Claims for Patent: 11,357,772

Summary for Patent: 11,357,772

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):	Stamler; David (Menlo Park, CA), Huang; Michael (Ladera Ranch, CA)
Assignee:	AUSPEX PHARMACEUTICALS, INC. (Parsippany, NJ)
Application Number:	17/154,312
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 at least about 6 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 the daily amount of the deutetrabenazine upward by 6 mg/day or more to a subsequent daily amount if the degree of control of abnormal involuntary movement is inadequate and the initial daily amount is tolerable; d) optionally, 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) if any subsequent amount is not tolerated, decreasing the daily amount downward by 6 mg/day or more to a subsequent daily amount. 2. The method as recited in claim 1, wherein the abnormal involuntary movement is associated with, or caused by, a movement disorder. 3. The method as recited in claim 2, wherein the movement disorder is Huntington's disease. 4. The method as recited in claim 2, wherein the movement disorder is tardive dyskinesia. 5. The method as recited in claim 2, wherein the movement disorder is Tourette syndrome. 6. The method as recited in claim 2, wherein the abnormal involuntary movement is chorea. 7. The method as recited in claim 2, wherein the abnormal involuntary movement is chorea associated with Huntington's disease. 8. The method as recited in claim 2, wherein the abnormal involuntary movement is akathisia. 9. The method as recited in claim 2, wherein the abnormal involuntary movement is dyskinesia. 10. The method as recited in claim 2, wherein the abnormal involuntary movement is tremor. 11. The method as recited in claim 2, wherein the abnormal involuntary movement is tic. 12. The method as recited in claim 2, wherein the abnormal involuntary movement is tic associated with Tourette syndrome. 13. The method as recited in 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. 14. The method as recited in claim 1, wherein the daily amount of deutetrabenazine is administered in one dose or two doses. 15. The method as recited in claim 14, wherein the daily amount of deutetrabenazine is from 24-48 mg. 16. The method as recited in claim 14, wherein the daily amount of deutetrabenazine is from 36-48 mg. 17. The method as recited in claim 14, wherein the daily amount of deutetrabenazine is about 6 mg. 18. The method as recited in claim 14, wherein the daily amount of deutetrabenazine is about 12 mg. 19. The method as recited in claim 14, wherein the daily amount of deutetrabenazine is about 18 mg. 20. The method as recited in claim 14, wherein the daily amount of deutetrabenazine is about 24 mg. 21. The method as recited in claim 14, wherein the daily amount of deutetrabenazine is about 30 mg. 22. The method as recited in claim 14, wherein the daily amount of deutetrabenazine is about 36 mg. 23. The method as recited in claim 14, wherein the daily amount of deutetrabenazine is about 42 mg. 24. The method as recited in claim 14, wherein the daily amount of deutetrabenazine is about 48 mg. 25. The method as recited in claim 1, wherein the initial daily amount of deutetrabenazine is about 6 mg. 26. The method as recited in claim 1, wherein the initial daily amount of deutetrabenazine is about 12 mg. 27. The method as recited in claim 1, wherein the initial daily amount of deutetrabenazine is about 18 mg. 28. The method as recited in claim 1, wherein the initial daily amount of deutetrabenazine is about 24 mg. 29. The method as recited in claim 1, wherein the initial daily amount of deutetrabenazine is about 30 mg. 30. The method as recited in claim 1, wherein the initial daily amount of deutetrabenazine is about 36 mg. 31. The method as recited in claim 1, wherein the initial daily amount of deutetrabenazine is about 42 mg. 32. The method as recited in claim 1, wherein the initial daily amount of deutetrabenazine is about 48 mg. 33. The method as recited in claim 1, 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 about 6 mg and the second dose is about 6 mg; the first dose is about 9 mg and the second dose is about 9 mg; the first dose is about 12 mg and the second dose is about 12 mg; the first dose is about 15 mg and the second dose is about 15 mg; the first dose is about 18 mg and the second dose is about 18 mg; the first dose is about 21 mg and the second dose is about 21 mg; or the first dose is about 24 mg and the second dose is about 24 mg. 34. The method as recited in claim 1, wherein the daily amount of deutetrabenazine administered is less than or equal to about 48 mg for a subject concurrently receiving a strong CYP2D6 inhibitor. 35. The method as recited in claim 1, wherein the daily amount of deutetrabenazine administered is less than or equal to about 36 mg for a subject concurrently receiving a strong CYP2D6 inhibitor. 36. The method as recited in 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). 37. The method as recited in claim 36, 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. 38. The method as recited in claim 36, wherein the chorea is reduced by at least 10%; by at least 15%; or by at least 20%. 39. The method as recited in claim 1, wherein the treatment does not significantly change the QTcF value in the subject. 40. The method as recited in claim 1, wherein the treating the abnormal involuntary movement comprises maintaining control of abnormal involuntary movements in a human subject with a movement disorder, comprising administering to the subject a therapeutically effective daily amount of deutetrabenazine for a period of time sufficient to do one or more of the following: reduce chorea by at least 10%; improve motor function by at least 10%; improve physical functioning; improve swallowing; improve balance; reduce abnormal involuntary movements in subjects with tardive dyskinesia; reduce motor tics; reduce vocal/phonic tics; reduce motor and vocal/phonic tics; reduce impairment in subjects with Tourette syndrome; reduce the severity of Tourette syndrome; reduce the patient global impression of severity in subjects with Tourette Syndrome; or much or very much improve the subject's patient of clinical global impression of change. 41. The method of claim 1, wherein the increase in the daily amount of deutetrabenzine is by 6 mg. 42. The method of claim 1, wherein the increase in the daily amount of deutetrabenzine is by 12 mg. 43. The method of claim 1, wherein the treatment results in maintaining control of abnormal involuntary movements in a human subject with a movement disorder. 44. 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.