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

Afferent Pharmaceuticals, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)24 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Chronic Cough

Interventions

GefapixantDRUG

Oral tablets, BID

PlaceboDRUG

Oral tablets, BID

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

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%

Outcomes

Primary Outcomes

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.

Time frame: Baseline (Day 0) and Day 14 of each study period

Secondary Outcomes

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.

Time frame: 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.

Time frame: Baseline (Day 0) and Day 14 of each study period

Change From Baseline of Nighttime Cough Severity Score Using a Visual Analogue Scale (VAS)

Data from ClinicalTrials.gov

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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.

Time frame: 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.

Time frame: 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).

Time frame: 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).

Time frame: 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).

Time frame: 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).

Time frame: Baseline (Day 0) and Day 15 of each study period