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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03449147
Recruitment Status : Completed
First Posted : February 28, 2018
Results First Posted : September 2, 2021
Last Update Posted : September 2, 2021
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme LLC

Tracking Information
First Submitted Date  ICMJE February 22, 2018
First Posted Date  ICMJE February 28, 2018
Results First Submitted Date  ICMJE August 9, 2021
Results First Posted Date  ICMJE September 2, 2021
Last Update Posted Date September 2, 2021
Actual Study Start Date  ICMJE March 15, 2018
Actual Primary Completion Date August 20, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 9, 2021)
  • Model-Based Geometric Mean Ratio (GMR) of 24-Hour Coughs Per Hour at Week 24/Baseline [ Time Frame: Baseline, 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.
  • Number of Participants Who Experienced At Least One Adverse Event (AE) During Treatment and Follow-up [ Time Frame: Up to 54 Weeks ]
    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.
  • Number of Participants Who Discontinued a Study Drug Due to an AE [ Time Frame: Up to 52 weeks ]
    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.
Original Primary Outcome Measures  ICMJE
 (submitted: February 22, 2018)
  • 24-hour Coughs per Hour at Week 24 [ Time Frame: Week 24 ]
    Assessment of 24-hour coughs per hour (average hourly cough frequency based on 24-hour sound recordings), to be evaluated using a digital recording device which records sounds from the lungs and trachea through a chest contact sensor, as well as ambient sounds through a lapel microphone.
  • Percentage of Participants Experiencing At Least One Adverse Event (AE) During Treatment and Follow-up [ Time Frame: Up to 54 weeks ]
    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.
  • Percentage of Participants Who Have a Study Drug Discontinued Due to an AE [ Time Frame: Up 52 weeks ]
    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).
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 9, 2021)
  • Model-Based GMR of Awake Coughs Per Hour at Week 24/Baseline [ Time Frame: Baseline, Week 24 ]
    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.
  • Percentage of Participants With a ≥1.3 Point Change From Baseline in the Leicester Questionnaire (LCQ) Total Score at Week 24 [ Time Frame: Baseline, 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.
  • Percentage of Participants With a ≤-30% Change From Baseline in 24-hour Coughs Per Hour at Week 24 [ Time Frame: Baseline, 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% change (≥30% reduction) in 24-hour coughs per hour at week 24. The percentage of participants (logistic regression model-based) with a ≤ -30% change from baseline in 24-hour coughs per hour at Week 24 (≥30% reduction from baseline) is presented.
  • Percentage of Participants With ≤-1.3 Point Change From Baseline of Mean Weekly Cough Severity Diary (CSD) Total Score at Week 24 [ Time Frame: Baseline, 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 change from baseline in CSD at Week 24 (or ≥1.3 point reduction from baseline) is reported.
  • Percentage of Participants With ≤-2.7 Point Change From Baseline of Mean Weekly CSD Total Score at Week 24 [ Time Frame: Baseline, 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 change from baseline in CSD at Week 24 (or ≥2.7 point reduction from baseline) is reported.
  • Percentage of Participants With a ≤-30 Millimeter (mm) Change From Baseline in Cough Severity Visual Analog Scale (VAS) Score at Week 24 [ Time Frame: Baseline, 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 ≤-30 mm change from baseline in cough severity VAS score at Week 24 is reported.
Original Secondary Outcome Measures  ICMJE
 (submitted: February 22, 2018)
  • Change From Baseline of Awake Coughs Per Hour at Week 24 [ Time Frame: Baseline, Week 24 ]
    To evaluate the efficacy of gefapixant by assessment of coughs per hour while the participant is awake, evaluated using a chest contact sensor to record sounds from the lungs and trachea and a lapel microphone to record ambient sounds.
  • Percentage of Participants With a ≥1.3-point Increase from Baseline in the Leicester Questionnaire (LCQ) Total Score at Week 24 [ Time Frame: Baseline, Week 24 ]
    To evaluate the ability of gefapixant to provide a clinically significant improvement in cough-specific health related quality of life (HRQoL), as indicated by a ≥1.3-point increase from Baseline in the LCQ total score at Week 24. The 19-item LCQ assesses the impact of cough severity in three 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.
  • Percentage of Participants With a ≥30% Reduction From Baseline in 24-hour Coughs Per Hour at Week 24 [ Time Frame: Baseline, Week 24 ]
    To evaluate the efficacy of gefapixant based on clinically meaningful (≥30%) reduction from Baseline in 24-hour coughs per hour at Week 24. Coughs per hour are evaluated using a chest contact sensor to record sounds from the lungs and trachea and a lapel microphone to record ambient sounds.
  • Percentage of Participants with ≥1.3-point Reduction of Mean Weekly Cough Severity Diary (CSD) Total Score at Week 24 [ Time Frame: Baseline, Week 24 ]
    To evaluate the efficacy of gefapixant based on the percentage of participants with ≥1.3-point reduction of the mean weekly CSD total score at Week 24. Participants will record their cough frequency, intensity, and disruption due to cough using the 7-item CSD. Participants will rate each item using an 11-point scale ranging from 0 to 10 with higher scores indicating greater severity.
