A Study to Assess the Efficacy of Gefapixant (MK-7264/AF-219), in Participants With Chronic Cough (MK-7264-006)

Study Overview
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Brief Summary
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This is a randomised, double-blind, placebo-controlled, crossover, single centre study of gefapixant (AF-219/MK-7264) in participants with idiopathic or treatment resistant chronic cough designed to evaluate the effectiveness of gefapixant in reducing daytime objective cough frequency.

Official Title
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A Study to Assess the Efficacy of AF-219, a P2X3 Receptor Antagonist, in Subjects With Chronic Cough (EPiCC)

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: History of cough for more than 8 weeks Normal chest radiograph Idiopathic or treatment resistant cough (idiopathic defined as a cough for which no objective evidence of an underlying trigger can be determined after investigation or a cough that is unresponsive to 8 weeks of targeted treatment for identified underlying triggers including reflux disease, asthma and post-nasal drip [treatment-resistant]). Exclusion Criteria: Current smoker Individuals who have given up smoking within the past 6 months, or those with >20 pack-year smoking history Treatment with an angiotensin-converting-enzyme inhibitor (ACE-inhibitor) as the potential cause of a participant's cough, or requiring treatment with an ACE-inhibitor during the study or within 4 weeks prior to Day 0 Forced Expiratory Volume (FEV1)/Forced Vital Capacity (FVC) <60%

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Gefapixant 600 mg>Placebo<br>Gefapixant, 600 mg, twice daily (BID), taken orally for 2 weeks followed by a 2-week washout period and then placebo to gefapixant, BID, taken orally for 2 weeks. | Drug: Gefapixant<br>* Oral tablets, BID<br>* Other names: MK-7264;Drug: Placebo<br>* Oral tablets, BID<br>|
| Experimental: Placebo>Gefapixant 600 mg<br>Placebo to gefapixant BID, taken orally for 2 weeks followed by a 2-week washout period and then gefapixant, 600 mg, BID, taken orally for 2 weeks. | Drug: Gefapixant<br>* Oral tablets, BID<br>* Other names: MK-7264;Drug: Placebo<br>* Oral tablets, BID<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Daytime Objective Cough Frequency | Daytime Objective Cough Frequency (per hour) is the total number of cough events during the monitoring period (in general, 24-hr interval) the participant is awake divided by the total duration (in hours) for the monitoring period the participants is awake. 24-hour sound recordings were collected using a digital recording device. Change from baseline in awake cough frequency = (post-treatment awake cough frequency - baseline awake cough frequency). A negative result indicates a decrease in cough frequency, while a positive result indicates an increase in cough frequency. | Baseline (Day 0) and Day 14 of each study period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline of Daytime Cough Severity Score Using a Visual Analogue Scale (VAS) | Cough Severity VAS: scored from 0 to 100 using a 10 mm visual analogue scale with 0 at 0mm and 100 at 100mm with 0 representing no cough and 100 the most severe cough. Change from baseline in daytime cough severity = (post-treatment daytime cough severity - baseline daytime cough severity). A negative result indicates a decrease in cough severity, while a positive result indicates an increase in cough severity. | Baseline (Day 0) and Day 15 of each study period | 
| Change From Baseline in Nighttime Objective Cough Frequency | Nighttime Objective Cough Frequency = Total number of cough events during the monitoring period the participant is asleep divided by the total duration (in hours) for the monitoring period the participant is asleep. 24 hour sound recording were collected with a digital recording device. Change from baseline in nighttime cough frequency = (post-treatment nighttime cough frequency - baseline nighttime cough frequency). A negative result indicates a decrease in cough frequency, while a positive result indicates an increase in cough frequency. | Baseline (Day 0) and Day 14 of each study period | 
| Change From Baseline of Nighttime Cough Severity Score Using a Visual Analogue Scale (VAS) | Cough Severity VAS: scored from 0 to 100 using a 10 mm visual analogue scale with 0 at 0mm and 100 at 100mm with 0 representing no cough and 100 the most severe cough. Change from baseline in nighttime cough severity = (post-treatment nighttime cough severity - baseline nighttime cough severity). A negative result indicates a decrease in cough severity, while a positive result indicates an increase in cough severity. | Baseline (Day 0) and Day 15 of each study period | 
| Change From Baseline of 24-hour Objective Cough Frequency | Total (0-24 hours) Objective Cough Frequency = Total number of cough events during the monitoring period divided by the total duration (in hours, i.e., 24 hours mostly) for the monitoring period. 24-hour sound recordings were collected using a digital recording device. A negative result indicates a decrease in cough frequency, while a positive result indicates an increase in cough frequency. | 24 hours at Baseline (Day 0) and Day 14 of each study period | 
| Global Rating of Change Score for Cough Frequency | At the end of each study period, participants were asked to complete the global rating of change scale questionnaire. The participants were asked to record whether their cough frequency was worse, about the same, or better. If better or worse, the participants were then asked by how much with a 7-category rating scale. Therefore, a 15-point ordered scale was used (1=minimum, a very great deal better to 15=maximum, a very great deal worse with a score of 8=indicating no change). | Day 15 of each study period | 
| Global Rating of Change Score for Cough Severity | At the end of each study period, participants were asked to complete the global rating of change scale questionnaire. The participants were asked to record whether their cough severity was worse, about the same, or better. If better or worse, the participants were then asked by how much with a 7-category rating scale. Therefore, a 15-point ordered scale was used (1=minimum, a very great deal better to 15=maximum, a very great deal worse with a score of 8=indicating no change). | Day 15 of each study period | 
| Change From Baseline in Cough-specific Quality of Life Questionnaire (CQLQ) | The CQLQ Questionnaire included 28 items that described negative aspects of quality of life specific to chronic cough. Subscales include: Physical complaints, Psychosocial issues, Functional abilities, Emotional wellbeing, Extreme physical complaints, and Personal safety fears. Participants indicated their degree of agreement with each statement on a 4 point scale (1 = strongly disagree; 2 = disagree; 3 = agree; 4 = strongly agree). CQLQ scores (28 for least impact, 112 for highest impact) used a mixed effect model with terms for treatment sequence, participant within sequence, treatment, and period. Change from baseline in CQLQ scores = (posttreatment CQLQ scores - baseline CQLQ scores). A negative result indicates a decrease in CQLQ scores (lowest cough impact on health-related quality of life), while a positive result indicates an increase in CQLQ scores (highest cough impact on health-related quality of life). | Baseline (Day 0) and Day 15 of each study period | 
| Change From Baseline in Urge to Cough Questionnaire (UtCQ) 100 mm Visual Analogue Scale | UtCQ is determined through the use of a 100mm visual analogue scale (VAS) (ranging between 0 for no urge to cough and 100 for severe urge to cough). Change from baseline in UtCQ scores = (post-treatment UtCQ scores - baseline UtCQ scores). A negative result indicates a decrease in UtCQ scores (lowest impact), while a positive result indicates an increase in UtCQ scores (highest impact). | Baseline (Day 0) and Day 15 of each study period |