A Study of Gefapixant (MK-7264) in Japanese Adult Participants With Refractory or Unexplained Chronic Cough (MK-7264-038)

A Phase 3, Randomized, Double-blind Clinical Study to Evaluate the Long-term Safety and Efficacy of MK-7264 in Japanese Adult Participants With Refractory or Unexplained Chronic Cough

The primary objective of this study is to evaluate the safety of two doses of gefapixant (MK-7264) in Japanese adult participants with refractory or unexplained chronic cough.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 175
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Akita, Japan, 010-8543
    • Akita University Hospital ( Site 3851)
  • Fukui, Japan, 918-8503
    • Fukui-ken Saiseikai Hospital ( Site 3874)
  • Gifu, Japan, 500-8717
    • Gifu Prefectural General Medical Center ( Site 3824)
  • Kagoshima, Japan, 890-0073
    • Tochigi Takao Clinic ( Site 3833)
  • Nagano, Japan, 380-8582
    • Nagano Red Cross Hospital ( Site 3859)
  • Niigata, Japan, 950-1104
    • Saiseikai Niigata Hospital ( Site 3831)
  • Oita, Japan, 870-0033
    • Oita Red Cross Hospital ( Site 3837)
  • Oita, Japan, 870-0921
    • Yamagata Clinic ( Site 3813)
  • Okinawa, Japan, 904-2143
    • Chibana Clinic ( Site 3809)
  • Shizuoka, Japan, 420-0803
    • Ito ENT Clinic ( Site 3816)
  • Tokyo, Japan, 103-0028
    • Nihonbashi Egawa Clinic ( Site 3805)
  • Tokyo, Japan, 130-8587
    • The Fraternity Memorial Hospital ( Site 3873)
  • Tokyo, Japan, 142-8666
    • Showa University Hospital ( Site 3896)
  • Tokyo, Japan, 150-0013
    • Ebisu Clinic Koukokukai Medical Corporation ( Site 3804)
  • Tokyo, Japan, 157-0072
    • Kono Medical Clinic ( Site 3894)
  • Tokyo, Japan, 170-0003
    • Medical Corporation Kouwakai Kouwa Clinic ( Site 3895)
  • Tokyo, Japan, 173-0015
    • Tokyo Metropolitan Geriatric Hospital ( Site 3905)
  • Aichi
    • Nagoya, Aichi, Japan, 455-8530
      • Chubu Rosai Hospital ( Site 3839)
    • Nagoya, Aichi, Japan, 460-0001
      • National Hospital Organization Nagoya Medical Center ( Site 3898)
    • Nagoya, Aichi, Japan, 467-8602
      • Nagoya City University Hospital ( Site 3899)
  • Fukuoka
    • Chikushino, Fukuoka, Japan, 818-8502
      • Fukuoka University Chikushi Hospital ( Site 3886)
    • Kasuya-gun, Fukuoka, Japan, 811-2310
      • Oishi Clinic ( Site 3818)
    • Koga, Fukuoka, Japan, 811-3195
      • National Hospital Organization Fukuokahigashi Medical Center ( Site 3849)
    • Yanagawa, Fukuoka, Japan, 832-0059
      • Nagata Hospital ( Site 3815)
  • Gifu
    • Mizunami, Gifu, Japan, 509-6134
      • Tohno Chuo Clinic ( Site 3883)
  • Gunma
    • Shibukawa, Gunma, Japan, 377-0280
      • National Hospital Organization Shibukawa Medical Center ( Site 3843)
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 064-0804
      • Idaimae Minamiyojo Int Clinic ( Site 3903)
  • Hyogo
    • Himeji, Hyogo, Japan, 670-0849
      • Terada Clinic Respiratory Medicine & General Practice ( Site 3907)
    • Itami, Hyogo, Japan, 664-8533
      • Kinki Central Hospital ( Site 3910)
    • Kobe, Hyogo, Japan, 653-0013
      • Kobe City Hospital Organization Kobe City Medical Center West Hospital ( Site 3868)
  • Ibaraki
    • Higashiibaraki-gun, Ibaraki, Japan, 311-3193
      • National Hospital Organization Mito Medical Center ( Site 3846)
    • Naka-gun, Ibaraki, Japan, 319-1113
      • National Hospital Organization Ibarakihigashi National Hospital ( Site 3917)
    • Toride, Ibaraki, Japan, 302-0022
      • JA Toride Medical Center ( Site 3822)
    • Tsuchiura, Ibaraki, Japan, 300-8585
