RT Journal Article
SR Electronic
T1 Late Breaking Abstract - The neurokinin-1 receptor antagonist orvepitant improves chronic cough symptoms: results from a Phase 2b trial
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP PA600
DO 10.1183/13993003.congress-2019.PA600
VO 54
IS suppl 63
A1 Smith, Jaclyn
A1 Ballantyne, Elizabeth
A1 Kerr, Mary
A1 Mcgarvey, Lorcan
A1 Morice, Alyn
A1 Sher, Mandel
A1 Trower, Michael
A1 Pawsey, Stephen
YR 2019
UL http://erj.ersjournals.com/content/54/suppl_63/PA600.abstract
AB Background: No proven therapies exist for refractory chronic cough (CC). Neurokinin(NK)-1 antagonists may modulate the central neural hypersensitivity causing CC. The NK-1 antagonist orvepitant was assessed in CC in a Phase 2b dose-ranging study.Methods: A randomised, controlled, parallel group study recruited subjects with CC ≥1 yr and awake cough count >10/hr. Subjects took placebo (PBO) or one of 3 orvepitant doses (10, 20 or 30mg) once daily for 12-wks. Primary endpoint was awake cough frequency (CF) at Wk-12, using a VitaloJAK ambulatory cough monitor. Other efficacy measures were the patient recorded outcomes (PROs): Leicester Cough Questionnaire (LCQ), Cough Severity (CS) & Urge-to-Cough (UTC) VASs, and global ratings of change (GRoC).Results: 315 subjects were randomised and 275 were evaluable at Wk-12. Orvepitant 30mg resulted in clinically relevant and significant improvements in PROs in the full analysis set (FAS) at Wk 12: LCQ (PBO-corrected improvement 1.6, p=0.009), CS VAS (9.0mm, p=0.034) and UTC VAS (11.8mm, p=0.005). GRoC scores: for cough severity p=0.054, and frequency p=0.124. The CF endpoint was not significant in the FAS due to an exaggerated PBO response at Wk 12, most evident in the lower CF subjects. In a pre-defined sub-group of higher CF subjects (≥study median awake CF at baseline), a greater efficacy signal is evident with 30mg orvepitant in primary (geometric mean ratio vs PBO 0.71, p=0.066) and secondary efficacy endpoints (e.g. LCQ 1.9, p=0.041), with most being significant despite the study not being powered for sub-group analyses. Orvepitant was safe and well-tolerated.Conclusions: These data support orvepitant’s further evaluation in CC.FootnotesCite this article as: European Respiratory Journal 2019; 54: Suppl. 63, PA600.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).