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    Clinical Trial Results:
    A 12-Week Study to Assess the Efficacy and Safety of AF 219 in Subjects With Refractory Chronic Cough

    Summary
    EudraCT number
    		 2015-005064-42
    Trial protocol
    		 GB  
    Global end of trial date
    04 Nov 2016

    Results information
    Results version number
    		 v3(current)
    This version publication date
    19 Jan 2019
    First version publication date
    12 Nov 2017
    Other versions
    		 v1 , v2
    Version creation reason

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    7264-012
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02612610
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 MK-7264-012: Merck Protocol Number
    Sponsors
    Sponsor organisation name
    Merck Sharp & Dohme Corp.
    Sponsor organisation address
    2000 Galloping Hill Road, Kenilworth, NJ, United States, 07033
    Public contact
    Clinical Trials Disclosure, ClinicalTrialsDisclosure@merck.com, ClinicalTrialsDisclosure@merck.com
    Scientific contact
    Clinical Trials Disclosure, Merck Sharp & Dohme Corp., 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
    04 Nov 2016
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    04 Nov 2016
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    This study is designed to evaluate the efficacy of three dose regimens of gefapixant ([MK-7264] 7.5 mg, 20 mg, and 50 mg) relative to placebo in reducing awake objective cough frequency. The primary hypothesis for this trial is that at least one dose regimen of gefapixant is superior to placebo with respect to the mean change from baseline in awake cough frequency (on the log scale).
    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
    15 Dec 2015
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United Kingdom: 88
    Country: Number of subjects enrolled
    United States: 165
    Worldwide total number of subjects
    253
    EEA total number of subjects
    88
    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)
    152
    From 65 to 84 years
    101
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Of 367 screened, 253 were randomised to treatment with placebo or 7.5 mg, 20 mg, or 50 mg gefapixant. One participant randomised to receive 7.5 mg gefapixant was discontinued before receiving treatment.

    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, Monitor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo
    Arm description
    		 Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo to gefapixant
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Dose-matched placebo tablet to gefapixant administered twice daily.

    Arm title
    		 Gefapixant 7.5 mg
    Arm description
    		 Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Gefapixant
    Investigational medicinal product code
    Other name
    MK-7264, AF-219
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Gefapixant administered as one 7.5 mg tablet twice daily.

    Arm title
    		 Gefapixant 20 mg
    Arm description
    		 Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Gefapixant
    Investigational medicinal product code
    Other name
    MK-7264, AF-219
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Gefapixant administered as one 20 mg tablet twice daily.

    Arm title
    		 Gefapixant 50 mg
    Arm description
    		 Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Gefapixant
    Investigational medicinal product code
    Other name
    MK-7264, AF-219
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Gefapixant administered as one 50 mg tablet twice daily.

    Number of subjects in period 1
    		Placebo Gefapixant 7.5 mg Gefapixant 20 mg Gefapixant 50 mg
    Started
    63
    64
    63
    63
    Treated
    63
    63
    63
    63
    Completed
    58
    56
    58
    50
    Not completed
    5
    8
    5
    13
         Consent withdrawn by subject
    1
    1
    -
    2
         Physician decision
    -
    1
    -
    -
         Adverse event, non-fatal
    2
    2
    3
    10
         Cough Improvement
    -
    -
    1
    -
         Lost to follow-up
    -
    1
    -
    -
         Lack of efficacy
    1
    2
    -
    1
         Noncompliance
    1
    -
    -
    -
         Protocol deviation
    -
    1
    1
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.

    Reporting group title
    Gefapixant 7.5 mg
    Reporting group description
    		 Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.

    Reporting group title
    Gefapixant 20 mg
    Reporting group description
    		 Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.

    Reporting group title
    Gefapixant 50 mg
    Reporting group description
    		 Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.

    Reporting group values
    		 Placebo Gefapixant 7.5 mg Gefapixant 20 mg Gefapixant 50 mg Total
    Number of subjects
    		 63 64 63 63 253
    Age categorical
    Units: Subjects
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 60.0 ± 10.9 59.9 ± 10.46 61.8 ± 9.13 59.3 ± 9.19 -
    Gender, Male/Female
    Units: Subjects
        Female
    		 47 48 48 50 193
        Male
    		 16 16 15 13 60

    End points

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    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.

    Reporting group title
    Gefapixant 7.5 mg
    Reporting group description
    		 Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.

    Reporting group title
    Gefapixant 20 mg
    Reporting group description
    		 Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.

    Reporting group title
    Gefapixant 50 mg
    Reporting group description
    		 Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.

    Primary: Change from Baseline in Awake Objective Cough Frequency after 12 Weeks of Treatment (Day 84)

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    End point title
    		 Change from Baseline in Awake Objective Cough Frequency after 12 Weeks of Treatment (Day 84)
    End point description
    Awake Objective Cough Frequency (per hour) was defined as the total number of cough events during the monitoring period while the participant was awake divided by the total duration for the monitoring period that the participant was awake. 24 hour sound recordings were made at Baseline ([BL], Study Day -1) and at Week 12 (Day 84) using a digital recording device. An independent cough monitoring center documented the time of each cough event over the 24 hour period, as well as the time when the participant went to sleep and the time the participant woke. Least-squares (LS) mean change from BL (in log scale) with associated standard error (SE) reported for each treatment group. Change from BL in Awake Objective Cough Frequency = (Post-Treatment Awake Cough Frequency minus BL Awake Cough Frequency). All randomized participants who had taken at least 1 dose of study medication and provided at least 1 BL and ≥1 post BL endpoint observation during the treatment period were analysed.
    End point type
    Primary
    End point timeframe
    Baseline Visit (Day -1), Day 84
    End point values
    		 Placebo Gefapixant 7.5 mg Gefapixant 20 mg Gefapixant 50 mg
    Number of subjects analysed
    61
    59
    59
    57
    Units: log coughs/hour
        least squares mean (standard error)
    -0.40 ± 0.11
    -0.64 ± 0.11
    -0.65 ± 0.11
    -0.86 ± 0.11
    Statistical analysis title
    		 Day 84 Awake Cough Freq: 7.5 mg gefapixant v PBO
    Statistical analysis description
    Estimated treatment differences (gefapixant vs. placebo [PBO]) and corresponding 95% confidence intervals (CIs) were estimated using a mixed effect repeated measures (MMRM) model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value (on log scale) as a covariate.
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0971
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.25
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.54
         upper limit
    		 0.05
    Statistical analysis title
    		 Day 84 Awake Cough Freq: 20 mg gefapixant v PBO
    Statistical analysis description
    Estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value (on log scale) as a covariate.
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0928
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.25
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.54
         upper limit
    		 0.04
    Statistical analysis title
    		 Day 84 Awake Cough Freq: 50 mg gefapixant v PBO
    Statistical analysis description
    Estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value (on log scale) as a covariate.
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    118
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0027
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.46
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.76
         upper limit
    		 -0.16

    Secondary: Change from Baseline in 24-Hour Objective Cough Frequency after 4 Weeks of Treatment (Day 28)

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    End point title
    		 Change from Baseline in 24-Hour Objective Cough Frequency after 4 Weeks of Treatment (Day 28)
    End point description
    24-hr Objective Cough Frequency was defined as the total number of cough events during the monitoring period divided by the total duration in hours for the monitoring period (generally 24 hours). 24 hour sound recordings were made at Baseline (Study Day -1) and at Week 4 (Day 28) using a digital recording device. An independent cough monitoring center documented the time of each cough event over the 24 hour period, as well as the time when the participant went to sleep and the time the participant woke. LS mean change from baseline (in log scale) with associated SE reported for each treatment group. Change from Baseline in 24-Hour Objective Cough Frequency = (Post-Treatment 24-Hour Cough Frequency minus Baseline 24-Hour Cough Frequency). All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period were analysed.
    End point type
    Secondary
    End point timeframe
    Baseline (Study Day -1), Day 28
    End point values
    		 Placebo Gefapixant 7.5 mg Gefapixant 20 mg Gefapixant 50 mg
    Number of subjects analysed
    61
    59
    59
    57
    Units: log coughs/hour
        least squares mean (standard error)
    -0.41 ± 0.10
    -0.59 ± 0.10
    -0.46 ± 0.10
    -0.93 ± 0.10
    Statistical analysis title
    		 Day 28 Awake Cough Freq: 7.5 mg gefapixant v PBO
    Statistical analysis description
    Day 28 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value (on log scale) as a covariate.
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1914
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.19
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.47
         upper limit
    		 0.09
    Statistical analysis title
    		 Day 28 Awake Cough Freq: 20 mg gefapixant v PBO
    Statistical analysis description
    Day 28 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value (on log scale) as a covariate.
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.7099
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.05
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.33
         upper limit
    		 0.23
    Statistical analysis title
    		 Day 28 Awake Cough Freq: 50 mg gefapixant v PBO
    Statistical analysis description
    Day 28 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value (on log scale) as a covariate.
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    118
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0003
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.52
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.8
         upper limit
    		 -0.24

    Secondary: Change from Baseline in 24-Hour Objective Cough Frequency after 8 Weeks of Treatment (Day 56)

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    End point title
    		 Change from Baseline in 24-Hour Objective Cough Frequency after 8 Weeks of Treatment (Day 56)
    End point description
    24-hr Objective Cough Frequency was defined as the total number of cough events during the monitoring period divided by the total duration in hours for the monitoring period (generally 24 hours). 24 hour sound recordings were made at Baseline (Study Day -1) and at Week 8 (Day 56) using a digital recording device. An independent cough monitoring center documented the time of each cough event over the 24 hour period, as well as the time when the participant went to sleep and the time the participant woke. LS mean change from baseline (in log scale) with associated SE reported for each treatment group. Change from Baseline in 24-Hour Objective Cough Frequency = (Post-Treatment 24-Hour Cough Frequency minus Baseline 24-Hour Cough Frequency). All randomised participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period were analysed.
    End point type
    Secondary
    End point timeframe
    Baseline (Study Day -1), Day 56
    End point values
    		 Placebo Gefapixant 7.5 mg Gefapixant 20 mg Gefapixant 50 mg
    Number of subjects analysed
    61
    59
    59
    57
    Units: log coughs/hour
        least squares mean (standard error)
    -0.31 ± 0.11
    -0.71 ± 0.11
    -0.59 ± 0.11
    -0.93 ± 0.11
    Statistical analysis title
    		 Day 56 24-hour Cough Freq: 7.5 mg gefapixant v PBO
    Statistical analysis description
    Day 56 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value (on log scale) as a covariate.
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0099
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.71
         upper limit
    		 -0.1
    Statistical analysis title
    		 Day 56 24-hour Cough Freq: 20 mg gefapixant v PBO
    Statistical analysis description
    Day 56 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value (on log scale) as a covariate.
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0695
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.28
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.58
         upper limit
    		 0.02
    Statistical analysis title
    		 Day 56 24-hour Cough Freq: 50 mg gefapixant v PBO
    Statistical analysis description
    Day 56 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value (on log scale) as a covariate.
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    118
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0001
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.62
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.93
         upper limit
    		 -0.31

