Composition and method for treating neurological disease
View Patent ↗The present disclosure is directed to methods of treating neurological disorders in a patient such as Parkinson's disease, drug-induced extrapyramidal reactions, and/or levodopa-induced dyskinesia comprising administering to the patient once daily in the morning a pharmaceutical composition comprising about 50 mg to about 400 mg of extended-release amantadine or a pharmaceutically acceptable salt thereof.
1. A method of treating Parkinson's disease in a patient, comprising:
i) administering to the patient once daily in the morning a pharmaceutical composition comprising about 129 mg of amantadine free base equivalent for about one week;
ii) increasing the dose of amantadine by administering to the patient once daily in the morning a pharmaceutical composition comprising about 193 mg of amantadine free base equivalent;
wherein each of the pharmaceutical compositions comprises i) an extended release component comprising amantadine free base equivalent; and ii) an immediate release component comprising about 48 mg of amantadine free base equivalent;
wherein each of the pharmaceutical compositions is a solid oral dosage form,
wherein the maximum daily dose of amantadine is about 322 mg of amantadine free base equivalent,
wherein the mean C max of the pharmaceutical composition comprising about 129 mg of amantadine free base equivalent after a single-dose administration is between about 50% and about 125% of the mean C max provided by the same quantity of amantadine or a pharmaceutically acceptable salt thereof in an immediate release form; and
wherein the mean C max of the pharmaceutical composition comprising about 193 mg of amantadine free base equivalent after a single-dose administration is between about 50% and about 175% of the mean C max provided by the same quantity of amantadine or a pharmaceutically acceptable salt thereof in an immediate release form.
2. The method of claim 1 , wherein the mean C max of the pharmaceutical composition comprising about 129 mg of amantadine free base equivalent after a single-dose administration is between about 75% and about 100% of the mean C max provided by the same quantity of amantadine or a pharmaceutically acceptable salt thereof in an immediate release form.
3. The method of claim 1 , wherein the mean C max of the pharmaceutical composition comprising about 129 mg of amantadine free base equivalent after a single-dose administration is between about 200 and about 500 ng/mL.
4. The method of claim 3 , wherein the mean C max of the pharmaceutical composition comprising about 129 mg of amantadine free base equivalent after a single-dose administration is between about 265 and about 390 ng/mL.
5. The method of claim 1 , wherein the mean C max of the pharmaceutical composition comprising about 193 mg of amantadine free base equivalent after a single-dose administration is between about 100% and about 125% of the mean C max provided by the same quantity of amantadine or a pharmaceutically acceptable salt thereof in an immediate release form.
6. The method of claim 1 , wherein the mean C max of the pharmaceutical composition comprising about 193 mg of amantadine free base equivalent after a single-dose administration is between about 200 and about 700 ng/mL.
7. The method of claim 6 , wherein the mean C max of the pharmaceutical composition comprising about 193 mg of amantadine free base equivalent after a single-dose administration is between about 370 and about 550 ng/mL.
8. A method of treating Parkinson's disease in a patient, comprising:
i) administering to the patient once daily in the morning a pharmaceutical composition comprising about 129 mg of amantadine free base equivalent for about one week;
ii) increasing the dose of amantadine by administering to the patient once daily in the morning a pharmaceutical composition comprising about 193 mg of amantadine free base equivalent;
wherein each of the pharmaceutical compositions comprises i) an extended release component comprising amantadine free base equivalent; and ii) an immediate release component comprising about 48 mg of amantadine free base equivalent,
wherein each of the pharmaceutical compositions is a solid oral dosage form,
wherein the maximum daily dose of amantadine is about 322 mg of amantadine free base equivalent,
wherein the mean AUC 0-∞ of the pharmaceutical composition comprising about 129 mg of amantadine free base equivalent after a single-dose administration is between 65% and about 135% of the mean AUC 0-∞ provided by the same quantity of amantadine or a pharmaceutically acceptable salt thereof in an immediate release form, and
wherein the mean AUC 0-∞ of the pharmaceutical composition comprising about 193 mg of amantadine free base equivalent after a single-dose administration is between 85% and about 225% of the mean AUC 0-∞ provided by the same quantity of amantadine or a pharmaceutically acceptable salt thereof in an immediate release form.
