Gefapixant in two randomised dose-escalation studies in chronic cough

Background Gefapixant has previously demonstrated efficacy in the treatment refractory chronic cough at a high, daily dose. Objectives 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 endpoint 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 (VAS) and Cough Severity Diary (CSD). Results In clinical studies, gefapixant doses ≥30 mg produced maximal improvements in cough frequency compared with placebo (p Conclusions P2X3 antagonism with gefapixant demonstrates anti-tussive efficacy and improved tolerability at lower doses than previously investigated. Longer duration studies are warranted.