approved by the IRB. Sage Therapeutics, Inc. collaborated with the principal investigator (RR) who designed the trial and all investigators who performed the trial and collected data. All authors guarantee the accuracy and completeness of the data, data analyses, and the fidelity of this disclosure to the study protocol. research group Written informed consent was provided during screening and was required for inclusion. The diagnosis of MDD was made using a Structured Clinical Interview-I (SCID-I) of Axis I of the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5), administered by a qualified healthcare professional. Individuals were also screened using the 17-item Hamilton Depression Rating Scale (HAM-D) to ensure a symptom severity score of at least 22. The Hamilton Anxiety Rating Scale (HAM-A), the Montgomery-Asperger Depression Rating Scale (MADRS), and the Clinical Global Impression-Severity (CGI-S) scale were also performed. Patients with a total score of 17-23 on the 17-item HAM-D scale were considered to have moderate depression; a total score ≥24 was considered to have severe depression. Patient history and information on concomitant medications were collected. The study population included individuals aged 18-65 years (inclusive) in both sexes (inclusion / exclusion criteria below). Individuals were hospitalized for 7 days prior to the study phase and thereafter at the investigator's discretion. Individuals received standard care for adult hospitalized patients diagnosed with MDD and were permitted to maintain a stable dose of medication for treating psychosis that had been initiated at least 14 days prior to screening. Exclusion criteria include: history of suicide attempt, history of treatment-resistant depression, recent history of other acute or chronic conditions or clinically significant hyperactivity, positive pregnancy test, history of epileptic seizures, bipolar disorder, schizophrenia, and / or affective schizophrenia. A complete list of exclusion criteria is provided in the supplementary appendix. program Compound 1 was provided as a 6 mg / mL aqueous solution, which was further diluted with sterile water to achieve the selected dose administered orally. Participants received an open-label 30 mg oral dose of Compound 1 with food at 8:00 PM (+ / - 15 minutes) from Day 1 to Day 14. Individuals experiencing moderate or serious adverse events (as determined by the investigator) while receiving the 30 mg dose of the study drug had their dose reduced to 20 mg for the remainder of the treatment period. Any individual who was intolerant to the 20 mg dose was discontinued from the study. Vital signs were collected daily. Other study procedures and plasma collection for PK parameters were performed at various times during the 14-day open-label treatment period (procedures are detailed in the Supplementary Appendix). Treatment follow-up was conducted on an outpatient basis and included follow-up at 1 week (21 + / - 1 day) and 2 weeks (28 + / - 1 day) after the last dose of the study drug. Results: The primary endpoints for the safety and tolerability of compound 1 were assessed by the following: frequency and severity of adverse events, vital signs, changes in clinical laboratory measurements, physical examination, electrocardiogram (ECG), Stanford Sleepiness Scale (SSS) score, and suicidal ideation using the Columbia-Suicide Severity Rating Scale (C-SSRS, Supplementary Table 1). Secondary efficacy endpoints included: change from baseline in total HAM-D score, HAM-D response (defined as a 50% or greater reduction in total HAM-D score from baseline), HAM-D remission (defined as a total HAM-D score ≤7), change from baseline in HAM-A score, and change from baseline in MADRS score. The pharmacokinetic profile of compound 1 was also determined from plasma samples. Statistical analysis Continuous parameters are summarized as n, mean, and standard deviation, while categorical variables are summarized as frequency counts and percentages. For HAM-D, HAM-A, and MADRS total scores, p-values ​​of change from baseline were calculated using a mixed-effects model for repeated measures with visits as a fixed effect, adjusted for the baseline total score. All statistical analyses were performed using SAS. ® The statistical software version 9.3 (SAS Institute Inc, Cary, NC) was used for implementation. result : This study recruited 13 individuals with a mean (SD) age of 48.0 years (12.8) and a range of 20–64 years. The baseline mean (SD) values ​​for HAM-D, HAM-A, and MADRS were 27.2 (3.1), 23.2 (5.7), and 36.9 (5.2), respectively (Table 20). All 13 individuals enrolled in this study completed the study. Individual demographic characteristics are summarized in Table 20. surface 20 Individual characteristics and demographics The efficacy compound 1 produced a rapid and sustained reduction across all depressive endpoints. Compound 1 significantly reduced depressive symptoms as assessed by the HAM-D total score, decreasing from a mean total score of 27.2 at baseline to 7.3 on day 15, a mean reduction of 19.9 points (p < 0.0001) (Figure 7A). A significant reduction in depressive symptoms was observed as early as day 2 (p < 0.05) (Figure 7A). These changes persisted until the end of the study, two weeks after study drug discontinuation (day 28, p < 0.0001) (Figure 7A). The reduction in depressive symptoms as assessed by the MADRS total score followed the same pattern observed with HAM-D, decreasing from