Clinical Formulation Bridging of Gefapixant, a P2X3-Receptor Antagonist, for the Treatment of Chronic Cough.

ABSTRACT: Gefapixant is a P2X3-receptor antagonist being developed for treatment of refractory or unexplained chronic cough. Four phase 1 studies were conducted in healthy participants that bridged the early-phase gefapixant formulation (F01) to the phase 3 (F04A) and intended commercial (F04B) formulations. In addition, food and proton pump inhibitor (PPI) coadministration effects on gefapixant exposure were assessed. The gefapixant free base formulation (F01) was used in the initial early-phase clinical studies. Adding citric acid to the F01 formulation (to generate F02) enhanced drug solubilization, resulting in similar bioavailability and mitigating food and gastric pH effects. The subsequently developed gefapixant citrate salt formulation (F04) achieved exposures that were comparable to F02 in

SUBMITTER: Gupta P 

PROVIDER: S-EPMC9540877 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature