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Background  The purinoceptor subtype P2X 3  has been shown to have significant involvement in the cough reflex; the heterotrimer version of the purinoceptor (P2X 2/3 ) has been implicated in taste disturbance. The most advanced clinical candidate antagonist gefapixant has low selectivity among P2X 3  receptors and induced taste disturbance, whereas newly developed sivopixant has high selectivity towards P2X 3  versus  P2X 2/3 .    Methods  In a phase 2a, randomised, double-blind, placebo-controlled, crossover, multicentre study, adult patients with refractory or unexplained chronic cough received oral sivopixant 150 mg or placebo once daily for 2 weeks, followed by a 2–3-week washout period, and then crossed over to placebo or sivopixant for 2 weeks. Efficacy and safety of sivopixant were evaluated.    Results  Of 31 randomised patients, 15 in the sivopixant-first group and 15 in the placebo-first group completed the study. After 2 weeks’ treatment, the placebo-adjusted ratios of the average hourly number of coughs to baseline during daytime (primary endpoint) and over 24 h (secondary endpoint) were −31.6% (p=0.0546) and −30.9% (p=0.0386), respectively. Sivopixant also improved health-related quality of life. Treatment-related adverse events occurred in 12.9% and 3.2% of patients during sivopixant and placebo administration, respectively. Mild taste disturbance occurred in two patients (6.5%) during sivopixant administration.    Conclusions  Sivopixant reduced objective cough frequency and improved health-related quality of life, with a low incidence of taste disturbance, among patients with refractory or unexplained chronic cough.

Randomised trial of the P2X3 receptor antagonist sivopixant for refractory chronic cough

Randomised trial of the P2X₃ receptor antagonist sivopixant for refractory chronic cough