a mean total score of 36.9 at baseline to 10.5 on day 15, a mean reduction of 26.4 points (p < 0.0001) (Figure 7B). The reduction in MADRS persisted until day 28 (p < 0.0001) (Figure 7B). Compound 1 also reduced anxiety symptoms as assessed by the HAM-A total score, decreasing from a mean total score of 23.2 at baseline to 7.7 on day 15, a mean reduction of 15.5 points (p < 0.0001) (Figure 7C). These changes persisted until the end of the study (day 28, p < 0.0001) (Figure 7C). In 11 of the 13 individuals (85%), the total HAM-D score decreased by at least 50% on day 15 (defined as a HAM-D response) (Figure 8), and this HAM-D response persisted until day 28. The treatment effect was durable because the change persisted throughout the treatment period and after treatment interruption. The HAM-D response rates were higher on days 15 and 28 regardless of whether antidepressants were present at enrollment (5 / 5, 100%, day 15; 4 / 5, 80%, day 28) or absent (6 / 8, 75.0%, day 15; 6 / 8, 75%, day 28). In 8 out of 13 individuals (62%), a total HAM-D score ≤ 7 at the end of the treatment period (defined as HAM-D remission) and this HAM-D remission persisted until day 28 (Figure 2). The remission rate was 39% by day 6 and remained stable after treatment was interrupted between day 15 and day 28 (Figure 2). Safety and Pharmacokinetics: Compound 1 was generally well tolerated with no major adverse events (SAEs) or interruptions due to AEs. Almost all individuals experienced at least one emergency treatment adverse event (TEAE) (12 / 13; 92.3%; Table 2). The most common AEs were sedation (6 individuals), headache (4 individuals), somnolence (3 individuals), dizziness (3 individuals), and myalgia (3 individuals) (Table 21). Suicidal ideation was assessed using the Columbia Suicide Severity Rating Scale (C-SSRS). One individual engaged in non-suicidal self-harming behavior since their last visit between days 10 and 13 (Supplementary Figure 1). No clinically relevant changes were found in clinical hematology, urinalysis, vital signs, or ECG. No clinically relevant changes were found in clinical chemistry, except for one individual who showed a mild and transient increase in ALT, AST, and alkaline phosphatase, which resolved without being relevant to any clinical findings and did not lead to dose adjustment or interruption of the study drug. surface twenty one Emergency treatment adverse events (TEAE) . Pharmacokinetic (PK) parameters were derived from plasma samples (Table 22). PK and exposure data were consistent with those observed in a previous Phase 1 study of compound 1 in healthy volunteers (SAD / MAD controls). The median plasma concentration of compound 1 after administration of compound 1 was... max It reaches its maximum value at 1.1 hours, with a half-life of 10.3 hours. Under steady-state conditions, the geometric mean C... max and C avg,ss The values ​​were 101.0 ng / mL and 41.4 ng / mL, respectively. Similarly, under steady-state conditions, the AUC... 0-t and AUC inf The geometric mean values ​​were 992.5 h•ng / mL and 1150.7 h•ng / mL, respectively. surface twenty two Pharmacokinetic parameters, number 7 sky. CV% = Coefficient of variation. N=13 Inclusion criteria 1. The individual has signed an ICF prior to the implementation of any study-specific procedures. 2. The individual is an active male or female aged 18 to 65 years (inclusive). 3. The individual is in good physical health and has no clinically significant findings, as determined by the investigator during a physical examination, 12-lead ECG, or clinical laboratory testing. 4. The individual agrees to comply with the study requirements. 5. The individual is diagnosed with MDD, if diagnosed by SCID-I and has been present for at least 4 weeks. 6. The individual's total HAM-D score is ≥22 at screening and on Day 1 (before medication administration). 7. The individual agrees to delay initiating other antidepressants or anti-anxiety medications and any novel drug therapy regimens during the screening and treatment period, including, if necessary, benzodiazepines. 8. The individual agrees to practice acceptable and effective methods of contraception during screening and throughout the study participation. Highly effective contraceptive methods include sexual abstinence (for both men and women); vasectomy; or a combination of spermicide-containing condoms and highly effective female partners (for men); and hormonal methods of contraception (i.e., established oral, implantable, injectable, or transdermal hormone use); intrauterine device (IUD); intrauterine contraceptive system; and mechanical / barrier contraceptive methods (i.e., condoms or occluders [diaphragms or cervical / fornix caps] combined with spermicide [foams, gels, films, creams, or suppositories]) (for women). Exclusion criteria 1. The individual has a history of suicide attempt. 2. The individual has a recent history of metabolic, liver, kidney, blood, lung, cardiovascular, gastrointestinal, musculoskeletal, dermatological, genitourinary, neurological, or ocular, ear, nose, or throat conditions, or any other acute or chronic condition that the investigator believes will limit the individual's ability to complete or participate in this clinical study, or has clinically significant active manifestations. 3. The individual has a history of treatment-resistant depression, defined as persistent depressive symptoms despite treatment with adequate doses of antidepressants from two different classes for an adequate period of time (i.e., at least 4 weeks). 