Efficacy and Safety of Gefapixant (MK-7264) in Adult Participants With Recent Onset Chronic Cough (MK-7264-043)

Chronic Cough Clinical Trial

Official title:

A Phase 3b Randomized, Double-blind, Placebo Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Gefapixant in Adult Participants With Recent Onset Chronic Cough

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04193202
• Other study ID #: 7264-043
• Secondary ID: MK-7264-0432019-
• Status: Completed
• Phase: Phase 3
• Start date: May 21, 2020
• Est. completion date: November 3, 2021

Study information

• Verified date: May 2023
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the efficacy and safety of gefapixant in participants with recent onset chronic cough (duration >8 weeks after onset of cough symptoms) for <12 months and a diagnosis of refractory or unexplained chronic cough. The primary hypothesis is that gefapixant is superior to placebo in improving cough-related quality of life measured as change from baseline in the Leicester Cough Questionnaire (LCQ) total score at Week 12.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 419
• Est. completion date: November 3, 2021
• Est. primary completion date: October 19, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Chest radiograph or CT thorax (within 1 year of Screening/Visit 1 and after the onset of chronic cough) not demonstrating any abnormality considered to be significantly contributing to the chronic cough or any other clinically significant lung disease, in the opinion of the principal investigator or the subinvestigator

• Has chronic cough (defined as duration of >8 weeks after onset of cough symptoms) for <12 months prior to the screening visit (<14 months after onset of cough symptoms)

• Has a diagnosis of refractory chronic cough or unexplained chronic cough

• Female participants are not pregnant, not breastfeeding, not of childbearing potential, or agree to follow contraceptive guidance

Exclusion Criteria:

• Is a current smoker

• Has given up smoking within 12 months of screening

• Is a former smoker with a smoking history greater than 20 pack-years (1 pack of 20 cigarettes per day for 20 years)

• Has a history of respiratory tract infection or recent change in pulmonary status within 4 weeks of screening

• Has a history of chronic bronchitis, defined as cough that produces >1 tablespoon of phlegm, that occurs every day for at least 3 months in a row

• Has a history of malignancy =5 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer or cervical cancer

• Is a user of recreational or illicit drugs or a recent history (within the last year) of drug or alcohol abuse

• Has a history of anaphylaxis or cutaneous adverse drug reaction to sulfonamide-containing drugs

• Has a known allergy to gefapixant or its excipients

• Has donated or lost =1 unit (~300 mL) of blood within 8 weeks prior to first dose of gefapixant

• Has previously received gefapixant

• Is currently participating or has participated in an interventional clinical study within 30 days of participating in this current study

Related Conditions & MeSH terms

• Chronic Cough
• Cough

Intervention

Drug:
• Gefapixant
Administered twice daily as an oral tablet of 45 mg
• Placebo
Administered twice daily as a placebo oral tablet matching gefapixant

