EP-4736951-A2 - (S)-(4,5-DIHYDRO-7H-THIENO[2,3-C]PYRAN-7-YL)-N-METHYLMETHANAMINE FOR TREATING, PREVENTING AND/OR MANAGING A NEUROLOGICAL AND/OR PSYCHIATRIC DISORDER

Abstract

The present disclosure relates to methods of treating neurological or psychiatric diseases or disorders, such as schizophrenia. Compound 1, or a pharmaceutically acceptable salt thereof, is an antipsychotic agent with a non-D2 mechanism of action. Adverse events associated with antipsychotic agents that target the D2 dopamine receptor can be reduced by treating disorders with Compound 1, or a pharmaceutically acceptable salt thereof.

Inventors

• BOWEN, CARRIE A.
• HOPKINS, SETH CABOT
• SYNAN, COLLEEN M.

Assignees

• Sumitomo Pharma America, Inc.

Dates

Publication Date

20260506

Application Date

20210413

Claims (17)

1. A Compound 1 or a pharmaceutically acceptable salt thereof, for use in the treatment of a symptom of insomnia, anxiety, or headache in a patient having schizophrenia, wherein a therapeutically effective amount of Compound 1, or a pharmaceutically acceptable salt thereof is to be administered in the evening or at night, or at about bedtime.
2. A Compound 1 or a pharmaceutically acceptable salt thereof, for use in the treatment of an anxiety disorder, wherein a therapeutically effective amount of Compound 1, or a pharmaceutically acceptable salt thereof is to be administered in the evening or at night, or at about bedtime.
3. A Compound 1 or a pharmaceutically acceptable salt thereof, for use in the treatment of a depressive disorder, wherein a therapeutically effective amount of Compound 1, or a pharmaceutically acceptable salt thereof is to be administered in the evening or at night, or at about bedtime.
4. A Compound 1 or a pharmaceutically acceptable salt thereof, for use in the treatment of a sleep disorder caused by a psychiatric condition, wherein a therapeutically effective amount of Compound 1, or a pharmaceutically acceptable salt thereof is to be administered in the evening or at night, or at about bedtime.
5. The Compound 1, or a pharmaceutically acceptable salt thereof, for use according to any one of claims 1 to 4, wherein Compound 1, or a pharmaceutically acceptable salt thereof, is to be administered in the evening or at night.
6. The Compound 1, or a pharmaceutically acceptable salt thereof, for use according to any one of claims 1 to 4, wherein Compound 1, or a pharmaceutically acceptable salt thereof, is to be administered at about bedtime.
7. The Compound 1, or a pharmaceutically acceptable salt thereof, for use according to any one of claims 1 to 6, wherein Compound 1, or a pharmaceutically acceptable salt thereof, is to be administered once daily.
8. The Compound 1, or a pharmaceutically acceptable salt thereof, for use according to any one of claims 1 to 7, wherein Compound 1, or a pharmaceutically acceptable salt thereof, is to be administered at a daily dose of from about 10 mg/day to about 100 mg/day, preferably at a daily dose of about 25 mg to about 100 mg, more preferably at a daily dose of about 50 mg/day or at a daily dose of about 75 mg/day, or at a daily dose of about 100 mg/day.
9. The Compound 1, or a pharmaceutically acceptable salt thereof, for use according to any one of claims 1 to 8, wherein the administration achieves a maximum plasma concentration of Compound 1, or a pharmaceutically acceptable salt thereof, at 1 to 4 hours after a single oral dose and at 2 to 4 hours after multiple oral doses.
10. The Compound 1, or a pharmaceutically acceptable salt thereof, for use according to any one of claims 1 to 9, wherein the Compound 1, or a pharmaceutically acceptable salt thereof, is to be administered daily at a first dose, followed by administration of Compound 1, or a pharmaceutically acceptable salt thereof, daily at a therapeutic dose.
11. The Compound 1, or a pharmaceutically acceptable salt thereof, for use according to claim 10, wherein the first dose is about 50 mg/day and/or the therapeutic dose is about 25 mg/day, about 50 mg/day, about 75 mg/day or about 100 mg/day.
12. The Compound 1, or a pharmaceutically acceptable salt thereof, for use according to claim 10 or 11, wherein the first dose is to be administered daily for three days.
13. The Compound 1, or a pharmaceutically acceptable salt thereof, for use according to any one of claims 9 to 12, wherein the Compound 1, or a pharmaceutically acceptable salt thereof, is to be administered daily at a second dose, after administration of the Compound 1, or a pharmaceutically acceptable salt thereof, daily at a first dose and before administration of the Compound 1, or a pharmaceutically acceptable salt thereof, daily at a therapeutic dose.
14. The Compound 1, or a pharmaceutically acceptable salt thereof, for use according to claim 13, wherein the second dose is to be administered daily for four days.
15. The Compound 1, or a pharmaceutically acceptable salt thereof, for use according to claim 13 or 14, wherein the second dose is about 75 mg/day.
16. The Compound 1, or a pharmaceutically acceptable salt thereof, for use according to any one of claims 1 to 15, wherein the hydrochloride salt of Compound 1 is to be administered.
17. The Compound 1, or a pharmaceutically acceptable salt thereof, for use according to any one of claims 1 to 16, wherein crystalline Form A of the hydrochloride salt of Compound 1 is to be administered.