      • National Hospital Organization Kasumigaura Medical Center ( Site 3844)
  • Ishikawa
    • Kanazawa, Ishikawa, Japan, 920-8530
      • Ishikawa Prefectural Central Hospital ( Site 3915)
    • Kanazawa, Ishikawa, Japan, 920-8610
      • Japan Community Health care Organization Kanazawa Hospital ( Site 3817)
    • Komatsu, Ishikawa, Japan, 923-8560
      • Komatsu Municipal Hospital ( Site 3892)
  • Kagawa
    • Takamatsu, Kagawa, Japan, 761-8073
      • Kamei Internal Medicine and Respiratory Clinic ( Site 3904)
  • Kanagawa
    • Fujisawa, Kanagawa, Japan, 251-8550
      • Fujisawa City Hospital ( Site 3891)
    • Kawasaki, Kanagawa, Japan, 210-0852
      • Association of Healthcare Corporation Koukankai Koukan Clinic ( Site 3878)
    • Yokohama, Kanagawa, Japan, 231-8682
      • Yokohama City Minato Red Cross Hospital ( Site 3906)
    • Yokohama, Kanagawa, Japan, 234-8503
      • Saiseikai Yokohamashi Nanbu Hospital ( Site 3897)
    • Yokohama, Kanagawa, Japan, 236-0051
      • Kanagawa Cardiovascular and Respiratory Center ( Site 3908)
  • Mie
    • Matsusaka, Mie, Japan, 515-8544
      • Matsusaka City Hospital ( Site 3825)
  • Nagano
    • Matsumoto, Nagano, Japan, 390-0872
      • Koyama Medical Clinic ( Site 3838)
  • Niigata
    • Nagaoka, Niigata, Japan, 940-2085
      • Nagaoka Red Cross Hospital ( Site 3877)
  • Okayama
    • Tsukubo-gun, Okayama, Japan, 701-0304
      • National Hospital Organization Minami-Okayama Medical Center ( Site 3901)
  • Osaka
    • Higashiosaka, Osaka, Japan, 577-0843
      • Kawaguchi Respiratory Clinic ( Site 3890)
    • Kishiwada, Osaka, Japan, 596-8501
      • Kishiwada City Hospital ( Site 3880)
    • Osakasayama, Osaka, Japan, 589-8511
      • Kindai University Hospital ( Site 3871)
    • Sakai, Osaka, Japan, 591-8037
      • Sasaki Naika Clinic ( Site 3872)
    • Sakai, Osaka, Japan, 591-8555
      • National Hospital Organization Kinki-chuo Chest Medical Center ( Site 3900)
  • Saitama
    • Kawaguchi, Saitama, Japan, 332-0012
      • Sugiura Clinic ( Site 3806)
  • Shimane
    • Matsue, Shimane, Japan, 690-8556
      • National Hospital Organization Matsue Medical Center ( Site 3848)
  • Shizuoka
    • Hamamatsu, Shizuoka, Japan, 430-8525
      • JapanOrganizationOfOccupationalHealthAndSafety HamamatsuRosaiHospital ( Site 3821)
    • Hamamatsu, Shizuoka, Japan, 432-8580
      • Hamamatsu Medical Center ( Site 3866)
    • Hamamatsu, Shizuoka, Japan, 434-8511
      • National Hospital Organization Tenryu Hospital ( Site 3823)
  • Tokyo
    • Hachioji, Tokyo, Japan, 193-0998
      • Tokyo Medical University Hachioji Medical Center ( Site 3911)
    • Kiyose, Tokyo, Japan, 204-8585
      • National Hospital Organization Tokyo National Hospital ( Site 3909)
    • Kodaira, Tokyo, Japan, 187-0044
      • Kiheibashi Otolaryngology ( Site 3828)
  • Yamaguchi
    • Shimonoseki, Yamaguchi, Japan, 750-8520
      • Shimonoseki City Hospital ( Site 3902)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Chest radiograph or computed tomography scan of the thorax 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 sub-investigator.
• Chronic cough for ≥ 4 months and a diagnosis of refractory or unexplained chronic cough.
• Persistent cough, despite treatment in accordance with the latest guideline of cough from the Japanese Respiratory Society, cough is a burden to the participant, and needs further treatment.
• If female, is not pregnant, not breast-feeding, and either is not a woman of childbearing potential or agrees to follow the contraceptive guidance.