Locations

Country	Name	City	State
Canada	Recherche GCP Research ( Site 0802)	Montreal	Quebec
Canada	Clinique Specialisee en Allergie de la Capitale - CSAC ( Site 0800)	Quebec
Canada	Diex Recherche Quebec Inc ( Site 0805)	Quebec
Colombia	Centro Especializado en Enfermedades Pulmonares. ( Site 0410)	Bogota	Distrito Capital De Bogota
Colombia	MedPlus Medicina Prepagada S.A. ( Site 0402)	Bogota	Distrito Capital De Bogota
Colombia	Instituto Neumologico del Oriente ( Site 0403)	Floridablanca	Santander
Colombia	Fundacion Centro de Investigacion Clinica CIC ( Site 0401)	Medellin	Antioquia
Colombia	Universidad Pontificia Bolivariana - Clinica Universitaria Bolivariana ( Site 0408)	Medellin	Antioquia
Colombia	Healthy Medical Center S.A.S ( Site 0404)	Zipaquira	Cundinamarca
Germany	Pneumologisches Studienzentrum ( Site 0911)	Berlin
Germany	Pneumologicum im Suedstadtforum ( Site 0916)	Hannover	Niedersachsen
Germany	Zentrum fuer ambulante pneumologische Forschung Marburg GbR ( Site 0910)	Marburg	Hessen
Germany	Ballenberger Freytag Wenisch Institut fuer klinische Forschung GmbH ( Site 0917)	Neu-Isenburg	Hessen
Guatemala	Celan SA ( Site 0500)	Guatemala
Guatemala	Clinica Medica Especializada en Neumologia ( Site 0502)	Guatemala
Guatemala	Clinica Medica Especializada en Neumologia y Tisiologia ( Site 0504)	Guatemala
Guatemala	Clinica Privada Dr. Jose Francisco Flores Lopez ( Site 0503)	Guatemala
Guatemala	Instituto De Alergias y Enfermedades Respiratorias ( Site 0501)	Guatemala
Guatemala	Private Clinic ( Site 0505)	Guatemala
Korea, Republic of	Konkuk University Medical Center ( Site 1504)	Seoul
Korea, Republic of	Seoul National University Hospital ( Site 1501)	Seoul
Korea, Republic of	Severance Hospital Yonsei University Health System ( Site 1503)	Seoul
Korea, Republic of	Asan Medical Center ( Site 1505)	Songpagu	Seoul
Korea, Republic of	Wonju Severance Christian Hospital ( Site 1502)	Wonju-si	Kang-won-do
Peru	Asociacion Civil por la Salud ( Site 0602)	Lima
Peru	Hospital Nacional Arzobispo Loayza ( Site 0607)	Lima
Peru	Clinica Belen ( Site 0604)	Piura
Peru	Clinica Ricardo Palma ( Site 0601)	San Isidro	Lima
Poland	Centrum Medyczne Pratia Bydgoszcz ( Site 1206)	Bydgoszcz	Kujawsko-pomorskie
Poland	Centrum Medyczne Pratia Katowice ( Site 1205)	Katowice	Slaskie
Poland	Centrum Medyczne Silmedic Sp z o o ( Site 1204)	Katowice	Slaskie
Poland	Gyncentrum Clinic Sp. z o.o. ( Site 1208)	Katowice	Slaskie
Poland	Specjalistyczny osrodek .All-Med. Grazyna Pulka ( Site 1203)	Krakow	Malopolskie
Poland	NZOZ CENTRUM ALERGOLOGII ( Site 1207)	Lublin	Lubelskie
Poland	RCMed ( Site 1202)	Sochaczew	Mazowieckie
Poland	Centrum Medyczne Pulawska ( Site 1215)	Warsaw	Mazowieckie
Poland	Centrum Medyczne Lucyna Andrzej Dymek - Zawadzkie ( Site 1200)	Zawadzkie	Opolskie
Russian Federation	RSBHI Belgorod regional clinical hospital of Prelate Ioasafa ( Site 1417)	Belgorod	Belgorodskaya Oblast
Russian Federation	GBUZ Regional Clinical Hospital 3 ( Site 1421)	Chelyabinsk	Chelyabinskaya Oblast
Russian Federation	City Clinical Hospital No. 3 them. M. A. Podgorbunskogo ( Site 1401)	Kemerovo	Kemerovskaya Oblast
Russian Federation	Moscow City Clinical Hospital Number 13 ( Site 1460)	Moscow	Moskva
Russian Federation	Open Joint Stock Company Clinical and Diagnostic Center Euromedservice ( Site 1467)	Moscow	Moskva
Russian Federation	Clinic of FSBEI HE OmSMU of Minzdrav ( Site 1439)	Omsk	Omskaya Oblast
Russian Federation	advisory diagnostic center No.85 ( Site 1455)	Saint Petersburg	Sankt-Peterburg
Russian Federation	GBUZ LO Center of Occupational Pathology ( Site 1447)	Saint Petersburg	Sankt-Peterburg
Russian Federation	SEIHPE Saint Petersburg SMU ( Site 1435)	Saint Petersburg	Sankt-Peterburg
Russian Federation	SPb SBHI City Consultative Diagnostic Center 1 ( Site 1409)	Saint Petersburg	Sankt-Peterburg
Russian Federation	Saratov City Clinical Hospital 2 n.a. V.I. Razumovsky ( Site 1453)	Saratov	Saratovskaya Oblast
Russian Federation	Limited Liability Company Kurator ( Site 1425)	St. Petersburg	Sankt-Peterburg
Russian Federation	State health Agency Ulyanovsk regional clinical hospital ( Site 1415)	Ulyanovsk	Ul Yanovskaya Oblast
Russian Federation	Voronezh Regional Clinical Hospital #1 ( Site 1441)	Voronezh	Voronezskaja Oblast
Russian Federation	SBCIH of the Yaroslavl region Central city hospital ( Site 1429)	Yaroslavl	Yaroslavskaya Oblast
Russian Federation	Family Clinic ( Site 1465)	Yekaterinburg	Sverdlovskaya Oblast
Spain	Hospital Clinico San Carlos ( Site 1822)	Madrid
Spain	Hospital General Universitario Gregorio Maranon ( Site 1823)	Madrid	Madrid, Comunidad De
Spain	Hospital Ramon y Cajal ( Site 1815)	Madrid
Spain	Hospital Parc Tauli ( Site 1821)	Sabadell	Barcelona
Spain	Hospital Clinico Universitario de Santiago ( Site 1820)	Santiago de Compostela	La Coruna
Ukraine	Kherson City Clinical Hospital n.a. Y.Y. Karabelesh ( Site 2811)	Kherson	Khersonska Oblast
Ukraine	F.G.Yanovskyy Institute of Phthisiology and Pulmonology ( Site 2802)	Kyiv	Kyivska Oblast
Ukraine	F.G.Yanovskyy Institute of Phthisiology and Pulmonology ( Site 2808)	Kyiv	Kyivska Oblast
Ukraine	Medical Center of LLC Medical Clinic Blahomed ( Site 2815)	Kyiv
Ukraine	SE O.S.Kolomiychenko Institute of Otolaryngology of NAMS of Ukraine ( Site 2817)	Kyiv	Kyivska Oblast
Ukraine	SE Road Clinical Hospital 2 of Kyiv station ( Site 2812)	Kyiv	Kyivska Oblast
Ukraine	Volyn Regional Clinical Hospital ( Site 2816)	Lutsk	Volynska Oblast
Ukraine	City Polyclinic N20 ( Site 2806)	Odesa	Odeska Oblast
Ukraine	Odesa regional clinical hospital ( Site 2804)	Odesa	Odeska Oblast
Ukraine	Poltava City Clinical Hospital -1 ( Site 2813)	Poltava	Poltavska Oblast
Ukraine	Vinnytsia Regional Clinical Hospital n.a. M.I. Pyrogov ( Site 2814)	Vinnytsia	Vinnytska Oblast
Ukraine	Private Small-Scale Enterprise Medical Centre "Pulse" ( Site 2809)	Vinnytsya	Vinnytska Oblast
Ukraine	MI Zaporizhzhia City Multispecialty Clinical Hospital 9 ( Site 2803)	Zaporizhzhia	Zaporizka Oblast
Ukraine	Zhytomyr Central City Hospital No. 1 ( Site 2807)	Zhytomyr	Zhytomyrska Oblast
United Kingdom	Medinova North London Dedicated Research Centre ( Site 2705)	Northwood
United Kingdom	Medinova South London Research Centre ( Site 2706)	Orpington	Kent
United Kingdom	MeDiNova Yorkshire Dedicated Research Centre ( Site 2715)	Shipley	Bradford
United Kingdom	West Walk Surgery ( Site 2700)	Yate	Gloucestershire
United States	Albuquerque Clinical Trials ( Site 0030)	Albuquerque	New Mexico
United States	Bellingham Asthma & Allergy ( Site 0011)	Bellingham	Washington
United States	Montefiore Einstein Center ( Site 0022)	Bronx	New York
United States	American Health Research ( Site 0047)	Charlotte	North Carolina
United States	Allergic Disease and Asthma Center ( Site 0027)	Greenville	South Carolina
United States	AAPRI Clinical Research Institute ( Site 0051)	Lincoln	Rhode Island
United States	Clinical Research Institute of Southern Oregon, PC ( Site 0028)	Medford	Oregon
United States	Center for Clinical Trials, LLC ( Site 0035)	Paramount	California
United States	Pulmonary Associates, PA ( Site 0016)	Phoenix	Arizona
United States	Northwest Research Center ( Site 0039)	Portland	Oregon
United States	Diagnostics Research Group ( Site 0021)	San Antonio	Texas
United States	Springfield Clinic, LLP ( Site 0018)	Springfield	Illinois
United States	Allergy & Asthma Center ( Site 0001)	Waco	Texas
United States	Chesapeake Clinical Research, Inc ( Site 0037)	White Marsh	Maryland
United States	Tidewater Physician Multispecialty Group, PC ( Site 0048)	Williamsburg	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Canada,  Colombia,  Germany,  Guatemala,  Korea, Republic of,  Peru,  Poland,  Russian Federation,  Spain,  Ukraine,  United Kingdom, 

