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

Primary Purpose

Chronic Cough

Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Gefapixant
Placebo
Sponsored by
Afferent Pharmaceuticals, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Cough

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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%

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Experimental

    Arm Label

    Gefapixant 600 mg>Placebo

    Placebo>Gefapixant 600 mg

    Arm Description

    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.

    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.

    Outcomes

    Primary Outcome Measures

    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.

    Secondary Outcome Measures

    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.
    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.
    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.
    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.
    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).
    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).
    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).
    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).

    Full Information

    First Posted
    September 9, 2011
    Last Updated
    November 10, 2020
    Sponsor
    Afferent Pharmaceuticals, Inc.
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    1. Study Identification

    Unique Protocol Identification Number
    NCT01432730
    Brief Title
    A Study to Assess the Efficacy of Gefapixant (MK-7264/AF-219), in Participants With Chronic Cough (MK-7264-006)
    Acronym
    EPICC
    Official Title
    A Study to Assess the Efficacy of AF-219, a P2X3 Receptor Antagonist, in Subjects With Chronic Cough (EPiCC)
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    November 2020
    Overall Recruitment Status
    Completed
    Study Start Date
    September 22, 2011 (Actual)
    Primary Completion Date
    February 7, 2013 (Actual)
    Study Completion Date
    February 21, 2013 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Afferent Pharmaceuticals, Inc.

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Chronic Cough

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Crossover Assignment
    Masking
    ParticipantInvestigator
    Allocation
    Randomized
    Enrollment
    24 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Gefapixant 600 mg>Placebo
    Arm Type
    Experimental
    Arm Description
    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.
    Arm Title
    Placebo>Gefapixant 600 mg
    Arm Type
    Experimental
    Arm Description
    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.
    Intervention Type
    Drug
    Intervention Name(s)
    Gefapixant
    Other Intervention Name(s)
    AF-219, MK-7264
    Intervention Description
    Oral tablets, BID
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo
    Intervention Description
    Oral tablets, BID
    Primary Outcome Measure Information:
    Title
    Change From Baseline in Daytime Objective Cough Frequency
    Description
    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 Outcome Measure Information:
    Title
    Change From Baseline of Daytime Cough Severity Score Using a Visual Analogue Scale (VAS)
    Description
    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
    Title
    Change From Baseline in Nighttime Objective Cough Frequency
    Description
    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
    Title
    Change From Baseline of Nighttime Cough Severity Score Using a Visual Analogue Scale (VAS)
    Description
    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
    Title
    Change From Baseline of 24-hour Objective Cough Frequency
    Description
    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
    Title
    Global Rating of Change Score for Cough Frequency
    Description
    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
    Title
    Global Rating of Change Score for Cough Severity
    Description
    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
    Title
    Change From Baseline in Cough-specific Quality of Life Questionnaire (CQLQ)
    Description
    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
    Title
    Change From Baseline in Urge to Cough Questionnaire (UtCQ) 100 mm Visual Analogue Scale
    Description
    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
    Other Pre-specified Outcome Measures:
    Title
    Baseline Daytime Cough Frequency
    Description
    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.
    Time Frame
    Baseline (Day 0) of each study period
    Title
    Baseline Daytime Cough Severity Score Using a Visual Analogue Scale (VAS)
    Description
    Cough Severity VAS is 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.
    Time Frame
    Baseline (Day 0) of each study period
    Title
    Baseline Nighttime Objective Cough Frequency
    Description
    Nighttime Objective Cough Frequency is the 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.
    Time Frame
    Baseline (Day 0) of each study period
    Title
    Baseline Nighttime Cough Severity Score Using a Visual Analogue Scale (VAS)
    Description
    Nighttime cough severity was 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.
    Time Frame
    Baseline (Day 0) of each study period
    Title
    Baseline 24-Hour Objective Cough Frequency
    Description
    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.
    Time Frame
    Baseline (Day 0) of each study period
    Title
    Baseline Cough-specific Quality of Life Questionnaire (CQLQ)
    Description
    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) of each study period
    Title
    Baseline Urge to Cough Questionnaire (UtCQ) 100 mm Visual Analogue Scale
    Description
    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").
    Time Frame
    Baseline (Day 0) of each study period

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    80 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    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%
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Medical Director
    Organizational Affiliation
    Afferent Pharmaceuticals, Inc.
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
    IPD Sharing URL
    http://engagezone.msd.com/ds_documentation.php
    Citations:
    PubMed Identifier
    25467586
    Citation
    Abdulqawi R, Dockry R, Holt K, Layton G, McCarthy BG, Ford AP, Smith JA. P2X3 receptor antagonist (AF-219) in refractory chronic cough: a randomised, double-blind, placebo-controlled phase 2 study. Lancet. 2015 Mar 28;385(9974):1198-205. doi: 10.1016/S0140-6736(14)61255-1. Epub 2014 Nov 25.
    Results Reference
    derived

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

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