Physics

Internal medicine

Pathology

Adverse effect

Placebo

Crossover study

Refractory (planetary science)

Asthma

Alternative medicine

Chronic cough

Tolerability

Ambulatory

Anesthesia

Medicine

Astrobiology

European Respiratory Journal

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&lt;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.

Gefapixant in two randomised dose-escalation studies in chronic cough