Safety and efficacy of P2X3 antagonist BAY 1902607 in refractory chronic cough

Abstract

Background: ATP activates purinergic P2X receptors and is considered an important mediator in refractory chronic cough (RCC). We report a Phase 2a trial of BAY 1902607, a P2X3 receptor antagonist with high selectivity, in RCC. Methods: This double-blind, placebo-controlled, randomized study included a two-way crossover of oral BAY 1902607 (20, 80, 150, or 250 mg BID, 4 days each) and placebo BID in adult non-smokers with RCC lasting for ≥1 year (NCT03535168). The primary endpoints were VitaloJak-monitored 24-hour cough frequency and frequency/severity of AEs; other endpoints included cough severity measured by VAS at baseline and in each dosing period. Results: 23 patients were randomized (female, n=18 [78%]; Caucasian, n=22 [96%]; median [range] age: 60 [43–77] years; never-smokers, n=14 [61%]). BAY 1902607 doses ≥80 mg significantly decreased geometric mean 24-hour cough counts per hour vs placebo after 4 days of treatment: 80 mg, 17% (p=0.015); 150 mg, 28% (p Conclusions: BAY 1902607 significantly reduced 24-hour cough frequency and severity at doses ≥80 mg. Despite high P2X3 receptor selectivity of BAY 1902607, dose-related AEs of taste disturbance were observed in many patients.