4. The individual has a known allergy to compound 1, allopregnantlone, or related compounds. 5. The individual had a positive pregnancy test at screening or prior to day 1 of study drug administration. 6. The individual had detectable antibodies against hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) at screening. 7. The individual has active psychosis according to the investigator's assessment. 8. The individual has a history of epileptic seizures. 9. The individual has a history of bipolar disorder, schizophrenia, and / or affective schizophrenia. 10. The individual has a history of alcohol or drug dependence (including benzodiazepines) within the 12 months prior to screening. 11. The individual has been exposed to another investigational drug or device within 30 days prior to screening. 12. The individual has been treated or randomized in this study (e.g., Part A) or any other study previously using Compound 1 (i.e., the individual may not have received the investigational drug and may be re-enrolled). 13. The individual has been administered a psychotropic drug initiated within 14 days prior to screening and / or is not taking it at a stable dose. 14. Use of any known strong inhibitor and / or inducer of cytochrome P450 (CYP) 3A4 within 14 days or five half-lives (whichever is longer) prior to receiving the first dose of the study drug, or consumption of grapefruit juice, grapefruit, Seville orange, or St. John's Wort, or products containing such ingredients, within 30 days prior to receiving the first dose of the study drug. 15. The individual tested positive for the drug and / or alcohol at screening or before day 1 of administration. Procedural Details: Part A of this study consisted of a maximum 7-day screening period (day -7 to day -1), a 14-day treatment period, and a 2-week follow-up period (up to day 28). During the screening period (day -7 to day -1), individual eligibility was assessed after obtaining informed consent (ICF), and the severity of each individual's MDD was evaluated using the HAM-D assessment. Screening period assessments were conducted on an outpatient basis. If applicable, this may include standard care data collected prior to obtaining informed consent as screening data (if appropriate), such as laboratory tests, ECGs, physical examinations, and vital signs performed within the preceding 48 hours, provided that the requirements for retrospective collection for screening evaluation are fully met. If applicable, to ensure protocol compliance, any standard care data suitable for inclusion as screening data must include the exact nature and timing of the data collection. During the 14-day study treatment period, individuals remained hospitalized for at least the first 7 days and thereafter at the investigator's discretion. Follow-up assessments were conducted on an outpatient basis. The study was conducted as follows: Starting on Day 1, individuals received an open-label oral solution of Compound 1 with food (as outlined in section 9.2.1) at 8:00 PM (±15 minutes). Individuals received 30 mg of the oral solution of Compound 1 from Day 1 to Day 14, provided tolerance was maintained. The study drug (oral solution of Compound 1 or a matched placebo) was administered at the research center for at least the first 7 days of the treatment period, including from Day 1 until the completion of the study drug administration on Day 14. After evaluation on Day 7, individuals were discharged after a minimum of 7 days of hospitalization. If their clinical condition did not permit discharge, the investigators extended the hospitalization period. Individuals discharged from the inpatient ward received the study drug as outpatients for the remainder of the 14-day treatment period. For the outpatient phase, administration was conducted at the clinical site, or, where appropriate, at home where permitted by local regulations. Home administration of the study drug was carried out according to a site-specific plan by healthcare professionals trained in the protocol and delivery of the study drug. Safety monitoring of individuals will be conducted during treatment and follow-up, including monitoring for adverse events / major adverse events, routine clinical laboratory evaluations, physical examinations, vital signs, and ECG. During treatment, individuals will receive the study drug unless there are dose-limiting safety / tolerability concerns. Supplementary Table 1 : Columbia Suicide Severity Rating Scale (C-SSRS): Suicidal ideation was monitored during the study. This scale consists of assessments of an individual's life and recent experiences as a whole who has suicidal ideation and behavior. N=13. *An individual answered "yes" from day 10 to day 13. Example 15. A phase 2, double-blind, placebo-controlled clinical trial of compound 1 in adult patients with moderate to severe major depressive disorder (MDD) ("Part B"). In a randomized, double-blind, parallel-group, placebo-controlled trial, eligible patients (minimum total HAM-D score of 22 on the Hamilton Depression Rating Scale) were stratified based on their antidepressant treatment (current / stable or untreated / discontinued for ≥30 days) and randomized in a 1:1 ratio to receive either Compound 1 capsules (30 mg) or a matched placebo. All doses of the study drug were administered in the evening with food. The study consisted of a 14-day treatment period