• Jaclyn Smith, David Allman, Huda Badri, Robert Miller, Julie Morris, Imran Satia, Andrew Wood, and Michael K Trower.
• Division of Infection Immunity and Respiratory Medicine, University of Manchester, Manchester, England; Manchester University NHS Foundation Trust, Manchester, England. Electronic address: Jacky.Smith@manchester.ac.uk.
• Chest. 2020 Jan 1; 157 (1): 111-118.

BackgroundSubstance P and the neurokinin-1 (NK-1) receptor are implicated in chronic refractory cough pathophysiology. We assessed the efficacy and safety of orvepitant, a brain-penetrant NK-1 antagonist, in an open-label study in CRC patients with chronic refractory cough.MethodsThirteen patients with daytime cough frequency >3 to <250 coughs/h took orvepitant 30 mg once daily for 4 weeks. Objective cough frequency was measured over 24 h at baseline and weeks 1, 4, and 8. The primary end point was change from Baseline in daytime cough frequency at week 4. Secondary end points included cough severity visual analog scale (VAS) score, global ratings of change for cough frequency and severity, and Cough-specific Quality of Life Questionnaire score.ResultsAll patients completed the study. Mean baseline cough frequency was 71.4/h. A statistically and clinically significant improvement in objective daytime cough frequency was observed at week 4: reduction from baseline of 18.9 (26%) coughs/h (95% CI, 9.6-28.3; P < .001). This effect was apparent at week 1 (reduction from baseline of 27.0 [38%] coughs/h [95% CI, 11.4-42.7; P = .001]) and sustained after drug discontinuation at week 8 (reduction from baseline of 20.4 [29%] coughs/h [95% CI, 3.2-37.5; P = .020]). Statistically significant improvements were seen for severity VAS and quality of life. Orvepitant was safe and well-tolerated.ConclusionsOrvepitant resulted in a significant and sustained improvement in objective cough frequency, severity VAS, and quality of life; appeared safe; and merits further clinical investigation.Trial RegistryEU Clinical Trials Register; No.: 2014-003947-36; URL: www.clinicaltrialsregister.eu.Copyright © 2019. Published by Elsevier Inc.

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