US 12,233,033 B2
Amantadine compositions, preparations thereof, and methods of use
Gregory T. Went, San Francisco, CA (US); Timothy J. Fultz, Jasper, GA (US); Sangita Ghosh, Foster City, CA (US); and Natalie McClure, Portola Valley, CA (US)
Assigned to Adamas Pharma, LLC, Rockville, MD (US)
Filed by Adamas Pharma, LLC, Emeryville, CA (US)
Filed on Jun. 4, 2021, as Appl. No. 17/339,618.
Application 16/677,431 is a division of application No. 16/409,554, filed on May 10, 2019, granted, now 11,077,073.
Application 17/339,618 is a continuation of application No. 16/677,431, filed on Nov. 7, 2019, granted, now 11,065,213, issued on Jul. 20, 2021.
Application 16/409,554 is a continuation of application No. PCT/US2018/047754, filed on Aug. 23, 2018.
Claims priority of provisional application 62/549,921, filed on Aug. 24, 2017.
Prior Publication US 2022/0117914 A1, Apr. 21, 2022
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 31/136 (2006.01); A61K 9/00 (2006.01); A61K 9/50 (2006.01); A61K 31/13 (2006.01); A61P 25/16 (2006.01); A61P 25/28 (2006.01)
CPC A61K 31/136 (2013.01) [A61K 9/0053 (2013.01); A61K 9/501 (2013.01); A61K 9/5015 (2013.01); A61K 9/5026 (2013.01); A61K 9/5031 (2013.01); A61K 9/5042 (2013.01); A61K 9/5047 (2013.01); A61K 9/5078 (2013.01); A61K 31/13 (2013.01); A61P 25/16 (2018.01); A61P 25/28 (2018.01)] 34 Claims
 
1. A method of reducing levodopa-induced dyskinesia (LID) in a subject with Parkinson's disease in need thereof, comprising orally administering once daily to the subject an oral pharmaceutical composition comprising:
a drug, wherein the drug is amantadine or a pharmaceutically acceptable salt thereof, and wherein said oral pharmaceutical composition comprises from 50 mg to 500 mg of the amantadine or an equivalent amount of the pharmaceutically acceptable salt thereof; and
at least one excipient that modifies the release of at least a portion of said drug;
wherein said oral pharmaceutical composition has a dissolution profile of said drug which shows (a) and/or (b):
(a)
(i) 0% to 10% in 2 hours, and
(ii) 3% to 14% in 4 hours, and
(iii) 23% to 40% in 6 hours, and
(iv) not less than 80% in 12 hours;
(b)
(i) not more than 10% dissolution at 2 hours, and
(ii) 5% to 13% dissolution at 4 hours, and
(iii) 20% to 43% dissolution at 6 hours, and
(iv) at least 80% dissolution at 12 hours;
wherein the dissolution profile is determined with a USP Type 2 apparatus (paddles) at 50 rpm at 37.0±0.5° C. with 500 ml water as the dissolution medium; and
wherein said oral pharmaceutical composition provides (i) a Tmax for amantadine of 11 to 19 hours, (ii) an AUC0-inf for amantadine of 44 to 72 ng*hr/ml per mg of said drug, and (iii) a pAUC0-8 for amantadine of 1.0 to 2.0 ng*hr/ml per mg of said drug, when said oral pharmaceutical composition is dosed in healthy subjects of a single dose, human pharmacokinetic study, wherein the subjects are dosed in the morning after an overnight fast;
wherein LID is reduced in the subject.