and a 4-week follow-up period. The mean total HAM-D score at baseline was 25.2 in the Compound 1 group and 25.7 in the placebo group (overall range 22–33), representing patients with moderate to severe MDD. Approximately 90% of patients in each group completed the study. In this trial, treatment with compound 1 for 14 days was associated with a statistically significant mean reduction of 17.6 points in the total HAM-D score from baseline to day 15 (the primary endpoint), compared to a mean reduction of 10.7 points in the placebo-associated total HAM-D score (mean difference of -7.0 compared to placebo; p < 0.0001). The improvement in the total HAM-D score compared to placebo was significant up to the morning of day 2 after the first dose and was durable until the end of week 6 follow-up, with statistical significance recorded up to week 4. On day 15, 64% of patients receiving compound 1 achieved remission, defined as a total HAM-D score of 7 or lower, compared to 23% of patients receiving placebo (p = 0.0005). All other secondary endpoints were also highly significant on day 15 (p < 0.0021). Compound 1 was generally well tolerated with no major or serious adverse events; the most common AEs were headache, dizziness, nausea, and somnolence. The rate of discontinuation due to adverse events (AEs) was low; overall AE reporting was similar between the drug (53%) and placebo (46%), with the safety profile consistent with that observed in earlier trials. From placebo control 2 Summary of best results from the periodic trials Until the end of treatment ( No. 15 sky ) Effects on depressive symptoms: • On day 15, treatment with compound 1 was statistically significantly associated with a mean reduction of 17.6 points in the total Hamilton Depression Rating Scale (HAM-D) score from baseline, compared to a mean reduction of 10.7 points in the placebo-associated total score (p < 0.0001). • The majority of patients receiving compound 1 (64%) achieved remission on day 15, as determined by a total HAM-D score of 7 or less (compared to 23% in placebo-received patients, p = 0.0005). • Other secondary endpoints (e.g., MADRS, CGI-I) were also highly significant on day 15 (p < 0.0021). Effects on depressive symptoms over time: • A statistically significant mean decrease in the Hamilton Depression Rating Scale (HAM-D) total score from baseline was observed after the first dose (day 2) and maintained until week 4, two weeks after the end of treatment (p < 0.0318). • At week 4, the mean decrease in the total HAM-D score from baseline was 15.6 in the compound 1 group and 11.9 in the placebo group (p = 0.0243). • At week 6, the mean decrease in the total HAM-D score in the compound 1 group was 15.0, which was a numerical but not statistically significant improvement compared to the 13.0 decrease in the placebo group. • The remission rates at weeks 4 and 6 were 52% and 45% in patients treated with compound 1, respectively, compared to 28% and 33% in the placebo group, with statistical significance maintained at week 4 (p = 0.0221) rather than week 6. Safety and tolerability • Compound 1 was generally well tolerated in the trial. The overall incidence of adverse events was 53% in the compound 1 treatment group and 46% in the placebo group. • There were no deaths, major or serious adverse events. • The rate of discontinuation of study drug treatment due to adverse events was low; two patients (4.4%) were treated with compound 1 and none were treated with placebo. Inclusion Criteria • Individuals diagnosed with major depressive disorder, if diagnosed by the Structured Clinical Interview with the Disorders of the DSM-IV Axis (SCID-I) and have been present for at least 4 weeks. Exclusion criteria • History of suicide attempt • History of treatment-resistant depression, defined as persistent depressive symptoms despite adequate treatment with sufficient doses of antidepressants from two different classes for an adequate period of time • Active psychosis • History of seizures • History of bipolar disorder, schizophrenia, and / or affective schizophrenia Equivalent Forms and Scope: In the claims, unless the context clearly indicates the opposite or otherwise, articles such as "a" and "the" may mean one or more. Unless the context clearly indicates the opposite or otherwise, if one, more, or all group members are present, used in, or otherwise associated with a given product or process, it is considered to fall within the claims or description including "or" among one or more members of the group. This invention includes embodiments in which exactly one group member is present, used in, or otherwise associated with a given product or process. This invention includes embodiments in which one or more or all group members are present, used in, or otherwise associated with a given product or process. Furthermore, this invention encompasses all variations, combinations, and arrangements in which one or more limitations, elements, clauses, and descriptive terms from one or more of the listed technical solutions are introduced into another technical solution. For example, any technical solution belonging to another technical solution may be modified to include one or more limitations found in any other technical solution belonging to the same basic technical solution. If elements are presented in list form (e.g., in Markush group format), each subgroup of such elements is also disclosed, and any element may be removed from that