    Secondary: Change from Baseline in 24-Hour Objective Cough Frequency after 12 Weeks of Treatment (Day 84)

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    End point title
    		 Change from Baseline in 24-Hour Objective Cough Frequency after 12 Weeks of Treatment (Day 84)
    End point description
    24-hr Objective Cough Frequency was defined as the total number of cough events during the monitoring period divided by the total duration in hours for the monitoring period (generally 24 hours). 24 hour sound recordings were made at Baseline (Study Day -1) and at Week 12 (Day 84) using a digital recording device. An independent cough monitoring center documented the time of each cough event over the 24 hour period, as well as the time when the participant went to sleep and the time the participant woke. LS mean change from baseline (in log scale) with associated SE reported for each treatment group. Change from Baseline in 24-Hour Objective Cough Frequency = (Post-Treatment 24-Hour Cough Frequency minus Baseline 24-Hour Cough Frequency). All randomised participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period were analysed.
    End point type
    Secondary
    End point timeframe
    Baseline (Study Day -1), Day 84
    End point values
    		 Placebo Gefapixant 7.5 mg Gefapixant 20 mg Gefapixant 50 mg
    Number of subjects analysed
    61
    59
    59
    57
    Units: log coughs/hour
        least squares mean (standard error)
    -0.39 ± 0.10
    -0.62 ± 0.10
    -0.64 ± 0.10
    -0.86 ± 0.11
    Statistical analysis title
    		 Day 84 24-hour Cough Freq: 7.5 mg gefapixant v PBO
    Statistical analysis description
    Day 84 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value (on log scale) as a covariate.
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0991
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.24
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.52
         upper limit
    		 0.04
    Statistical analysis title
    		 Day 84 24-hour Cough Freq: 20 mg gefapixant v PBO
    Statistical analysis description
    Day 84 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value (on log scale) as a covariate.
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0811
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.25
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.53
         upper limit
    		 0.03
    Statistical analysis title
    		 Day 84 24-hour Cough Freq: 50 mg gefapixant v PBO
    Statistical analysis description
    Day 84 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value (on log scale) as a covariate.
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    118
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0014
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.47
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.76
         upper limit
    		 -0.19

    Secondary: Change from Baseline in Awake Objective Cough Frequency after 4 Weeks of Treatment (Day 28)

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    End point title
    		 Change from Baseline in Awake Objective Cough Frequency after 4 Weeks of Treatment (Day 28)
    End point description
    Awake Objective Cough Frequency (per hour) was defined as the total number of cough events during the monitoring period while the participant was awake divided by the total duration for the monitoring period that the participant was awake. 24 hour sound recordings were made at Baseline (Study Day -1) and at Week 4 (Day 28) using a digital recording device. An independent cough monitoring center documented the time of each cough event over the 24 hour period, as well as the time when the participant went to sleep and the time the participant woke. LS mean change from baseline (in log scale) with associated SE reported for each treatment group. Change from Baseline in Awake Objective Cough Frequency = (Post-Treatment Awake Cough Frequency minus Baseline Awake Cough Frequency). All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period were analysed.
    End point type
    Secondary
    End point timeframe
    Baseline (Study Day -1), Day 28,
    End point values
    		 Placebo Gefapixant 7.5 mg Gefapixant 20 mg Gefapixant 50 mg
    Number of subjects analysed
    61
    59
    59
    57
    Units: log coughs/hour
        least squares mean (standard error)
    -0.41 ± 0.10
    -0.62 ± 0.10
    -0.48 ± 0.10
    -0.90 ± 0.11
    Statistical analysis title
    		 Day 28 Awake Cough Freq: 7.5 mg gefapixant v PBO
    Statistical analysis description
    Day 28 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value (on log scale) as a covariate.
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1468
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.21
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.5
         upper limit
    		 0.07
    Statistical analysis title
    		 Day 28 Awake Cough Freq: 20 mg gefapixant v PBO
    Statistical analysis description
    Day 28 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value (on log scale) as a covariate.
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.5874
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.08
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.36
         upper limit
    		 0.2
    Statistical analysis title
    		 Day 28 Awake Cough Freq: 50 mg gefapixant v PBO
    Statistical analysis description
    Day 28 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value (on log scale) as a covariate.
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    118
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0008
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.49
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.78
         upper limit
    		 -0.21

    Secondary: Change from Baseline in Awake Objective Cough Frequency after 8 Weeks of Treatment (Day 56)

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    End point title
    		 Change from Baseline in Awake Objective Cough Frequency after 8 Weeks of Treatment (Day 56)
    End point description
    Awake Objective Cough Frequency (per hour) was defined as the total number of cough events during the monitoring period while the participant was awake divided by the total duration for the monitoring period that the participant was awake. 24 hour sound recordings were made at Baseline (Study Day -1) and at Week 8 (Day 56) using a digital recording device. An independent cough monitoring center documented the time of each cough event over the 24 hour period, as well as the time when the participant went to sleep and the time the participant woke. LS mean change from baseline (in log scale) with associated SE reported for each treatment group. Change from Baseline in Awake Objective Cough Frequency = (Post-Treatment Awake Cough Frequency minus Baseline Awake Cough Frequency). All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period were analysed.
    End point type
    Secondary
    End point timeframe
    Baseline (Study Day -1), Day 56
    End point values
    		 Placebo Gefapixant 7.5 mg Gefapixant 20 mg Gefapixant 50 mg
    Number of subjects analysed
    61
    59
    59
    57
    Units: log coughs/hour
        least squares mean (standard error)
    -0.31 ± 0.11
    -0.70 ± 0.12
    -0.63 ± 0.11
    -0.90 ± 0.12
    Statistical analysis title
    		 Day 56 Awake Cough Freq: 7.5 mg gefapixant v PBO
    Statistical analysis description
    Day 56 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value (on log scale) as a covariate.
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0177
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 Mixed Effect Repeated Measures model
    Point estimate
    -0.39
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.7
         upper limit
    		 -0.07
    Statistical analysis title
    		 Day 56 Awake Cough Freq: 20 mg gefapixant v PBO
    Statistical analysis description
    Day 56 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value (on log scale) as a covariate.
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0498
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.32
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.63
         upper limit
    		 0
    Statistical analysis title
    		 Day 56 Awake Cough Freq: 50 mg gefapixant v PBO
    Statistical analysis description
    Day 56 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value (on log scale) as a covariate.
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    118
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0004
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.59
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.92
         upper limit
    		 -0.27

    Secondary: Change from Baseline in Awake Objective Cough Frequency at the Follow-up Visit (Day 98)

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    End point title
    		 Change from Baseline in Awake Objective Cough Frequency at the Follow-up Visit (Day 98)
    End point description
    Awake Objective Cough Frequency (per hour) was defined as the total number of cough events during the monitoring period (in general, 24-hr interval) while the participant was awake divided by the total duration (in hours) for the monitoring period that the participant was awake. 24 hour sound recordings were made at Baseline (Study Day -1) and at the Follow-up visit (Day 98) using a digital recording device. An independent cough monitoring center documented the time of each cough event over the 24 hour period, as well as the time when the participant went to sleep and the time the participant woke. Change from Baseline in Awake Objective Cough Frequency = (Post-Treatment Awake Cough Frequency minus Baseline Awake Cough Frequency). All randomised participants who had taken at least 1 dose of study medication and provided baseline and follow-up visit (Day 98) data during the treatment period were analysed.
    End point type
    Secondary
    End point timeframe
    Baseline (Study Day -1), Day 98
    End point values
    		 Placebo Gefapixant 7.5 mg Gefapixant 20 mg Gefapixant 50 mg
    Number of subjects analysed
    58
    55
    56
    51
    Units: coughs/hour
        arithmetic mean (standard deviation)
    -6.4 ± 22.72
    -9.3 ± 47.72
    -7.4 ± 29.24
    -16.2 ± 39.00
    No statistical analyses for this end point

    Secondary: Change from Baseline in Cough Severity Visual Analogue Scale (VAS) after 4 Weeks of Treatment (Day 28)

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    End point title
    		 Change from Baseline in Cough Severity Visual Analogue Scale (VAS) after 4 Weeks of Treatment (Day 28)
    End point description
    Cough VAS was scored from 0 to 100 using a 100 mm visual analogue scale. Participants were asked to mark on a 100 mm scale between 0 (no cough) and 100 (the worst cough severity). Cough VAS was evaluated at Baseline (Study Day -1) and at Week 4 (Day 28). Baseline cough VAS was defined as the cough VAS at Baseline (Study Day -1). LS mean change from baseline with associated SE reported for each treatment group. All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period were analysed.
    End point type
    Secondary
    End point timeframe
    Baseline (Study Day -1), Day 28
    End point values
    		 Placebo Gefapixant 7.5 mg Gefapixant 20 mg Gefapixant 50 mg
    Number of subjects analysed
    61
    59
    59
    57
    Units: units on a scale
        least squares mean (standard error)
    -15.2 ± 3.02
    -21.6 ± 3.05
    -18.1 ± 3.04
    -25. ± 3.09
    Statistical analysis title
    		 Day 28 Cough Severity VAS: 7.5 mg gefapixant v PBO
    Statistical analysis description
    Day 28 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1318
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -6.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -14.8
         upper limit
    		 1.9
    Statistical analysis title
    		 Day 28 Cough Severity VAS: 20 mg gefapixant v PBO
    Statistical analysis description
    Day 28 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.4917
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -2.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -11.3
         upper limit
    		 5.4
    Statistical analysis title
    		 Day 28 Cough Severity VAS: 50 mg gefapixant v PBO
    Statistical analysis description
    Day 28 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    118
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0228
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -9.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -18.2
         upper limit
    		 -1.4

    Secondary: Change from Baseline in Cough Severity VAS after 8 Weeks of Treatment (Day 56)

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    End point title
    		 Change from Baseline in Cough Severity VAS after 8 Weeks of Treatment (Day 56)
    End point description
    Cough VAS was scored from 0 to 100 using a 100 mm visual analogue scale. Participants were asked to mark on a 100 mm scale between 0 (no cough) and 100 (the worst cough severity). Cough VAS was evaluated at Baseline (Study Day -1) and at Week 8 (Day 56). Baseline cough VAS was defined as the cough VAS at Baseline (Study Day -1). LS mean change from baseline with associated SE reported for each treatment group. All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period were analysed.
    End point type
    Secondary
    End point timeframe
    Baseline (Study Day -1), Day 56
    End point values
    		 Placebo Gefapixant 7.5 mg Gefapixant 20 mg Gefapixant 50 mg
    Number of subjects analysed
    61
    59
    59
    57
    Units: units on a scale
        least squares mean (standard error)
    -16.1 ± 3.18
    -18.8 ± 3.19
    -19.4 ± 3.18
    -26.9 ± 3.33
    Statistical analysis title
    		 Day 56 Cough Severity VAS: 7.5 mg gefapixant v PBO
    Statistical analysis description
    Day 56 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.554
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -2.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -11.5
         upper limit
    		 6.2
    Statistical analysis title
    		 Day 56 Cough Severity VAS: 20 mg gefapixant v PBO
    Statistical analysis description
    Day 56 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.4702
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -3.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -12
         upper limit
    		 5.6
    Statistical analysis title
    		 Day 56 Cough Severity VAS: 50 mg gefapixant v PBO
    Statistical analysis description
    Day 56 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    118
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0197
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -10.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -19.8
         upper limit
    		 -1.7

