COUGH-1 and COUGH-2 are the first companion Phase 3 trials ever conducted in patients with refractory chronic cough, a cough that persists despite appropriate treatment of underlying conditions, or unexplained chronic cough, a cough where the underlying cause cannot be identified despite a thorough evaluation. In these studies, adult patients treated with gefapixant 45 mg twice daily demonstrated a statistically significant reduction in 24-hour cough frequency (measured objectively, as coughs per hour, using 24-hour sound recordings) versus placebo at 12 weeks (COUGH-1) (18.45% reduction relative to placebo, 95% CI [-32.92, -0.86; p=0.041]) and 24 weeks (COUGH-2) (14.64% reduction relative to placebo, 95% CI [-26.07, -1.43; p=0.031]). The gefapixant 15 mg twice daily treatment arms did not meet the primary efficacy endpoint in either Phase 3 study.
'It is estimated that between 5 and 10% of adults globally suffer from chronic cough. A subset of these patients have refractory or unexplained chronic cough and appear more sensitive to various triggers that do not typically cause cough in healthy subjects. These include everyday things such as talking, laughing, a change in air temperature or exposure to aerosols or food odors, and to date treatment options are extremely limited for these patients,' said Dr.
'COUGH-1 and COUGH-2 are the first companion Phase 3 trials in refractory or unexplained chronic cough, underscoring
These results were presented at the virtual
Study design and additional data from COUGH-1 and COUGH-2
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. A total of 2,044 participants(75% female, mean age 58 years, mean cough duration 11 years) were treated in COUGH-1 (n=730) and COUGH-2 (n=1,314). 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 cough frequency at Week 12, and 24-hour cough frequency at week 24, respectively, measured using an ambulatory digital audio recording device. Secondary endpoints in both trials included awake coughs per hour and percentage of participants with a greater than 1.3-point increase from baseline in the Leicester Cough Questionnaire (LCQ) total score. 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 (AE) during treatment and follow up, and the percentage of patients discontinuing treatment because of adverse events.
In COUGH-1 and COUGH-2, treatment with gefapixant 45 mg twice daily resulted in a significant reduction in objectively measured 24-hour cough frequency in participants with refractory or unexplained chronic cough. In these studies, on average, participants receiving gefapixant 45 mg twice daily in the COUGH-1 trial experienced a 62% reduction in cough frequency, and in the COUGH-2 trial experienced a 63% reduction in cough frequency, compared with baseline.
The secondary endpoints in COUGH-1 and COUGH-2 support the primary observation of the studies. Awake cough frequency results were generally similar to the 24-hour cough frequency outcome, reaching statistical significance in the 45 mg twice daily group in COUGH-2 (15.79% estimated relative reduction, 95% CI [-27.27, -2.50; p=0.022]) and trending towards significance in COUGH-1 (17.68% estimated relative reduction, 95% CI [-32.57, 0.50; p=0.056]). Significantly more participants in the gefapixant 45 mg twice daily group at week 24 demonstrated a clinically important improvement in cough-related quality of life, with an odds ratio of 1.41 (p=0.042) compared with placebo. Of the participants in the 45 mg group, 77.1% experienced a clinically important level of improvement in their quality of life related to cough, as measured using the LCQ.
The safety and tolerability profile of gefapixant was consistent with that reported in previous studies. The incidence of serious AEs was similar between treatments (
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