group. It should be understood that, generally, if an invention or a morphology of the invention is referred to as including specific elements and / or features, then certain embodiments of the invention or a morphology of the invention are composed of or substantially composed of such elements and / or features. For the purpose of brevity, such embodiments are not explicitly described herein in the same language. It should also be noted that the terms "comprising" and "containing" are intended to be open-ended and allow for the inclusion of other elements or steps. Where a scope is given, the endpoint is included. Furthermore, unless otherwise indicated or clearly apparent from the context and understanding of one skilled in the art, values ​​expressed as ranges are contemplated in different embodiments of the invention as any particular value or subrange within the stated range up to one-tenth of the unit of the lower limit of the range, unless the context clearly indicates otherwise. This application relates to various issued patents, published patent applications, journal articles, and other publications, all of which are incorporated herein by reference. In the event of any conflict between any incorporated reference and this specification, this specification shall prevail. Furthermore, any particular embodiment of the invention within the prior art may be expressly excluded from any one or more claims. Since such embodiments are believed to be known to those skilled in the art, such embodiments may be excluded even if such exclusion is not expressly stated herein. For any reason, whether or not related to the existence of prior art, any particular embodiment of the invention may be excluded from any claim. Those skilled in the art can identify or determine the many equivalent forms of the specific embodiments described herein using only conventional experiments. The scope of the embodiments of the invention described herein is not intended to be limited to the above description, but rather to be as set forth in the appended claims. Those skilled in the art should understand that various changes and modifications can be made without departing from the spirit or scope of the invention, as defined in the following claims. picture 1. Plot the average (± standard deviation) plasma concentration of compound 1 over time according to the drug administration conditions (linear scale). picture 2. Plot the average (± standard deviation) plasma concentration of compound 1 over time based on the drug administration conditions (semi-logarithmic scale). picture 3A drawing format A is an example of an XRPD pattern. picture 3B illustrates an exemplary unit cell of form A along the b-axis. picture The 3C plotting format A shows the example TGA (upper) and DSC (lower) curves. picture 3D plotting of an illustrative VT-XRPD pattern of form A and an illustrative XRPD pattern of form K superimposed at a selected temperature. picture 3E illustrates the illustrative DVS isotherm of form A at 25°C. picture 3F illustrates an illustrative XRPD pattern of form A before and after an illustrative DVS measurement at 25°C. picture 4A drawing format C is an example of an XRPD pattern. picture 4B illustrates an exemplary unit cell of form C along the b-axis. picture 4C illustrates the TGA (upper) and DSC (lower) curves of form C. picture 4D plotting of an illustrative XRPD pattern of form C and an illustrative XRPD pattern of form K superimposed at the selected temperature. picture 4E illustrates the superposition of exemplary XRPD patterns of form C at the selected temperature with or without N2 atmosphere. picture 4F shows an illustrative DVS isotherm of form C at 25°C. picture 4G illustrates the superposition of illustrative XRPD patterns of form C before and after DVS measurement at 25°C. picture 5. An example of an XRPD pattern for drawing form K. picture 6. An illustrative XRPD pattern superposition is shown, indicating the time-dependent transformation of form A to form C in ethyl acetate in the presence of seed crystals of form C at elevated temperatures. picture 7A ,picture 7B and diagram 7C illustrates the exemplary HAM-D mean (SE) total score, MADRS mean (SE) score, and HAM-A mean (SE) total score of compound 1 in a phase 2 open-label study evaluating compound 1 in individuals with major depressive disorder. HAM-D average (SE) Overall score MADRS average (SE) Ratings and HAM-A average (SE) Overall score. (Image) 7A. Record the total HAM-D score, as indicated across 28 days. N = 13 at each time point. Day 2 and 3 + p < 0.05; * Day 4, 5, 6, 7, 8, 15, 21, and 28 p < 0.0001. BL = baseline. picture 7B. Record the total MADRS score, as indicated across 28 days. N = 13 at each time point. Day 2 and 3 + p < 0.05; * Day 4, 5, 6, 7, 8, 15, 21, and 28 p < 0.0001. BL = baseline. picture 7C. Record the total HAM-A score, as indicated across 28 days. N = 13 at each time point. Day 3 + p < 0.05. *At days 8, 15, 21, and 28, p < 0.0001. BL = baseline. picture Figure 8 illustrates the exemplary HAM-D response and HAM-D remission rate of compound 1 in individuals with major depressive disorder in a phase 2 open-label study evaluating compound 1. HAM-D reaction and HAM-D Remission rate. HAM-D response was defined as a reduction of ≥50% in the total HAM-D score from baseline. HAM-D remission was defined as a reduction in the total HAM-D score to ≤7. N=13. On day 15, remission of depression was observed in 8 of the 13 individuals (62%).

