Efficacy and Safety of Gefapixant (MK-7264) in Women With Chronic Cough and Stress Urinary Incontinence (MK-7264-042)

A Phase 3b Randomized, Double-blind, Placebo Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Gefapixant in Women With Chronic Cough and Stress Urinary Incontinence

The purpose of this study is to evaluate the efficacy and safety of gefapixant, in improving symptoms of cough-induced stress urinary incontinence (SUI) in adult female participants with refractory or unexplained chronic cough. The primary hypothesis is that gefapixant is superior to placebo in reducing the frequency of cough-induced SUI episodes over 12 weeks.

Study Overview

• Status: Completed
• Conditions: Chronic Cough
• Intervention / Treatment: Drug: Gefapixant; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 376
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1426ANZ
    • Centro Medico Dra De Salvo ( Site 0300)
  • Tucuman, Argentina, T4000IAQ
    • Investigaciones en Patologias Respiratorias ( Site 0302)
• Colombia
  • Antioquia
    • Medellin, Antioquia, Colombia, 050021
      • Fundacion Centro de Investigacion Clinica CIC ( Site 0401)
    • Medellin, Antioquia, Colombia, 050036
      • Universidad Pontificia Bolivariana - Clinica Universitaria Bolivariana ( Site 0408)
  • Cundinamarca
    • Zipaquira, Cundinamarca, Colombia, 250252
      • Healthy Medical Center S.A.S ( Site 0404)
  • Distrito Capital De Bogota
    • Bogota, Distrito Capital De Bogota, Colombia, 110221
      • Medplus Medicina Prepagada ( Site 0402)
• Germany
  • Berlin, Germany, 10625
    • Praxis an der Oper ( Site 0912)
  • Bayern
    • Augsburg, Bayern, Germany, 86150
      • Praxis Dr. Wehgartner-Winkler ( Site 0906)
  • Hessen
    • Marburg, Hessen, Germany, 35037
      • Zentrum fuer ambulante pneumologische Forschung Marburg GbR ( Site 0900)
    • Neu-Isenburg, Hessen, Germany, 63263
      • Ballenberger Freytag Wenisch Institut fuer klinische Forschung GmbH ( Site 0905)
  • Niedersachsen
    • Hannover, Niedersachsen, Germany, 30173
      • Pneumologicum im Suedstadtforum ( Site 0908)
• Guatemala
  • Guatemala, Guatemala, 01010
    • Bethel Soluciones Medicas S.A. ( Site 0506)
  • Guatemala, Guatemala, 01010
    • Centro de Investigaciones Clinicas de Latinoamerica S.A. - CELAN ( Site 0500)
  • Guatemala, Guatemala, 01010
    • Clinica Medica Especializada en Neumologia y Tisiologia ( Site 0504)
  • Guatemala, Guatemala, 01011
    • Clinica Medica Especializada en Neumologia ( Site 0502)
  • Guatemala, Guatemala, 01011
    • Private Clinic ( Site 0505)
  • Guatemala, Guatemala, 01015
    • Clinica Privada Dr. Jose Francisco Flores Lopez ( Site 0503)
• Israel
  • Haifa, Israel, 34362
    • Carmel Medical Center ( Site 1104)
  • Jerusalem, Israel, 9103102
    • Shaare Zedek Medical Center ( Site 1107)
  • Jerusalem, Israel, 9112001
    • Hadassah Ein Karem Jerusalem ( Site 1108)
  • Petah Tikva, Israel, 4941492
    • Rabin Medical Center ( Site 1102)
  • Ramat Gan, Israel, 5265601
    • Chaim Sheba Medical Center ( Site 1101)
  • Rehovot, Israel, 7610001
    • Kaplan Medical Center ( Site 1103)
  • Tel-Aviv, Israel, 6423906
    • Sourasky Medical Center ( Site 1100)
• Korea, Republic of
  • Seoul, Korea, Republic of, 03312
    • The Catholic University of Korea Eunpyeong St Mary s Hospital ( Site 1506)
  • Seoul, Korea, Republic of, 05030
    • Konkuk University Medical Center ( Site 1504)
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center ( Site 1505)
  • Jeonrabugdo
    • Jeonju-si, Jeonrabugdo, Korea, Republic of, 54907
      • Jeonbuk National University Hospital ( Site 1507)
  • Kang-won-do
    • Wonju-si, Kang-won-do, Korea, Republic of, 26426
      • Wonju Severance Christian Hospital ( Site 1502)
• Peru
  • Lima, Peru, 15046
    • Asociacion Civil por la Salud ( Site 0602)
  • Lima, Peru, 15082
    • Hospital Nacional Arzobispo Loayza ( Site 0607)
  • Piura, Peru, 20001
    • Clinica Belen ( Site 0604)
  • Lima
    • San Isidro, Lima, Peru, 15036
      • Clinica Ricardo Palma ( Site 0601)
• Russian Federation
  • Belgorodskaya Oblast
    • Belgorod, Belgorodskaya Oblast, Russian Federation, 308007
      • RSBHI Belgorod regional clinical hospital of Prelate Ioasafa ( Site 1416)
  • Chelyabinskaya Oblast
    • Chelyabinsk, Chelyabinskaya Oblast, Russian Federation, 454021
      • GBUZ Regional Clinical Hospital 3 ( Site 1420)
  • Kemerovskaya Oblast
    • Kemerovo, Kemerovskaya Oblast, Russian Federation, 650000
      • City Clinical Hospital No. 3 them. M. A. Podgorbunskogo ( Site 1400)
  • Moskovskaya Oblast
    • Krasnogorsk, Moskovskaya Oblast, Russian Federation, 143403
      • Krasnogorsk City Hospital Number 1 ( Site 1470)
  • Moskva
    • Moscow, Moskva, Russian Federation, 115419
      • Open Joint Stock Company Clinical and Diagnostic Center Euromedservice ( Site 1466)
  • Novosibirskaya Oblast
    • Novosibirsk, Novosibirskaya Oblast, Russian Federation, 630102
