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-10213393-B1
Publication Date
2019-02-26
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 Parkinson’s disease in a patient by administering once daily in the morning a pharmaceutical composition comprising amantadine free base equivalent. The composition includes an extended release component and an immediate release component comprising about 48 mg of amantadine free base equivalent, and the pharmaceutical compositions are osmotic devices comprising an osmotic agent and an osmotic coating.
The treatment includes a dose escalation schedule with a first once-daily morning dose and subsequent increasing doses administered once daily in the morning. The method specifies dosing around about 129 mg of amantadine free base equivalent and increasing the dose to about 193 mg and, in some formulations, to about 258 mg, with a maximum daily dose of about 322 mg.
The pharmaceutical compositions provide a mean change in amantadine plasma concentration as a function of time (dC/dT) between about 40% and about 70% of the dC/dT provided by the same quantity of amantadine, or a pharmaceutically acceptable salt thereof, in an immediate release form. Additional formulations further constrain composition behavior using quantitative pharmacokinetic endpoints and dissolution performance under specified test conditions, and may include fed versus fasting relative bioavailability constraints.
Claims Coverage
The partial set includes four independent claims, all directed to treating Parkinson’s disease using once-daily morning osmotic extended-release plus immediate-release amantadine formulations with defined dosing and a mean dC/dT criterion relative to immediate release. Across the independent claims, the inventive features are consistent: ER and IR components in an osmotic device, specific amantadine free base equivalent amounts including about 48 mg in the immediate release component, a maximum daily dose of about 322 mg, and a dC/dT comparison measured in a single-dose human pharmacokinetic study over 0 to 4 hours.
Once daily morning osmotic amantadine ER/IR composition with osmotic agent and osmotic coating
The method administers once daily in the morning a pharmaceutical composition that is an osmotic device comprising an osmotic agent and an osmotic coating, where each composition comprises an extended release component comprising amantadine free base equivalent and an immediate release component comprising about 48 mg of amantadine free base equivalent.
Weekly dose escalation to specified amantadine free base equivalent amounts capped at maximum daily dose
The method includes administering a pharmaceutical composition comprising about 129 mg of amantadine free base equivalent for one week, then increasing the dose by administering once daily in the morning a pharmaceutical composition comprising about 193 mg of amantadine free base equivalent, and in another independent claim additional escalation to about 258 mg, with a maximum daily dose of about 322 mg of amantadine free base equivalent.
dC/dT criterion relative to immediate release in a 0 to 4 hour single-dose human PK study
Each pharmaceutical composition provides a mean change in amantadine plasma concentration as a function of time (dC/dT) that is between about 40% and about 70% of the dC/dT provided by the same quantity of amantadine, or a pharmaceutically acceptable salt thereof, in an immediate release form, wherein the dC/dT values are measured in a single dose human pharmacokinetic study over the time period between 0 and 4 hours after administration.
Consisting essentially of ER/IR components within osmotic device
In the variants using “consists essentially of,” each pharmaceutical composition consists essentially of an extended release component consisting essentially of amantadine free base equivalent and an immediate release component consisting essentially of about 48 mg of amantadine free base equivalent within an osmotic device comprising an osmotic agent and an osmotic coating, while maintaining the same maximum daily dose and dC/dT criterion.
Across the independent claims, the invention centers on a Parkinson’s disease treatment method using once-daily morning osmotic devices with an ER component and a defined immediate release component of about 48 mg, with weekly or staged dose escalation to a capped maximum daily dose of about 322 mg and a required mean dC/dT reduction of about 40% to about 70% of immediate release based on single-dose human PK measurements over 0 to 4 hours.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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