Description

CROSS REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Application No. 63/039,722 filed June 16, 2020 and U.S. Provisional Application No. 63/009,595, filed April 14, 2020, the contents of which are hereby incorporated by reference herein in their entirety. TECHNICAL FIELD The present disclosure relates to methods of treating neurological and psychiatric diseases and disorders. BACKGROUND The D2 dopamine receptor is a primary target for both typical and atypical antipsychotic agents. Wang et al. NATURE 555, 269-273 (2018). However, many drugs that target the D2 dopamine receptor cause serious or potentially life-threatening side effects. Wang et al. NATURE 555, 269-273 (2018). Despite decades of research on non-D2 mechanisms of action, developing non-D2 antipsychotic therapies that are both safe and effective has been challenging. Girgis et al., J. PSYCHIATRIC RES. (2018), https://doi.org/10.1016/j.jpsychires.2018.07.006. In particular, after performing a comprehensive review of literature relating to experimental treatments for schizophrenia, including 250 studies between 1970 to 2017 with glutamatergic, serotonergic, cholinergic, neuropeptidergic, hormone-based, dopaminergic, metabolic, vitamin/naturopathic, histaminergic, infection/inflammation-based, and otherwise miscellaneous mechanisms for treating schizophrenia, Girgis states, "Despite there being several promising [non-D2] targets, such as allosteric modulation of the NMDA and α7 nicotinic receptors, we cannot confidently state that any of the mechanistically novel experimental treatments covered in this review are definitely effective for the treatment of schizophrenia and ready for clinical use." Accordingly, there is a need for therapeutic agents having efficacy in treating neurological and psychiatric diseases and disorders (e.g., schizophrenia) with lower incidence of adverse events. As disclosed herein, Compound 1 has received Breakthrough Therapy Designation from the United States Food and Drug Administration (FDA) as a novel agent for the treatment of people with schizophrenia. Breakthrough Therapy Designation is intended to expedite the development and review of drugs for serious or life-threatening conditions when preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapy on one or more clinically significant endpoints. The FDA granted Breakthrough Therapy Designation for Compound 1 based on pivotal, Phase 2 data from clinical trials disclosed herein. SUMMARY The present disclosure relates to methods of treating neurological and psychiatric diseases and disorders. In some embodiments, provided is a method of treating a patient having a neurological or psychiatric disease or disorder, comprising orally administering to the patient Compound 1 or a pharmaceutically acceptable salt thereof, in the evening or at night, or at about bedtime. In some embodiments, provided is a method of treating a neurological or psychiatric disease or disorder in a patient, comprising administering to the patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof, in the evening or at night, or at about bedtime, wherein the method minimizes adverse events in the patient. In some embodiments, the method minimizes adverse events associated with antipsychotic agents with affinity to dopamine D2 receptors. In some embodiments, provided is a method of treating a neurological or psychiatric disease or disorder in a patient, comprising administering to the patient a therapeutically effective amount of Compound 1, or a pharmaceutically acceptable salt thereof, in the evening or at night, or at about bedtime, wherein the method is substantially devoid of adverse events. In some embodiments, a risk of adverse events in the patient is about the same as or similar to placebo. In some embodiments, provided is a method of treating a neurological or psychiatric disease or disorder in a patient, wherein the method is substantially devoid of adverse events of an antipsychotic agent having affinity to dopamine D2 receptors, comprising administering to the patient a therapeutically effective amount of an antipsychotic agent with no direct affinity to dopamine D2 receptors selected from Compound 1, or a pharmaceutically acceptable salt thereof, in the evening or at night, or at about bedtime. In some embodiments, provided is a method of minimizing adverse events in a patient in need of treatment for a neurological or psychiatric disease or disorder, the method comprising administering to the patient a therapeutically effective amount of an antipsychotic agent with no direct affinity to dopamine D2 receptors in the evening or at night, or at about bedtime, wherein the antipsychotic agent is Compound 1, or a pharmaceutically acceptable salt thereof, and wherein the method minimizes adverse events associated with antipsychotic agents with affini