      • City Clinical Hospital of Emergency Care #2 ( Site 1448)
  • Omskaya Oblast
    • Omsk, Omskaya Oblast, Russian Federation, 644050
      • Clinic of FSBEI HE OmSMU of Minzdrav ( Site 1438)
  • Permskiy Kray
    • Perm, Permskiy Kray, Russian Federation, 614109
      • Perm Clinical Center of the Federal Medical and Biological Agency ( Site 1450)
  • Sankt-Peterburg
    • Saint Petersburg, Sankt-Peterburg, Russian Federation, 195279
      • Medi Kom ( Site 1456)
    • Saint Petersburg, Sankt-Peterburg, Russian Federation, 197022
      • SEIHPE Saint Petersburg SMU ( Site 1434)
    • St. Petersburg, Sankt-Peterburg, Russian Federation, 196240
      • Limited Liability Company Kurator ( Site 1424)
  • Saratovskaya Oblast
    • Saratov, Saratovskaya Oblast, Russian Federation, 410012
      • Saratov City Clinical Hospital 2 n.a. V.I. Razumovsky ( Site 1452)
  • Sverdlovskaya Oblast
    • Yekaterinburg, Sverdlovskaya Oblast, Russian Federation, 620109
      • Family Clinic ( Site 1464)
  • Ul Yanovskaya Oblast
    • Ulyanovsk, Ul Yanovskaya Oblast, Russian Federation, 432063
      • State health Agency Ulyanovsk regional clinical hospital ( Site 1414)
  • Voronezskaja Oblast
    • Voronezh, Voronezskaja Oblast, Russian Federation, 394066
      • Voronezh Regional Clinical Hospital #1 ( Site 1440)
  • Yaroslavskaya Oblast
    • Yaroslavl, Yaroslavskaya Oblast, Russian Federation, 150040
      • SBCIH of the Yaroslavl region Central city hospital ( Site 1428)
• Spain
  • Barcelona
    • Sabadell, Barcelona, Spain, 08208
      • Hospital Parc Tauli ( Site 1806)
  • Cataluna
    • Barcelona, Cataluna, Spain, 08036
      • Hospital Clinic i Provincial de Barcelona ( Site 1804)
  • La Coruna
    • Santiago de Compostela, La Coruna, Spain, 15706
      • Hospital Clinico Universitario de Santiago ( Site 1805)
  • Madrid, Comunidad De
    • Madrid, Madrid, Comunidad De, Spain, 28007
      • Hospital General Universitario Gregorio Maranon ( Site 1808)
• Ukraine
  • Kyiv, Ukraine, 01023
    • Medical Center of LLC Medical Clinic Blahomed ( Site 2815)
  • Kyivska Oblast
    • Kyiv, Kyivska Oblast, Ukraine, 03038
      • F.G.Yanovskyy Institute of Phthisiology and Pulmonology ( Site 2808)
    • Kyiv, Kyivska Oblast, Ukraine, 03038
      • F.G.Yanovskyy Institute of Phthisiology and Pulmonology ( Site 2819)
    • Kyiv, Kyivska Oblast, Ukraine, 03049
      • SE Road Clinical Hospital 2 of Kyiv station ( Site 2812)
    • Kyiv, Kyivska Oblast, Ukraine, 03057
      • SE O.S.Kolomiychenko Institute of Otolaryngology of NAMS of Ukraine ( Site 2817)
  • Odeska Oblast
    • Odesa, Odeska Oblast, Ukraine, 65025
      • Odesa regional clinical hospital ( Site 2804)
    • Odesa, Odeska Oblast, Ukraine, 65114
      • City Polyclinic N20 ( Site 2806)
  • Poltavska Oblast
    • Poltava, Poltavska Oblast, Ukraine, 36039
      • Municipal enterprise "1st City clinical hospital of Poltava -Internal medicine department ( Site 281
  • Vinnytska Oblast
    • Vinnytsya, Vinnytska Oblast, Ukraine, 21001
      • Private Small-Scale Enterprise Medical Centre "Pulse" ( Site 2809)
  • Volynska Oblast
    • Lutsk, Volynska Oblast, Ukraine, 43005
      • Volyn Regional Clinical Hospital ( Site 2816)
• United Kingdom
  • Coventry, United Kingdom, CV3 4FJ
    • Medinova Warwickshire Dedicated Research Centre ( Site 2715)
  • England
    • Harrow, England, United Kingdom, HA2 0RQ
      • GP Direct ( Site 2714)
  • Gloucestershire
    • Yate, Gloucestershire, United Kingdom, BS37 4AX
      • West Walk Surgery ( Site 2700)
  • Northamptonshire
    • Corby, Northamptonshire, United Kingdom, NN18 9EZ
      • Medinova Lakeside Dedicated Research Centre ( Site 2712)
  • Southwark
    • London, Southwark, United Kingdom, SE5 9RS
      • Kings College Hospital NHS Foundation Trust ( Site 2702)
  • Surrey
    • Orpington, Surrey, United Kingdom, BR5 3QG
      • Accellacare South London Quality Research Centre ( Site 2706)
  • West Berkshire
    • Wokingham, West Berkshire, United Kingdom, RG40 1XS
      • Wokingham Medical Centre ( Site 2708)
  • Worcestershire
    • Northwood, Worcestershire, United Kingdom, HA6 2RN
      • Medinova North London Dedicated Research Centre ( Site 2705)
• United States
  • California
    • Paramount, California, United States, 90723
      • Center for Clinical Trials, LLC ( Site 0021)
  • Florida
    • Jupiter, Florida, United States, 33458
      • Health Awareness, Inc. ( Site 0038)
    • Miami, Florida, United States, 33173
      • Well Pharma Medical Research, Corp. ( Site 0040)
    • Sweetwater, Florida, United States, 33172
      • Lenus Research & Medical Group Llc ( Site 0007)
    • Winter Park, Florida, United States, 32789
      • Florida Pulmonary Research Institute, LLC ( Site 0008)
  • Maine
    • Bangor, Maine, United States, 04401
      • Paul A. Shapero, MD ( Site 0037)
  • Maryland
    • White Marsh, Maryland, United States, 21162
      • Chesapeake Clinical Research, Inc ( Site 0022)
  • Missouri
