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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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)

Conditions
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Chronic Cough

Intervention / Treatment
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* Drug: Placebo
* Drug: Gefapixant 15 mg BID
* Drug: Gefapixant 45 mg BID


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Participants will receive a matching placebo tablet BID during the 24-week main study period and the 28-week extension period. | Drug: Placebo<br>* Placebo tablet administered orally BID<br>|
| Experimental: Gefapixant 15 mg BID<br>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. | Drug: Placebo<br>* Placebo tablet administered orally BID<br>Drug: Gefapixant 15 mg BID<br>* Gefapixant 15 mg tablet administered orally BID<br>* Other names: MK-7264;|
| Experimental: Gefapixant 45 mg BID<br>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. | Drug: Placebo<br>* Placebo tablet administered orally BID<br>Drug: Gefapixant 45 mg BID<br>* Gefapixant 45 mg tablet administered orally BID<br>* Other names: MK-7264;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Model-Based Geometric Mean Ratio (GMR) of 24-Hour Coughs Per Hour at Week 24/Baseline | 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 | 
| Number of Participants Who Experienced At Least One Adverse Event (AE) During Treatment and Follow-up | 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 a 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 |
| --- | --- | --- |
| 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 Change 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% Change 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% 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. | Baseline, Week 24 | 
| Percentage of Participants With ≤-1.3 Point Change 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 change from baseline in CSD at Week 24 (or ≥1.3 point reduction from baseline) is reported. | Baseline, Week 24 | 
| Percentage of Participants With ≤-2.7 Point Change 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 change from baseline in CSD at Week 24 (or ≥2.7 point reduction from baseline) is reported. | Baseline, Week 24 | 
| Percentage of Participants With a ≤-30 Millimeter (mm) Change 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 ≤-30 mm change from baseline in cough severity VAS score at Week 24 is reported. | Baseline, Week 24 |