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-10500171-B2
Publication Date
2019-12-10
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 provides a method of treating a drug-induced extrapyramidal reaction in an adult patient by administering a pharmaceutical composition that includes amantadine in an extended release form and amantadine in an immediate release form together with an osmotic agent. The composition comprises 258 mg of amantadine free base equivalent and an osmotic device having a semipermeable membrane.
The composition is structured to provide pharmacokinetic exposure relative to the same daily quantity of amantadine provided in an immediate release form. In related aspects, the mean steady-state Cavg of the composition is at least 95% of the mean steady-state Cavg provided by the immediate release form, or the steady-state AUC0-24 is at least 95% of the steady-state AUC0-24 provided by the same daily quantity in immediate release form.
Additional aspects include steady-state Cmax being comparable to the steady-state Cmax provided by the same daily quantity in immediate release form, steady-state being achieved by about Day 6, and plasma concentration at steady state being at least 85% of the concentration provided by the same daily quantity in an immediate release form. Additional plasma concentration constraints include a steady-state plasma concentration between about 609 and about 662 ng/mL.
Claims Coverage
The partial content includes four independent claims for treatment of drug-induced extrapyramidal reaction in an adult, with a shared inventive concept: an osmotic-agent-containing pharmaceutical composition combining extended-release amantadine or salt and immediate-release amantadine or salt, specifying 258 mg amantadine free base equivalent and pharmacokinetic performance relationships to immediate release dosing.
Osmotic agent with extended release plus immediate release amantadine at 258 mg free base equivalent and Cavg exposure equivalence
Administering to an adult patient a pharmaceutical composition comprising an osmotic agent and amantadine or a pharmaceutically acceptable salt thereof in an extended release form, and amantadine or a pharmaceutically acceptable salt thereof in an immediate release form; the composition comprises 258 mg of amantadine free base equivalent; and the mean steady-state Cavg of the composition is at least 95% of the mean steady-state Cavg provided by the same daily quantity in an immediate release form.
Osmotic agent with extended release plus immediate release amantadine at 258 mg free base equivalent and AUC0-24 exposure equivalence
Administering to an adult patient a pharmaceutical composition comprising an osmotic agent and amantadine or a pharmaceutically acceptable salt thereof in an extended release form, and amantadine or a pharmaceutically acceptable salt thereof in an immediate release form; the composition comprises 258 mg of amantadine free base equivalent; and the steady-state AUC0-24 for the composition is at least 95% of the steady-state AUC0-24 provided by the same daily quantity in an immediate release form.
Osmotic agent with extended release plus immediate release amantadine at 258 mg free base equivalent and steady-state Cmax comparability
Administering to an adult patient a pharmaceutical composition comprising an osmotic agent and amantadine or a pharmaceutically acceptable salt thereof in an extended release form, and amantadine or a pharmaceutically acceptable salt thereof in an immediate release form; the composition comprises 258 mg of amantadine free base equivalent; and the steady-state Cmax of the composition is comparable to the steady-state Cmax provided by the same daily quantity in an immediate release form.
Osmotic agent with extended release plus immediate release amantadine at 258 mg free base equivalent and steady-state by about day 6
Administering to an adult patient a pharmaceutical composition comprising an osmotic agent and amantadine or a pharmaceutically acceptable salt thereof in an extended release form, and amantadine or a pharmaceutically acceptable salt thereof in an immediate release form; the composition comprises 258 mg of amantadine free base equivalent; and steady-state is achieved by about Day 6.
Across the independent claims, the coverage is directed to adult treatment of drug-induced extrapyramidal reaction using an osmotic-agent-containing composition that combines an extended release amantadine component with an immediate release amantadine component, specifies 258 mg of amantadine free base equivalent, and requires either Cavg exposure equivalence, AUC0-24 exposure equivalence, Cmax comparability, or attainment of steady-state by about Day 6.
Stated Advantages
Provides mean steady-state Cavg that is at least 95% of mean steady-state Cavg provided by the same daily quantity of immediate release amantadine or salt.
Provides steady-state AUC0-24 that is at least 95% of steady-state AUC0-24 provided by the same daily quantity of immediate release amantadine or salt.
Provides steady-state Cmax that is comparable to steady-state Cmax provided by the same daily quantity of immediate release amantadine or salt.
Achieves steady-state by about Day 6.
Documented Applications
Treating a drug-induced extrapyramidal reaction in an adult patient.
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