NK-1 antagonist compositions and methods for use in treating depression
Inventors
Chase, Thomas N. • Clarence-Smith, Kathleen E.
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11813247-B2
Publication Date
2023-11-14
Expiration Date
Abstract
The present invention describes the combination of a NK1-antagonist with pramipexole or a pharmaceutically acceptable salt or solvate thereof, useful for treating depressive disorders, including major depressive disorder.
Core Innovation
The patent describes a pharmaceutical combination for use in treating depressive disorders by combining an NK1-antagonist with pramipexole. The combination includes an NK1-antagonist in a dosage unit form and pramipexole, or a pharmaceutically acceptable salt or solvate thereof, in a dosage unit form, both admixed with a pharmaceutical carrier or vehicle. The NK1-antagonist is characterized as being an amount per unit form of from 1 mg to 600 mg, and pramipexole is characterized as being an amount per unit form equivalent to from 0.125 mg to 21 mg of pramipexole dihydrochloride monohydrate.
The disclosed concept includes specific NK1-antagonist examples such as aprepitant, fosaprepitant, rolapitant, and netupitant. The patent further supports that the NK1-antagonist can be used as an adverse-effect inhibitor to enable safe administration of pramipexole at higher doses than pramipexole would be administered alone, including up to about 10× above a PD motor-symptom–recommended maximum and possibly above the maximal tolerated dose when pramipexole is given alone. An illustrative Phase I study is described in which co-administration of aprepitant attenuates pramipexole gastrointestinal dose-limiting adverse events and increases the maximum tolerated dose compared with dosing pramipexole alone.
The document also describes formulation and dosing concepts for the combination, including fixed-dose versus separate administration, and different pramipexole formulation types such as immediate release, extended release, and transdermal therapeutic system. It provides extensive support for dosing ranges and pramipexole dosage ranges stated as pramipexole-equivalent values, including ranges of greater than about 4.5 mg to 21 mg/day and up to about 45 mg/day, and for NK1-antagonist dosage ranges, including the aprepitant sub-range.
Claims Coverage
The coverage centers on a single independent claim directed to an NK1-antagonist plus pramipexole pharmaceutical combination in dosage unit form, specifying the component dosage ranges and admixture with a pharmaceutical carrier or vehicle. Dependent claims refine the independent claim by further constraining dosage sub-ranges and by specifying aprepitant as the NK1-antagonist.
Nk1-antagonist plus pramipexole unit-dose admixture
A pharmaceutical combination comprising a NK1-antagonist in dosage unit form in an amount per unit form of from 1 mg to 600 mg, in admixture with a pharmaceutical carrier or vehicle, and pramipexole or a pharmaceutically acceptable salt or solvate thereof in an amount per unit form equivalent to from 0.125 mg to 21 mg of pramipexole dihydrochloride monohydrate.
Fixed-dose dosage unit composition for both components
A fixed-dose pharmaceutical combination in which both the NK1-antagonist and pramipexole, or a pharmaceutically acceptable salt or solvate, are present in dosage unit amounts and admixed with a pharmaceutical carrier or vehicle.
Aprepitant as the nk1-antagonist with defined unit dosage
The combination where the NK1-antagonist is aprepitant and is administered in a unit amount ranging from 10 mg to 250 mg.
Across the independent claim and its dependents, the inventive coverage is the unit-dose pharmaceutical combination of an NK1-antagonist and pramipexole, with component admixture to a pharmaceutical carrier or vehicle and defined per-unit dosage ranges, further narrowed by pramipexole sub-ranges and by specifying aprepitant within a defined NK1-antagonist unit dosage interval.
Stated Advantages
Attenuates pramipexole gastrointestinal dose-limiting adverse events when co-administered with an NK1-antagonist (aprepitant).
Increases maximum tolerated dose compared with pramipexole dosed alone.
Documented Applications
Treatment of depressive disorders, including major depressive disorder, using an NK1-antagonist combined with pramipexole.
An illustrative Phase I study of aprepitant co-administration with pramipexole to assess attenuation of gastrointestinal dose-limiting adverse events and effects on maximum tolerated dose.
Interested in licensing this patent?