9. The method of claim 8 , wherein the mean AUC 0-∞ of the pharmaceutical composition comprising about 129 mg of amantadine free base equivalent after a single-dose administration is between about 90% and about 110% of the mean AUC 0-∞ provided by the same quantity of amantadine or a pharmaceutically acceptable salt thereof in an immediate release form.
10. The method of claim 8 , wherein the mean AUC 0-∞ of the pharmaceutical composition comprising about 129 mg of amantadine free base equivalent after a single-dose administration is between about 6,000 and about 12,000 ng·h/mL.
11. The method of claim 8 , wherein the mean AUC 0-∞ of the pharmaceutical composition comprising about 193 mg of amantadine free base equivalent after a single-dose administration is between about 130% and about 180% of the mean AUC 0-∞ provided by the same quantity of amantadine or a pharmaceutically acceptable salt thereof in an immediate release form.
12. The method of claim 8 , wherein the mean AUC 0-∞ of the pharmaceutical composition comprising about 193 mg of amantadine free base equivalent after a single-dose administration is between about 8,000 and about 20,000 ng·h/mL.
13. A method of treating Parkinson's disease in a patient, comprising:
i) administering to the patient once daily in the morning a pharmaceutical composition comprising about 129 mg of amantadine free base equivalent for about one week;
ii) increasing the dose of amantadine by administering to the patient once daily in the morning a pharmaceutical composition comprising about 193 mg of amantadine free base equivalent for at least one week;
iii) increasing the dose of amantadine by administering to the patient once daily in the morning a pharmaceutical composition comprising about 258 mg of amantadine free base equivalent;
wherein each of the pharmaceutical compositions comprises i) an extended release component comprising amantadine free base equivalent; and ii) an immediate release component comprising about 48 mg of amantadine free base equivalent,
wherein each of the pharmaceutical compositions is a solid oral dosage form,
wherein the maximum daily dose of amantadine is about 322 mg of amantadine free base equivalent,
wherein the mean C max of the pharmaceutical composition comprising about 129 mg of amantadine free base equivalent after a single-dose administration is between about 50% and about 125% of the mean C max provided by the same quantity of amantadine or a pharmaceutically acceptable salt thereof in an immediate release form,
wherein the mean C max of the pharmaceutical composition comprising about 193 mg of amantadine free base equivalent after a single-dose administration is between about 50% and about 175% of the mean C max provided by the same quantity of amantadine or a pharmaceutically acceptable salt thereof in an immediate release form, and
wherein the mean C max of the pharmaceutical composition comprising about 258 mg of amantadine free base equivalent after a single-dose administration is between about 95% and about 250% of the mean C max provided by the same quantity of amantadine or a pharmaceutically acceptable salt thereof in an immediate release form.
14. The method of claim 13 , wherein the mean C max of the pharmaceutical composition comprising about 129 mg of amantadine free base equivalent after a single-dose administration is between about 75% and about 100% of the mean C max provided by the same quantity of amantadine or a pharmaceutically acceptable salt thereof in an immediate release form.
15. The method of claim 13 , wherein the mean C max of the pharmaceutical composition comprising about 129 mg of amantadine free base equivalent after a single-dose administration is between about 200 and about 500 ng/mL.
16. The method of claim 15 , wherein the mean C max of the pharmaceutical composition comprising about 129 mg of amantadine free base equivalent after a single-dose administration is between about 265 and about 390 ng/mL.
17. The method of claim 13 , wherein the mean C max of the pharmaceutical composition comprising about 193 mg of amantadine free base equivalent after a single-dose administration is between about 100% and about 125% of the mean C max provided by the same quantity of amantadine or a pharmaceutically acceptable salt thereof in an immediate release form.
18. The method of claim 13 , wherein the mean C max of the pharmaceutical composition comprising about 193 mg of amantadine free base equivalent after a single-dose administration is between about 200 and about 700 ng/mL.
19. The method of claim 18 , wherein the mean C max of the pharmaceutical composition comprising about 193 mg of amantadine free base equivalent after a single-dose administration is between about 370 and about 550 ng/mL.