Exclusion Criteria:

• Current smoker, or has given up smoking within 12 months of Screening.
• History of upper or lower respiratory tract infection or recent clinically significant change in pulmonary status.
• Has a history of chronic bronchitis.
• Current use of an angiotensin converting enzyme inhibitor (ACEI) or has taken an ACEI within 3 months of Screening.
• Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m^2 OR ≥30 mL/min/1.73 m^2 and <50 mL/min/1.73 m^2 at Visit 1 with unstable renal function (defined as a ≥50% increase of serum creatinine compared to a value obtained at least 6 months prior to Visit 1).
• History of malignancy ≤ 5 years.
• User of recreational or illicit drugs or has had a recent history (within the last year) of drug or alcohol abuse or dependence.
• Systolic blood pressure >160 mm Hg or a diastolic blood pressure >90 mm Hg at Screening.
• History of cutaneous adverse drug reaction to sulfonamide antibiotics or other sulfonamide-containing drugs.
• Known allergy/sensitivity or contraindication to gefapixant.
• Donated or lost ≥1 unit of blood within 8 weeks prior to the first dose of gefapixant.
• Previously received gefapixant or is currently participating in or has participated in an interventional clinical study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Gefapixant 15 mg BID; Participants will receive gefapixant 15 mg tablet and placebo tablet to match gefapixant 45 mg twice daily (BID) during the study period (52 weeks).	Drug: Gefapixant; Gefapixant 15 mg or 45 mg tablet administered orally BID; Other Names: MK-7264; Drug: Placebo; Placebo matched to gefapixant 15 mg or 45 mg administered orally BID
Experimental: Gefapixant 45 mg BID; Participants will receive gefapixant 45 mg tablet and placebo tablet to match gefapixant 15 mg BID during the study period (52 weeks).	Drug: Gefapixant; Gefapixant 15 mg or 45 mg tablet administered orally BID; Other Names: MK-7264; Drug: Placebo; Placebo matched to gefapixant 15 mg or 45 mg administered orally BID

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Experienced at Least One Adverse Event (AE)	An AE is 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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.	Up to 54 Weeks
Number of Participants Who Discontinued Study Drug Due to an AE	An AE is 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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.	Up to 52 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the Leicester Cough Questionnaire (LCQ) Total Score at Week 12	The LCQ is a 19-item cough-specific health-related quality of life (HRQoL) questionnaire which contains three domains (physical, psychological and social), calculated as a mean score for each domain ranging from 1 to 7 and total score ranging from 3 to 21. Each item on the LCQ is assessed using a 7-point Likert scale ranging from 1 to 7. Higher scores indicate better HRQoL. The least squares mean of the change from baseline is based on a longitudinal analysis of covariance (ANCOVA) model.	Baseline, Week 12
Change From Baseline in LCQ Total Score	The LCQ is a 19-item cough-specific HRQoL questionnaire which contains three domains (physical, psychological and social), calculated as a mean score for each domain ranging from 1 to 7 and total score ranging from 3 to 21. Each item on the LCQ is assessed using a 7-point Likert scale ranging from 1 to 7. Higher scores indicate better HRQoL. The least squares mean of the change from baseline is based on a longitudinal analysis of covariance (ANCOVA) model at weeks 4, 8, 12, 24, 38 and 52 of treatment.	Baseline, up to 52 Weeks
Percentage of Participants With a ≥1.3 Point Change From Baseline in the LCQ Total Score	The LCQ is a 19-item cough-specific HRQoL questionnaire which contains three domains (physical, psychological and social), calculated as a mean score for each domain ranging from 1 to 7 and total score ranging from 3 to 21. Each item on the LCQ is assessed using a 7-point Likert scale ranging from 1 to 7. Higher scores indicate better HRQoL. A clinically meaningful improvement from baseline in HRQoL was defined as ≥1.3-point increase in the LCQ total score at weeks 4, 8, 12, 24, 38 and 52 of treatment.	Baseline, Up to 52 Weeks

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Niimi A, Sagara H, Kikuchi M, Arano I, Sato A, Shirakawa M, La Rosa C, Muccino D. A phase 3, randomized, double-blind, clinical study to evaluate the long-term safety and efficacy of gefapixant in Japanese adult participants with refractory or unexplained chronic cough. Allergol Int. 2022 Oct;71(4):498-504. doi: 10.1016/j.alit.2022.05.006. Epub 2022 Jun 23.

Study record dates

Study Major Dates

• Study Start (Actual): October 31, 2018
• Primary Completion (Actual): October 7, 2020
• Study Completion (Actual): October 7, 2020

Study Registration Dates

• First Submitted: October 3, 2018
• First Submitted That Met QC Criteria: October 3, 2018
• First Posted (Actual): October 4, 2018

Study Record Updates

• Last Update Posted (Actual): November 1, 2021
• Last Update Submitted That Met QC Criteria: September 30, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Cough
• Other Study ID Numbers: 7264-038; MK-7264-038 (Other Identifier: Merck Protocol Number); 184154 (Registry Identifier: JAPIC-CTI)

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