US2021169862A1PendingUtilityA1

Methods for the Administration of Certain VMAT2 Inhibitors

74
Assignee: NEUROCRINE BIOSCIENCES INCPriority: Jan 27, 2017Filed: Dec 17, 2020Published: Jun 10, 2021
Est. expiryJan 27, 2037(~10.5 yrs left)· nominal 20-yr term from priority
Inventors:Christopher F. O`BrienHaig P. Bozigian
A61P 25/14A61K 9/0053A61P 1/16A61K 31/4375A61K 31/4745A61K 9/48C07D 455/06A61K 31/4709A61K 31/4525A61K 31/495A61K 31/473A61P 25/00A61P 25/18
74
PatentIndex Score
0
Cited by
0
References
0
Claims

Abstract

Provided are methods of administering a vesicular monoamine transport 2 (VMAT2) inhibitor chosen from valbenazine and (+)-α-3-isobutyl-9,10-dimethoxy-1,3,4,6,7,11b-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 being treated with a strong cytochrome P450 3A4 (CYP3A4) inducer.

Claims

exact text as granted — not AI-modified
1 - 78 . (canceled) 
     
     
         79 . A method of ameliorating one or more symptoms of a neurological or psychiatric disease or disorder in a patient, wherein the patient is also being administered a strong cytochrome P450 3A4 (CYP3A4) inducer, comprising:
 discontinuing the administration of the strong CYP3A4 inducer, and then   orally administering to the patient 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 a pharmaceutically acceptable salt thereof, thereby avoiding the concomitant use of the VMAT2 inhibitor with the strong CYP3A4 inducer.   
     
     
         80 . The method of  claim 79 , wherein the strong CYP3A4 inducer is chosen from nevirapine, pentobarbital, phenytoin, lumacaftor, rifabutin, rifampin, carbamazepine, fosphenytoin, phenobarbital, primidone, enzalutamide, mitotane, and St. John's Wort. 
     
     
         81 . The method of  claim 79 , wherein the strong CYP3A4 inducer is chosen from rifampin, carbamazepine, phenytoin, and St. John's Wort. 
     
     
         82 . The method of  claim 79 , wherein the strong CYP3A4 inducer is rifampin. 
     
     
         83 . The method of  claim 79 , wherein the VMAT2 inhibitor is administered in the form of a capsule. 
     
     
         84 . The method of  claim 79 , wherein the neurological or psychiatric disease or disorder is a hyperkinetic movement disorder. 
     
     
         85 . The method of  claim 84 , wherein the hyperkinetic movement disorder is tardive dyskinesia. 
     
     
         86 . The method of  claim 84 , wherein the hyperkinetic movement disorder is chorea. 
     
     
         87 . The method of  claim 86 , wherein the hyperkinetic movement disorder is chorea associated with Huntington's disease. 
     
     
         88 . The method of  claim 79 , wherein the VMAT2 inhibitor is a pharmaceutically acceptable 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. 
     
     
         89 . The method of  claim 79 , 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. 
     
     
         90 . The method of  claim 79 , wherein the 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 is in polymorphic Form I. 
     
     
         91 . The method of  claim 79 , 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 free base 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 free base once daily after one week. 
     
     
         92 . The method of  claim 79 , 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 free base once daily. 
     
     
         93 . The method of  claim 79 , 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 free base once daily. 
     
     
         94 . The method of  claim 79 , 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 free base once daily. 
     
     
         95 . A method of ameliorating one or more symptoms of a neurological or psychiatric disease or disorder in a patient, 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 a pharmaceutically acceptable salt thereof;   (b) subsequently determining that the patient is being administered a strong cytochrome P450 3A4 (CYP3A4) inducer;   (c) discontinuing the administration of the strong CYP3A4 inducer; and   (d) continuing the administration of the VMAT2 inhibitor.   
     
     
         96 . The method of  claim 95 , wherein the strong CYP3A4 inducer is chosen from rifampin, carbamazepine, phenytoin, and St. John's Wort. 
     
     
         97 . The method of  claim 95 , wherein the strong CYP3A4 inducer is rifampin. 
     
     
         98 . The method of  claim 95 , wherein the neurological or psychiatric disease or disorder is a hyperkinetic movement disorder. 
     
     
         99 . The method of  claim 98 , wherein the hyperkinetic movement disorder is tardive dyskinesia. 
     
