Claims for Patent: 12,016,858

Summary for Patent: 12,016,858

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 Huang
Assignee:	Auspex Pharmaceuticals Inc
Application Number:	US17/400,194
Patent Claims:	1. A method for treating abnormal involuntary movement in a subject comprising a) administering to the subject an initial daily amount of deutetrabenazine of 12 mg per day; b) determining after about one week the degree of control of abnormal involuntary movement achieved with the initial daily amount and the tolerability of the initial daily amount; c) increasing a daily amount of the deutetrabenazine by 6 mg/day or more to a subsequent daily amount if the degree of control of abnormal involuntary movement is inadequate and the daily amount is tolerable; d) optionally, repeating step c) until the degree of control of abnormal involuntary movement is adequate and the daily amount of the deutetrabenazine is tolerable; and e) optionally, if any daily amount is not tolerated, decreasing the daily amount by 6 mg/day or more to a subsequent daily amount. 2. The method of claim 1, wherein the abnormal involuntary movement is associated with, or caused by, a movement disorder. 3. The method of claim 2, wherein the movement disorder is Huntington's disease. 4. The method of claim 2, wherein the movement disorder is tardive dyskinesia. 5. The method of claim 2, wherein the abnormal involuntary movement is chorea. 6. The method of claim 2, wherein the abnormal involuntary movement is chorea associated with Huntington's disease. 7. The method of claim 2, wherein the abnormal involuntary movement is akathisia. 8. The method of claim 2, wherein the abnormal involuntary movement is dyskinesia. 9. The method of claim 2, wherein the abnormal involuntary movement is tremor. 10. The method of claim 1, wherein tolerability is determined by assessment of one or more of the subject's levels of depression, anxiety, insomnia, somnolence, fatigue, dizziness, restlessness, agitation, irritability, akathisia, tardive dyskinesia, swallowing, parkinsonism, vomiting and nausea. 11. The method of claim 1, wherein the daily amount of deutetrabenazine is administered in one dose or two doses. 12. The method of claim 11, wherein the daily amount of deutetrabenazine is from 24-48 mg. 13. The method of claim 11, wherein the daily amount of deutetrabenazine is from 36-48 mg. 14. The method of claim 11, wherein the daily amount of deutetrabenazine is 12 mg. 15. The method of claim 11, wherein the daily amount of deutetrabenazine is 18 mg. 16. The method of claim 11, wherein the daily amount of deutetrabenazine is 24 mg. 17. The method of claim 11, wherein the daily amount of deutetrabenazine is 30 mg. 18. The method of claim 11, wherein the daily amount of deutetrabenazine is 36 mg. 19. The method of claim 11, wherein the daily amount of deutetrabenazine is 42 mg. 20. The method of claim 11, wherein the daily amount of deutetrabenazine is 48 mg. 21. The method of claim 11, wherein the daily amount of deutetrabenazine is administered in one dose. 22. The method of claim 11, wherein the daily amount of deutetrabenazine is administered in two doses, consisting of a first dose and a second dose; wherein: the first dose is 6 mg and the second dose is 6 mg; the first dose is 9 mg and the second dose is 9 mg; the first dose is 12 mg and the second dose is 12 mg; the first dose is 15 mg and the second dose is 15 mg; the first dose is 18 mg and the second dose is 18 mg; the first dose is 21 mg and the second dose is 21 mg; or the first dose is 24 mg and the second dose is 24 mg. 23. The method of claim 1, wherein the initial daily amount of deutetrabenazine is administered in one dose or two doses. 24. The method of claim 1, wherein the initial daily amount of deutetrabenazine is 12 mg. 25. The method of claim 1, wherein the initial daily amount of deutetrabenazine is 24 mg. 26. The method of claim 1, wherein the initial daily amount of deutetrabenazine is 36 mg. 27. The method of claim 1, wherein the initial daily amount of deutetrabenazine is administered in one dose. 28. The method of claim 23, wherein the initial daily amount of deutetrabenazine is administered in two doses, consisting of a first dose and a second dose; wherein: the first dose is 6 mg and the second dose is 6 mg; the first dose is 9 mg and the second dose is 9 mg; the first dose is 12 mg and the second dose is 12 mg; the first dose is 15 mg and the second dose is 15 mg; the first dose is 18 mg and the second dose is 18 mg; the first dose is 21 mg and the second dose is 21 mg; or the first dose is 24 mg and the second dose is 24 mg. 29. The method of claim 1, wherein the daily amount of deutetrabenazine administered is less than or equal to 48 mg for a subject concurrently receiving a strong CYP2D6 inhibitor. 30. The method of claim 1, wherein the daily amount of deutetrabenazine administered is less than or equal to 36 mg for a subject concurrently receiving a strong CYP2D6 inhibitor. 31. The method of claim 1, wherein the abnormal involuntary movement is chorea associated with Huntington's disease and wherein chorea is reduced by at least 0.5 points as measured by the Total Maximal Chorea (TMC) score of the Unified Huntington's Disease Rating Scale (UHDRS). 32. The method of claim 31, wherein the reduction in the TMC score is at least 1 point; at least 1.5 points; at least 2 points; or at least 2.5 points. 33. The method of claim 31, wherein the chorea is reduced by at least 10%; by at least 15%; or by at least 20%. 34. The method of claim 1, wherein the treatment does not significantly change the QTcF value in the subject. 35. The method of claim 1, wherein the treatment results in one or more of the following: reducing chorea by at least 10%; improving motor function by at least 10%; improving physical functioning; improving swallowing; improving balance; reducing abnormal involuntary movements in subjects with tardive dyskinesia; or much or very much improving the subject's patient of clinical global impression of change. 36. The method of claim 1, wherein the increase in the daily amount of deutetrabenzine is by 6 mg or by 12 mg. 37. The method of claim 36, wherein the increase in the daily amount of deutetrabenzine is by 6 mg. 38. The method of claim 36, wherein the increase in the daily amount of deutetrabenzine is by 12 mg. 39. The method of claim 1, wherein the treatment results in maintaining control of abnormal involuntary movements in a human subject with a movement disorder. 40. The method of claim 1, wherein if the degree of control of abnormal involuntary movement is adequate and the daily amount of the deutetrabenazine is tolerable, a maintenance dose is administered to the subject.