Abstract
Background We present study designs, dose selection and preliminary patient characteristics from two phase 3 clinical trials of gefapixant, a P2X3 receptor antagonist, in refractory chronic cough (RCC) or unexplained chronic cough (UCC).
Methods COUGH-1 (NCT03449134) and COUGH-2 (NCT03449147) are randomised, placebo-controlled, double-blind, parallel-group trials in subjects with RCC or UCC (age ≥18 years; cough duration ≥1 year; Cough Severity Visual Analogue Scale score ≥40 mm). The primary efficacy study periods are 12 weeks (40-week extension; COUGH-1) and 24 weeks (28-week extension; COUGH-2). Interventions include placebo, gefapixant 15 mg and gefapixant 45 mg (1:1:1 ratio). The primary efficacy endpoints are average 24-h cough frequency at Week 12 (COUGH-1) and Week 24 (COUGH-2). Awake cough frequency, patient-reported outcomes and responder analyses are secondary endpoints.
Results The doses of 45 mg (to provide maximal efficacy and acceptable tolerability) and 15 mg (to provide acceptable efficacy and improved tolerability) were selected based on phase 1 and 2 studies. In COUGH-1, 730 participants have been randomised and treated; 74% are female with mean age of 59 years (39% over 65 years), and mean baseline duration of cough of 11.5 years. In COUGH-2, 1314 participants have been randomised and treated; 75% are female with mean age of 58 years (33% over 65 years), and mean baseline duration of cough of 11.1 years.
Conclusions These global studies include participants with baseline characteristics consistent with previous RCC and UCC studies and will inform the efficacy and safety profile of gefapixant in the treatment of patients with RCC and UCC.
Abstract
This protocol describes the design of two global, phase 3 studies with >2000 participants with refractory or unexplained chronic cough, designed to confirm efficacy and safety of gefapixant, a P2X3 receptor antagonist, at doses of 45 mg and 15 mg https://bit.ly/2Xzgu74
Footnotes
COUGH-1 (NCT03449134) and COUGH-2 (NCT03449147) are registered at www.clinicaltrials.gov. The Merck Sharp & Dohme Corp. (a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA) data sharing policy, including restrictions, is available at http://engagezone.msd.com/ds_documentation.php. Requests for access to the clinical study data can be submitted through the EngageZone site or via e-mail to dataaccess{at}merck.com.
Support statement: Funding for this research was provided by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Funding information for this article has been deposited with the Crossref Funder Registry.
Conflict of interest: D.R. Muccino is an employee of Merck & Co., Inc., Kenilworth, NJ, USA.
Conflict of interest: A.H. Morice reports grants and personal fees from Merck during the conduct of the study.
Conflict of interest: S.S. Birring reports clinical trial fees to his institution by Merck during the conduct of the study; a grant for an investigator-led study from Merck, personal fees for scientific advisory work from Merck, Bayer, Sanofi, Pfizer, Patara and Menlo, and speaker fees from Roche, outside the submitted work.
Conflict of interest: P.V. Dicpinigaitis reports consulting fees from Merck during the conduct of the study.
Conflict of interest: I.D. Pavord reports speaker fees, advisory board honoraria, sponsorship to attend scientific meetings and payments for organising educational events from AstraZeneca; speaker fees, advisory board honoraria and sponsorship to attend scientific meetings from Boehringer Ingelheim; a speaker fee from Aerocrine; speaker fees and advisory board honoraria from Almirall and Novartis; speaker fees, advisory board honoraria and sponsorship to attend scientific meetings from GlaxoSmithKline; advisory board honoraria from Genentech and Regeneron; speaker honoraria, payments for organising educational events and sponsorship to attend scientific meetings from Teva; speaker honoraria and a research grant from Chiesi; advisory board honoraria, speaker fees and grant support from Sanofi; advisory board honoraria from Circassia and Knopp; and funding as a Senior Investigator from NIHR, outside the submitted work.
Conflict of interest: C. Assaid is an employee of Merck & Co., Inc., Kenilworth, NJ, USA.
Conflict of interest: H.J. Kleijn reports that the contributions to the paper were performed as a paid consultant (employee of Certara) for Merck.
Conflict of interest: A. Hussain is an employee of Merck & Co., Inc., Kenilworth, NJ, USA.
Conflict of interest: C. La Rosa is an employee of Merck & Co., Inc., Kenilworth, NJ, USA.
Conflict of interest: L. McGarvey reports personal fees from Afferent Pharmaceuticals and Merck & Co., Inc., grants, personal fees and nonfinancial support from Chiesi, personal fees and nonfinancial support from Boehringer Ingelheim, grants and nonfinancial support from Glaxo Smith Kline, grants and personal fees from Almirall, personal fees from AstraZeneca, and grants from NC3R, during the conduct of the study; and grants from the European Union Interreg VA Health & Life Science Programme outside the submitted work;.
Conflict of interest: J.A. Smith reports funding for a commercial study paid to Manchester University NHS Foundation Trust, and personal fees for advisory boards and consultancy work from Merck Inc., during the conduct of the study; funding for a commercial study paid to Manchester University NHS Foundation Trust, and personal fees for advisory boards and consultancy work from GlaxoSmithKline, a grant to Christie Hospital and commercial funding for a clinical trial, and consultancy fees from NeRRe Pharmaceuticals, commercial funding for clinical trials and consultancy fees from Menlo and Bayer, consultancy fees from Boehringer Ingelheim, Genentech and Neomed, provision of cough monitoring equipment by Vitalograph, consultancy fees from Chiesi, a grant paid to Manchester University NHS Foundation Trust and personal fees from Afferent, consultancy fees from Bellus, and funding for a commercial study paid to Manchester University NHS Foundation Trust by and consultancy work for Axalbion, outside the submitted work. In addition, J.A. Smith has a patent, “A method for generating output data”, licenced.
- Received July 7, 2020.
- Accepted July 29, 2020.
- Copyright ©ERS 2020
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