Phase 3 Study of Gefapixant in Japan Shows Good Safety, Tolerability Profile

A phase 3 safety and tolerability study of gefapixant conducted in Japan found it had an acceptable safety profile, with no serious treatment-related adverse events (AEs).

Gefapixant is approved in Japan but remains investigational in the United States for chronic cough (CC). Worldwide, the estimated prevalence of CC, defined as lasting at least 8 weeks, is about 10%.

Previous phase 3 global trials (COUGH-1 and COUGH-2) found the P2X3-receptor antagonist significantly reduced objective 24-hour cough frequency in participants with refractory or unexplained chronic cough (RCC or UCC) at a dosage of 45 mg twice daily, with an acceptable safety profile.

Besides safety and tolerability, this study also assessed cough-specific quality of life using the Leicester Cough Questionnaire (LCQ), which explores the impact of cough across 3 domains (physical, psychological, and social). The LCQ severity scores range from 3 to 21, with lower scores indicating worse impairment.

In this study, participants aged 20 years and older with chronic cough lasting at least 4 months were screened for inclusion. They needed a diagnosis of RCC or UCC despite having past treatment aligned with Japanese Respiratory Society (JRS) guidelines, and chest imaging conducted within 5 years.

JRS guidelines recommend systematic evaluation for potential comorbid conditions linked with cough, including cough-variant asthma, atopic cough (characterized by dry cough with nonasthmatic eosinophilic airway inflammation and lack of response to bronchodilators), gastroesophageal reflux disease, and postinfectious cough.

After screening and randomization, 169 patients were included in the final analysis. They were randomized 1:1 to receive gefapixant 15 mg (n = 84) or 45 mg (n = 85) twice daily for 52 weeks. The mean age of the participants was 58 and most (63%) were female. Mean cough duration was 9 years, and 87% were considered to have RCC; about two-thirds of participants were never smokers and mean baseline LCQ total score was 13.9.

Most (95%) participants reported AEs, with more AEs occuring in the group receiving the higher dosage: 79 (94%) in the 15-mg group and 82 (96%) in the 45-mg group.

Most treatment-related AEs affected taste and were mild to moderate in intensity; they resolved during or after study treatment, with the exception of 1 person in the 15-mg group.

Discontinuation due to AEs occurred in 6 (7%) and 17 (20%) participants receiving gefapixant 15 mg and 45 mg, respectively.

There were no serious treatment-related AEs or deaths.

LCQ total scores improved from baseline through week 52, with about half of participants seeing clinically meaningful improvements (ie, ≥1.3-point increase in LCQ total score). Score improvement also appeared to be numerically greater at the lower dose, but the study was not designed or powered to assess efficacy over time or between treatment groups, and no placebo group was included, so the LCQ data are only descriptive.

The lack of a control group is the main limitation of the study, but the authors noted that placebo groups were included and reported in other trials.

Reference

Niimi A, Sagara H, Kikuchi M, et al. A phase 3, randomized, double-blind, clinical study to evaluate the long-term safety and efficacy of gefapixant in Japanese adult participants with refractory or unexplained chronic cough. Allergol Int. 2022;71(4):498-504. doi:10.1016/j.alit.2022.05.006