The effect of baseline factors on treatment response with MK-7264, a P2X3 antagonist, in refractory chronic cough.

Objectives: We evaluated demographic and baseline characteristics associated with efficacy response with MK-7264, a P2X3 antagonist, in refractory chronic cough patients. Methods: Patients with chronic cough (duration of ≥1 year) refractory to treatment enrolled in a double-blind, parallel group study (NCT02612610) conducted in the US and UK and were randomized to placebo or MK-7264 (7.5 mg BID, 20 mg BID, or 50 mg BID). Awake Cough Frequency (ACF; coughs/hr) after 12 weeks was the primary endpoint; treatment effect was evaluated using a mixed model repeated measures analysis of log-transformed change from baseline adjusting for log-transformed baseline cough count, duration of cough, country, age, sex, visit, and treatment-by-visit interaction. Results: 253 patients (mean age 60 years; 76% female) were randomized. Adjusted to placebo, ACF was significantly reduced by MK-7264 50 mg (p=0.0027) (1); we observed a statistically significant country effect with a larger reduction in ACF in the US vs. the UK. Demographic and baseline cough characteristics between the two countries were comparable. Conclusions: This analysis suggests consistent treatment effect with MK-7264 across a range of factors (e.g. baseline cough count, duration of cough, age, sex, visit, and treatment-by-visit interaction), though some difference in response by region was observed. Further assessment across a broader range of subjects and regions would be informative. Reference: (1) Smith JA et al. American Thoracic Society 2017.