We evaluated the effect of
gefapixant on
cough reflex sensitivity to evoked tussive challenge.In this phase 2, double-blind, two-period study, patients with
chronic cough (CC) and healthy volunteers (HV) were randomised to single-dose
gefapixant 100 mg or placebo in a crossover fashion. Sequential inhalational challenges with
ATP,
citric acid,
capsaicin and distilled water were performed 1, 3 and 5 h after dosing. Mean concentrations evoking ≥2
coughs (C2) and ≥5
coughs (C5) post dose versus baseline were co-primary endpoints. Objective
cough frequency (coughs·h-1) over 24 h and a
cough severity visual analogue scale (VAS) were assessed in CC patients. Adverse events were monitored.24 CC patients and 12 HV were randomised (mean age 61 and 38 years, respectively). The
cough challenge threshold increased for
ATP by 4.7-fold (C2, p≤0.001) and 3.7-fold (C5, p=0.007) for
gefapixant versus placebo in CC patients; in HV, C2 and C5 increased 2.4-fold (C2, p=0.113; C5, p=0.003). The distilled water C2 and C5 thresholds increased significantly (p<0.001) by
a factor of 1.4 and 1.3, respectively, in CC patients.
Gefapixant had no effect on
capsaicin or
citric acid challenge. Median
cough frequency was reduced by 42% and the least squares mean
cough severity VAS was 18.0 mm lower for
gefapixant versus placebo in CC patients.
Dysgeusia was the most frequent adverse event (75% of HV and 67% of CC patients).
ATP-evoked
cough was significantly inhibited by
gefapixant 100 mg, demonstrating peripheral target engagement.
Cough count and severity were reduced in CC patients. Distilled water may also evoke
cough through a purinergic pathway.