Abstract
BACKGROUND: ATP acting via P2X3 receptors is an important mediator of refractory chronic cough (RCC). This phase 2a double-blinded crossover study assessed the safety, tolerability and efficacy of eliapixant (BAY 1817080), a selective P2X3 receptor antagonist, in adults with RCC attending specialist centres. METHODS: In period A, patients received placebo for 2 weeks then eliapixant 10 mg for 1 week. In period B, patients received eliapixant 50, 200 and 750 mg twice daily for 1 week per dose level. Patients were randomised 1:1 to period A-B (n=20) or B-A (n=20). The primary efficacy end-point was change in cough frequency assessed over 24 h. The primary safety end-point was frequency and severity of adverse events (AEs). RESULTS: 37 patients completed randomised therapy. Mean cough frequency fell by 17.4% versus baseline with placebo. Eliapixant reduced cough frequency at doses ≥50 mg (reduction versus placebo at 750 mg: 25% (90% CI 11.5-36.5%); p=0.002). Doses ≥50 mg also significantly reduced cough severity. AEs, mostly mild or moderate, were reported in 65% of patients with placebo and 41-49% receiving eliapixant. Cumulative rates of taste-related AEs were 3% with placebo and 5-21% with eliapixant; all were mild. CONCLUSIONS: Selective P2X3 antagonism with eliapixant significantly reduced cough frequency and severity, confirming this as a viable therapeutic pathway for RCC. Taste-related side-effects were lower at therapeutic doses than with the less selective P2X3 antagonist gefapixant. Selective P2X3 antagonism appears to be a novel therapeutic approach for RCC.