Claims for Patent: 10,512,617

Summary for Patent: 10,512,617

Title:	Composition and method for treating neurological disease
Abstract:	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.
Inventor(s):	Meyer; Glenn A. (Wilmington, NC), Faour; Joaquina (Ciudad Autonoma de Buenos Aires, AR), Pastini; Ana Cristina (Ciudad Autonoma de Buenos Aires, AR), Befumo; Marcelo Fernando (Ciudad Autonoma de Buenos Aires, AR)
Assignee:	Osmotica Kereskedelmi es Szolgaltato Korlatolt Felelossegu Tarsasag (Budapest, HU)
Application Number:	16/250,608
Patent Claims:	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.sub.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.sub.max provided by the same quantity of amantadine or a pharmaceutically acceptable salt thereof in an immediate release form; and wherein the mean C.sub.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.sub.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.sub.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.sub.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.sub.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.sub.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.sub.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.sub.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.sub.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.sub.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.sub.0-.infin. 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.sub.0-.infin. provided by the same quantity of amantadine or a pharmaceutically acceptable salt thereof in an immediate release form, and wherein the mean AUC.sub.0-.infin. 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.sub.0-.infin. 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.sub.0-.infin. 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.sub.0-.infin. 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.sub.0-.infin. 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 ngh/mL. 11. The method of claim 8, wherein the mean AUC.sub.0-.infin. 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.sub.0-.infin. 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.sub.0-.infin. 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 ngh/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.sub.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.sub.max provided by the same quantity of amantadine or a pharmaceutically acceptable salt thereof in an immediate release form, wherein the mean C.sub.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.sub.max provided by the same quantity of amantadine or a pharmaceutically acceptable salt thereof in an immediate release form, and wherein the mean C.sub.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.sub.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.sub.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.sub.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.sub.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.sub.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.sub.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.sub.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.sub.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.sub.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.sub.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.sub.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.sub.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.sub.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.sub.0-.infin. 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.sub.0-.infin. provided by the same quantity of amantadine or a pharmaceutically acceptable salt thereof in an immediate release form, wherein the mean AUC.sub.0-.infin. 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.sub.0-.infin. provided by the same quantity of amantadine or a pharmaceutically acceptable salt thereof in an immediate release form, and wherein the mean AUC.sub.0-.infin. 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.sub.0-.infin. 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.sub.0-.infin. 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.sub.0-.infin. 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.sub.0-.infin. 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 ngh/mL. 26. The method of claim 23 wherein the mean AUC.sub.0-.infin. 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.sub.0-.infin. 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.sub.0-.infin. 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 ngh/mL. 28. The method of claim 23, wherein the mean AUC.sub.0-.infin. 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.sub.0-.infin. 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.sub.0-.infin. 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 ngh/mL.