    Secondary: Change from Baseline in Cough Severity VAS after 12 Weeks of Treatment (Day 84)

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    End point title
    		 Change from Baseline in Cough Severity VAS after 12 Weeks of Treatment (Day 84)
    End point description
    Cough VAS was scored from 0 to 100 using a 100 mm visual analogue scale. Participants were asked to mark on a 100 mm scale between 0 (no cough) and 100 (the worst cough severity). Cough VAS was evaluated at Baseline (Study Day -1) and at Week 12 (Day 84). Baseline cough VAS was defined as the cough VAS at Baseline (Study Day -1). LS mean change from baseline with associated SE reported for each treatment group. All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period were analysed.
    End point type
    Secondary
    End point timeframe
    Baseline (Study Day -1), Day 84
    End point values
    		 Placebo Gefapixant 7.5 mg Gefapixant 20 mg Gefapixant 50 mg
    Number of subjects analysed
    61
    59
    59
    57
    Units: units on a scale
        least squares mean (standard error)
    -16.7 ± 3.04
    -21.1 ± 3.08
    -23.1 ± 3.05
    -27.9 ± 3.16
    Statistical analysis title
    		 Day 84 Cough Severity VAS: 7.5 mg gefapixant v PBO
    Statistical analysis description
    Day 84 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.302
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -4.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -12.9
         upper limit
    		 4
    Statistical analysis title
    		 Day 84 Cough Severity VAS: 20 mg gefapixant v PBO
    Statistical analysis description
    Day 84 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1365
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -6.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -14.8
         upper limit
    		 2
    Statistical analysis title
    		 Day 84 Cough Severity VAS: 50 mg gefapixant v PBO
    Statistical analysis description
    Day 84 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    118
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0108
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -11.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -19.7
         upper limit
    		 -2.6

    Secondary: Change from Baseline in Cough Severity VAS At Day 85/Early Termination

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    End point title
    		 Change from Baseline in Cough Severity VAS At Day 85/Early Termination
    End point description
    Cough VAS was scored from 0 to 100 using a 100 mm visual analogue scale. Participants were asked to mark on a 100 mm scale between 0 (no cough) and 100 (the worst cough severity). Cough VAS was evaluated at Baseline (Study Day -1) and at Day 85/Early Termination. Baseline cough VAS was defined as the cough VAS at Baseline (Study Day -1). LS mean change from baseline with associated SE reported for each treatment group. All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period were analysed.
    End point type
    Secondary
    End point timeframe
    Baseline (Study Day -1), Day 85
    End point values
    		 Placebo Gefapixant 7.5 mg Gefapixant 20 mg Gefapixant 50 mg
    Number of subjects analysed
    61
    59
    59
    57
    Units: unit on a scale
        least squares mean (standard error)
    -15.2 ± 3.00
    -19.2 ± 3.04
    -23.4 ± 3.03
    -31.1 ± 3.09
    Statistical analysis title
    		 Day 85 Cough Severity VAS: 7.5 mg gefapixant v PBO
    Statistical analysis description
    Day 85/Early Termination estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.3509
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -12.3
         upper limit
    		 4.4
    Statistical analysis title
    		 Day 85 Cough Severity VAS: 20 mg gefapixant v PBO
    Statistical analysis description
    Day 85/Early Termination estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0519
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -8.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -16.6
         upper limit
    		 0.1
    Statistical analysis title
    		 Day 85 Cough Severity VAS: 50 mg gefapixant v PBO
    Statistical analysis description
    Day 85/Early Termination estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    118
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0003
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -15.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -24.3
         upper limit
    		 -7.5

    Secondary: Percentage of Participants with ≥70%, ≥50%, and ≥30% Change in Awake Objective Cough Frequency after 4 Weeks of Treatment (Day 28)

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    End point title
    		 Percentage of Participants with ≥70%, ≥50%, and ≥30% Change in Awake Objective Cough Frequency after 4 Weeks of Treatment (Day 28)
    End point description
    Awake Objective Cough Frequency (per hour) was defined as the total number of cough events during the monitoring period (in general, 24-hr interval) while the participant was awake divided by the total duration (in hours) for the monitoring period that the participant was awake. 24 hour sound recordings were made at Baseline (Study Day -1) and at Week 4 (Day 28) using a digital recording device. An independent cough monitoring center documented the time of each cough event over the 24 hour period, as well as the time when the participant went to sleep and the time the participant woke. The percentages of participants that met responder criteria for ≥70%, ≥50%, and ≥30% change (reduction) from baseline levels in Awake Objective Cough Frequency were reported for each treatment group at Day 28. All randomised participants who had taken ≥1 dose of study medication and provided ≥1 baseline and ≥1 Day 28 endpoint observation during the treatment period were analysed.
    End point type
    Secondary
    End point timeframe
    Baseline (Study Day -1), Day 28
    End point values
    		 Placebo Gefapixant 7.5 mg Gefapixant 20 mg Gefapixant 50 mg
    Number of subjects analysed
    60
    55
    59
    55
    Units: percentage of participants
    number (not applicable)
        ≥70% Change
    15.0
    25.5
    16.9
    34.5
        ≥50% Change
    23.3
    38.2
    30.5
    47.3
        ≥30% Change
    46.7
    63.6
    50.8
    60.0
    Statistical analysis title
    		 Day 28: ≥70% Change: 7.5 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a generalized linear mixed model (GLMM) with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified Cochran Mantel Haenszel (CMH) test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    115
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1387
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 28: ≥70% Change: 20 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    119
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.7238
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 28: ≥70% Change: 50 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    115
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0144
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 28: ≥50% Change: 7.5 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    115
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0922
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 28: ≥50% Change: 20 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    119
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.3812
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 28: ≥50% Change: 50 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    115
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0088
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 28: ≥30% Change: 7.5 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    115
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0653
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 28: ≥30% Change: 20 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    119
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.6443
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 28: ≥30% Change: 50 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    115
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1511
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval

    Secondary: Percentage of Participants with ≥70%, ≥50%, and ≥30% Change in Awake Objective Cough Frequency after 8 Weeks of Treatment (Day 56)

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    End point title
    		 Percentage of Participants with ≥70%, ≥50%, and ≥30% Change in Awake Objective Cough Frequency after 8 Weeks of Treatment (Day 56)
    End point description
    Awake Objective Cough Frequency (per hour) was defined as the total number of cough events during the monitoring period (in general, 24-hr interval) while the participant was awake divided by the total duration (in hours) for the monitoring period that the participant was awake. 24 hour sound recordings were made at Baseline (Study Day -1) and at Week 8 (Day 56) using a digital recording device. An independent cough monitoring center documented the time of each cough event over the 24 hour period, as well as the time when the participant went to sleep and the time the participant woke. The percentages of participants that met responder criteria for ≥70%, ≥50%, and ≥30% change (reduction) from baseline levels in Awake Objective Cough Frequency were reported for each treatment group at Day 56. All randomised participants who had taken ≥1 dose of study medication and provided ≥1 baseline and ≥1 Day 56 endpoint observation during the treatment period were analysed.
    End point type
    Secondary
    End point timeframe
    Baseline (Study Day -1), Day 56
    End point values
    		 Placebo Gefapixant 7.5 mg Gefapixant 20 mg Gefapixant 50 mg
    Number of subjects analysed
    57
    56
    59
    51
    Units: percentage of participants
    number (not applicable)
        ≥70% Change
    10.5
    32.1
    22.0
    31.4
        ≥50% Change
    26.3
    46.4
    39.0
    54.9
        ≥30% Change
    47.4
    64.3
    55.9
    72.5
    Statistical analysis title
    		 Day 56: ≥70% Change: 7.5 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a generalized linear mixed model (GLMM) with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified Cochran Mantel Haenszel (CMH) test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    113
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0045
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 56: ≥70% Change: 20 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    116
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0947
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 56: ≥70% Change: 50 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    108
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.008
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 56: ≥50% Change: 7.5 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    113
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0283
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 56: ≥50% Change: 20 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    116
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1493
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 56: ≥50% Change: 50 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    108
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0026
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 56: ≥30% Change: 7.5 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    113
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0652
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 56: ≥30% Change: 20 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    116
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.3601
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 56: ≥30% Change: 50 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    108
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0086
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval

    Secondary: Percentage of Participants with ≥70%, ≥50%, and ≥30% Change in Awake Objective Cough Frequency after 12 Weeks of Treatment (Day 84)

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    End point title
    		 Percentage of Participants with ≥70%, ≥50%, and ≥30% Change in Awake Objective Cough Frequency after 12 Weeks of Treatment (Day 84)
    End point description
    Awake Objective Cough Frequency (per hour) was defined as the total number of cough events during the monitoring period (in general, 24-hr interval) while the participant was awake divided by the total duration (in hours) for the monitoring period that the participant was awake. 24 hour sound recordings were made at Baseline (Study Day -1) and at Week 12 (Day 84) using a digital recording device. An independent cough monitoring center documented the time of each cough event over the 24 hour period, as well as the time when the participant went to sleep and the time the participant woke. The percentages of participants that met responder criteria for ≥70%, ≥50%, and ≥30% change (reduction) from baseline levels in Awake Objective Cough Frequency were reported for each treatment group at Day 84. All randomised participants who had taken ≥1 dose of study medication and provided ≥1 baseline and ≥1 Day 84 endpoint observation during the treatment period were analysed.
    End point type
    Secondary
    End point timeframe
    Baseline (Study Day -1), Day 84
    End point values
    		 Placebo Gefapixant 7.5 mg Gefapixant 20 mg Gefapixant 50 mg
    Number of subjects analysed
    57
    56
    56
    51
    Units: percentage of participants
    number (not applicable)
        ≥70% Change
    15.8
    21.4
    23.2
    31.4
        ≥50% Change
    24.6
    44.6
    32.1
    51.0
        ≥30% Change
    43.9
    64.3
    48.2
    80.4
    Statistical analysis title
    		 Day 84: ≥70% Change: 7.5 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a generalized linear mixed model (GLMM) with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified Cochran Mantel Haenszel (CMH) test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    113
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.3893
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 84: ≥70% Change: 20 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    113
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.2803
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 84: ≥70% Change: 50 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    108
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0427
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 84: ≥50% Change: 7.5 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    113
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0209
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 84: ≥50% Change: 20 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    113
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.3401
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 84: ≥50% Change: 50 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    108
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0031
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 84: ≥30% Change: 7.5 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    113
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0283
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 84: ≥30% Change: 20 mg gefapixant v placebo
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    113
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.6233
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 84: ≥30% Change: 50 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    108
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0001
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval

