PMID- 33986030
OWN - NLM
STAT- MEDLINE
DCOM- 20211213
LR  - 20231108
IS  - 1399-3003 (Electronic)
IS  - 0903-1936 (Print)
IS  - 0903-1936 (Linking)
VI  - 58
IP  - 5
DP  - 2021 Nov
TI  - Eliapixant (BAY 1817080), a P2X3 receptor antagonist, in refractory chronic 
      cough: a randomised, placebo-controlled, crossover phase 2a study.
LID - 10.1183/13993003.04240-2020 [doi]
LID - 2004240
AB  - BACKGROUND: ATP acting via P2X3 receptors is an important mediator of refractory 
      chronic cough (RCC). This phase 2a double-blinded crossover study assessed the 
      safety, tolerability and efficacy of eliapixant (BAY 1817080), a selective P2X3 
      receptor antagonist, in adults with RCC attending specialist centres. METHODS: In 
      period A, patients received placebo for 2 weeks then eliapixant 10 mg for 1 week. 
      In period B, patients received eliapixant 50, 200 and 750 mg twice daily for 
      1 week per dose level. Patients were randomised 1:1 to period A-B (n=20) or B-A 
      (n=20). The primary efficacy end-point was change in cough frequency assessed 
      over 24 h. The primary safety end-point was frequency and severity of adverse 
      events (AEs). RESULTS: 37 patients completed randomised therapy. Mean cough 
      frequency fell by 17.4% versus baseline with placebo. Eliapixant reduced cough 
      frequency at doses >/=50 mg (reduction versus placebo at 750 mg: 25% (90% CI 
      11.5-36.5%); p=0.002). Doses >/=50 mg also significantly reduced cough severity. 
      AEs, mostly mild or moderate, were reported in 65% of patients with placebo and 
      41-49% receiving eliapixant. Cumulative rates of taste-related AEs were 3% with 
      placebo and 5-21% with eliapixant; all were mild. CONCLUSIONS: Selective P2X3 
      antagonism with eliapixant significantly reduced cough frequency and severity, 
      confirming this as a viable therapeutic pathway for RCC. Taste-related 
      side-effects were lower at therapeutic doses than with the less selective P2X3 
      antagonist gefapixant. Selective P2X3 antagonism appears to be a novel 
      therapeutic approach for RCC.
CI  - Copyright (c)The authors 2021.
FAU - Morice, Alyn
AU  - Morice A
AUID- ORCID: 0000-0002-6135-9610
AD  - Respiratory Research Group, Hull York Medical School, University of Hull, Hull, 
      UK a.h.morice@hull.ac.uk.
FAU - Smith, Jaclyn A
AU  - Smith JA
AUID- ORCID: 0000-0001-8837-4928
AD  - Manchester University NHS Foundation Trust and Manchester Academic Health Science 
      Centre, Manchester, UK.
FAU - McGarvey, Lorcan
AU  - McGarvey L
AD  - Wellcome Wolfson Institute of Experimental Medicine, School of Medicine, 
      Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, UK.
FAU - Birring, Surinder S
AU  - Birring SS
AD  - Centre for Human and Applied Physiological Sciences, School of Basic and Medical 
      Biosciences, Faculty of Life Sciences and Medicine, King's College Hospital, 
      London, UK.
FAU - Parker, Sean M
AU  - Parker SM
AD  - North Tyneside Hospital, Northumbria Healthcare NHS Foundation Trust, North 
      Shields, UK.
FAU - Turner, Alice
AU  - Turner A
AD  - Institute of Applied Health Research and Population Sciences, University of 
      Birmingham, Birmingham, UK.
FAU - Hummel, Thomas
AU  - Hummel T
AUID- ORCID: 0000-0001-9713-0183
AD  - Smell and Taste Clinic, Dept of Otorhinolaryngology, TU Dresden, Dresden, 
      Germany.
FAU - Gashaw, Isabella
AU  - Gashaw I
AD  - Bayer AG, Berlin, Germany.
FAU - Fels, Lueder
AU  - Fels L
AD  - Bayer AG, Berlin, Germany.
FAU - Klein, Stefan
AU  - Klein S
AD  - Bayer AG, Berlin, Germany.
FAU - Francke, Klaus
AU  - Francke K
AD  - Bayer AG, Berlin, Germany.
FAU - Friedrich, Christian
AU  - Friedrich C
AD  - Bayer AG, Berlin, Germany.
