Claims for Patent: 11,564,917

Summary for Patent: 11,564,917

Title:	Methods for the treatment of abnormal involuntary movement disorders
Abstract:	Disclosed herein are new dosage regimens for deuterium-substituted benzoquinoline compounds, and methods for the treatment of abnormal muscular activity, movement disorders, and related conditions.
Inventor(s):	David Stamler, Michael Fangching HUANG
Assignee:	Auspex Pharmaceuticals Inc
Application Number:	US15/722,208
Patent Claims:	1. A method of treating abnormal involuntary movements in a human subject having Tardive Dyskinesia; wherein if the subject is male, the subject does not have a QTcF value >450 ms on a 12-lead electrocardiogram (ECG) at baseline; or wherein if the subject is female, the subject does not have a QTcF value >460 ms on a 12-lead electrocardiogram (ECG) at baseline; comprising: administering to the subject a dose of deutetrabenazine of less than or equal to about 24 mg; wherein the administration results in an improvement in motor function in the subject, as compared to the subject's motor function prior to the administration, and a maximal increase in the subject's QTcF of less than 5 ms. 2. The method of claim 1, wherein the subject is administered a total daily amount of deutetrabenazine in two doses. 3. The method of claim 2, wherein the total daily amount of deutetrabenazine is less than or equal to 48 mg. 4. The method of claim 2, wherein the total daily amount of deutetrabenazine is less than or equal to 42 mg. 5. The method of claim 2, wherein the total daily amount of deutetrabenazine is less than or equal to 36 mg. 6. The method of claim 5, wherein the subject is concurrently receiving a strong CYP2D6 inhibitor. 7. The method of claim 6, wherein the strong CYP2D6 inhibitor is fluoxetine, paroxetine, bupropion, quinidine, cinacalcet, or ritonavir. 8. The method of claim 6, wherein the strong CYP2D6 inhibitor is paroxetine, fluoxetine, or bupropion. 9. The method of claim 1, resulting in no clinically significant adverse event in the subject. 10. The method of claim 1, wherein the improvement in motor function is a reduction in the severity of abnormal involuntary movements, as measured by the Abnormal Involuntary Movement Scale. 11. The method of claim 10, wherein the improvement is a 10% reduction in Abnormal Involuntary Movement Scale score. 12. The method of claim 10, wherein the improvement is a 50% reduction in Abnormal Involuntary Movement Scale score. 13. The method of claim 10, wherein the improvement is a 90% reduction in Abnormal Involuntary Movement Scale score. 14. The method of claim 1, wherein the improvement in motor function is measured by the Clinical Global Impression of Change or the modified Craniocervical Dystonia score. 15. The method of claim 9, resulting in no significant increase in insomnia, depression, anxiety, agitation, suicidal ideation, akathisia, irritability, fatigue, parkinsonism or dysphagia in the subject. 16. The method of claim 1, further comprising administering to the subject another therapeutic agent useful in the treatment of Tardive Dyskinesia. 17. The method of claim 1, further comprising concomitantly administering a dopamine receptor antagonist with the deutetrabenazine. 18. The method of claim 1, wherein the subject is an adult. 19. The method of claim 1, wherein the subject is at least 18 years of age. 20. The method of claim 2, wherein the total daily amount of deutetrabenazine is administered in two equal doses. 21. The method of claim 2, wherein the total daily amount of deutetrabenazine is from about 24 mg to about 48 mg. 22. The method of claim 2, wherein the total daily amount of deutetrabenazine is from about 36 mg to about 48 mg. 23. The method of claim 2, wherein the total daily amount of deutetrabenazine is from about 24 mg to about 36 mg. 24. The method of claim 1, further comprising the steps a) administering to the subject an initial daily amount of deutetrabenazine in two doses; b) determining after about one week that the degree of control of abnormal involuntary movement achieved with the initial daily amount of the deutetrabenazine is inadequate and that the initial daily amount of the deutetrabenazine is tolerable; and c) increasing the daily amount of the deutetrabenazine upward by 6 mg/day to a subsequent daily amount. 25. The method of claim 24, wherein: the first dose is about 6 mg and the second dose is about 6 mg; or the first dose is about 9 mg and the second dose is about 9 mg; or the first dose is about 12 mg and the second dose is about 12 mg. 26. The method of claim 24, wherein the first dose is about 6 mg and the second dose is about 6 mg. 27. The method of claim 24, further comprising after about one week, repeating steps b) and c) provided that abnormal involuntary movement is reduced and the daily amount of deutetrabenazine is tolerated. 28. The method of claim 24, wherein if the subsequent daily amount is not tolerated, decreasing the amount of deutetrabenazine by 6 mg/day to a subsequent daily amount. 29. The method of claim 24, further comprising: d) repeating steps b) and c) until the degree of control of abnormal involuntary movement is adequate and the daily amount of the deutetrabenazine is tolerable; and e) decreasing the daily amount by 6 or more mg/day to another subsequent daily amount of deutetrabenazine when a subsequent amount of deutetrabenazine is intolerable. 30. The method of claim 1, resulting in no significant increase in depression or suicidal ideation. 31. The method of claim 1, wherein the subject has an underlying psychiatric illness. 32. The method of claim 1, wherein the subject is administered a total daily amount of deutetrabenazine in one dose.