LATE-BREAKING ABSTRACT: Tackling the burden of chronic cough: A dose escalation study of AF-219

Introduction: Chronic cough is a challenging problem as available medications lack proven efficacy. AF-219, a P2X3 antagonist, effectively reduced cough frequency in 2 previous phase 2 trials at doses 50-600mg BID 1 . The present study explored the dose response relationship below 50mg BID. Methods: A randomized, double-blind, placebo-controlled, crossover, dose escalation study of AF-219 recruited patients with chronic cough ≥1 year and cough severity VAS≥40mm. Patients received 16 days of AF-219 or placebo, dose escalated every 4 days (7.5mg, 15mg, 30mg, 50mg BID consecutively); after ≥15days washout patients crossed over. Awake cough frequency was measured with an ambulatory cough monitor (VitaloJak). Results: 30 patients (12 naive, 18 previously treated at higher doses) at 10 US sites were randomized; mean age 60yrs, median cough duration 13yrs, 80% female. AF-219 30 and 50mg BID produced equivalent, marked reductions in awake cough vs. placebo (p 0.05). Patient perception of improvements in cough severity lagged the objective measure. Separation between efficacy and tolerability was seen, with few patients reporting taste AEs at 7.5 and 15mg (none in naive group). Conclusion: Lower doses of AF-219 produced marked reductions in cough frequency; fewer patients noted reduced taste, portending promising efficacy and tolerability in studies of longer duration. 1 Lancet 2015;385:1198.