A Study of Gefapixant (MK-7264) in Adult Participants With Chronic Cough (MK-7264-030)-China Extension

A Phase 3, Randomized, Double-Blind, Placebo-Controlled, 12-Month Study to Evaluate the Efficacy and Safety of MK-7264 in Adult Participants With Chronic Cough (PN030)

The primary objective of this study will be to evaluate the efficacy of gefapixant (MK-7264) in reducing cough frequency as measured over a 24-hour period. It is hypothesized that at least one dose of gefapixant is superior to placebo in reducing coughs per hour (over 24 hours) at Week 24.

Study Overview

• Status: Completed
• Conditions: Chronic Cough
• Intervention / Treatment: Drug: Placebo; Drug: Gefapixant 45 mg twice daily (BID); Drug: Gefapixant 15 mg BID; Drug: Gefapixant 45 mg BID

Detailed Description

This study will have a main 24-week treatment period and a 28-week extension period of treatment. Participants at selected sites and countries who complete the main and extension study periods may consent to participate in an observational, 3-month, Off-treatment Durability Study Period.

• Study Type: Interventional
• Enrollment (Actual): 161
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100191
    • Peking University Third Hospital ( Site 5005)
  • Fujian
    • Fuzhou, Fujian, China, 350005
      • The First Affiliated Hospital of Fujian Medical University ( Site 5017)
  • Guangdong
    • Guangzhou, Guangdong, China, 510120
      • The First Affiliated Hospital of Guangzhou Medical University ( Site 5000)
  • Inner Mongolia
    • Hohhot, Inner Mongolia, China, 010017
      • Inner Mongolia Autonomous Region Hospital ( Site 5018)
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • The First Affiliated Hospital of Nanchang University ( Site 5012)
  • Liaoning
    • Shenyang, Liaoning, China, 110004
      • ShengJing Hospital of China Medical University ( Site 5024)
  • Shanghai
    • Shanghai, Shanghai, China, 200080
      • Shanghai General Hospital ( Site 5010)
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • The First Affiliated Hospital of Zhejiang University ( Site 5014)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Chest radiograph or computed tomography scan of the thorax (within 5 years 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 sub-investigator
• Has had chronic cough for at least 1 year with a diagnosis of refractory chronic cough or unexplained chronic cough
• Is a female who is not pregnant, not breastfeeding, not of childbearing potential, or agrees to follow contraceptive guidance
• Provides written informed consent and is willing and able to comply with the study protocol (including use of the digital cough recording device and completion of study questionnaires)

Exclusion Criteria:

• Is a current smoker or has given up smoking within 12 months of Screening, or is a former smoker with greater than 20 pack-years
• Has a history of respiratory tract infection or recent clinically significant change in pulmonary status
• Has a history of chronic bronchitis
• Is currently taking an angiotensin converting enzyme inhibitor (ACEI), or has used an ACEI within 3 months of Screening
• Has an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m^2 at Screening OR an eGFR ≥30 mL/min/1.73 m^2 and <50 mL/min/1.73 m^2 at Screening with unstable renal function
• Has a history of malignancy <=5 years
• Is a user of recreational or illicit drugs or has had a recent history of drug or alcohol abuse or dependence
• Has a history of anaphylaxis or cutaneous adverse drug reaction (with or without systemic symptoms) to sulfonamide antibiotics or other sulfonamide-containing drugs
• Has a known allergy/sensitivity or contraindication to gefapixant
• Has donated or lost >=1 unit of blood within 8 weeks prior to the first dose of gefapixant
• Has 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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Participants will receive a matching placebo tablet BID during the 24-week main study period and during the 28-week extension period.	Drug: Placebo; Placebo tablet administered orally BID
Experimental: Gefapixant 45 mg BID; Participants will receive a gefapixant 45 mg tablet BID during the main study period (24 weeks) and also during the extension period (28 weeks).	Drug: Gefapixant 45 mg twice daily (BID); Gefapixant 45 mg tablet to be administered orally BID; Other Names: MK-7264; Drug: Gefapixant 45 mg BID; Gefapixant 45 mg tablet to be administered orally BID; Other Names: MK-7264
Experimental: Gefapixant 15 mg BID; Participants will receive a gefapixant 15 mg tablet BID during the main study period (24 weeks) and also during the extension period (28 weeks).	Drug: Gefapixant 15 mg BID; Gefapixant 15 mg tablet to be administered orally BID; Other Names: MK-7264

