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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Chronic Cough

Intervention / Treatment
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* Drug: Gefapixant
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 20 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
Masking: Double


Arms and Interventions

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

What is the study measuring?
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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 |