Camlipixant in Refractory Chronic Cough: A Phase 2b, Randomized, Placebo-controlled Trial (SOOTHE).

Rationale: There is no broadly accessible treatment for patients with refractory chronic cough, a disease characterized by chronic cough that persists despite treatment for other cough-related etiologies or has no identified underlying cause. Objectives: SOOTHE (NCT04678206), a Phase 2b, randomized, placebo-controlled trial, evaluated the efficacy and safety of P2X3 antagonist camlipixant in adults with refractory chronic cough (cough duration ≥1 year; baseline awake cough frequency ≥25 coughs/hour). Methods: After a single-blind, 16-day placebo run-in, patients were randomized (1:1:1:1) to receive camlipixant 12.5, 50, or 200 mg twice-daily, or placebo for 4 weeks. The primary endpoint was change from baseline to Day 28 in objective 24-hour cough frequency. Secondary endpoints included cough severity and cough-related quality of life. Measurements and Main Results: Overall, 310 patients were randomized. A statistically significant reduction in placebo-adjusted 24-hour cough frequency was seen in the 50 mg (-34.4%; 95% confidence interval: -50.5 to -13.3; P=0.0033) and 200 mg (-34.2%; 95% confidence interval: -50.7 to -12.2; P=0.0047) camlipixant arms. All camlipixant arms showed a trend for greater improvement in Cough Severity Visual Analog Scale and Leicester Cough Questionnaire over placebo. Camlipixant was well tolerated with no serious treatment emergent adverse events reported. Taste alteration occurred in 4.8-6.5% of patients in camlipixant arms (vs. 0% with placebo); these were usually mild-moderate. Conclusions: Camlipixant treatment reduced cough frequency and improved patient reported outcomes in patients with refractory chronic cough, with an acceptable safety profile. Clinical trial registration available at www.clinicaltrials.gov, ID: NCT04678206.