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Model-Based Geometric Mean Ratio (GMR) of 24-Hour Coughs Per Hour at Week 24	24-hour coughs per hour was defined as the average hourly cough frequency based on 24-hour sound recordings using a digital recording device (cough monitor). A longitudinal analysis of covariance (ANCOVA) model was applied to log-transformed cough data to determine geometric mean (GM) 24-hour coughs per hour at baseline and week 24. The GMR (Week 24 GM 24-hour coughs per hour divided by Baseline GM 24-hour coughs per hour) is reported.	Baseline, Week 24
Percentage of Participants Who Experienced At Least One Adverse Event (AE) During Treatment and Follow-up	Assessment of participants who have at least one AE during the main study period (24 weeks), the treatment extension period (28 weeks), and during 2 weeks of follow-up by telephone.	Up to 54 weeks
Percentage of Participants Who Discontinued Treatment Due to an AE	Assessment of participants who stop study treatment due to an AE during the main study period (24 weeks) or the treatment extension period (28 weeks).	Up 52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Model-Based GMR of Awake Coughs Per Hour at Week 24/Baseline	Awake coughs per hour was defined as the average hourly cough frequency while the participant is awake, based on a 24-hour interval of sound recordings using a digital recording device (cough monitor). ANCOVA model was applied to log-transformed cough data to determine GM of awake coughs per hour at baseline and week 24. The GMR (Week 24 GM awake coughs per hour divided by Baseline GM awake coughs per hour) is reported.	Baseline, Week 24
Percentage of Participants With a ≥1.3-point Increase From Baseline in the Leicester Questionnaire (LCQ) Total Score at Week 24	The 19-item LCQ assessed the impact of chronic cough in three health-related quality of life (HRQoL) domains (physical, social and psychological). The LCQ is calculated as a mean score for each domain ranging from 1 to 7, with a total score ranging from 3 to 21. 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 Week 24. The percentage of participants (logistic regression model-based) with a ≥1.3-point increase in the LCQ total score at Week 24 is presented.	Baseline, Week 24
Percentage of Participants With a ≥30% Reduction From Baseline in 24-hour Coughs Per Hour at Week 24	24-hour coughs per hour was defined as the average hourly cough frequency based on 24-hour sound recordings using a digital recording device (cough monitor). A clinically meaningful improvement from baseline is defined as a ≥30% reduction in 24-hour coughs per hour at week 24. The percentage of participants (logistic regression model-based) with a ≥30% reduction from baseline in 24-hour coughs per hour at Week 24 (≥30% reduction from baseline) is presented.	Baseline, Week 24
Percentage of Participants With ≥1.3-point Reduction From Baseline of Mean Weekly Cough Severity Diary (CSD) Total Score at Week 24	The 7-item CSD was used to record participants' daily cough frequency, cough intensity, and disruption due to cough. Each item was rated on an 11-point scale ranging from 0 (best) to 10 (worst); the total daily CSD score was the sum of these seven item scores (Min=0, Max=70). Mean weekly CSD total score was defined as the average of the mean total daily scores collected during the week prior to each visit. The percentage of participants (logistic regression model-based) with a ≥1.3 point reduction from baseline in CSD at Week 24 is reported.	Baseline, Week 24
Percentage of Participants With ≥2.7-point Reduction From Baseline of Mean Weekly CSD Total Score at Week 24	The 7-item CSD was used to record participants' daily cough frequency, cough intensity, and disruption due to cough. Each item was rated on an 11-point scale ranging from 0 (best) to 10 (worst); the total daily CSD score was the sum of these seven item scores (Min=0, Max=70). Mean weekly CSD total score was defined as the average of the mean total daily scores collected during the week prior to each visit. The percentage of participants (logistic regression model-based) with a ≥2.7 point reduction from baseline in CSD at Week 24 is reported.	Baseline, Week 24
Percentage of Participants With a ≥30 mm Reduction From Baseline in Cough Severity Visual Analog Scale (VAS) Score at Week 24	The VAS is a single-item questionnaire with the response on a 100- point scale ranging from 0 ("No Cough") to 100 ("Extremely Severe Cough"). Mean weekly VAS score was defined as the average of the VAS scores collected during the week prior to each visit. The percentage of participants (logistic regression model-based) with a ≥30mm reduction from baseline in cough severity VAS score at Week 24 is reported.	Baseline, Week 24

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

• Merck Clinical Trials Information

Study record dates

Study Major Dates

• Study Start (Actual): May 17, 2019
• Primary Completion (Actual): September 15, 2022
• Study Completion (Actual): September 15, 2022

Study Registration Dates

• First Submitted: August 18, 2020
• First Submitted That Met QC Criteria: August 24, 2020
• First Posted (Actual): August 25, 2020

Study Record Updates

• Last Update Posted (Actual): January 12, 2024
• Last Update Submitted That Met QC Criteria: January 11, 2024
• Last Verified: January 1, 2024

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: 7264-030 China Extension; MK-7264-030 (Other Identifier: Merck Protocol Number); MK-7264-030-02 (Other Identifier: Merck Protocol 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
• product manufactured in and exported from the U.S.: Yes