References & Publications (1)

McGarvey L, Sher M, Shvarts YG, Lu S, Wu WC, Xu P, Schelfhout J, La Rosa C, Nguyen AM, Reyfman PA, Afzal AS. The Efficacy and Safety of Gefapixant in a Phase 3b Trial of Patients with Recent-Onset Chronic Cough. Lung. 2023 Apr;201(2):111-118. doi: 10.1007 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in the Leicester Cough Questionnaire (LCQ) Total Score at Week 12	Participants will be asked to complete the LCQ to assess the impact of their cough severity on health related quality of life (HRQoL) over the past 2 weeks. The LCQ is a 19-item, cough-specific HRQoL questionnaire. Each item on the LCQ assesses symptoms using a 7-point scale ranging from 1 to 7. The LCQ contains three domains on physical, psychological, and social functioning, and each domain score is calculated as the mean score of the items (range: 1 to 7) within the domain. The LCQ total score is the sum of the 3 domains, with a range from 3 (lowest total score) to 21 (highest total score). Higher scores indicate better HRQoL. The change from baseline in LCQ total score is calculated.	Baseline, Week 12
Secondary	Change From Baseline in the Cough Severity Visual Analog Scale (VAS) Score at Week 12	Participants will be asked to complete the VAS questionnaire to assess the severity of their cough over the past 24-hours. The Cough Severity VAS is a single-item questionnaire asking the participant to rate the severity of their cough on a 100-point scale ranging from 0 ("No Cough") to 100 ("Extremely Severe Cough"). Higher scores indicate greater severity of cough. The change from baseline in VAS score is calculated.	Baseline, Week 12
Secondary	Percentage of Participants With One or More Adverse Events (AEs)	An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants with one or more AEs is presented.	Up to approximately 14 weeks
Secondary	Percentage of Participants Who Discontinue Study Drug Due to an AE	An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who discontinue study drug due to an AE is presented.	Up to approximately 12 weeks