A Randomized, Placebo-Controlled Study to Investigate the Safety, Tolerability, and Pharmacokinetics of 3 Weeks of Orally Administered Gefapixant in Healthy Younger and Older Adults

Purpose Patients with chronic cough are typically female and have a mean age of similar to 60 years. However, initial pharmacokinetic (PK) characterization of the P2X3-receptor antagonist gefapixant, developed to treat refractory or unexplained chronic cough, was performed in healthy participants who were predominantly younger adult males. The objective of this Phase 1 study was to assess the safety, tolerability, and PK of gefapixant in younger (18-55 years) and older (65-80 years) males and females. Methods A randomized, double-blind, placebo-controlled study was conducted. Healthy adult participants were stratified into 4 cohorts by age and sex (younger males/females and older males/females) and randomized 4:1 (younger adults) or 3:1 (older adults) to receive gefapixant 300 mg twice daily (BID) for 1 week, followed by gefapixant 600 mg BID for 2 weeks or placebo. Safety, tolerability, and PK were assessed. Results Of 36 randomized and treated participants, 28 (100%) receiving gefapixant and 6 (75%) receiving placebo reported >= 1 adverse event (AE). The most common treatment-related AEs in the gefapixant group were taste related. Predefined renal/urologic AEs were reported by 7 (25%) participants receiving gefapixant (all mild to moderate in severity). Gefapixant exposure was generally lower in younger males compared with younger females and older adults; however, differences may have been due to estimated glomerular filtration rate. Conclusion The safety profile of gefapixant 300-600 mg BID was generally consistent with previous studies. Additional characterization of gefapixant PK as a function of age and sex using population PK modeling is warranted.

Automated summary

This study aimed to assess the safety, tolerability, and pharmacokinetics (PK) of gefapixant in males and females of different ages. The results showed that the safety profile of gefapixant was consistent with previous studies. Further research is warranted to examine the PK of gefapixant in relation to age and sex.