Compositions for the Treatment of CNS-Related Conditions

1 . A method of treating a CNS-related condition comprising orally administering once a day to a human subject in need thereof:

a. 200-500 mg amantadine or a pharmaceutically acceptable salt thereof provided in extended release dosage form, wherein said extended release amantadine or pharmaceutically acceptable salt thereof provides a change in plasma concentration as a function of time (dC/dT) that is less than 40% of the dC/dT of the same quantity of an immediate release form of amantadine, wherein dC/dT is measured in a single dose human PK study between the period of 0 to Tmax of the immediate release form of amantadine; and

b. a therapeutically effective amount of donepezil or a pharmaceutically acceptable salt thereof, wherein the CNS-related condition is selected from a group consisting of Alzheimer's disease, dementia, Parkinson's disease, multiple sclerosis, traumatic brain injury, fatigue, and neuropsychiatric disorders.

2 . The method of claim 1 , wherein the amount of amantadine or pharmaceutically acceptable salt thereof ranges between 300 to 500 mg per dose.

3 . The method of claim 1 , wherein the extended release amantadine has an in vitro dissolution profile in water that is substantially identical to its in vitro dissolution profile in a dissolution medium having a pH of 1.2 and wherein said in vitro dissolution is less than 20% in one hour, less than 30% in two hours, 40-80% in six hours, and greater than or equal to 80% in 12 hours as measured using a USP type II (paddle) dissolution system at 50 rpm, at a temperature of 37±0.5 C.

4 . The method of claim 1 , wherein at least 95% of the amantadine is in extended release form.

5 . The method of claim 1 , wherein said amantadine or a pharmaceutically acceptable salt thereof and said donepezil or a pharmaceutically acceptable salt thereof are administered simultaneously.

6 . The method of claim 1 , wherein said amantadine or a pharmaceutically acceptable salt thereof and said donepezil or a pharmaceutically acceptable salt thereof are administered as a single composition.

7 . A method of reducing the potential for an adverse effect in a human being treated for a CNS-related condition comprising orally administering once a day to a human subject in need thereof a pharmaceutical composition comprising:

a. 200-500 mg amantadine or a pharmaceutically acceptable salt thereof provided in extended release dosage form, wherein said extended release amantadine or pharmaceutically acceptable salt thereof provides a change in plasma concentration as a function of time (dC/dT) that is less than 40% of the dC/dT of the same quantity of an immediate release form of amantadine, wherein dC/dT is measured in a single dose human PK study between the period of 0 to Tmax of the immediate release form of amantadine; and

b. a therapeutically effective amount of donepezil or a pharmaceutically acceptable salt thereof, wherein the CNS-related condition is selected from a group consisting of Alzheimer's disease, dementia, Parkinson's disease, multiple sclerosis, traumatic brain injury, fatigue, and neuropsychiatric disorders;

and further wherein said adverse event is related to amantadine.

8 . The method of claim 7 , wherein the composition is in a unit dosage form comprising 300 to 500 mg amantadine or a pharmaceutically acceptable salt thereof.

9 . The method of claim 7 , wherein the donepezil or a pharmaceutically acceptable salt thereof is in an immediate release form.

10 . The method of claim 7 , wherein the composition comprises 1 to 20 mg donepezil hydrochloride.

11 . The method of claim 7 , wherein the dosage form is in a capsule.

12 . The method of claim 7 , wherein said amantadine or a pharmaceutically acceptable salt thereof and said donepezil or a pharmaceutically acceptable salt thereof are provided in a unit dosage form.

13 . The method of claim 7 , wherein the composition comprises 200 to 500 mg amantadine hydrochloride.

14 . The method of claim 7 , wherein the composition comprises at least 200 mg amantadine hydrochloride and 1 to 20 mg donepezil hydrochloride.

15 . In a method of treating a subject for CNS-related condition comprising administering to said subject an amantadine drug selected from the group consisting of amantadine and a pharmaceutically acceptable salt thereof, and a therapeutically effective amount of a donepezil drug selected from the group consisting of donepezil and a pharmaceutically acceptable salt thereof, the improvement comprising:

a. said amantadine drug is administered in an extended release dosage form, wherein said extended release amantadine provides a change in plasma concentration as a function of time (dC/dT) in a defined time period of 0 to Tmax of an immediate release form of amantadine after administration, as measured in a single dose PK study, that is less than 40% of the change in plasma concentration (dC/dT) of the same quantity of said immediate release form of said amantadine drug during said defined time period; and

b. said amantadine drug is administered once daily in a range of 200 to 500 mg;

wherein said CNS-related condition is selected from the group consisting of Alzheimer's disease, dementia, Parkinson's disease, multiple sclerosis, traumatic brain injury, fatigue, and neuropsychiatric disorders.

16 . The method of claim 15 , wherein said amantadine drug daily dose is 300 to 500 mg.

17 . The method of claim 15 , wherein said amantadine drug and said donepezil drug are administered as a composition.

18 . The method of claim 16 , wherein said amantadine drug and said donepezil drug are administered as a unit dosage form.

19 . The method of claim 17 , wherein said donepezil drug is administered as an immediate release form.

20 . The method of claim 18 , wherein said donepezil drug is administered as an immediate release form.