Gefapixant effective treatment for unexplained chronic cough: Lancet

A phase 3 clinical study conducted by Prof Lorcan P McGarvey and team has revealed that for refractory chronic cough or unexplained chronic cough, gefapixant 45 mg twice a day was the first medication to show effectiveness with an acceptable safety profile. The findings of this study were published in The Lancet.

Gefapixant, which is an oral P2X3 receptor antagonist has previously been found to be effective and safe in the treatment of refractory chronic cough and unexplained chronic cough. As a result, the purpose of this study was to confirm the effectiveness and safety of gefapixant in patients with unexplained chronic cough and refractory chronic cough.

COUGH-1 and COUGH-2 were both phase 3 studies that were double-blind, randomized, parallel-group, placebo-controlled. COUGH-1 was carried out in 156 locations across 17 nations, whereas COUGH-2 was carried out in 175 sites across 20 countries. Participants in this research had to be 18 years old or older and have a diagnosis of refractory chronic cough or unexplained chronic cough for at least a year. Participants had to have a cough intensity visual analogue scale score of 40 mm or above at both screening and baseline. Using a computer-generated allocation schedule, eligible individuals were randomly assigned (1:1:1) to one of three treatments: placebo, gefapixant 15 mg twice per day, or gefapixant 45 mg twice per day. All research medications were administered orally. The primary outcome in COUGH-1 was the placebo-adjusted mean change in 24-hour cough frequency after 12 weeks and 24 weeks in COUGH-2.

The findings were as follow:

1. Gefapixant 45 mg twice daily reduced the 24-hour cough frequency significantly more than placebo at week 12 in COUGH-1 and week 24 in COUGH-2.

2. In all investigations, gefapixant 15 mg twice a day did not show a significant reduction in cough frequency when compared to placebo.

3. Ageusia, dysgeusia, hypergeusia, hypogeusia, and taste abnormality were the most prevalent adverse events associated with taste disturbance.

In conclusion, gefapixant dosage assessment twice per day shows significant positive effect and in future this treatment should be considered very often for any unexplained chronic cough.

Reference:

McGarvey, L. P., Birring, S. S., Morice, A. H., Dicpinigaitis, P. V., Pavord, I. D., Schelfhout, J., Nguyen, A. M., Li, Q., Tzontcheva, A., Iskold, B., Green, S. A., Rosa, C. L., Muccino, D. R., & Smith, J. A. (2022). Efficacy and safety of gefapixant, a P2X3 receptor antagonist, in refractory chronic cough and unexplained chronic cough (COUGH-1 and COUGH-2): results from two double-blind, randomised, parallel-group, placebo-controlled, phase 3 trials. In The Lancet (Vol. 399, Issue 10328, pp. 909–923). Elsevier BV. https://doi.org/10.1016/s0140-6736(21)02348-5