Inhibition of P2X3 by MK-7264 reduces 24-hour cough frequency in a randomized, controlled, Phase 2b clinical trial

Abstract

Introduction: MK-7264 (formerly AF-219) is a P2X3 receptor antagonist that has been shown to reduce cough frequency in patients with chronic cough. Methods: This 12-week, double-blind, parallel group study conducted at 46 sites in the US and UK randomized patients with refractory chronic cough (≥1 year) to placebo or MK-7264 at doses of 7.5 mg BID, 20 mg BID, or 50 mg BID. Awake Cough Frequency (coughs/hr) was the primary endpoint (1); 24-hour Cough Frequency was a key secondary endpoint. Responder analyses assessed the % of patients with 30%, 50%, and 70% reduction of cough frequency from baseline. Results: 253 patients (mean age 60 years; 76% female) were randomized to placebo (n=63), and the 7.5 mg (n=64), 20 mg (n=63), and 50 mg (n=63) doses of MK-7264. Awake Cough Frequency was significantly reduced by MK-7264 50 mg vs. placebo (p=0.003) (1). 24-hour Cough frequency was significantly reduced with the 50 mg dose vs. placebo (p=0.001); additionally, the 50 mg group had the highest % of patients with at least a 70% reduction in 24-hr cough frequency (table). Overall, MK-7264 was well tolerated with dysgeusia the most common AE (48% for MK-7264 50 mg) Conclusions: MK-7264 significantly reduced the 24 hour cough frequency in patients with refractory chronic cough after 12 weeks of treatment compared with placebo. Reference: (1) Smith JA et al. American Thoracic Society 2017