Claims

1. Use of a compound 1 for preparing a medicament for treating postpartum depression in individuals in need: Compound 1 wherein the medicament comprises a therapeutically effective amount of the compound as a solid dosage form in the form of tablets or capsules, administered substantially simultaneously with food, wherein substantially simultaneously with food means within approximately 60 minutes before or after the ingestion of food.

2. Use of a solid crystalline form of compound 1 for the preparation of a medicament for treating postpartum depression in individuals in need: Compound 1 wherein the medicament comprises a therapeutically effective amount of the solid crystalline form of compound 1 as a solid dosage form in the form of tablets or capsules, administered substantially simultaneously with food; wherein substantially simultaneously with food means within approximately 60 minutes before or after ingestion of food; and wherein the solid crystalline form of compound 1 has an X-ray powder diffraction pattern with characteristic peaks between and including the following 2θ values: 9.7 to 10.1, 11.6 to 12.0, 13.2 to 13.6, 14.2 to 14.6, 14.6 to 15.0, 16.8 to 17.2, 20.5 to 20.9, 21.3 to 21.7, 21.4 to 21.8 and 22.4 to 22.

8.

3. As claimed in claim 1 or 2, wherein compound 1 or the solid crystalline form of compound 1 is administered to the individual once daily for 14 days.

4. As requested in item 1 or 2, wherein the food contains a high-fat diet.

5. As requested in item 1 or 2, wherein the food comprises a regular diet.

6. As requested in item 1 or 2, wherein the food contains approximately 800-1000 calories.

7. As requested in item 1 or 2, wherein the food contains approximately 300-800 calories.

8. As claimed in claim 1 or 2, wherein the solid dosage form is a capsule.

9. As claimed in claim 1 or 2, wherein administering the therapeutically effective amount of compound 1 or the solid crystalline form of compound 1 substantially simultaneously with food increases the bioavailability of compound 1 or the solid crystalline form of compound 1 compared to not administering it with food, and wherein the bioavailability is increased by about 10% or more, about 20% or more, about 30% or more, about 40% or more, about 50% or more, or about 55% or more.