    Secondary: Percentage of Participants with ≥70%, ≥50%, and ≥30% Change in Awake Objective Cough Frequency at the Follow-up Visit (Day 98)

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    End point title
    		 Percentage of Participants with ≥70%, ≥50%, and ≥30% Change in Awake Objective Cough Frequency at the Follow-up Visit (Day 98)
    End point description
    Awake Objective Cough Frequency (per hour) was defined as the total number of cough events during the monitoring period (in general, 24-hr interval) while the participant was awake divided by the total duration (in hours) for the monitoring period that the participant was awake. 24 hour sound recordings were made at Baseline (Study Day -1) and at the Follow-up visit (Day 98) using a digital recording device. An independent cough monitoring center documented the time of each cough event over the 24 hour period, as well as the time when the participant went to sleep and the time the participant woke. The percentages of participants that met responder criteria for ≥70%, ≥50%, and ≥30% change (reduction) from baseline levels in Awake Objective Cough Frequency were reported for each treatment group at Day 98. All randomised participants who had taken ≥1 dose of study medication and provided ≥1 baseline and ≥1 Day 98 endpoint observation during the treatment period were analysed.
    End point type
    Secondary
    End point timeframe
    Baseline (Study Day -1), Day 98
    End point values
    		 Placebo Gefapixant 7.5 mg Gefapixant 20 mg Gefapixant 50 mg
    Number of subjects analysed
    58
    55
    56
    51
    Units: percentage of participants
    number (not applicable)
        ≥70% Change
    13.8
    18.2
    14.3
    23.5
        ≥50% Change
    25.9
    32.7
    25.0
    39.2
        ≥30% Change
    51.7
    56.4
    50.0
    58.8
    Statistical analysis title
    		 Day 98: ≥70% Change: 7.5 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a generalized linear mixed model (GLMM) with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified Cochran Mantel Haenszel (CMH) test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    113
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.4925
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 98: ≥70% Change: 20 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    114
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.9007
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 98: ≥70% Change: 50 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    109
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1602
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 98: ≥50% Change: 7.5 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    113
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.344
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 98: ≥50% Change: 20 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    114
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.9876
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 98: ≥50% Change: 50 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    109
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0993
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 98: ≥30% Change: 7.5 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    113
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.5968
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 98: ≥30% Change: 20 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    114
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.8726
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 98: ≥30% Change: 50 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    109
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.4092
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval

    Secondary: Percentage of Participants with ≥70%, ≥50%, and ≥30% Change in 24-Hour Objective Cough Frequency after 4 Weeks of Treatment (Day 28)

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    End point title
    		 Percentage of Participants with ≥70%, ≥50%, and ≥30% Change in 24-Hour Objective Cough Frequency after 4 Weeks of Treatment (Day 28)
    End point description
    24-hr Objective Cough Frequency was defined as the total number of cough events during the monitoring period divided by the total duration in hours for the monitoring period (generally 24 hours). 24 hour sound recordings were made at Baseline (Study Day -1) and at Week 4 (Day 28) using a digital recording device. An independent cough monitoring center documented the time of each cough event over the 24 hour period, as well as the time when the participant went to sleep and the time the participant woke. The percentages of participants that met responder criteria for ≥70%, ≥50%, and ≥30% change (reduction) from baseline levels in 24-hr Objective Cough Frequency were reported for each treatment group at Day 28. All randomised participants who had taken ≥1 dose of study medication and provided ≥1 baseline and ≥1 Day 28 endpoint observation during the treatment period were analysed.
    End point type
    Secondary
    End point timeframe
    Baseline (Study Day -1), Day 28
    End point values
    		 Placebo Gefapixant 7.5 mg Gefapixant 20 mg Gefapixant 50 mg
    Number of subjects analysed
    60
    55
    59
    55
    Units: percentage of participants
    number (not applicable)
        ≥70% Change
    13.3
    25.5
    15.3
    34.5
        ≥50% Change
    21.7
    34.5
    30.5
    50.9
        ≥30% Change
    51.7
    58.2
    45.8
    67.3
    Statistical analysis title
    		 Day 28: ≥70% Change: 7.5 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a generalized linear mixed model (GLMM) with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified Cochran Mantel Haenszel (CMH) test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    115
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0781
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 28: ≥70% Change: 20 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    119
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.7098
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 28: ≥70% Change: 50 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    115
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0068
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 28: ≥50% Change: 7.5 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    115
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1284
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 28: ≥50% Change: 20 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    119
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.267
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 28: ≥50% Change: 50 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    115
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0013
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 28: ≥30% Change: 7.5 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    115
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.4343
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 28: ≥30% Change: 20 mg gefapixant v placebo
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    119
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.5384
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 28: ≥30% Change: 50 mg gefapixant v placebo
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    115
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0822
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval

    Secondary: Percentage of Participants with ≥70%, ≥50%, and ≥30% Change in 24-Hour Objective Cough Frequency after 8 Weeks of Treatment (Day 56)

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    End point title
    		 Percentage of Participants with ≥70%, ≥50%, and ≥30% Change in 24-Hour Objective Cough Frequency after 8 Weeks of Treatment (Day 56)
    End point description
    24-hr Objective Cough Frequency was defined as the total number of cough events during the monitoring period divided by the total duration in hours for the monitoring period (generally 24 hours). 24 hour sound recordings were made at Baseline (Study Day -1) and at Week 8 (Day 56) using a digital recording device. An independent cough monitoring center documented the time of each cough event over the 24 hour period, as well as the time when the participant went to sleep and the time the participant woke. The percentages of participants that met responder criteria for ≥70%, ≥50%, and ≥30% change (reduction) from baseline levels in 24-hr Objective Cough Frequency were reported for each treatment group at Day 56. All randomised participants who had taken ≥1 dose of study medication and provided ≥1 baseline and ≥1 Day 56 endpoint observation during the treatment period were analysed.
    End point type
    Secondary
    End point timeframe
    Baseline (Study Day -1), Day 56
    End point values
    		 Placebo Gefapixant 7.5 mg Gefapixant 20 mg Gefapixant 50 mg
    Number of subjects analysed
    57
    56
    59
    51
    Units: percentage of participants
    number (not applicable)
        ≥70% Change
    7.0
    32.1
    22.0
    37.3
        ≥50% Change
    28.1
    50.0
    32.2
    52.9
        ≥30% Change
    45.6
    62.5
    54.2
    78.4
    Statistical analysis title
    		 Day 56: ≥70% Change: 7.5 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a generalized linear mixed model (GLMM) with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified Cochran Mantel Haenszel (CMH) test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    113
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0006
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 56: ≥70% Change: 20 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    116
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0223
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 56: ≥70% Change: 50 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    108
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0001
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 56: ≥50% Change: 7.5 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    113
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0165
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 56: ≥50% Change: 20 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    116
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.6255
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 56: ≥50% Change: 50 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    108
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0085
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 56: ≥30% Change: 7.5 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    113
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0722
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 56: ≥30% Change: 20 mg gefapixant v placebo
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    116
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.3577
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 56: ≥30% Change: 50 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    108
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0006
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval

    Secondary: Percentage of Participants with ≥70%, ≥50%, and ≥30% Change in 24-Hour Objective Cough Frequency after 12 Weeks of Treatment (Day 84)

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    End point title
    		 Percentage of Participants with ≥70%, ≥50%, and ≥30% Change in 24-Hour Objective Cough Frequency after 12 Weeks of Treatment (Day 84)
    End point description
    24-hr Objective Cough Frequency was defined as the total number of cough events during the monitoring period divided by the total duration in hours for the monitoring period (generally 24 hours). 24 hour sound recordings were made at Baseline (Study Day -1) and at Week 12 (Day 84) using a digital recording device. An independent cough monitoring center documented the time of each cough event over the 24 hour period, as well as the time when the participant went to sleep and the time the participant woke. The percentages of participants that met responder criteria for ≥70%, ≥50%, and ≥30% change (reduction) from baseline levels in 24-hr Objective Cough Frequency were reported for each treatment group at Day 84. All randomised participants who had taken ≥1 dose of study medication and provided ≥1 baseline and ≥1 Day 84 endpoint observation during the treatment period were analysed.
    End point type
    Secondary
    End point timeframe
    Baseline (Study Day -1), Day 84
    End point values
    		 Placebo Gefapixant 7.5 mg Gefapixant 20 mg Gefapixant 50 mg
    Number of subjects analysed
    57
    56
    56
    51
    Units: percentage of participants
    number (not applicable)
        ≥70% Change
    14.0
    19.6
    25.0
    31.4
        ≥50% Change
    24.6
    44.6
    32.1
    54.9
        ≥30% Change
    42.1
    62.5
    50.0
    78.4
    Statistical analysis title
    		 Day 84: ≥70% Change: 7.5 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a generalized linear mixed model (GLMM) with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified Cochran Mantel Haenszel (CMH) test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    113
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.3845
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 84: ≥70% Change: 20 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    113
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1177
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 84: ≥70% Change: 50 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    108
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0236
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 84: ≥50% Change: 7.5 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    113
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0192
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 84: ≥50% Change: 20 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    113
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.3301
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 84: ≥50% Change: 50 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    108
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0008
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 84: ≥30% Change: 7.5 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    113
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0285
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 84: ≥30% Change: 20 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    113
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.3856
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 84: ≥30% Change: 50 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    108
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0001
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval

    Secondary: Percentage of Participants with ≥70%, ≥50%, and ≥30% Change in 24-Hour Objective Cough Frequency at the Follow-up Visit (Day 98)

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    End point title
    		 Percentage of Participants with ≥70%, ≥50%, and ≥30% Change in 24-Hour Objective Cough Frequency at the Follow-up Visit (Day 98)
    End point description
    24-hr Objective Cough Frequency was defined as the total number of cough events during the monitoring period divided by the total duration in hours for the monitoring period (generally 24 hours). 24 hour sound recordings were made at Baseline (Study Day -1) and at Week 14 (Day 98) using a digital recording device. An independent cough monitoring center documented the time of each cough event over the 24 hour period, as well as the time when the participant went to sleep and the time the participant woke. The percentages of participants that met responder criteria for ≥70%, ≥50%, and ≥30% change (reduction) from baseline levels in 24-hr Objective Cough Frequency were reported for each treatment group at Day 98. All randomised participants who had taken ≥1 dose of study medication and provided ≥1 baseline and ≥1 Day 98 endpoint observation during the treatment period were analysed.
    End point type
    Secondary
    End point timeframe
    Baseline (Study Day -1), Day 98
    End point values
    		 Placebo Gefapixant 7.5 mg Gefapixant 20 mg Gefapixant 50 mg
    Number of subjects analysed
    58
    55
    56
    51
    Units: percentage of participants
    number (not applicable)
        ≥70% Change
    12.1
    20.0
    16.1
    21.6
        ≥50% Change
    25.9
    34.5
    25.0
    39.2
        ≥30% Change
    46.6
    52.7
    46.4
    54.9
    Statistical analysis title
    		 Day 98: ≥70% Change: 7.5 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a generalized linear mixed model (GLMM) with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified Cochran Mantel Haenszel (CMH) test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    113
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.2441
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 98: ≥70% Change: 20 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    114
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.5055
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 98: ≥70% Change: 50 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    109
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1602
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 98: ≥50% Change: 7.5 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    113
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.2721
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 98: ≥50% Change: 20 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    114
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.9763
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 98: ≥50% Change: 50 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    109
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0993
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 98: ≥30% Change: 7.5 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    113
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.4575
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 98: ≥30% Change: 20 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    114
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.9706
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 98: ≥30% Change: 50 mg gefapixant v PBO
    Statistical analysis description
    Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorised as discontinued or missing
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    109
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.3258
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval

