Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43865   clinical trials with a EudraCT protocol, of which   7286   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Phase 3b Randomized, Double-blind, Placebo Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Gefapixant in Adult Participants with Recent Onset Chronic Cough

    Summary
    EudraCT number
    		 2019-002308-42
    Trial protocol
    		 DE   GB   PL   ES  
    Global end of trial date
    03 Nov 2021

    Results information
    Results version number
    		 v1(current)
    This version publication date
    21 Oct 2022
    First version publication date
    21 Oct 2022
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    7264-043
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04193202
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Merck Sharp & Dohme LLC
    Sponsor organisation address
    126 East Lincoln Avenue, P.O. Box 2000, Rahway, NJ, United States, 07065
    Public contact
    Clinical Trials Disclosure, Merck Sharp & Dohme LLC, ClinicalTrialsDisclosure@merck.com
    Scientific contact
    Clinical Trials Disclosure, Merck Sharp & Dohme LLC, ClinicalTrialsDisclosure@merck.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    03 Nov 2021
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    03 Nov 2021
    Global end of trial reached?
    Yes
    Global end of trial date
    03 Nov 2021
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The purpose of this study is to evaluate the efficacy and safety of gefapixant in participants with recent onset chronic cough (duration >8 weeks after onset of cough symptoms) for <12 months and a diagnosis of refractory or unexplained chronic cough. The primary hypothesis is that gefapixant is superior to placebo in improving cough-related quality of life measured as change from baseline in the Leicester Cough Questionnaire (LCQ) total score at Week 12.
    Protection of trial subjects
    This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    21 May 2020
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Canada: 5
    Country: Number of subjects enrolled
    Colombia: 58
    Country: Number of subjects enrolled
    Germany: 14
    Country: Number of subjects enrolled
    Guatemala: 45
    Country: Number of subjects enrolled
    Peru: 44
    Country: Number of subjects enrolled
    Poland: 37
    Country: Number of subjects enrolled
    Russian Federation: 80
    Country: Number of subjects enrolled
    Korea, Republic of: 3
    Country: Number of subjects enrolled
    Spain: 5
    Country: Number of subjects enrolled
    Ukraine: 95
    Country: Number of subjects enrolled
    United Kingdom: 17
    Country: Number of subjects enrolled
    United States: 16
    Worldwide total number of subjects
    419
    EEA total number of subjects
    56
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    339
    From 65 to 84 years
    80
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 A total of 498 participants were screened, and 419 were randomized in the study. All non-randomized participants were screen failures.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Gefapixant
    Arm description
    		 Participants receive gefapixant at a dose of 45 mg administered as an oral tablet twice daily for 12 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Gefapixant
    Investigational medicinal product code
    Other name
    MK-7264
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    45 mg twice daily administration

    Arm title
    		 Placebo
    Arm description
    		 Participants receive placebo matching gefapixant, administered as an oral tablet twice daily for 12 weeks.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo matching gefapixant twice daily administration

    Number of subjects in period 1
    		Gefapixant Placebo
    Started
    208
    211
    Treated
    206
    209
    Completed
    192
    201
    Not completed
    16
    10
         Adverse event, serious fatal
    -
    1
         Physician decision
    1
    1
         Consent withdrawn by subject
    11
    5
         Adverse event, non-fatal
    2
    1
         Protocol deviation
    2
    2

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Gefapixant
    Reporting group description
    		 Participants receive gefapixant at a dose of 45 mg administered as an oral tablet twice daily for 12 weeks.

    Reporting group title
    Placebo
    Reporting group description
    		 Participants receive placebo matching gefapixant, administered as an oral tablet twice daily for 12 weeks.

