Claims for Patent: 11,654,142

Summary for Patent: 11,654,142

Title:	Methods for the administration of certain VMAT2 inhibitors
Abstract:	Provided are methods of administering a vesicular monoamine transport 2 (VMAT2) inhibitor chosen from valbenazine and (+)-α-3-isobutyl-9,10-dimethoxy-1,3,4,6,7,1 1b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol, or a pharmaceutically acceptable salt and/or isotopic variant thereof, to a patient in need thereof wherein the patient is also being administered digoxin.
Inventor(s):	Christopher F. O'Brien, Haig P. Bozigian
Assignee:	Neurocrine Biosciences Inc
Application Number:	US17/075,234
Patent Claims:	1. A method for treating a patient with a hyperkinetic movement disorder, wherein the hyperkinetic movement disorder is chorea associated with Huntington's disease, and wherein the patient is also being co-administered digoxin, comprising: a. orally administering to the patient a therapeutically effective amount of a vesicular monoamine transporter 2 (VMAT2) inhibitor chosen from (S)-2-amino-3-methyl-butyric acid (2R,3R,11bR)-3-isobutyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-yl ester and pharmaceutically acceptable salts thereof; b. monitoring the digoxin concentration in the patient's blood; and c. reducing the dose of digoxin when the digoxin exposure in the patient's blood is increased as compared with the digoxin level in a patient who is administered digoxin alone. 2. The method of claim 1, wherein the digoxin exposure is measured as the area under the plasma concentration versus time curve from 0 hours extrapolated to infinity or measured as the maximum observed blood plasma concentration (Cmax) at the time of maximum plasma concentration (tmax). 3. The method of claim 1, wherein the increased digoxin exposure increases the risk of one or more exposure-related adverse reactions. 4. The method of claim 1, further comprising monitoring the patient for one or more exposure-related adverse reactions. 5. The method of claim 4, wherein the one or more exposure-related adverse reactions is selected from headache, anxiety, insomnia, diarrhea, restlessness, and abnormal dreams. 6. The method of claim 1, further comprising obtaining a baseline serum digoxin concentration prior to administering to the patient the therapeutically effective amount of the VMAT2 inhibitor. 7. The method of claim 1, wherein the VMAT2 inhibitor is administered in the form of a tablet or capsule. 8. The method of claim 1, wherein the VMAT2 inhibitor is a pharmaceutically acceptable salt of (S)-2-amino-3-methyl-butyric acid (2R,3R,11bR)-3isobutyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]H-pyrido[2,1a]isoquinolin-2-yl ester. 9. The method of claim 1, wherein the VMAT2 inhibitor is a ditosylate salt of (S)-2-amino-3-methyl-butyric acid (2R,3R,11bR)-3-isobutyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-yl ester. 10. The method of claim 1, wherein the therapeutically effective amount is an amount equivalent to about 40 mg as measured by (S)-2-amino-3-methyl-butyric acid (2R,3R,11bR)-3-isobutyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro -2H-pyrido[2,1-a]isoquinolin-2-yl ester once daily for one week, and an amount equivalent to about 80 mg as measured by (S)-2-amino-3-methyl-butyric acid (2R,3R,11bR)-3-isobutyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-yl ester once daily after one week. 11. The method of claim 1, wherein the therapeutically effective amount is an amount equivalent to between about 20 mg to about 160 mg as measured by (S)-2-amino-3-methyl-butyric acid (2R,3R,11bR)-3-isobutyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-yl ester once daily. 12. The method of claim 1, wherein the therapeutically effective amount is an amount equivalent to about 40 mg as measured by (S)-2-amino-3-methyl-butyric acid (2R,3R,11bR)-3-isobutyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro -2H-pyrido[2,1-a]isoquinolin-2-yl ester once daily. 13. The method of claim 1, wherein the therapeutically effective amount is an amount equivalent to about 60 mg as measured by (S)-2-amino-3-methyl-butyric acid (2R,3R,11bR)-3-isobutyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro -2H-pyrido[2,1-a]isoquinolin-2-yl ester once daily. 14. The method of claim 1, wherein the therapeutically effective amount is an amount equivalent to about 80 mg as measured by (S)-2-amino-3-methyl-butyric acid (2R,3R,11bR)-3-isobutyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro -2H-pyrido[2,1-a]isoquinolin-2-yl ester once daily. 15. The method of claim 1, wherein the co-administration of the VMAT2 inhibitor with digoxin increases digoxin levels because of inhibition of intestinal P-glycoprotein (P-gp) by the VMAT2 inhibitor.