IPF COMFORT Study: A randomised, controlled trial evaluating the safety and efficacy of orvepitant as a treatment for chronic cough in IPF

We investigated orvepitant, a selective antagonist of the NK1 receptor, as a treatment for chronic cough in IPF. This phase 2, randomised, double blind, placebo-controlled, 2-period cross-over study tested orvepitant 10 mg and 30 mg once daily in patients with confirmed IPF. Treatment periods were 4-wks with a wash-out of 3-wks. Eligible subjects had a mean score of ≥5 on a 0-10 cough severity numerical rating scale (NRS) in the last 7 days of screening. Assessments included daily and periodic patient-reported outcome measures and cough frequency monitoring for efficacy, and safety tests. The primary endpoint was weekly mean of the Daily Cough Severity NRS at wk 4. 80 patients were randomised. There was a significant period effect due to a marked placebo response in Period A, hence both cross over (XO) and additional by period (PB) analyses are presented. At wk 4, Daily Cough Severity NRS scores decreased with orvepitant 30mg compared to placebo in both XO (-0.58 pts, p=0.054) and PB (-1.17 pts, p=0.009) analyses. There were also reductions in the cough frequency verbal rating scale (XO: -0.23, p=0.010; PB: -0.35, p=0.018) and urge to cough NRS (XO: -0.46, p=0.092; PB: -0.84, p=0.042) scores. Wk 2 findings were similar. Leicester Cough Questionnaire QoL scores were improved (XO: 1.24, p=0.025; PB:1.94, p=0.015) and more subjects reported their cough improved with orvepitant 30 mg (69%) than placebo (44%) on a global rating of change. The 10 mg dose was not different to placebo. Both doses were well tolerated with no safety concerns. Orvepitant 30 mg once daily improved multiple patient-reported measures of cough burden in patients with IPF.