Gefapixant reduces chronic cough frequency in large pooled analysis
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Gefapixant 45 mg twice daily resulted in clinically important reductions in cough frequency compared with placebo in patients with refractory or unexplained chronic cough.
The results are from a pooled analysis of the large, randomized, phase 3 COUGH-1 and COUGH-2 trials.
“Refractory and unexplained chronic cough are characterized by frequent coughing that can last for several years and seriously disrupt the lives of these patients. Currently, there are no approved drugs for these patients,” Jaclyn Smith, PhD, professor of respiratory medicine in the division of infection, immunity and respiratory medicine at Manchester University and honorary consultant at Manchester University NHS Foundation Trust, U.K., said during a presentation at the American Thoracic Society International Conference. “Gefapixant is a P2X3 receptor antagonist that has recently demonstrated significant reductions in 24-hour cough frequency at a dose of 45 mg twice daily compared with placebo in ... [the] COUGH-1 and COUGH-2 [trials].”
The pooled analysis included 2,044 participants (mean age, 58 years; 75% women) with refractory chronic cough or unexplained chronic cough. Mean cough duration was 11 years and nearly two-thirds had refractory chronic cough. Participants were randomly assigned to receive twice-daily gefapixant (Merck) 15 mg (n = 684), 45 mg (n = 682) or placebo (n = 678). Researchers recorded 24-hour cough frequency and awake cough frequency using an ambulatory recording device (VitaloJAK). Objective cough frequency was assessed at week 12 in COUGH-1 and at week 24 in COUGH-2.
“The pooled analysis of COUGH-1 and COUGH-2 is the largest prospective analysis of clinical trial data in chronic cough to date,” according to the researchers.
In the pooled analysis, twice-daily gefapixant 45 mg resulted in a relative reduction in 24-hour cough of 18.59% and a relative reduction in awake cough frequency of 17.38%. Twice-daily gefapixant at 15 mg was not associated with significant reductions in 24-hour cough (–0.97%) or awake cough frequency (0.28).
In addition, more patients assigned gefapixant 45 mg met various 24-hour cough frequency responder definitions at week 12 compared with placebo.
The incidence of serious adverse events was similar among patients who received both gefapixant doses or placebo (6% for all). Adverse events related to taste were the most commonly reported adverse event for those who received gefapixant 45 mg (65%) or 15 mg (18%). Taste-related adverse events were reported in fewer patients who received placebo (7%).
“This pooled analysis of COUGH-1 and COUGH-2 clinical trials supports the primary findings that gefapixant 45 mg twice daily reduces objective cough frequency in refractory and unexplained cough compared with placebo,” Smith said.