    • Columbia, Missouri, United States, 65201
      • University of Missouri ENT & Allergy Center ( Site 0010)
  • Nevada
    • Las Vegas, Nevada, United States, 89119
      • Alliance for Multispecialty Research, LLC ( Site 0035)
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Albuquerque Clinical Trials ( Site 0019)
  • North Carolina
    • Charlotte, North Carolina, United States, 28277
      • American Health Research ( Site 0027)
    • Gastonia, North Carolina, United States, 28054
      • Clinical Research of Gastonia ( Site 0016)
    • Wilmington, North Carolina, United States, 28401
      • PMG Research of Wilmington ( Site 0004)
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University ( Site 0003)
  • Rhode Island
    • Warwick, Rhode Island, United States, 02886
      • AAPRI Clinical Research Institute ( Site 0031)
  • Texas
    • San Antonio, Texas, United States, 78229
      • Diagnostics Research Group ( Site 0013)
  • Virginia
    • Newport News, Virginia, United States, 23606
      • TPMG Clinical Research ( Site 0025)
    • Williamsburg, Virginia, United States, 23188
      • Tidewater Physician Multispecialty Group, PC ( Site 0028)
  • Washington
    • Bellingham, Washington, United States, 98225
      • Bellingham Asthma & Allergy ( Site 0006)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Has a chest radiograph or computed tomography scan of the thorax (within 5 years of Screening and after the onset of chronic cough) not demonstrating any abnormality considered to be significantly contributing to the chronic cough or any other lung disease
• Has chronic cough (defined as duration of >8 weeks after onset of cough symptoms) for ≥12 months
• Has a diagnosis of refractory chronic cough or unexplained chronic cough
• Has symptoms of SUI, defined as involuntary loss of urine on effort, physical exertion, or on sneezing or coughing, for ≥3 months
• Is a female who is not pregnant, not breastfeeding, not of childbearing potential, or agrees 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
• Has a history of surgery to treat SUI within 1 year of screening
• Has a history of other specialized treatments for SUI, including intravesical balloon or urethral bulking agent therapy
• Has other external incontinence device currently or within 1 month of screening
• Has a history of Grade 3 or higher pelvic organ prolapse previously documented or diagnosed on screening
• Has a neurogenic bladder
• Has a history of adult nocturnal incontinence
• Has a history of continuous urine leakage within 1 month of screening
• Has a history of interstitial cystitis
• Has a history of neurological disease or injury
• Has active or recurrent urinary tract infection
• Has a history of having a permanent urinary catheter or any urinary catheterization within 3 months of screening
• Has a history of malignancy ≤5 years prior to signing informed consent
• Is a user of recreational or illicit drugs or a recent history (within the last year) of drug or alcohol abuse
• 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
• Requires certain medications and/or other therapies that may impact their cough or bladder function
• Has previously received gefapixant
• Is currently participating or has participated in an interventional clinical study within 30 days of participating in this current study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Gefapixant; Participants will receive gefapixant at a dose of 45 mg administered as an oral tablet twice daily for 12 weeks.	Drug: Gefapixant; Administered twice daily as an oral tablet of 45 mg; Other Names: MK-7264
Placebo Comparator: Placebo; Participants will receive placebo matching gefapixant, administered as an oral tablet twice daily for 12 weeks.	Drug: Placebo; Administered twice daily as a placebo oral tablet matching gefapixant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Average Daily Cough-induced Stress Urinary Incontinence (SUI) Episodes at Week 12	Cough-induced SUI episodes were assessed using an event-driven electronic Incontinence Diary where the participant recorded the main cause of each urinary incontinence episode as coughing, another stress reason, or other cause. Episodes of incontinence were recorded for the week before baseline and treatment visit. Average daily cough induced SUI episodes were calculated as (sum of daily cough-induced SUI episodes in a week)/number of days recorded. The percent change from baseline in the average daily cough-induced SUI episodes to Week 12 are presented.	Baseline and week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Adverse Events	An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experienced an adverse event are presented.	Up to ~16 weeks
Percentage of Participants Who Discontinued Study Intervention Due to AEs	An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who discontinued study intervention due to an adverse event are presented.	Up to ~14 weeks