    Secondary: Change from Baseline in Sleep Objective Cough Frequency After 4 Weeks of Treatment (Day 28)

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    End point title
    		 Change from Baseline in Sleep Objective Cough Frequency After 4 Weeks of Treatment (Day 28)
    End point description
    Sleep Objective Cough Frequency was defined as the total number of cough events during the monitoring period while the participant was asleep divided by the total duration in hours for the monitoring period that the participant was asleep. 24 hour sound recordings were made at Baseline (Study Day -1) and at Week 4 (Day 28) using a digital recording device. An independent cough monitoring center documented the time of each cough event over the 24 hour period, as well as the time when the participant went to sleep and the time the participant woke. LS mean change from baseline (in log scale) with associated SE reported for each treatment group. Change from Baseline in Sleep Objective Cough Frequency = (Post-Treatment Objective Sleep Cough Frequency minus Baseline Sleep Cough Frequency). All randomized participants who had taken ≥1 dose of study medication and provided ≥1 baseline and ≥1 post baseline endpoint observation during the treatment period were analysed.
    End point type
    Secondary
    End point timeframe
    Baseline (Study Day -1), Day 28
    End point values
    		 Placebo Gefapixant 7.5 mg Gefapixant 20 mg Gefapixant 50 mg
    Number of subjects analysed
    61
    59
    59
    57
    Units: log coughs/hour
        least squares mean (standard error)
    -0.37 ± 0.19
    -0.37 ± 0.20
    -0.38 ± 0.19
    -0.49 ± 0.20
    Statistical analysis title
    		 Day 28 Sleep Cough Freq: 7.5 mg gefapixant v PBO
    Statistical analysis description
    Day 28 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value (on log scale) as a covariate.
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.9858
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.53
         upper limit
    		 0.54
    Statistical analysis title
    		 Day 28 Sleep Cough Freq: 20 mg gefapixant v PBO
    Statistical analysis description
    Day 28 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value (on log scale) as a covariate.
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.9813
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.01
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.53
         upper limit
    		 0.52
    Statistical analysis title
    		 Day 28 Sleep Cough Freq: 50 mg gefapixant v PBO
    Statistical analysis description
    Day 28 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value (on log scale) as a covariate.
    Comparison groups
    Gefapixant 50 mg v Placebo
    Number of subjects included in analysis
    118
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.6746
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.65
         upper limit
    		 0.42

    Secondary: Change from Baseline in Sleep Objective Cough Frequency After 8 Weeks of Treatment (Day 56)

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    End point title
    		 Change from Baseline in Sleep Objective Cough Frequency After 8 Weeks of Treatment (Day 56)
    End point description
    Sleep Objective Cough Frequency was defined as the total number of cough events during the monitoring period while the participant was asleep divided by the total duration in hours for the monitoring period that the participant was asleep. 24 hour sound recordings were made at Baseline (Study Day -1) and at Week 8 (Day 56) using a digital recording device. An independent cough monitoring center documented the time of each cough event over the 24 hour period, as well as the time when the participant went to sleep and the time the participant woke. LS mean change from baseline (in log scale) with associated SE reported for each treatment group. Change from Baseline in Sleep Objective Cough Frequency = (Post-Treatment Objective Sleep Cough Frequency minus Baseline Sleep Cough Frequency). All randomized participants who had taken ≥1 dose of study medication and provided ≥1 baseline and ≥1 post baseline endpoint observation during the treatment period were analysed.
    End point type
    Secondary
    End point timeframe
    Baseline (Study Day -1), Day 56
    End point values
    		 Placebo Gefapixant 7.5 mg Gefapixant 20 mg Gefapixant 50 mg
    Number of subjects analysed
    61
    59
    59
    57
    Units: log coughs/hour
        least squares mean (standard error)
    -0.40 ± 0.20
    -0.72 ± 0.20
    -0.40 ± 0.20
    -0.80 ± 0.21
    Statistical analysis title
    		 Day 56 Sleep Cough Freq: 7.5 mg gefapixant v PBO
    Statistical analysis description
    Day 56 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value (on log scale) as a covariate.
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.2583
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.32
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.88
         upper limit
    		 0.24
    Statistical analysis title
    		 Day 56 Sleep Cough Freq: 20 mg gefapixant v PBO
    Statistical analysis description
    Day 56 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value (on log scale) as a covariate.
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.9826
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.01
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.55
         upper limit
    		 0.56
    Statistical analysis title
    		 Day 56 Sleep Cough Freq: 50 mg gefapixant v PBO
    Statistical analysis description
    Day 56 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value (on log scale) as a covariate.
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    118
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1672
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.98
         upper limit
    		 0.17

    Secondary: Change from Baseline in Sleep Objective Cough Frequency After 12 Weeks of Treatment (Day 84)

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    End point title
    		 Change from Baseline in Sleep Objective Cough Frequency After 12 Weeks of Treatment (Day 84)
    End point description
    Sleep Objective Cough Frequency was defined as the total number of cough events during the monitoring period while the participant was asleep divided by the total duration in hours for the monitoring period that the participant was asleep. 24 hour sound recordings were made at Baseline (Study Day -1) and at Week 12 (Day 84) using a digital recording device. An independent cough monitoring center documented the time of each cough event over the 24 hour period, as well as the time when the participant went to sleep and the time the participant woke. LS mean change from baseline (in log scale) with associated SE reported for each treatment group. Change from Baseline in Sleep Objective Cough Frequency = (Post-Treatment Objective Sleep Cough Frequency minus Baseline Sleep Cough Frequency) All randomized participants who had taken ≥1 dose of study medication and provided ≥1 baseline and ≥1 post baseline endpoint observation during the treatment period were analysed.
    End point type
    Secondary
    End point timeframe
    Baseline (Study Day -1), Day 84
    End point values
    		 Placebo Gefapixant 7.5 mg Gefapixant 20 mg Gefapixant 50 mg
    Number of subjects analysed
    61
    59
    59
    57
    Units: log coughs/hour
        least squares mean (standard error)
    -0.72 ± 0.19
    -0.58 ± 0.20
    -0.65 ± 0.19
    -0.44 ± 0.20
    Statistical analysis title
    		 Day 84 Sleep Cough Freq: 7.5 mg gefapixant v PBO
    Statistical analysis description
    Day 84 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value (on log scale) as a covariate.
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.6102
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.14
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.4
         upper limit
    		 0.68
    Statistical analysis title
    		 Day 84 Sleep Cough Freq: 20 mg gefapixant v PBO
    Statistical analysis description
    Day 84 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value (on log scale) as a covariate.
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.7782
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.08
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.46
         upper limit
    		 0.61
    Statistical analysis title
    		 Day 84 Sleep Cough Freq: 50 mg gefapixant v PBO
    Statistical analysis description
    Day 84 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value (on log scale) as a covariate.
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    118
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.3167
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.28
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.27
         upper limit
    		 0.83

    Secondary: Change from Baseline in Weekly Mean Daily Cough Severity Diary (CSD) Total Score at Week 1

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    End point title
    		 Change from Baseline in Weekly Mean Daily Cough Severity Diary (CSD) Total Score at Week 1
    End point description
    The daily CSD instrument has a total of 7 items, each with scores ranging from 0 (best) to 10 (worst). The total daily CSD is the sum of these 7 item scores (Min=0, Max=70). Mean total daily score (the sum of 7 item scores divided by 7) was derived for each day. Weekly mean total daily score was defined as the average of the mean total daily scores for each week. LS mean change from baseline with associated SE reported for each treatment group. Baseline was defined as the average CSD scores collected during the week prior to Day 1 (Study Day -7 to Day -1). All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period were analysed.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 1
    End point values
    		 Placebo Gefapixant 7.5 mg Gefapixant 20 mg Gefapixant 50 mg
    Number of subjects analysed
    61
    59
    59
    57
    Units: score on a scale
        least squares mean (standard error)
    -1.0 ± 0.15
    -0.7 ± 0.15
    -0.7 ± 0.15
    -1.10 ± 0.15
    Statistical analysis title
    		 Week 1 CSD Total Score: 7.5 mg gefapixant v PBO
    Statistical analysis description
    Week 1 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1545
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.1
         upper limit
    		 0.7
    Statistical analysis title
    		 Week 1 CSD Total Score: 20 mg gefapixant v PBO
    Statistical analysis description
    Week 1 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.2013
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.1
         upper limit
    		 0.7
    Statistical analysis title
    		 Week 1 CSD Total Score: 50 mg gefapixant v PBO
    Statistical analysis description
    Week 1 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    118
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.9962
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.4
         upper limit
    		 0.4

    Secondary: Change from Baseline in Weekly Mean Daily CSD Total Score at Week 2

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    End point title
    		 Change from Baseline in Weekly Mean Daily CSD Total Score at Week 2
    End point description
    The daily CSD instrument has a total of 7 items, each with scores ranging from 0 (best) to 10 (worst). The total daily CSD is the sum of these 7 item scores (Min=0, Max=70). Mean total daily score (the sum of 7 item scores divided by 7) was derived for each day. Weekly mean total daily score was defined as the average of the mean total daily scores for each week. LS mean change from baseline with associated SE reported for each treatment group. Baseline was defined as the average CSD scores collected during the week prior to Day 1 (Study Day -7 to Day -1). All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period were analysed.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 2
    End point values
    		 Placebo Gefapixant 7.5 mg Gefapixant 20 mg Gefapixant 50 mg
    Number of subjects analysed
    61
    59
    59
    57
    Units: score on a scale
        least squares mean (standard error)
    -1.0 ± 0.18
    -0.9 ± 0.19
    -1.0 ± 0.19
    -1.5 ± 0.19
    Statistical analysis title
    		 Week 2 CSD Total Score: 7.5 mg gefapixant v PBO
    Statistical analysis description
    Week 2 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.7328
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.4
         upper limit
    		 0.6
    Statistical analysis title
    		 Week 2 CSD Total Score: 20 mg gefapixant v PBO
    Statistical analysis description
    Week 2 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.7635
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.4
         upper limit
    		 0.6
    Statistical analysis title
    		 Week 2 CSD Total Score: 50 mg gefapixant v PBO
    Statistical analysis description
    Week 2 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    118
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0951
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.9
         upper limit
    		 0.1