10. As claimed in claim 9, wherein the bioavailability is based on a comparison of the AUC values ​​of compound 1 or its solid crystalline form when present in the capsule; where appropriate, wherein the AUC value is the AUC0-t value.

11. As claimed in claim 9, wherein the AUC0-t value is a comparison, and wherein the AUC0-t value of compound 1 or the solid crystalline form of compound 1 when administered in capsules and with food is higher than the AUC0-t value of compound 1 or the solid crystalline form of compound 1 when administered in capsules and without food.

12. As claimed in claim 11, wherein the AUC0-t value of compound 1 or the solid crystalline form of compound 1 when administered in capsules and with food is increased by at least 10% compared to the AUC0-t value of compound 1 or the solid crystalline form of compound 1 when administered in capsules and without food.

13. As used in claim 12, wherein the percentage is increased to at least 20%, at least 30%, at least 40%, or at least 55%.

14. As claimed in claim 1 or 2, wherein the therapeutically effective amount of compound 1 or the solid crystalline form of compound 1 is about 20 mg to about 60 mg or about 25 mg to about 50 mg.

15. As claimed in claim 1 or 2, wherein the individual’s baseline HAM-D total score is at least 18; or wherein, after treatment of the individual with the compound, the HAM-D total score is reduced by at least 15 relative to the baseline HAM-D total score.

16. As requested in paragraph 1 or 2, wherein at night and no more than 15 minutes before the individual falls asleep, the system administers compound 1 in a solid dosage form, either in tablet or capsule form, or in a solid crystalline form.

17. As used in claim 2, wherein the peak between 9.7 and 10.1, including the peak between 9.7 and 10.1, is at 2θ of 9.9 degrees; the peak between 11.6 and 12.0, including the peak between 11.6 and 12.0, is at 2θ of 11.8 degrees; the peak between 13.2 and 13.6, including the peak between 13.2 and 13.6, is at 2θ of 13.4 degrees; the peak between 14.2 and 14.6, including the peak between 14.2 and 14.6, is at 2θ of 14.4 degrees; and the peak between 14.6 and 15.0, including the peak between 14.6 and 15.0, is at 2θ of 9.9 degrees; the peak between 14.6 and 15.0, including the peak between 14.6 and 15.0, is at 2θ of 9.9 degrees; the peak between 14.7 and 10.1, including the peak between 14.7 and 10.1 ... 14.8 degrees, the peak between 16.8 and 17.2, including the peak between 16.8 and 17.2, is 17.0 degrees at 2θ, the peak between 20.5 and 20.9, including the peak between 20.5 and 20.9, is 20.7 degrees at 2θ, the peak between 21.3 and 21.7, including the peak between 21.3 and 21.7, is 21.5 degrees at 2θ, the peak between 21.4 and 21.8, including the peak between 21.4 and 21.8, is 21.6 degrees at 2θ, and the peak between 22.4 and 22.8, including the peak between 22.4 and 22.8, is 22.6 degrees at 2θ.

18. As claimed in claim 2, wherein the solid crystalline form of compound 1 has an X-ray powder diffraction pattern with characteristic peaks between and including the following 2θ values: 9.7 to 10.1, 14.6 to 15.0, 16.8 to 17.2, 20.5 to 20.9 and 21.3 to 21.

7.

19. As claimed in claim 18, wherein the peak between 9.7 and 10.1, including the peak between 9.7 and 10.1, is at 2θ 9.9 degrees; the peak between 14.6 and 15.0, including the peak between 14.6 and 15.0, is at 2θ 14.8 degrees; the peak between 16.8 and 17.2, including the peak between 16.8 and 17.2, is at 2θ 17.0 degrees; the peak between 20.5 and 20.9, including the peak between 20.5 and 20.9, is at 2θ 20.7 degrees; and the peak between 21.3 and 21.7, including the peak between 21.3 and 21.7, is at 2θ 21.5 degrees.

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