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Birring SS, Cardozo L, Dmochowski R, Dicpinigaitis P, Afzal A, La Rosa C, Lu S, Nguyen AM, Yao R, Reyfman PA. Efficacy and safety of gefapixant in women with chronic cough and cough-induced stress urinary incontinence: a phase 3b, randomised, multicentre, double-blind, placebo-controlled trial. Lancet Respir Med. 2024 Aug 30:S2213-2600(24)00222-4. doi: 10.1016/S2213-2600(24)00222-4. Online ahead of print.

Helpful Links

• Merck Clinical Trials Information

Study record dates

Study Major Dates

• Study Start (Actual): May 10, 2020
• Primary Completion (Actual): August 18, 2022
• Study Completion (Actual): September 2, 2022

Study Registration Dates

• First Submitted: December 9, 2019
• First Submitted That Met QC Criteria: December 9, 2019
• First Posted (Actual): December 10, 2019

Study Record Updates

• Last Update Posted (Actual): November 5, 2024
• Last Update Submitted That Met QC Criteria: October 23, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Cough; Urinary Incontinence, Stress; Signs and symptoms; Respiration disorders; Respiratory tract diseases; Signs and symptoms, respiratory
• Additional Relevant MeSH Terms: Urogenital Diseases; Mental Disorders; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urination Disorders; Lower Urinary Tract Symptoms; Urological Manifestations; Behavioral Symptoms; Elimination Disorders; Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Chronic Cough; Urinary Incontinence; Enuresis; Urinary Incontinence, Stress; Cough
• Other Study ID Numbers: 7264-042; MK-7264-042 (Other Identifier: MSD Protocol Number); 2019-002321-29 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No