    Reporting group values
    		 Gefapixant Placebo Total
    Number of subjects
    		 208 211 419
    Age categorical
    Units: Participants
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 166 173 339
        From 65-84 years
    		 42 38 80
        85 years and over
    		 0 0 0
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 52.6 ± 13.8 52.5 ± 13.7 -
    Sex: Female, Male
    Units: Participants
        Female
    		 136 135 271
        Male
    		 72 76 148
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 22 28 50
        Asian
    		 3 2 5
        Native Hawaiian or Other Pacific Islander
    		 0 0 0
        Black or African American
    		 3 0 3
        White
    		 151 152 303
        More than one race
    		 29 29 58
        Unknown or Not Reported
    		 0 0 0
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 71 76 147
        Not Hispanic or Latino
    		 136 134 270
        Unknown or Not Reported
    		 1 1 2
    Baseline Leicester Cough Questionnaire (LCQ)
    The LCQ is a 19-item, cough-specific health related qualify of life (HRQoL) questionnaire. Each item on the LCQ assesses symptoms using a scale ranging from 1 to 7. The LCQ contains three domains on physical, psychological, and social functioning, and each domain score is calculated as the mean score of the items (range: 1 to 7) within the domain. The LCQ total score is the sum of the 3 domains, with a range from 3 to 21 .Higher scores indicate better HRQoL. The population analyzed included 202 participants in the Gefapixant group and 200 in the Placebo group.
    Units: Scores on a scale
        arithmetic mean (standard deviation)
    		 10.8 ± 3.1 11.3 ± 2.8 -

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Gefapixant
    Reporting group description
    		 Participants receive gefapixant at a dose of 45 mg administered as an oral tablet twice daily for 12 weeks.

    Reporting group title
    Placebo
    Reporting group description
    		 Participants receive placebo matching gefapixant, administered as an oral tablet twice daily for 12 weeks.

    Primary: Change from baseline in the Leicester Cough Questionnaire (LCQ) total score at Week 12

    		 Close Top of page
    End point title
    		 Change from baseline in the Leicester Cough Questionnaire (LCQ) total score at Week 12
    End point description
    Participants will be asked to complete the LCQ to assess the impact of their cough severity on health related quality of life (HRQoL) over the past 2 weeks. The LCQ is a 19-item, cough-specific HRQoL questionnaire. Each item on the LCQ assesses symptoms using a 7-point scale ranging from 1 to 7. The LCQ contains three domains on physical, psychological, and social functioning, and each domain score is calculated as the mean score of the items (range: 1 to 7) within the domain. The LCQ total score is the sum of the 3 domains, with a range from 3 (lowest total score) to 21 (highest total score). Higher scores indicate better HRQoL. The change from baseline in LCQ total score is calculated. The population analyzed included all randomized participants who had taken at least one dose of study intervention, and had LCQ total score values at both baseline and week 12.
    End point type
    Primary
    End point timeframe
    Baseline, Week 12
    End point values
    		 Gefapixant Placebo
    Number of subjects analysed
    199
    199
    Units: Scores on a Scale
        least squares mean (confidence interval 95%)
    4.34 (3.84 to 4.83)
    3.59 (3.09 to 4.09)
    Statistical analysis title
    		 Treatment difference in Gefapixant vs. Placebo
    Statistical analysis description
    The estimated difference is the treatment difference in model based mean change from baseline at Week 12
    Comparison groups
    Gefapixant v Placebo
    Number of subjects included in analysis
    398
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.034 [1]
    Method
    		 Longitudinal ANCOVA
    Parameter type
    		 Estimated difference
    Point estimate
    0.75
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.06
         upper limit
    		 1.44
    Notes
    [1] - The model included terms for treatment group, visit, interaction of treatment by visit, gender, and baseline LCQ total score.

    Secondary: Change from baseline in the Cough Severity Visual Analog Scale (VAS) score at Week 12

    		 Close Top of page
    End point title
    		 Change from baseline in the Cough Severity Visual Analog Scale (VAS) score at Week 12
    End point description
    Participants will be asked to complete the VAS questionnaire to assess the severity of their cough over the past 24-hours. The Cough Severity VAS is a single-item questionnaire asking the participant to rate the severity of their cough on a 100-point scale ranging from 0 (“No Cough”) to 100 (“Extremely Severe Cough”). Higher scores indicate greater severity of cough. The change from baseline in VAS score is calculated. The population analyzed included all randomized participants who had taken at least one dose of study intervention, and had VAS total score values at both baseline and week 12. Participants were analyzed in the group as randomized.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12
    End point values
    		 Gefapixant Placebo
    Number of subjects analysed
    201
    205
    Units: Scores on a Scale
        least squares mean (confidence interval 95%)
    -31.79 (-35.37 to -28.20)
    -24.87 (-28.41 to -21.32)
    Statistical analysis title
    		 Treatment difference in gefapixant vs. placebo
    Statistical analysis description
    The estimated difference is the treatment difference in model based mean change from baseline at Week 12.
    Comparison groups
    Gefapixant v Placebo
    Number of subjects included in analysis
    406
    Analysis specification
    Pre-specified
    Analysis type
    		 other [2]
    P-value
    		 = 0.006 [3]
    Method
    		 Longitudinal ANCOVA
    Parameter type
    		 Estimated Difference
    Point estimate
    -6.92
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -11.88
         upper limit
    		 -1.97
    Notes
    [2] - The model included terms for treatment group, visit, interaction of treatment by visit, gender, and baseline mean weekly cough severity VAS score.
    [3] - Nominal p value, not controlled for multiplicity

