NK-1 antagonist compositions and methods for use in treating depression
Inventors
Chase, Thomas N. • Clarence-Smith, Kathleen E.
Assignees
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Publication Number
US-11266633-B2
Publication Date
2022-03-08
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 disclosure relates to treating a depressive disorder, including major depressive disorder (MDD), by administering an NK1-receptor antagonist together with pramipexole, or a pharmaceutically acceptable salt or solvate of pramipexole. The treatment is carried out by administering an effective daily dose of the NK1-antagonist in combination with an effective daily dose of pramipexole.
The disclosure addresses limitations associated with pramipexole dosing in the treatment of depression by extending the therapeutic window of pramipexole. By co-administering an NK1 antagonist, the disclosure permits substantially higher pramipexole daily doses in depression while reducing dose-limiting adverse effects, particularly gastrointestinal dose-limiting toxicity.
The disclosure further describes that the combination can be administered as separate or fixed-dose combinations, including immediate release or extended release formulations, and includes transdermal therapeutic systems. A Phase I study is described in which co-administration of aprepitant increased the maximum tolerated pramipexole dose and attenuated gastrointestinal dose-limiting toxicity.
Claims Coverage
Independent claim coverage centers on daily treatment of depressive disorders using an NK1-antagonist together with pramipexole, with dependent claims refining the inventive concept through example NK1-antagonists, daily dose ranges for both actives, and formulation options.
Daily administration of NK1-antagonist with pramipexole for depressive disorders
A method for treating a depressive disorder in a patient by administering an effective daily dose of an NK1-antagonist in combination with an effective daily dose of pramipexole or a pharmaceutically acceptable salt or solvate thereof.
Aprepitant as the NK1-antagonist
The method wherein the NK1-antagonist is aprepitant or a pharmaceutically acceptable salt or solvate thereof.
Pramipexole dose expressed as equivalence to pramipexole dihydrochloride monohydrate
The method wherein the effective daily dose of pramipexole or a pharmaceutically acceptable salt or solvate thereof in the combination is equivalent to 0.375 mg to 45 mg of pramipexole dihydrochloride monohydrate.
NK1-antagonist daily dose constraint
The method wherein the NK1-antagonist effective daily dose in the combination is within 1 μg to 600 mg.
Co-formulated unit-dose pharmaceutical composition with carrier or vehicle
The method wherein an NK1-antagonist and pramipexole or a pharmaceutically acceptable salt thereof are co-formulated as a dosage-unit pharmaceutical composition with specified per-unit amounts and mixed with a pharmaceutical carrier or vehicle.
Separate dosage-unit pharmaceutical compositions for each active
The method wherein both the NK1-antagonist and pramipexole or a pharmaceutically acceptable salt or solvate are formulated as separate dosage-unit pharmaceutical compositions in admixture with a pharmaceutical carrier or vehicle.
The claims focus on administering an NK1-antagonist with pramipexole for depressive disorders, including aprepitant embodiments, specified daily dose ranges for both actives, and co-formulated or separate dosage-unit compositions.
Stated Advantages
Inhibiting or attenuating dose-limiting adverse effects of pramipexole, particularly gastrointestinal dose-limiting toxicity.
Extending the therapeutic window of pramipexole to permit substantially higher pramipexole daily doses in depression.
Enabling full antidepressant efficacy by permitting higher pramipexole exposure while reducing dose-limiting adverse effects.
Documented Applications
Treatment of depressive disorders, including major depressive disorder (MDD), in a patient using an NK1-antagonist in combination with pramipexole.
A Phase I study showing that aprepitant co-administration increased maximum tolerated pramipexole dose and attenuated gastrointestinal dose-limiting toxicity.
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