Methods of using amantadine compositions

A method of increasing ON time without troublesome dyskinesia in a subject with Parkinson's disease in need thereof, wherein the subject has levodopa-induced dyskinesia (LID), the method 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:
• (i) not more than 9% dissolution at 2 hours,
• (ii) 3% to 14% dissolution at 4 hours,
• (iii) 20% to 43% dissolution at 6 hours, and
• (iv) at least 82% 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;
• wherein said oral pharmaceutical composition provides (i) a Tmax for amantadine of 11 to 19 hours, and (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;
• and
• wherein said oral pharmaceutical composition comprises less than 2000 ppm of organic solvent.

A method of reducing OFF time in a subject with Parkinson's disease in need thereof, wherein the subject has levodopa-induced dyskinesia (LID), the method 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:
• (i) not more than 9% dissolution at 2 hours,
• (ii) 3% to 14% dissolution at 4 hours,
• (iii) 20% to 43% dissolution at 6 hours, and
• (iv) at least 82% 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, and (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 said oral pharmaceutical composition comprises less than 2000 ppm of organic solvent;
• and
• wherein OFF time is reduced in the subject.

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:
• (i) not more than 10% dissolution at 2 hours;
• (ii) 5% to 13% dissolution at 4 hours;
• (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, and (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 said oral pharmaceutical composition comprises less than 2000 ppm of organic solvent;
• and
• wherein LID is reduced in the subject.

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:
• (i) not more than 9% dissolution at 2 hours,
• (ii) 3% to 14% dissolution at 4 hours,
• (iii) 20% to 43% dissolution at 6 hours, and
• (iv) at least 82% 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, and (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 said oral pharmaceutical composition comprises less than 2000 ppm of organic solvent;
• and
• wherein LID is reduced in the subject.