Composition and method for treating neurological disease
Inventors
Meyer, Glenn A. • Faour, Joaquina • Pastini, Ana Cristina • Befumo, Marcelo Fernando
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-10500170-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 pharmaceutical composition and method of treating Parkinson’s disease by administering amantadine in an extended release form together with amantadine in an immediate release form. The composition comprises 258 mg of amantadine free base equivalent and includes an osmotic agent, with pharmacokinetic exposure from the extended and immediate release combination meeting defined steady-state performance criteria relative to the same daily quantity of immediate-release amantadine.
The extended release component is implemented using an osmotic device that includes a semipermeable membrane. The disclosed formulation concept includes an osmotic pump system, a core and immediate-release layer, and an optional osmotic-orifice feature, including a laser-drilled orifice, to support controlled extended release.
The disclosed system targets extended-release absorption behavior and steady-state parameters, including mean steady-state Cavg comparisons, steady-state AUC0-24 comparisons, and steady-state Cmax comparability to immediate-release exposure provided by the same daily quantity. Steady-state is described as being achieved by about Day 6, and the document further reports that clinical outcomes for levodopa-induced dyskinesia are assessed using UDysRS and UDysRS-based measures, including reductions versus placebo and increased awake ON hours without troublesome dyskinesia.
Claims Coverage
The independent claims are clm-00001, clm-00007, clm-00013, and clm-00018, each directed to treating Parkinson’s disease by administering a combined extended-release and immediate-release amantadine composition in a defined amount and requiring specific pharmacokinetic performance conditions measured at steady state. In total, four inventive features are expressed across the independent claims.
Osmotic-agent extended release plus immediate release amantadine for Parkinson’s disease with Cavg equivalence
A method of treating Parkinson's disease comprising administering a pharmaceutical composition comprising an osmotic agent and amantadine in an extended release form and amantadine in an immediate release form, wherein 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 extended release plus immediate release amantadine for Parkinson’s disease with AUC0-24 equivalence
A method of treating Parkinson's disease comprising administering a pharmaceutical composition comprising an osmotic agent and amantadine in an extended release form and amantadine in an immediate release form, wherein 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 extended release plus immediate release amantadine for Parkinson’s disease with comparable Cmax
A method of treating Parkinson's disease comprising administering a pharmaceutical composition comprising an osmotic agent and amantadine in an extended release form and amantadine in an immediate release form, wherein 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 extended release plus immediate release amantadine for Parkinson’s disease with Day 6 steady state
A method of treating Parkinson's disease comprising administering a pharmaceutical composition comprising an osmotic agent and amantadine in an extended release form and amantadine in an immediate release form, wherein the composition comprises 258 mg of amantadine free base equivalent and steady-state is achieved by about Day 6.
Across the independent claims, the core coverage centers on administering a combined osmotic-agent extended-release and immediate-release amantadine composition totaling 258 mg amantadine free base equivalent to treat Parkinson’s disease, while meeting specific steady-state pharmacokinetic requirements. Dependent claims further specify structural and performance refinements, including osmotic device features such as a semipermeable membrane and quantitative exposure thresholds.
Stated Advantages
Reported reductions versus placebo in UDysRS/UDysRS outcomes for levodopa-induced dyskinesia.
Increases in awake ON hours without troublesome dyskinesia.
Documented Applications
Treating Parkinson’s disease in a patient using a pharmaceutical composition comprising osmotic-agent extended release amantadine with an immediate release amantadine component.
Treating levodopa-induced dyskinesia, assessed using UDysRS/UDysRS measures, including reductions versus placebo and increased awake ON hours without troublesome dyskinesia.
Planned or outlined treatment of drug-induced extrapyramidal reactions using symptom rating scales (SAS, BARS, AIMS, ESRS) [procedural detail omitted for safety].
Interested in licensing this patent?