# US 10,500,172 B2 · Composition and method for treating neurological disease > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,500,172 B2 - Document ID: US10500172B2 - Status: Granted - Kind: B2 - Application number: 16/250,686 - Filed: 2019-01-17 - Published: 2019-08-15 - Granted: 2019-12-10 - Earliest claimed: 2018-02-15 - Assignees: Osmotica Kereskedelmi és Szolgáltató Korlátolt Felelõsségû Társaság - Applicants: Osmotica Kereskedelmi és Szolgáltató Korlátolt Felelõsségû Társaság - Inventors: Glenn A. Meyer; Joaquina Faour; Ana Cristina Pastini; Marcelo Fernando Befumo - Web page: https://patentgrep.com/patent/US10500172B2 ## CPC - A61K 31/13: Amines {(A61K31/04 takes precedence)} - A61K 9/0004: {Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas} - A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration} - A61K 9/20: Pills, tablets, {discs, rods (A61K9/0004, A61K9/0007, A61K9/0056, A61K9/0065 take precedence; for reconstitution of a drink A61K9/0095)} - A61K 9/209: {containing drug in at least two layers or in the core and in at least one outer layer} - A61P 25/14: for treating abnormal movements, e.g. chorea, dyskinesia - A61P 25/16: Anti-Parkinson drugs - A61K 9/2072: {characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms (A61K9/0004, A61K9/0056, A61K9/0065 take precedence)} - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## 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. ## Claims ### Claim 1 A method of treating a drug-induced extrapyramidal reaction in an adult 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 Cmax 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 Cmax provided by the same quantity of amantadine or a pharmaceutically acceptable salt thereof in an immediate release form; and wherein the mean Cmax 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 Cmax provided by the same quantity of amantadine or a pharmaceutically acceptable salt thereof in an immediate release form. ### Claim 2 (depends on 1) The method of claim 1, wherein the mean Cmax 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 Cmax provided by the same quantity of amantadine or a pharmaceutically acceptable salt thereof in an immediate release form. ### Claim 3 (depends on 1) The method of claim 1, wherein the mean Cmax 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. ### Claim 4 (depends on 3) The method of claim 3, wherein the mean Cmax 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. ### Claim 5 (depends on 1) The method of claim 1, wherein the mean Cmax 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 Cmax provided by the same quantity of amantadine or a pharmaceutically acceptable salt thereof in an immediate release form. ### Claim 6 (depends on 1) The method of claim 1, wherein the mean Cmax 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. ### Claim 7 (depends on 6) The method of claim 6, wherein the mean Cmax 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. ### Claim 8 A method of treating a drug-induced extrapyramidal reaction in an adult 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 AUC0-∞ 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 AUC0-∞ provided by the same quantity of amantadine or a pharmaceutically acceptable salt thereof in an immediate release form, and wherein the mean AUC0-∞ 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 AUC0-∞ provided by the same quantity of amantadine or a pharmaceutically acceptable salt thereof in an immediate release form. ### Claim 9 (depends on 8) The method of claim 8, wherein the mean AUC0-∞ 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 AUC0-∞ provided by the same quantity of amantadine or a pharmaceutically acceptable salt thereof in an immediate release form. ### Claim 10 (depends on 8) The method of claim 8, wherein the mean AUC0-∞ 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. ### Claim 11 (depends on 8) The method of claim 8, wherein the mean AUC0-∞ 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 AUC0-∞ provided by the same quantity of amantadine or a pharmaceutically acceptable salt thereof in an immediate release form. ### Claim 12 (depends on 8) The method of claim 8, wherein the mean AUC0-∞ 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. ### Claim 13 A method of treating a drug-induced extrapyramidal reaction in an adult 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 Cmax 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 Cmax provided by the same quantity of amantadine or a pharmaceutically acceptable salt thereof in an immediate release form, wherein the mean Cmax 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 Cmax provided by the same quantity of amantadine or a pharmaceutically acceptable salt thereof in an immediate release form, and wherein the mean Cmax 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 Cmax provided by the same quantity of amantadine or a pharmaceutically acceptable salt thereof in an immediate release form. ### Claim 14 (depends on 13) The method of claim 13, wherein the mean Cmax 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 Cmax provided by the same quantity of amantadine or a pharmaceutically acceptable salt thereof in an immediate release form. ### Claim 15 (depends on 13) The method of claim 13, wherein the mean Cmax 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. ### Claim 16 (depends on 15) The method of claim 15, wherein the mean Cmax 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. ### Claim 17 (depends on 13) The method of claim 13, wherein the mean Cmax 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 Cmax provided by the same quantity of amantadine or a pharmaceutically acceptable salt thereof in an immediate release form. ### Claim 18 (depends on 13) The method of claim 13, wherein the mean Cmax 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. ### Claim 19 (depends on 18) The method of claim 18, wherein the mean Cmax 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. ### Claim 20 (depends on 13) The method of claim 13, wherein the mean Cmax 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 Cmax provided by the same quantity of amantadine or a pharmaceutically acceptable salt thereof in an immediate release form. ### Claim 21 (depends on 13) The method of claim 13, wherein the mean Cmax 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. ### Claim 22 (depends on 21) The method of claim 21, wherein the mean Cmax 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. ### Claim 23 A method of treating a drug-induced extrapyramidal reaction in an adult 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 AUC0-∞ 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 AUC0-∞ provided by the same quantity of amantadine or a pharmaceutically acceptable salt thereof in an immediate release form, wherein the mean AUC0-∞ 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 AUC0-∞ provided by the same quantity of amantadine or a pharmaceutically acceptable salt thereof in an immediate release form, and wherein the mean AUC0-∞ 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 AUC0-∞ provided by the same quantity of amantadine or a pharmaceutically acceptable salt thereof in an immediate release form. ### Claim 24 (depends on 23) The method of claim 23, wherein the mean AUC0-∞ 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 AUC0-∞ provided by the same quantity of amantadine or a pharmaceutically acceptable salt thereof in an immediate release form. ### Claim 25 (depends on 23) The method of claim 23, wherein the mean AUC0-∞ 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. ### Claim 26 (depends on 23) The method of claim 23 wherein the mean AUC0-∞ 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 AUC0-∞ provided by the same quantity of amantadine or a pharmaceutically acceptable salt thereof in an immediate release form. ### Claim 27 (depends on 23) The method of claim 23, wherein the mean AUC0-∞ 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. ### Claim 28 (depends on 23) The method of claim 23, wherein the mean AUC0-∞ 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 AUC0-∞ provided by the same quantity of amantadine or a pharmaceutically acceptable salt thereof in an immediate release form. ### Claim 29 (depends on 23) The method of claim 23, wherein the mean AUC0-∞ 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.