Composition and method for treating neurological disease
Inventors
Meyer, Glenn A. • Faour, Joaquina • Pastini, Ana Cristina • Befumo, Marcelo Fernando
Assignees
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Publication Number
US-11890261-B2
Publication Date
2024-02-06
Expiration Date
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.
Core Innovation
The invention describes treating a drug-induced extrapyramidal reaction in an adult patient by administering a pharmaceutical composition that includes amantadine or a pharmaceutically acceptable salt in both an extended release form and an immediate release form. The composition is characterized by a specified amount of amantadine free base equivalent and by an in vitro dissolution profile measured using a USP type II paddle dissolution system under defined conditions.
The dissolution behavior is required to limit rapid release in ethanol-containing conditions by not dose dumping in ethanol solutions containing up to 40% ethanol. Different embodiments specify different total amantadine free base equivalent amounts and different time-dependent dissolution percentage thresholds, including profiles measured in ethanol solutions with 0.1N HCl.
The invention is positioned as a once-daily morning approach combining extended-release amantadine with immediate-release amantadine, for treating drug-induced extrapyramidal reactions and Parkinson’s disease related adverse manifestations. The document also reports clinical findings including improved levodopa-induced dyskinesia measured by change in Unified Dyskinesia Rating Scale and increased awake ON hours without troublesome dyskinesia, without meaningful worsening on MDS-UPDRS.
Claims Coverage
The independent claims are directed to methods of treating a drug-induced extrapyramidal reaction in an adult patient using a pharmaceutical composition that contains both extended-release and immediate-release amantadine, with each independent claim further limited by a specific amantadine free base equivalent amount and a specified in vitro dissolution profile that avoids dose dumping in ethanol solutions up to 40% ethanol. Three independent claims are present in the provided material.
Extended-release and immediate-release amantadine combination for drug-induced extrapyramidal reactions
A method of treating a drug-induced extrapyramidal reaction in an adult patient by administering a pharmaceutical composition comprising amantadine or a pharmaceutically acceptable salt in an extended release form and amantadine or a pharmaceutically acceptable salt in an immediate release form.
129 mg amantadine free base equivalent with ethanol/HCl USP paddle dissolution no dose dumping
The composition comprises about 129 mg of amantadine free base equivalent and has an in vitro dissolution profile of about 35% in about 30 minutes, about 35% in about 1 hour, about 40% in about 1.5 hours, and no more than about 45% in about 2 hours, as measured in 5% ethanol in 0.1N HCl using a USP type II paddle dissolution system, wherein the composition does not dose dump in ethanol solutions containing up to 40% ethanol.
193 mg amantadine free base equivalent with ethanol/HCl USP paddle dissolution no dose dumping
The composition comprises about 193 mg of amantadine free base equivalent and has an in vitro dissolution profile of about 25% in about 30 minutes, about 25% in about 1 hour, about 30% in about 1.5 hours, and no more than about 35% in about 2 hours, as measured in 5% ethanol in 0.1N HCl using a USP type II paddle dissolution system, wherein the composition does not dose dump in ethanol solutions containing up to 40% ethanol.
258 mg amantadine free base equivalent with ethanol/HCl USP paddle dissolution no dose dumping
The composition comprises about 258 mg of amantadine free base equivalent and has an in vitro dissolution profile of about 20% in about 30 minutes, about 25% in about 1 hour, about 30% in about 1.5 hours, and no more than about 45% in about 2 hours, as measured in 5% ethanol in 0.1N HCl using a USP type II paddle dissolution system, wherein the composition does not dose dump in ethanol solutions containing up to 40% ethanol.
Across the independent claims provided, the inventive concept is the administration of a pharmaceutical composition combining extended-release and immediate-release amantadine to treat drug-induced extrapyramidal reactions, together with specific amantadine free base equivalent amounts and defined USP type II paddle in vitro dissolution profiles measured in ethanol and 0.1N HCl that are required to avoid dose dumping in ethanol solutions up to 40% ethanol.
Stated Advantages
Improved levodopa-induced dyskinesia measured by change in Unified Dyskinesia Rating Scale.
Increased awake ON hours without troublesome dyskinesia.
No meaningful worsening on MDS-UPDRS.
Documented Applications
Treating Parkinson’s disease.
Treating drug-induced extrapyramidal reactions.
Treating levodopa-induced dyskinesia.
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