  • Percentage of Participants with ≥2.7-point Reduction of Mean Weekly CSD Total Score at Week 24 [ Time Frame: Baseline, Week 24 ]
    To evaluate the efficacy of gefapixant based on the percentage of participants with ≥2.7-point reduction of the mean weekly CSD total score at Week 24. Participants will record their cough frequency, intensity, and disruption due to cough using the 7-item CSD. Participants will rate each item using an 11-point scale ranging from 0 to 10 with higher scores indicating greater severity.
  • Percentage of Participants With a ≥30 mm Reduction From Baseline in Cough Severity Visual Analog Scale (VAS) Score at Week 24 [ Time Frame: Baseline, Week 24 ]
    To evaluate the efficacy of gefapixant based on improvement from Baseline in cough severity, assessed by the proportion of participants with a ≥30 mm reduction from baseline in Cough Severity 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").
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Gefapixant (MK-7264) in Adult Participants With Chronic Cough (MK-7264-030)
Official Title  ICMJE 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)
Brief Summary The primary objectives of this study are to evaluate the efficacy of gefapixant (MK-7264) in reducing cough frequency as measured over a 24-hour period, and to determine the safety and tolerability of gefapixant. The primary hypothesis is that at least one dose of gefapixant is superior to placebo in reducing coughs per hour (over 24 hours) at Week 24.
Detailed Description This study will have a main 24-week treatment period and a 28-week extension period of treatment (total treatment period of 52 weeks). Participants at selected sites and countries who complete the main and extension study periods may consent to participate in an observational, 12-week, Off-treatment Durability Study Period. Any assessments conducted in the observational period will be exploratory.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Participants with refractory or unexplained chronic cough will be randomized to 1 of 3 treatment groups: gefapixant 45 mg twice daily (BID), gefapixant 15 mg BID, or placebo.
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Chronic Cough
Intervention  ICMJE
  • Drug: Placebo
    Placebo tablet administered orally BID
  • Drug: Gefapixant 15 mg BID
    Gefapixant 15 mg tablet administered orally BID
    Other Name: MK-7264
  • Drug: Gefapixant 45 mg BID
    Gefapixant 45 mg tablet administered orally BID
    Other Name: MK-7264
Study Arms  ICMJE
  • Placebo Comparator: Placebo
    Participants will receive a matching placebo tablet BID during the 24-week main study period and the 28-week extension period.
    Intervention: Drug: Placebo
  • Experimental: Gefapixant 15 mg BID
    Participants will receive a gefapixant 15 mg tablet BID and placebo tablet to match gefapixant 45 mg BID during the 24-week main study period and the 28-week extension period.
    Interventions:
    • Drug: Placebo
    • Drug: Gefapixant 15 mg BID
  • Experimental: Gefapixant 45 mg BID
    Participants will receive a gefapixant 45 mg tablet BID and placebo tablet to match gefapixant 15 mg BID during the 24-week main study period and during the 28-week extension period.
    Interventions:
    • Drug: Placebo
    • Drug: Gefapixant 45 mg BID
Publications * McGarvey LP, Birring SS, Morice AH, Dicpinigaitis PV, Pavord ID, Schelfhout J, Nguyen AM, Li Q, Tzontcheva A, Iskold B, Green SA, Rosa C, Muccino DR, Smith JA; COUGH-1 and COUGH-2 Investigators. Efficacy and safety of gefapixant, a P2X(3) receptor antagonist, in refractory chronic cough and unexplained chronic cough (COUGH-1 and COUGH-2): results from two double-blind, randomised, parallel-group, placebo-controlled, phase 3 trials. Lancet. 2022 Mar 5;399(10328):909-923. doi: 10.1016/S0140-6736(21)02348-5.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 25, 2020)
1317
Original Estimated Enrollment  ICMJE
 (submitted: February 22, 2018)
1290
Actual Study Completion Date  ICMJE October 30, 2020
Actual Primary Completion Date August 20, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
  • Currently participating in or has participated in an interventional clinical study within 30 days of screening
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Canada,   China,   Colombia,   Czechia,   Denmark,   Germany,   Guatemala,   Hungary,   Israel,   Italy,   Malaysia,   New Zealand,   Peru,   Poland,   South Africa,   Turkey,   Ukraine,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03449147
Other Study ID Numbers  ICMJE 7264-030
MK-7264-030 ( Other Identifier: Merck Protocol Number )
2017-003559-49 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php
Responsible Party Merck Sharp & Dohme LLC
Study Sponsor  ICMJE Merck Sharp & Dohme LLC
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Merck Sharp & Dohme LLC
PRS Account Merck Sharp & Dohme LLC
Verification Date August 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP