Amantadine compositions and methods of use

Abstract

Methods of nighttime administration of amantadine to reduce sleep disturbances in patient undergoing treatment with amantadine are described, as well as compositions of extended release amantadine that are suitable for nighttime administration.

1 - 28 . (canceled) 
     
     
         29 . A method of reducing, relative to placebo, dyskinesia in a human patient with Parkinson's disease receiving levodopa-based therapy comprising:
 administering to said human patient once daily from 0 to 4 hours before bedtime, an oral pharmaceutical composition comprising:
 (a) an amount effective to reduce, relative to placebo, dyskinesia in said human patient with Parkinson's disease receiving levodopa-based therapy, of a drug chosen from amantadine and pharmaceutically acceptable salts thereof; and 
 (b) at least one means for releasing said drug to provide (i) a Cmax of from about 1.0 to about 2.8 ng/mL per mg of amantadine, and (ii) an AUC 0-inf  of from about 40 to about 75 ng*hr/mL per mg of amantadine upon administration of a single dose of the composition to a healthy human subject in a fasted state; 
   wherein said dyskinesia is measured by the Unified Dyskinesia Rating Scale (UDysRS).   
     
     
         30 . The method of  claim 29 , wherein said drug is amantadine hydrochloride. 
     
     
         31 . The method of  claim 29 , wherein said oral pharmaceutical composition is at least one capsule. 
     
     
         32 . The method of  claim 29 , wherein said oral pharmaceutical composition is at least one tablet. 
     
     
         33 . The method of  claim 29 , wherein said oral pharmaceutical composition is administered orally once daily for at least 8 weeks. 
     
     
         34 . The method of  claim 29 , wherein said amount of said drug is from about 135 mg to about 275 mg of amantadine. 
     
     
         35 . The method of  claim 30 , wherein said amount of said drug is from about 170 mg to about 345 mg of amantadine hydrochloride. 
     
     
         36 . The method of  claim 29 , wherein the oral pharmaceutical composition is administered once daily from 0 to 3 hours before bedtime. 
     
     
         37 . The method of  claim 36 , wherein the at least one means for releasing said drug provides a Cmax of from about 1.6 to about 2.4 ng/ml per mg of amantadine. 
     
     
         38 . An oral pharmaceutical composition for once-daily administration from 0 to 4 hours before bedtime to a human patient with Parkinson's disease receiving levodopa-based therapy, comprising:
 (a) an amount effective to reduce, relative to placebo, dyskinesia in said human patient with Parkinson's disease receiving levodopa-based therapy, of a drug chosen from amantadine and pharmaceutically acceptable salts thereof; and   (b) at least one means for releasing said drug to provide (i) a Cmax of from about 1.0 to about 2.8 ng/mL per mg of amantadine, and (ii) an AUC 0-inf  of from about 40 to about 75 ng*hr/mL per mg of amantadine upon administration of a single dose of the composition to a healthy human subject in a fasted state;   wherein said dyskinesia is measured by the Unified Dyskinesia Rating Scale (UDysRS).   
     
     
         39 . The oral pharmaceutical composition of  claim 38 , wherein said drug is amantadine hydrochloride. 
     
     
         40 . The oral pharmaceutical composition of  claim 38 , wherein said oral pharmaceutical composition is at least one capsule. 
     
     
         41 . The oral pharmaceutical composition of  claim 38 , wherein said oral pharmaceutical composition is at least one tablet. 
     
     
         42 . The oral pharmaceutical composition of  claim 38 , wherein said oral pharmaceutical composition is administered orally once daily for at least 8 weeks. 
     
     
         43 . The oral pharmaceutical composition of  claim 38 , wherein said amount of said drug is from about 135 mg to about 275 mg of amantadine. 
     
     
         44 . The oral pharmaceutical composition of  claim 39 , wherein said amount of said drug is from about 170 mg to about 345 mg of amantadine hydrochloride. 
     
     
         45 . A method of reducing, relative to placebo, dyskinesia in a human patient with Parkinson's disease receiving levodopa-based therapy comprising:
 administering to said human patient once daily from 0 to 4 hours before bedtime, an oral pharmaceutical composition comprising
 (a) an amount effective to reduce, relative to placebo, dyskinesia in said human patient with Parkinson's disease receiving levodopa-based therapy, of a drug chosen from amantadine and pharmaceutically acceptable salts thereof; and 
 (b) at least one means for releasing said drug to provide a Tmax of from about 9 to about 15 hours of said drug upon administration of a single dose of the composition to a healthy human subject in a fasted state; 
 wherein said dyskinesia is measured by the Unified Dyskinesia Rating Scale (UDysRS). 
   
     
     
         46 . The method of  claim 45 , wherein said drug is amantadine hydrochloride. 
     
     
         47 . The method of  claim 45 , wherein said oral pharmaceutical composition is at least one capsule. 
     
     
         48 . The method of  claim 45 , wherein said oral pharmaceutical composition is at least one tablet. 
     
     
         49 . The method of  claim 45 , wherein said oral pharmaceutical composition is administered once daily for at least 8 weeks. 
     
     
         50 . The method of  claim 45 , wherein said amount of said drug is from about 135 mg to about 275 mg of amantadine. 
     
     
         51 . The method of  claim 46 , wherein said amount of said drug is from about 170 mg to about 345 mg of amantadine hydrochloride. 
     
     
         52 . An oral pharmaceutical composition for once-daily administration from 0 to 4 hours before bedtime to a human patient with Parkinson's disease receiving levodopa-based therapy, comprising:
 (a) an amount effective to reduce, relative to placebo, dyskinesia in said human patient with Parkinson's disease receiving levodopa-based therapy, of a drug chosen from amantadine and pharmaceutically acceptable salts thereof; and   (b) at least one means for releasing said drug to provide a Tmax of from about 9 to about 15 hours of said drug upon administration of a single dose of the composition to a healthy human subject in a fasted state;   wherein said dyskinesia is measured by the Unified Dyskinesia Rating Scale (UDysRS).   
     
     
         53 . The oral pharmaceutical composition of  claim 52 , wherein said drug is amantadine hydrochloride. 
     
     
         54 . The oral pharmaceutical composition of  claim 52 , wherein said oral pharmaceutical composition is at least one capsule. 
     
     
         55 . The oral pharmaceutical composition of  claim 52 , wherein said oral pharmaceutical composition is at least one tablet. 
     
     
         56 . The oral pharmaceutical composition of  claim 52 , wherein said oral pharmaceutical composition is administered orally once daily for at least 8 weeks. 
     
     
         57 . The oral pharmaceutical composition of  claim 52 , wherein said amount of said drug is from about 135 mg to about 275 mg of amantadine. 
     
     
         58 . The oral pharmaceutical composition of  claim 53 , wherein said amount of said drug is from about 170 mg to about 345 mg of amantadine hydrochloride.