Efficacy and safety of gefapixant in women with chronic cough and cough-induced stress urinary incontinence: a phase 3b, randomised, multicentre, double-blind, placebo-controlled trial

Lancet Respir Med. 2024 Nov;12(11):855-864. doi: 10.1016/S2213-2600(24)00222-4. Epub 2024 Aug 30.

Abstract

Background: Approximately two-thirds of women with chronic cough have cough-induced stress urinary incontinence (CSUI). We aimed to evaluate the efficacy and safety of gefapixant in reducing CSUI episodes in women with refractory or unexplained chronic cough.

Methods: This phase 3b, double-blind, randomised, placebo-controlled trial done at 90 sites in 12 countries enrolled women aged 18 years or older who had chronic cough for at least 1 year, a diagnosis of refractory or unexplained chronic cough, a cough severity visual analogue scale score of 40 mm or more (100 mm maximum), and CSUI for 3 months or more. Participants were randomised 1:1 to oral gefapixant or placebo for 12 weeks. The primary outcome was percentage change from baseline in daily CSUI episodes (7-day average) at week 12. This study is registered with ClinicalTrials.gov (NCT04193176).

Findings: From May 10, 2020, to Sept 2, 2022, 375 participants were randomised to and treated with gefapixant 45 mg twice daily (n=185) or placebo (n=190). Mean age was 56·4 years (SD 11·4), with mean chronic cough duration of 5·2 years (SD 6·6) and SUI duration of 4·0 years (SD 5·9). Least-squares mean percentage change from baseline in daily CSUI episodes was -52·8% (95% CI -58·4 to -47·1%) for gefapixant and -41·1% (-46·7 to -35·4%) for placebo (estimated treatment difference: -11·7% [95% CI -19·7 to -3·7]; p=0·004). 129 (70%) of 185 participants who received gefapixant and 71 (37%) of 190 participants who received placebo had at least one adverse event. Safety and tolerability were consistent with previous trials of gefapixant; the most frequent adverse events were taste related.

Interpretation: Gefapixant 45 mg twice daily is the first treatment to show efficacy versus placebo in reducing CSUI episodes in participants with refractory or unexplained chronic cough.

Funding: Merck Sharp & Dohme, a subsidiary of Merck & Co.

Publication types

  • Randomized Controlled Trial
  • Clinical Trial, Phase III
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Benzenesulfonamides
  • Chronic Cough
  • Chronic Disease
  • Cough* / drug therapy
  • Double-Blind Method
  • Female
  • Humans
  • Middle Aged
  • Pyrimidines / administration & dosage
  • Pyrimidines / adverse effects
  • Pyrimidines / therapeutic use
  • Sulfonamides / administration & dosage
  • Sulfonamides / adverse effects
  • Sulfonamides / therapeutic use
  • Treatment Outcome
  • Urinary Incontinence, Stress* / drug therapy

Substances

  • Gefapixant
  • Sulfonamides
  • Pyrimidines
  • Benzenesulfonamides

Associated data

  • ClinicalTrials.gov/NCT04193176