    Secondary: Change from Baseline in Weekly Mean Daily CSD Total Score at Week 3

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    End point title
    		 Change from Baseline in Weekly Mean Daily CSD Total Score at Week 3
    End point description
    The daily CSD instrument has a total of 7 items, each with scores ranging from 0 (best) to 10 (worst). The total daily CSD is the sum of these 7 item scores (Min=0, Max=70). Mean total daily score (the sum of 7 item scores divided by 7) was derived for each day. Weekly mean total daily score was defined as the average of the mean total daily scores for each week. LS mean change from baseline with associated SE reported for each treatment group. Baseline was defined as the average CSD scores collected during the week prior to Day 1 (Study Day -7 to Day -1). All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period were analysed.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 3
    End point values
    		 Placebo Gefapixant 7.5 mg Gefapixant 20 mg Gefapixant 50 mg
    Number of subjects analysed
    61
    59
    59
    57
    Units: score on a scale
        least squares mean (standard error)
    -1.0 ± 0.20
    -1.2 ± 0.20
    -1.3 ± 0.20
    -1.5 ± 0.20
    Statistical analysis title
    		 Week 3 CSD Total Score: 7.5 mg gefapixant v PBO
    Statistical analysis description
    Week 3 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.5797
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.7
         upper limit
    		 0.4
    Statistical analysis title
    		 Week 3 CSD Total Score: 20 mg gefapixant v PBO
    Statistical analysis description
    Week 3 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.2499
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.9
         upper limit
    		 0.2
    Statistical analysis title
    		 Week 3 CSD Total Score: 50 mg gefapixant v PBO
    Statistical analysis description
    Week 3 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    118
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0612
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.1
         upper limit
    		 0

    Secondary: Change from Baseline in Weekly Mean Daily CSD Total Score at Week 4

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    End point title
    		 Change from Baseline in Weekly Mean Daily CSD Total Score at Week 4
    End point description
    The daily CSD instrument has a total of 7 items, each with scores ranging from 0 (best) to 10 (worst). The total daily CSD is the sum of these 7 item scores (Min=0, Max=70). Mean total daily score (the sum of 7 item scores divided by 7) was derived for each day. Weekly mean total daily score was defined as the average of the mean total daily scores for each week. LS mean change from baseline with associated SE reported for each treatment group. Baseline was defined as the average CSD scores collected during the week prior to Day 1 (Study Day -7 to Day -1). All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period were analysed.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 4
    End point values
    		 Placebo Gefapixant 7.5 mg Gefapixant 20 mg Gefapixant 50 mg
    Number of subjects analysed
    61
    59
    59
    57
    Units: score on a scale
        least squares mean (standard error)
    -1.2 ± 0.20
    -1.4 ± 0.20
    -1.5 ± 0.20
    -1.7 ± 0.20
    Statistical analysis title
    		 Week 4 CSD Total Score: 7.5 mg gefapixant v PBO
    Statistical analysis description
    Week 4 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.5358
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.7
         upper limit
    		 0.4
    Statistical analysis title
    		 Week 4 CSD Total Score: 20 mg gefapixant v PBO
    Statistical analysis description
    Week 4 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.3129
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.8
         upper limit
    		 0.3
    Statistical analysis title
    		 Week 4 CSD Total Score: 50 mg gefapixant v PBO
    Statistical analysis description
    Week 4 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    118
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1046
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1
         upper limit
    		 0.1

    Secondary: Change from Baseline in Weekly Mean Daily CSD Total Score at Week 5

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    End point title
    		 Change from Baseline in Weekly Mean Daily CSD Total Score at Week 5
    End point description
    The daily CSD instrument has a total of 7 items, each with scores ranging from 0 (best) to 10 (worst). The total daily CSD is the sum of these 7 item scores (Min=0, Max=70). Mean total daily score (the sum of 7 item scores divided by 7) was derived for each day. Weekly mean total daily score was defined as the average of the mean total daily scores for each week. LS mean change from baseline with associated SE reported for each treatment group. Baseline was defined as the average CSD scores collected during the week prior to Day 1 (Study Day -7 to Day -1). All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period were analysed.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 5
    End point values
    		 Placebo Gefapixant 7.5 mg Gefapixant 20 mg Gefapixant 50 mg
    Number of subjects analysed
    61
    59
    59
    57
    Units: score on a scale
        least squares mean (standard error)
    -1.1 ± 0.20
    -1.3 ± 0.20
    -1.5 ± 0.20
    -1.8 ± 0.21
    Statistical analysis title
    		 Week 5 CSD Total Score: 7.5 mg gefapixant v PBO
    Statistical analysis description
    Week 5 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.5796
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.7
         upper limit
    		 0.4
    Statistical analysis title
    		 Week 5 CSD Total Score: 20 mg gefapixant v PBO
    Statistical analysis description
    Week 5 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.143
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1
         upper limit
    		 0.1
    Statistical analysis title
    		 Week 5 CSD Total Score: 50 mg gefapixant v PBO
    Statistical analysis description
    Week 5 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    118
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0221
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.2
         upper limit
    		 -0.1

    Secondary: Change from Baseline in Weekly Mean Daily CSD Total Score at Week 6

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    End point title
    		 Change from Baseline in Weekly Mean Daily CSD Total Score at Week 6
    End point description
    The daily CSD instrument has a total of 7 items, each with scores ranging from 0 (best) to 10 (worst). The total daily CSD is the sum of these 7 item scores (Min=0, Max=70). Mean total daily score (the sum of 7 item scores divided by 7) was derived for each day. Weekly mean total daily score was defined as the average of the mean total daily scores for each week. LS mean change from baseline with associated SE reported for each treatment group. Baseline was defined as the average CSD scores collected during the week prior to Day 1 (Study Day -7 to Day -1). All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period were analysed.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 6
    End point values
    		 Placebo Gefapixant 7.5 mg Gefapixant 20 mg Gefapixant 50 mg
    Number of subjects analysed
    61
    59
    59
    57
    Units: score on a scale
        least squares mean (standard error)
    -1.0 ± 0.21
    -1.4 ± 0.21
    -1.5 ± 0.21
    -1.7 ± 0.21
    Statistical analysis title
    		 Week 6 CSD Total Score: 7.5 mg gefapixant v PBO
    Statistical analysis description
    Week 6 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1562
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1
         upper limit
    		 0.2
    Statistical analysis title
    		 Week 6 CSD Total Score: 20 mg gefapixant v PBO
    Statistical analysis description
    Week 6 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.071
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.1
         upper limit
    		 0
    Statistical analysis title
    		 Week 6 CSD Total Score: 50 mg gefapixant v PBO
    Statistical analysis description
    Week 6 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    118
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0274
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.2
         upper limit
    		 0.1

    Secondary: Change from Baseline in Weekly Mean Daily CSD Total Score at Week 7

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    End point title
    		 Change from Baseline in Weekly Mean Daily CSD Total Score at Week 7
    End point description
    The daily CSD instrument has a total of 7 items, each with scores ranging from 0 (best) to 10 (worst). The total daily CSD is the sum of these 7 item scores (Min=0, Max=70). Mean total daily score (the sum of 7 item scores divided by 7) was derived for each day. Weekly mean total daily score was defined as the average of the mean total daily scores for each week. LS mean change from baseline with associated SE reported for each treatment group. Baseline was defined as the average CSD scores collected during the week prior to Day 1 (Study Day -7 to Day -1). All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period were analysed.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 7
    End point values
    		 Placebo Gefapixant 7.5 mg Gefapixant 20 mg Gefapixant 50 mg
    Number of subjects analysed
    61
    59
    59
    57
    Units: score on a scale
        least squares mean (standard error)
    -1.2 ± 0.21
    -1.4 ± 0.22
    -1.5 ± 0.22
    -1.7 ± 0.22
    Statistical analysis title
    		 Week 7 CSD Total Score: 7.5 mg gefapixant v PBO
    Statistical analysis description
    Week 7 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.4464
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.8
         upper limit
    		 0.4
    Statistical analysis title
    		 Week 7 CSD Total Score: 20 mg gefapixant v PBO
    Statistical analysis description
    Week 7 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.332
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.9
         upper limit
    		 0.3
    Statistical analysis title
    		 Week 7 CSD Total Score: 50 mg gefapixant v PBO
    Statistical analysis description
    Week 7 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    118
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0792
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.1
         upper limit
    		 0.1

    Secondary: Change from Baseline in Weekly Mean Daily CSD Total Score at Week 8

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    End point title
    		 Change from Baseline in Weekly Mean Daily CSD Total Score at Week 8
    End point description
    The daily CSD instrument has a total of 7 items, each with scores ranging from 0 (best) to 10 (worst). The total daily CSD is the sum of these 7 item scores (Min=0, Max=70). Mean total daily score (the sum of 7 item scores divided by 7) was derived for each day. Weekly mean total daily score was defined as the average of the mean total daily scores for each week. LS mean change from baseline with associated SE reported for each treatment group. Baseline was defined as the average CSD scores collected during the week prior to Day 1 (Study Day -7 to Day -1). All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period were analysed.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 8
    End point values
    		 Placebo Gefapixant 7.5 mg Gefapixant 20 mg Gefapixant 50 mg
    Number of subjects analysed
    61
    59
    59
    57
    Units: score on a scale
        least squares mean (standard error)
    -1.3 ± 0.22
    -1.5 ± 0.22
    -1.6 ± 0.22
    -1.7 ± 0.23
    Statistical analysis title
    		 Week 8 CSD Total Score: 7.5 mg gefapixant v PBO
    Statistical analysis description
    Week 8 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.4716
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.8
         upper limit
    		 0.4
    Statistical analysis title
    		 Week 8 CSD Total Score: 20 mg gefapixant v PBO
    Statistical analysis description
    Week 8 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.4371
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.8
         upper limit
    		 0.4
    Statistical analysis title
    		 Week 8 CSD Total Score: 50 mg gefapixant v PBO
    Statistical analysis description
    Week 8 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    118
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1907
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1
         upper limit
    		 0.2

