Evaluation of Cough Triggers Among Responders and Non-Responders of Treatment with MK-7264, a P2X3 Receptor Antagonist

MK-7264 is a P2X3 receptor antagonist that has demonstrated reduction in cough frequency in patients with refractory chronic cough (1). We investigated whether therapeutic response to MK-7264 is limited to patients with specific triggers of cough. We evaluated a structured medical history questionnaire for refractory and unexplained chronic cough patients participating in a 12-week, randomized, placebo-controlled study of MK-7264 at doses of 7.5, 20, or 50 mg (Smith et al. Am J Respir Crit Care Med (195): Presented at the 2017 ATS Annual Meeting). ‘Some of the time to Always’ was considered a ‘Yes’ to a questionnaire item on potential cough triggers; ‘Little of the time to Never’ was considered ‘No.’ A post-hoc analysis evaluated the proportion of responders to MK-7264 (ie, reduction from baseline in Awake Cough Frequency [ACF] > 30% at Week 12) according to the ‘Yes’ or ‘No’ cough trigger categories. Of 253 randomized patients, 252 reported triggers. The most common questionnaire items leading to a ‘Yes’ as cough triggers were ‘My cough is unpredictable’ (79%), ‘A tickle in my throat’ (73%), and ‘An irritation in my throat’ (73%), ‘Poor Air Quality’ (50%) and ‘A change in air temperature’ (43%). Both non-responders and responders reported a high/similar rate (>80%) of 'Yes' to cough triggers of ‘Unpredictable’, ‘Tickle’, and ‘Throat Irritation’; a slightly higher rate of non-responders vs. responders reported ‘Yes’ to ‘Poor Air Quality’ (88% vs. 65%) and ‘Temperature Change’ (76% vs. 70%). Identification of specific triggers appears not to be associated with MK-7264 treatment response.