Gefapixant in two randomised dose-escalation studies in chronic cough

Abstract

Background and objectives: Gefapixant has previously demonstrated efficacy in the treatment of refractory chronic cough at a high daily dose. The current investigations explore efficacy and tolerability of gefapixant, a P2X3 receptor antagonist, for the treatment of chronic cough using a dose-escalation approach.

Materials and methods: Two randomised, double-blind, placebo-controlled, crossover, dose-escalation studies recruited participants with refractory chronic cough. Patients were assigned to receive ascending doses of gefapixant (study 1: 50-200 mg, study 2: 7.5-50 mg) or placebo for 16 days, then crossed-over after washout. The primary end-point was awake cough frequency assessed using a 24-h ambulatory cough monitor at baseline and on day 4 of each dose. Patient-reported outcomes included a cough severity visual analogue scale and the cough severity diary.

Results: In clinical studies, gefapixant doses ≥30 mg produced maximal improvements in cough frequency compared with placebo (p<0.05); reported cough severity measures improved at similar doses. Taste disturbance exhibited a different relationship with dose, apparently maximal at doses ≥150 mg.

Conclusions: P2X3 antagonism with gefapixant demonstrates anti-tussive efficacy and improved tolerability at lower doses than previously investigated. Studies of longer duration are warranted.

Conflict of interest statement

Conflict of interest: J.A. Smith reports research grants and personal fees for consultancy and advisory board work from Merck Inc., during the conduct of the study; research grants and personal fees for consultancy and advisory board work from GlaxoSmithKline, research grants and personal fees for consultancy from NeRRe Pharmaceuticals, Menlo, Bayer and Axalbion, personal fees for consultancy from Boehringer Ingleheim, Genentech, Neomed, Chiesi, Bellus and AstraZeneca, non-financial support (equipment provision) from Vitalograph, research grants from Afferent, outside the submitted work; in addition, has a patent “A method for generating output data” licensed. Conflict of interest: M.M. Kitt was an employee of Merck/Afferent, during the conduct of the study. Conflict of interest: P. Butera was an employee of Afferent Pharmaceuticals, Inc., during the conduct of the study. Conflict of interest: S.A. Smith reports personal fees for consultancy from Afferent Pharmaceuticals, during the conduct of the study. Conflict of interest: Y. Li reports personal fees for statistical work from Afferent/Merck and Co., Inc, during the conduct of the study. Conflict of interest: Z.J Xu has nothing to disclose. Conflict of interest: K. Holt has nothing to disclose. Conflict of interest: S. Sen has nothing to disclose. Conflict of interest: M.R. Sher reports personal fees from Afferent and Merck, during the conduct of the study; and is consultant to Bellus, Bayer, NeRRe with clinical studies with Menlo and NeRRe. Conflict of interest: A.P. Ford was an employee of Merck/Afferent, during the conduct of the study.

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