    Secondary: Percentage of participants with one or more adverse events (AEs)

    		 Close Top of page
    End point title
    		 Percentage of participants with one or more adverse events (AEs)
    End point description
    An AE is defined as 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. The percentage of participants with one or more AEs is presented. The population included all randomized participants who received at least 1 dose of study intervention. Participants were analyzed in the group as treated.
    End point type
    Secondary
    End point timeframe
    Up to approximately 14 weeks
    End point values
    		 Gefapixant Placebo
    Number of subjects analysed
    206
    209
    Units: Percentage of Participants
        number (not applicable)
    65.5
    43.1
    No statistical analyses for this end point

    Secondary: Percentage of participants who discontinue study drug due to an AE

    		 Close Top of page
    End point title
    		 Percentage of participants who discontinue study drug due to an AE
    End point description
    An AE is defined as 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. The percentage of participants who discontinue study drug due to an AE is presented. The population included all randomized participants who received at least 1 dose of study intervention. Participants were analyzed in the group as treated.
    End point type
    Secondary
    End point timeframe
    Up to approximately 12 weeks
    End point values
    		 Gefapixant Placebo
    Number of subjects analysed
    206
    209
    Units: Percentage of Participants
        number (not applicable)
    11.2
    1.9
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Up to 114 days
    Adverse event reporting additional description
    The deaths (all causes) population includes all randomized participants. The total number of participants exposed was 208 in the Gefapixant group and 211 in the Placebo group. Serious and other adverse events population includes all participants who received at least 1 dose of study intervention. Participants were analyzed in the group as treated.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    24.1
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 -

    Reporting group title
    Gefapixant
    Reporting group description
    		 -

    Serious adverse events
    		 Placebo Gefapixant
    Total subjects affected by serious adverse events
         subjects affected / exposed
    4 / 209 (1.91%)
    3 / 206 (1.46%)
         number of deaths (all causes)
    1
    0
         number of deaths resulting from adverse events
    0
    0
    Injury, poisoning and procedural complications
    Clavicle fracture
         subjects affected / exposed
    0 / 209 (0.00%)
    1 / 206 (0.49%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Myocardial ischaemia
         subjects affected / exposed
    0 / 209 (0.00%)
    1 / 206 (0.49%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Tonsillar cyst
         subjects affected / exposed
    1 / 209 (0.48%)
    0 / 206 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Depression
         subjects affected / exposed
    1 / 209 (0.48%)
    0 / 206 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    COVID-19
         subjects affected / exposed
    1 / 209 (0.48%)
    0 / 206 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COVID-19 pneumonia
         subjects affected / exposed
    2 / 209 (0.96%)
    0 / 206 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 209 (0.00%)
    1 / 206 (0.49%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Placebo Gefapixant
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    22 / 209 (10.53%)
    105 / 206 (50.97%)
    Nervous system disorders
    Ageusia
         subjects affected / exposed
    0 / 209 (0.00%)
    24 / 206 (11.65%)
         occurrences all number
    0
    24
    Headache
         subjects affected / exposed
    14 / 209 (6.70%)
    11 / 206 (5.34%)
         occurrences all number
    15
    12
    Hypogeusia
         subjects affected / exposed
    1 / 209 (0.48%)
    22 / 206 (10.68%)
         occurrences all number
    1
    22
    Dysgeusia
         subjects affected / exposed
    7 / 209 (3.35%)
    66 / 206 (32.04%)
         occurrences all number
    7
    70

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    20 Nov 2019
    Amendment #1: Correction to entry criteria and other clarifications
    20 Mar 2020
    Amendment #2: Addition of procedures/assessments required for specialized urine crystal analysis.
    05 Jan 2021
    Amendment #3: Removal of procedures/assessments for specialized urine crystal analysis added in Protocol Amendment 02 and other clarifications.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Mon Apr 29 04:53:20 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA