Authors: Jaclyn A. Smith, Michael M. Kitt, Peter Butera, Steven A. Smith, Yuping Li, Zhi Jin Xu, Kimberley Holt, Shilpi Sen, Mandel R. Sher, Anthony P. Ford
Published: 2020-01-16
DOI: 10.1183/13993003.01615-2019
Source: Full article
Background and objectivesGefapixant 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 methodsTwo 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.ResultsIn 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.ConclusionsP2X3 antagonism with gefapixant demonstrates anti-tussive efficacy and improved tolerability at lower doses than previously investigated. Studies of longer duration are warranted.