     
         100 . The method of  claim 98 , wherein the hyperkinetic movement disorder is chorea. 
     
     
         101 . The method of  claim 100 , wherein the hyperkinetic movement disorder is chorea associated with Huntington's disease. 
     
     
         102 . The method of  claim 95 , wherein the VMAT2 inhibitor is a pharmaceutically acceptable 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. 
     
     
         103 . The method of  claim 102 , 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. 
     
     
         104 . The method of  claim 95 , 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 free base 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 free base once daily after one week. 
     
     
         105 . The method of  claim 95 , 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 free base once daily. 
     
     
         106 . The method of  claim 95 , 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 free base once daily. 
     
     
         107 . The method of  claim 95 , 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 free base once daily. 
     
     
         108 . A method of ameliorating one or more symptoms of a neurological or psychiatric disease or disorder in a patient, wherein the patient is being administered a strong cytochrome P450 3A4 (CYP3A4) inducer, comprising:
 discontinuing the administration of the strong CYP3A4 inducer; and then   orally administering once daily to the patient a vesicular monoamine transporter 2 (VMAT2) inhibitor, which 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, in 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 free base 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 free base after one week, thereby avoiding the concomitant use of the VMAT2 inhibitor with the strong CYP3A4 inducer; and   wherein the patient has not been administered the VMAT 2 inhibitor prior to the discontinuation of the strong CYP3A4 inducer.   
     
     
         109 . The method of  claim 108 , wherein the neurological or psychiatric disease or disorder is a hyperkinetic movement disorder. 
     
     
         110 . The method of  claim 109 , wherein the hyperkinetic movement disorder is tardive dyskinesia. 
     
     
         111 . The method of  claim 109 , wherein the hyperkinetic movement disorder is chorea. 
     
     
         112 . The method of  claim 111 , wherein the hyperkinetic movement disorder is chorea associated with Huntington's disease. 
     
     
         113 . A method of ameliorating one or more symptoms of a neurological or psychiatric disease or disorder in a patient, wherein the patient is being administered a strong cytochrome P450 3A4 (CYP3A4) inducer, comprising:
 discontinuing the administration of the strong CYP3A4 inducer; and then   orally administering once daily to the patient a vesicular monoamine transporter 2 (VMAT2) inhibitor, which 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, in an amount chosen from about 40 mg, about 60 mg, and 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 free base, thereby avoiding the concomitant use of the VMAT2 inhibitor with the strong CYP3A4 inducer; and   wherein the patient has not been administered the VMAT 2 inhibitor prior to the discontinuation of the strong CYP3A4 inducer.   
     
     
         114 . The method of  claim 113 , wherein the neurological or psychiatric disease or disorder is a hyperkinetic movement disorder. 
     
     
         115 . The method of  claim 114 , wherein the hyperkinetic movement disorder is tardive dyskinesia. 
     
     
         116 . The method of  claim 114 , wherein the hyperkinetic movement disorder is chorea. 
     
     
         117 . The method of  claim 116 , wherein the hyperkinetic movement disorder is chorea associated with Huntington's disease. 
     
     
         118 . A method of ameliorating one or more symptoms of a neurological or psychiatric disease or disorder in a patient, comprising:
 (a) orally administering once daily to the patient a therapeutically effective amount of a vesicular monoamine transporter 2 (VMAT2) inhibitor, which 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, in an amount chosen from about 40 mg, about 60 mg, and 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 free base;   (b) subsequently determining that the patient is being administered a strong cytochrome P450 3A4 (CYP3A4) inducer;   (c) discontinuing the administration of the strong CYP3A4 inducer; and   (d) continuing the administration of the VMAT2 inhibitor, thereby avoiding the concomitant use of the VMAT2 inhibitor with the strong CYP3A4 inducer.   
     
     
         119 . The method of  claim 118 , wherein the neurological or psychiatric disease or disorder is a hyperkinetic movement disorder. 
     
     
         120 . The method of  claim 119 , wherein the hyperkinetic movement disorder is tardive dyskinesia. 
     
     
         121 . The method of  claim 119 , wherein the hyperkinetic movement disorder is chorea. 
     
     
         122 . The method of  claim 121 , wherein the hyperkinetic movement disorder is chorea associated with Huntington's disease.

Join the waitlist — get patent alerts

Track US2021169862A1 — get alerts on status changes and closely related new filings.

We store only your email — no account needed. See our privacy policy.