20. The method of claim 13 , wherein the mean C max of the pharmaceutical composition comprising about 258 mg of amantadine free base equivalent after a single-dose administration is between about 150% and about 175% of the mean C max provided by the same quantity of amantadine or a pharmaceutically acceptable salt thereof in an immediate release form.
21. The method of claim 13 , wherein the mean C max of the pharmaceutical composition comprising about 258 mg of amantadine free base equivalent after a single-dose administration is between about 400 and about 1,000 ng/mL.
22. The method of claim 21 , wherein the mean C max of the pharmaceutical composition comprising about 258 mg of amantadine free base equivalent after a single-dose administration is between about 540 and about 895 ng/mL.
23. A method of treating Parkinson's disease in a patient, comprising:
i) administering to the patient once daily in the morning a pharmaceutical composition comprising about 129 mg of amantadine free base equivalent for about one week;
ii) increasing the dose of amantadine by administering to the patient once daily in the morning a pharmaceutical composition comprising about 193 mg of amantadine free base equivalent for at least one week;
iii) increasing the dose of amantadine by administering to the patient once daily in the morning a pharmaceutical composition comprising about 258 mg of amantadine free base equivalent;
wherein each of the pharmaceutical compositions comprises i) an extended release component comprising amantadine free base equivalent; and ii) an immediate release component comprising about 48 mg of amantadine free base equivalent,
wherein each of the pharmaceutical compositions is a solid oral dosage form,
wherein the maximum daily dose of amantadine is about 322 mg of amantadine free base equivalent,
wherein the mean AUC 0-∞ of the pharmaceutical composition comprising about 129 mg of amantadine free base equivalent after a single-dose administration is between 65% and about 135% the mean AUC 0-∞ provided by the same quantity of amantadine or a pharmaceutically acceptable salt thereof in an immediate release form,
wherein the mean AUC 0-∞ of the pharmaceutical composition comprising about 193 mg of amantadine free base equivalent after a single-dose administration is between 85% and about 225% the mean AUC 0-∞ provided by the same quantity of amantadine or a pharmaceutically acceptable salt thereof in an immediate release form, and
wherein the mean AUC 0-∞ of the pharmaceutical composition comprising about 258 mg of amantadine free base equivalent after a single-dose administration is between about 130% and about 290% of the mean AUC 0-∞ provided by the same quantity of amantadine or a pharmaceutically acceptable salt thereof in an immediate release form.
24. The method of claim 23 , wherein the mean AUC 0-∞ of the pharmaceutical composition comprising about 129 mg of amantadine free base equivalent after a single-dose administration is between about 90% and about 110% of the mean AUC 0-∞ provided by the same quantity of amantadine or a pharmaceutically acceptable salt thereof in an immediate release form.
25. The method of claim 23 , wherein the mean AUC 0-∞ of the pharmaceutical composition comprising about 129 mg of amantadine free base equivalent after a single-dose administration is between about 6,000 and about 12,000 ng·h/mL.
26. The method of claim 23 wherein the mean AUC 0-∞ of the pharmaceutical composition comprising about 193 mg of amantadine free base equivalent after a single-dose administration is between about 130% and about 180% of the mean AUC 0-∞ provided by the same quantity of amantadine or a pharmaceutically acceptable salt thereof in an immediate release form.
27. The method of claim 23 , wherein the mean AUC 0-∞ of the pharmaceutical composition comprising about 193 mg of amantadine free base equivalent after a single-dose administration is between about 8,000 and about 20,000 ng·h/mL.
28. The method of claim 23 , wherein the mean AUC 0-∞ of the pharmaceutical composition comprising about 258 mg of amantadine free base equivalent after a single-dose administration is between about 175% and about 225% of the mean AUC 0-∞ provided by the same quantity of amantadine or a pharmaceutically acceptable salt thereof in an immediate release form.
29. The method of claim 23 , wherein the mean AUC 0-∞ of the pharmaceutical composition comprising about 258 mg of amantadine free base equivalent after a single-dose administration is between about 12,000 and about 26,000 ng·h/mL.