In these studies, the primary efficacy endpoints were met for the gefapixant 45 mg twice daily treatment arms – demonstrating a statistically significant decrease in 24-hour coughs per hour (average hourly cough frequency based on 24-hour sound recordings) versus placebo at 12 (COUGH-1) and 24 weeks (COUGH-2).
The gefapixant 15 mg twice daily treatment arms did not meet the primary efficacy endpoint in either Phase 3 study. The safety and tolerability profile of gefapixant during the trials to date is consistent with the previously reported Phase 2 study. The trials will continue for long-term follow-up to collect additional safety data.
“The burden for patients faced with this disease underscores the need for effective therapeutic options for refractory and unexplained chronic cough,” said Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories. “We are pleased gefapixant at the 45 mg dose met the primary efficacy endpoints in both Phase 3 studies and we look forward to sharing the detailed findings at an upcoming medical meeting.”
COUGH-1 (NCT03449134) and COUGH-2 (NCT03449147) are international Phase 3, randomized, double-blind, placebo-controlled, studies to evaluate the efficacy and safety of gefapixant in reducing cough frequency in adult participants with refractory or unexplained chronic cough.
COUGH-1 enrolled 732 participants and COUGH-2 enrolled 1,317 participants, with refractory or unexplained chronic cough for at least one year, as defined by guidelines from the American College of Chest Physicians (ACCP). In both studies, patients were randomized to one of three groups: gefapixant 45 mg twice daily, gefapixant 15 mg twice daily, or placebo. Participants remained on their assigned treatment at randomization throughout both studies.
The primary efficacy outcomes measure for COUGH-1 and COUGH-2 were 24-hour coughs per hour at Week 12, and 24-hour coughs per hour at week 24, respectively, measured using an ambulatory digital audio recording device. Secondary endpoints in both trials included awake coughs per hour, percentage of participants with a greater than 1.3-point increase from baseline in the Leicester Questionnaire (LCQ) total score, and percentage of participants with a greater than 30% reduction from baseline in 24-hour coughs per hour.
COUGH-1 had a 12-week treatment period and a 40-week extension period, while COUGH-2 had a 24-week treatment period and a 28-week extension period. Primary safety outcomes include the percentage of patients experiencing greater than one adverse event during treatment and follow up, and the percentage of patients discontinuing treatment because of adverse events.
Gefapixant is an investigational, orally administered, selective P2X3 receptor antagonist, for the treatment of refractory or unexplained chronic cough. It is believed that excessive activation of P2X3 receptors is associated with hyper-sensitization of sensory neurons. Neuronal hyper-sensitization in the airways and lungs, triggered by injury or infection, can cause an exaggerated, persistent and frequent urge to cough, otherwise known as chronic cough.
Source: Company Press Release