LA  - eng
SI  - ClinicalTrials.gov/NCT03310645
GR  - WT_/Wellcome Trust/United Kingdom
GR  - DH_/Department of Health/United Kingdom
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20211118
PL  - England
TA  - Eur Respir J
JT  - The European respiratory journal
JID - 8803460
RN  - 0 (Purinergic P2X Receptor Antagonists)
RN  - 0 (Receptors, Purinergic P2X3)
SB  - IM
MH  - Adult
MH  - Chronic Disease
MH  - *Cough/drug therapy
MH  - Cross-Over Studies
MH  - Double-Blind Method
MH  - Humans
MH  - *Purinergic P2X Receptor Antagonists
MH  - Receptors, Purinergic P2X3
MH  - Treatment Outcome
PMC - PMC8607926
COIS- Conflict of interest: A. Morice reports grants, personal fees, nonfinancial 
      support and other from Bayer AG and Bayer US, during the course of the study; 
      personal fees, nonfinancial support and other from Bellus Health and Merck Sharp 
      & Dohme Corp., personal fees and nonfinancial support from AstraZeneca, Chiesi 
      Ltd and Boehringer Ingelheim, grants, personal fees, nonfinancial support and 
      other from Sanofi, grants, personal fees and nonfinancial support from 
      GlaxoSmithKline, Respivant Sciences, Inc. and Philips Respironics, grants, 
      personal fees and other from NeRRe Therapeutics, grants from Menio Therapeutics, 
      outside the submitted work. Conflict of interest: J.A. Smith reports grants and 
      personal fees from Bayer AG, during the course of the study; grants and personal 
      fees from Bellus Health, Shionogi Inc. and Merck Inc., outside the submitted 
      work; and the VitaloJAK algorithm has been licensed by Manchester University NHS 
      Foundation Trust and the University of Manchester to Vitalograph Ltd and 
      Vitalograph Ireland (Ltd); Manchester University NHS Foundation Trust receives 
      royalties which may be shared with the clinical division in which J.A. Smith 
      works. Conflict of interest: L. McGarvey reports grants and personal fees from 
      Bayer AG, during the conduct of the study; grants, personal fees and nonfinancial 
      support from Chiesi, grants and personal fees from Merck & Co., Inc. and Bellus 
      Health, nonfinancial support from Boehringer Ingelheim, personal fees from 
      Applied Clinical Intelligence, Shionogi Inc., GlaxoSmithKline, NeRRe Therapeutics 
      and Nocion Therapeutics, other from AstraZeneca, outside the submitted work. 
      Conflict of interest: S.S. Birring reports grants and personal fees from Merck, 
      personal fees from Bayer, Shionogi Inc., Bellus Health, NeRRe Therapeutics, 
      Nocion Therapeutics, Boehringer Ingelheim and GlaxoSmithKline, outside the 
      submitted work. Conflict of interest: S.M. Parker reports personal fees for 
      consultancy from Menlo and Merck, outside the submitted work. Conflict of 
      interest: A. Turner has nothing to disclose. Conflict of interest: T. Hummel 
      reports grants from Sony, Smell and Taste Lab, Takasago and Aspuraclip, personal 
      fees from Frequency Therapeutics and Baiafoods, outside the submitted work. 
      Conflict of interest: I. Gashaw was an employee of Bayer AG when the study was 
      designed and conducted but is now an employee of Boehringer Ingelheim Pharma GmbH 
      & Co. KG, Ingelheim, Germany. Conflict of interest: L. Fels is an employee of 
      Bayer AG. Conflict of interest: S. Klein is an employee of Bayer AG. Conflict of 
      interest: K. Franke is an employee of Bayer AG. Conflict of interest: C. 
      Friedrich is an employee of Bayer AG.
EDAT- 2021/05/15 06:00
MHDA- 2021/12/15 06:00
PMCR- 2021/11/22
CRDT- 2021/05/14 05:55
PHST- 2020/11/17 00:00 [received]
PHST- 2021/04/05 00:00 [accepted]
PHST- 2021/05/15 06:00 [pubmed]
PHST- 2021/12/15 06:00 [medline]
PHST- 2021/05/14 05:55 [entrez]
PHST- 2021/11/22 00:00 [pmc-release]
AID - 13993003.04240-2020 [pii]
AID - ERJ-04240-2020 [pii]
AID - 10.1183/13993003.04240-2020 [doi]
PST - epublish
SO  - Eur Respir J. 2021 Nov 18;58(5):2004240. doi: 10.1183/13993003.04240-2020. Print 
      2021 Nov.