    Secondary: Change from Baseline in Weekly Mean Daily CSD Total Score at Week 9

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    End point title
    		 Change from Baseline in Weekly Mean Daily CSD Total Score at Week 9
    End point description
    The daily CSD instrument has a total of 7 items, each with scores ranging from 0 (best) to 10 (worst). The total daily CSD is the sum of these 7 item scores (Min=0, Max=70). Mean total daily score (the sum of 7 item scores divided by 7) was derived for each day. Weekly mean total daily score was defined as the average of the mean total daily scores for each week. LS mean change from baseline with associated SE reported for each treatment group. Baseline was defined as the average CSD scores collected during the week prior to Day 1 (Study Day -7 to Day -1). All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period were analysed.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 9
    End point values
    		 Placebo Gefapixant 7.5 mg Gefapixant 20 mg Gefapixant 50 mg
    Number of subjects analysed
    61
    59
    59
    57
    Units: score on a scale
        least squares mean (standard error)
    -1.3 ± 0.21
    -1.6 ± 0.22
    -1.7 ± 0.22
    -1.8 ± 0.22
    Statistical analysis title
    		 Week 9 CSD Total Score: 7.5 mg gefapixant v PBO
    Statistical analysis description
    Week 9 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.2772
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.9
         upper limit
    		 0.3
    Statistical analysis title
    		 Week 9 CSD Total Score: 20 mg gefapixant v PBO
    Statistical analysis description
    Week 9 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1132
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.1
         upper limit
    		 0.1
    Statistical analysis title
    		 Week 9 CSD Total Score: 50 mg gefapixant v PBO
    Statistical analysis description
    Week 9 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    118
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0737
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.2
         upper limit
    		 0.1

    Secondary: Change from Baseline in Weekly Mean Daily CSD Total Score at Week 10

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    End point title
    		 Change from Baseline in Weekly Mean Daily CSD Total Score at Week 10
    End point description
    The daily CSD instrument has a total of 7 items, each with scores ranging from 0 (best) to 10 (worst). The total daily CSD is the sum of these 7 item scores (Min=0, Max=70). Mean total daily score (the sum of 7 item scores divided by 7) was derived for each day. Weekly mean total daily score was defined as the average of the mean total daily scores for each week. LS mean change from baseline with associated SE reported for each treatment group. Baseline was defined as the average CSD scores collected during the week prior to Day 1 (Study Day -7 to Day -1). All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period were analysed.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 10
    End point values
    		 Placebo Gefapixant 7.5 mg Gefapixant 20 mg Gefapixant 50 mg
    Number of subjects analysed
    61
    59
    59
    57
    Units: score on a scale
        least squares mean (standard error)
    -1.2 ± 0.22
    -1.4 ± 0.22
    -1.6 ± 0.22
    -1.9 ± 0.22
    Statistical analysis title
    		 Week 10 CSD Total Score: 7.5 mg gefapixant v PBO
    Statistical analysis description
    Week 10 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.6266
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.8
         upper limit
    		 0.5
    Statistical analysis title
    		 Week 10 CSD Total Score: 20 mg gefapixant v PBO
    Statistical analysis description
    Week 10 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1769
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1
         upper limit
    		 0.2
    Statistical analysis title
    		 Week 10 CSD Total Score: 50 mg gefapixant v PBO
    Statistical analysis description
    Week 10 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    118
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0313
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.3
         upper limit
    		 -0.1

    Secondary: Change from Baseline in Weekly Mean Daily CSD Total Score at Week 11

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    End point title
    		 Change from Baseline in Weekly Mean Daily CSD Total Score at Week 11
    End point description
    The daily CSD instrument has a total of 7 items, each with scores ranging from 0 (best) to 10 (worst). The total daily CSD is the sum of these 7 item scores (Min=0, Max=70). Mean total daily score (the sum of 7 item scores divided by 7) was derived for each day. Weekly mean total daily score was defined as the average of the mean total daily scores for each week. LS mean change from baseline with associated SE reported for each treatment group. Baseline was defined as the average CSD scores collected during the week prior to Day 1 (Study Day -7 to Day -1). All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period were analysed.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 11
    End point values
    		 Placebo Gefapixant 7.5 mg Gefapixant 20 mg Gefapixant 50 mg
    Number of subjects analysed
    61
    59
    59
    57
    Units: score on a scale
        least squares mean (standard error)
    -1.1 ± 0.22
    -1.5 ± 0.22
    -1.7 ± 0.22
    -1.9 ± 0.23
    Statistical analysis title
    		 Week 10 CSD Total Score: 7.5 mg gefapixant v PBO
    Statistical analysis description
    Week 10 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.2058
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1
         upper limit
    		 0.2
    Statistical analysis title
    		 Week 10 CSD Total Score: 20 mg gefapixant v PBO
    Statistical analysis description
    Week 10 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0665
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.2
         upper limit
    		 0
    Statistical analysis title
    		 Week 10 CSD Total Score: 50 mg gefapixant v PBO
    Statistical analysis description
    Week 10 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    118
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0155
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.4
         upper limit
    		 -0.1

    Secondary: Change from Baseline in Weekly Mean Daily CSD Total Score at Week 12

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    End point title
    		 Change from Baseline in Weekly Mean Daily CSD Total Score at Week 12
    End point description
    The daily CSD instrument has a total of 7 items, each with scores ranging from 0 (best) to 10 (worst). The total daily CSD is the sum of these 7 item scores (Min=0, Max=70). Mean total daily score (the sum of 7 item scores divided by 7) was derived for each day. Weekly mean total daily score was defined as the average of the mean total daily scores for each week. LS mean change from baseline with associated SE reported for each treatment group. Baseline was defined as the average CSD scores collected during the week prior to Day 1 (Study Day -7 to Day -1). All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period were analysed.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12
    End point values
    		 Placebo Gefapixant 7.5 mg Gefapixant 20 mg Gefapixant 50 mg
    Number of subjects analysed
    61
    59
    59
    57
    Units: score on a scale
        least squares mean (standard error)
    -1.2 ± 0.22
    -1.5 ± 0.22
    -1.7 ± 0.22
    -1.9 ± 0.23
    Statistical analysis title
    		 Week 12 CSD Total Score: 7.5 mg gefapixant v PBO
    Statistical analysis description
    Week 12 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.2458
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1
         upper limit
    		 0.3
    Statistical analysis title
    		 Week 12 CSD Total Score: 20 mg gefapixant v PBO
    Statistical analysis description
    Week 12 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0662
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.2
         upper limit
    		 0
    Statistical analysis title
    		 Week 12 CSD Total Score: 50 mg gefapixant v PBO
    Statistical analysis description
    Week 12 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    118
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0197
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.4
         upper limit
    		 -0.1

    Secondary: Change from Baseline in Weekly Mean Daily Cough Score (DCS) at Week 1

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    End point title
    		 Change from Baseline in Weekly Mean Daily Cough Score (DCS) at Week 1
    End point description
    The DCS has a score ranging from 0 (best) to 10 (worst). Weekly mean daily score was defined as the average of the daily scores for each week. Baseline was defined as the average DCS score collected during the week prior to Day 1 (Day -7 to Day -1). Participants rated the severity of their cough using the DCS each day. LS mean change from baseline with associated SE reported for each treatment group. All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period were analysed.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 1
    End point values
    		 Placebo Gefapixant 7.5 mg Gefapixant 20 mg Gefapixant 50 mg
    Number of subjects analysed
    61
    59
    59
    57
    Units: score on a scale
        least squares mean (standard error)
    -1.1 ± 0.18
    -0.7 ± 0.18
    -0.8 ± 0.19
    -1.1 ± 0.19
    Statistical analysis title
    		 Week 1 DCS Total Score: 7.5 mg gefapixant v PBO
    Statistical analysis description
    Week 1 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1921
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.2
         upper limit
    		 0.8
    Statistical analysis title
    		 Week 1 DCS Total Score: 20 mg gefapixant v PBO
    Statistical analysis description
    Week 1 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.2428
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.2
         upper limit
    		 0.8
    Statistical analysis title
    		 Week 1 DCS Total Score: 50 mg gefapixant v PBO
    Statistical analysis description
    Week 1 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    118
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.7383
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.6
         upper limit
    		 0.4

    Secondary: Change from Baseline in Weekly Mean DCS at Week 2

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    End point title
    		 Change from Baseline in Weekly Mean DCS at Week 2
    End point description
    The DCS has a score ranging from 0 (best) to 10 (worst). Weekly mean daily score was defined as the average of the daily scores for each week. Baseline was defined as the average DCS score collected during the week prior to Day 1 (Day -7 to Day -1). Participants rated the severity of their cough using the DCS each day. LS mean change from baseline with associated SE reported for each treatment group. All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period were analysed.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 2
    End point values
    		 Placebo Gefapixant 7.5 mg Gefapixant 20 mg Gefapixant 50 mg
    Number of subjects analysed
    61
    59
    59
    57
    Units: score on a scale
        least squares mean (standard error)
    -1.4 ± 0.22
    -1.1 ± 0.23
    -1.1 ± 0.23
    -1.7 ± 0.23
    Statistical analysis title
    		 Week 2 DCS Total Score: 7.5 mg gefapixant v PBO
    Statistical analysis description
    Week 2 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.4033
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.4
         upper limit
    		 0.9
    Statistical analysis title
    		 Week 2 DCS Total Score: 20 mg gefapixant v PBO
    Statistical analysis description
    Week 2 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.4599
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.4
         upper limit
    		 0.9
    Statistical analysis title
    		 Week 2 DCS Total Score: 50 mg gefapixant v PBO
    Statistical analysis description
    Week 2 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    118
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.2837
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1
         upper limit
    		 0.3

    Secondary: Change from Baseline in Weekly Mean DCS at Week 3

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    End point title
    		 Change from Baseline in Weekly Mean DCS at Week 3
    End point description
    The DCS has a score ranging from 0 (best) to 10 (worst). Weekly mean daily score was defined as the average of the daily scores for each week. Baseline was defined as the average DCS score collected during the week prior to Day 1 (Day -7 to Day -1). Participants rated the severity of their cough using the DCS each day. LS mean change from baseline with associated SE reported for each treatment group. All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period were analysed.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 3
    End point values
    		 Placebo Gefapixant 7.5 mg Gefapixant 20 mg Gefapixant 50 mg
    Number of subjects analysed
    61
    59
    59
    57
    Units: score on a scale
        least squares mean (standard error)
    -1.4 ± 0.24
    -1.3 ± 0.24
    -1.6 ± 0.25
    -1.7 ± 0.25
    Statistical analysis title
    		 Week 3 DCS Total Score: 7.5 mg gefapixant v PBO
    Statistical analysis description
    Week 3 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.8084
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.6
         upper limit
    		 0.8
    Statistical analysis title
    		 Week 3 DCS Total Score: 20 mg gefapixant v PBO
    Statistical analysis description
    Week 3 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.6108
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.8
         upper limit
    		 0.5
    Statistical analysis title
    		 Week 3 DCS Total Score: 50 mg gefapixant v PBO
    Statistical analysis description
    Week 3 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    118
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.422
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.9
         upper limit
    		 0.4

