Safety, Tolerability, and Pharmacokinetics of Oral Camlipixant: A Randomized First‐In‐Human Study Using Single and Multiple Ascending Doses

Abstract

Camlipixant is a highly selective P2X3 receptor antagonist with demonstrated efficacy in pre‐clinical models of evoked cough. We report the safety, tolerability, and pharmacokinetics of camlipixant in healthy participants. This Phase 1, double‐blind, randomized study evaluated single ascending doses (SAD; 50/100/200/400/800/1200 mg) and multiple ascending doses (MAD; 100/200/400 mg, twice daily [BID]) of oral camlipixant versus placebo. Ninety participants were included (SAD n =  60; MAD n =  30). Treatment‐emergent adverse event (TEAE) incidence was similar between camlipixant (32/72) and placebo (9/18). TEAEs were mostly mild (83%), and the most common with camlipixant was dysgeusia, primarily at doses ≥400 mg (n =  13), versus 50–200 mg (n =  1). Camlipixant was rapidly absorbed (time to maximum plasma concentration SAD: 0.77–2.29 h; MAD: 0.50–2.00 h), with a short half‐life (SAD 4.28–6.71 h; MAD 7.60–8.39 h). In both cohorts, maximum plasma concentration (C _max ) increased proportionally with dose. The area under the curve extrapolated to infinity (AUC _0–∞ ) increased proportionally with dose in the SAD cohort; the increase was slightly supra‐proportional in the MAD cohort (steady state reached on Day 2). The geometric mean apparent volume of distribution ranged from 44.9 to 70.2 L and clearance from 5.7 to 10.4 L/h in the SAD cohort. Pharmacokinetics were unaffected by food (geometric mean fed/fasted ratio C _max 91.4% [90% confidence interval, CI, 69.8–119.6]; AUC _0–∞ 105.5% [90% CI, 89.8–124.0]). In summary, camlipixant was well tolerated, with pharmacokinetics supporting BID dosing and further clinical development for refractory chronic cough.