    Secondary: Change from Baseline in Weekly Mean DCS at Week 4

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    End point title
    		 Change from Baseline in Weekly Mean DCS at Week 4
    End point description
    The DCS has a score ranging from 0 (best) to 10 (worst). Weekly mean daily score was defined as the average of the daily scores for each week. Baseline was defined as the average DCS score collected during the week prior to Day 1 (Day -7 to Day -1). Participants rated the severity of their cough using the DCS each day. LS mean change from baseline with associated SE reported for each treatment group. All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period were analysed.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 4
    End point values
    		 Placebo Gefapixant 7.5 mg Gefapixant 20 mg Gefapixant 50 mg
    Number of subjects analysed
    61
    59
    59
    57
    Units: score on a scale
        least squares mean (standard error)
    -1.5 ± 0.24
    -1.6 ± 0.24
    -1.8 ± 0.24
    -1.9 ± 0.24
    Statistical analysis title
    		 Week 4 DCS Total Score: 7.5 mg gefapixant v PBO
    Statistical analysis description
    Week 4 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.8457
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.7
         upper limit
    		 0.6
    Statistical analysis title
    		 Week 4 DCS Total Score: 20 mg gefapixant v PBO
    Statistical analysis description
    Week 4 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.4044
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.9
         upper limit
    		 0.4
    Statistical analysis title
    		 Week 4 DCS Total Score: 50 mg gefapixant v PBO
    Statistical analysis description
    Week 4 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    118
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.3031
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1
         upper limit
    		 0.3

    Secondary: Change from Baseline in Weekly Mean DCS at Week 5

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    End point title
    		 Change from Baseline in Weekly Mean DCS at Week 5
    End point description
    The DCS has a score ranging from 0 (best) to 10 (worst). Weekly mean daily score was defined as the average of the daily scores for each week. Baseline was defined as the average DCS score collected during the week prior to Day 1 (Day -7 to Day -1). Participants rated the severity of their cough using the DCS each day. LS mean change from baseline with associated SE reported for each treatment group. All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period were analysed.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 5
    End point values
    		 Placebo Gefapixant 7.5 mg Gefapixant 20 mg Gefapixant 50 mg
    Number of subjects analysed
    61
    59
    59
    57
    Units: score on a scale
        least squares mean (standard error)
    -1.4 ± 0.23
    -1.4 ± 0.24
    -1.9 ± 0.24
    -2.1 ± 0.24
    Statistical analysis title
    		 Week 5 DCS Total Score: 7.5 mg gefapixant v PBO
    Statistical analysis description
    Week 5 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.9126
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.7
         upper limit
    		 0.6
    Statistical analysis title
    		 Week 5 DCS Total Score: 20 mg gefapixant v PBO
    Statistical analysis description
    Week 5 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1136
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.2
         upper limit
    		 0.1
    Statistical analysis title
    		 Week 5 DCS Total Score: 50 mg gefapixant v PBO
    Statistical analysis description
    Week 5 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    118
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0352
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.4
         upper limit
    		 0

    Secondary: Change from Baseline in Weekly Mean DCS at Week 6

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    End point title
    		 Change from Baseline in Weekly Mean DCS at Week 6
    End point description
    The DCS has a score ranging from 0 (best) to 10 (worst). Weekly mean daily score was defined as the average of the daily scores for each week. Baseline was defined as the average DCS score collected during the week prior to Day 1 (Day -7 to Day -1). Participants rated the severity of their cough using the DCS each day. LS mean change from baseline with associated SE reported for each treatment group. All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period were analysed.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 6
    End point values
    		 Placebo Gefapixant 7.5 mg Gefapixant 20 mg Gefapixant 50 mg
    Number of subjects analysed
    61
    59
    59
    57
    Units: score on a scale
        least squares mean (standard error)
    -1.2 ± 0.24
    -1.7 ± 0.24
    -1.9 ± 0.24
    -1.8 ± 0.24
    Statistical analysis title
    		 Week 6 DCS Total Score: 7.5 mg gefapixant v PBO
    Statistical analysis description
    Week 6 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1718
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.1
         upper limit
    		 0.2
    Statistical analysis title
    		 Week 6 DCS Total Score: 20 mg gefapixant v PBO
    Statistical analysis description
    Week 6 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0651
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.3
         upper limit
    		 0
    Statistical analysis title
    		 Week 6 DCS Total Score: 50 mg gefapixant v PBO
    Statistical analysis description
    Week 6 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    118
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0848
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.2
         upper limit
    		 0.1

    Secondary: Change from Baseline in Weekly Mean DCS at Week 7

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    End point title
    		 Change from Baseline in Weekly Mean DCS at Week 7
    End point description
    The DCS has a score ranging from 0 (best) to 10 (worst). Weekly mean daily score was defined as the average of the daily scores for each week. Baseline was defined as the average DCS score collected during the week prior to Day 1 (Day -7 to Day -1). Participants rated the severity of their cough using the DCS each day. LS mean change from baseline with associated SE reported for each treatment group. All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period were analysed.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 7
    End point values
    		 Placebo Gefapixant 7.5 mg Gefapixant 20 mg Gefapixant 50 mg
    Number of subjects analysed
    61
    59
    59
    57
    Units: score on a scale
        least squares mean (standard error)
    -1.5 ± 0.25
    -1.7 ± 0.25
    -1.9 ± 0.25
    -1.9 ± 0.25
    Statistical analysis title
    		 Week 7 DCS Total Score: 7.5 mg gefapixant v PBO
    Statistical analysis description
    Week 7 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.6715
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.8
         upper limit
    		 0.5
    Statistical analysis title
    		 Week 7 DCS Total Score: 20 mg gefapixant v PBO
    Statistical analysis description
    Week 7 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.3514
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1
         upper limit
    		 0.4
    Statistical analysis title
    		 Week 7 DCS Total Score: 50 mg gefapixant v PBO
    Statistical analysis description
    Week 7 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    118
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.2809
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.1
         upper limit
    		 0.3

    Secondary: Change from Baseline in Weekly Mean DCS at Week 8

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    End point title
    		 Change from Baseline in Weekly Mean DCS at Week 8
    End point description
    The DCS has a score ranging from 0 (best) to 10 (worst). Weekly mean daily score was defined as the average of the daily scores for each week. Baseline was defined as the average DCS score collected during the week prior to Day 1 (Day -7 to Day -1). Participants rated the severity of their cough using the DCS each day. LS mean change from baseline with associated SE reported for each treatment group. All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period were analysed.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 8
    End point values
    		 Placebo Gefapixant 7.5 mg Gefapixant 20 mg Gefapixant 50 mg
    Number of subjects analysed
    61
    59
    59
    57
    Units: score on a scale
        least squares mean (standard error)
    -1.7 ± 0.25
    -1.8 ± 0.25
    -1.9 ± 0.25
    -1.9 ± 0.26
    Statistical analysis title
    		 Week 8 DCS Total Score: 7.5 mg gefapixant v PBO
    Statistical analysis description
    Week 8 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.6022
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.9
         upper limit
    		 0.5
    Statistical analysis title
    		 Week 8 DCS Total Score: 20 mg gefapixant v PBO
    Statistical analysis description
    Week 8 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.4456
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1
         upper limit
    		 0.4
    Statistical analysis title
    		 Week 8 DCS Total Score: 50 mg gefapixant v PBO
    Statistical analysis description
    Week 8 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    118
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.4629
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1
         upper limit
    		 0.4

    Secondary: Change from Baseline in Weekly Mean DCS at Week 9

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    End point title
    		 Change from Baseline in Weekly Mean DCS at Week 9
    End point description
    The DCS has a score ranging from 0 (best) to 10 (worst). Weekly mean daily score was defined as the average of the daily scores for each week. Baseline was defined as the average DCS score collected during the week prior to Day 1 (Day -7 to Day -1). Participants rated the severity of their cough using the DCS each day. LS mean change from baseline with associated SE reported for each treatment group. All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period were analysed.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 9
    End point values
    		 Placebo Gefapixant 7.5 mg Gefapixant 20 mg Gefapixant 50 mg
    Number of subjects analysed
    61
    59
    59
    57
    Units: score on a scale
        least squares mean (standard error)
    -1.6 ± 0.25
    -1.9 ± 0.25
    -2.2 ± 0.25
    -2.0 ± 0.26
    Statistical analysis title
    		 Week 9 DCS Total Score: 7.5 mg gefapixant v PBO
    Statistical analysis description
    Week 9 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.3749
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1
         upper limit
    		 0.4
    Statistical analysis title
    		 Week 9 DCS Total Score: 20 mg gefapixant v PBO
    Statistical analysis description
    Week 9 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0854
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.3
         upper limit
    		 0.1
    Statistical analysis title
    		 Week 9 DCS Total Score: 50 mg gefapixant v PBO
    Statistical analysis description
    Week 9 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    118
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.2672
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.1
         upper limit
    		 0.3

    Secondary: Change from Baseline in Weekly Mean DCS at Week 10

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    End point title
    		 Change from Baseline in Weekly Mean DCS at Week 10
    End point description
    The DCS has a score ranging from 0 (best) to 10 (worst). Weekly mean daily score was defined as the average of the daily scores for each week. Baseline was defined as the average DCS score collected during the week prior to Day 1 (Day -7 to Day -1). Participants rated the severity of their cough using the DCS each day. LS mean change from baseline with associated SE reported for each treatment group. All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period were analysed.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 10
    End point values
    		 Placebo Gefapixant 7.5 mg Gefapixant 20 mg Gefapixant 50 mg
    Number of subjects analysed
    61
    59
    59
    57
    Units: score on a scale
        least squares mean (standard error)
    -1.5 ± 0.25
    -1.6 ± 0.25
    -2.1 ± 0.25
    -2.1 ± 0.26
    Statistical analysis title
    		 Week 10 DCS Total Score: 7.5 mg gefapixant v PBO
    Statistical analysis description
    Week 10 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.7255
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.8
         upper limit
    		 0.6
    Statistical analysis title
    		 Week 10 DCS Total Score: 20 mg gefapixant v PBO
    Statistical analysis description
    Week 10 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0918
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.3
         upper limit
    		 0.1
    Statistical analysis title
    		 Week 10 DCS Total Score: 50 mg gefapixant v PBO
    Statistical analysis description
    Week 10 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    118
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1263
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.2
         upper limit
    		 0.2

    Secondary: Change from Baseline in Weekly Mean DCS at Week 11

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    End point title
    		 Change from Baseline in Weekly Mean DCS at Week 11
    End point description
    The DCS has a score ranging from 0 (best) to 10 (worst). Weekly mean daily score was defined as the average of the daily scores for each week. Baseline was defined as the average DCS score collected during the week prior to Day 1 (Day -7 to Day -1). Participants rated the severity of their cough using the DCS each day. LS mean change from baseline with associated SE reported for each treatment group. All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period were analysed.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 11
    End point values
    		 Placebo Gefapixant 7.5 mg Gefapixant 20 mg Gefapixant 50 mg
    Number of subjects analysed
    61
    59
    59
    57
    Units: score on a scale
        least squares mean (standard error)
    -1.5 ± 0.25
    -1.8 ± 0.25
    -2.1 ± 0.25
    -2.2 ± 0.26
    Statistical analysis title
    		 Week 11 DCS Total Score: 7.5 mg gefapixant v PBO
    Statistical analysis description
    Week 11 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.4058
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1
         upper limit
    		 0.4
    Statistical analysis title
    		 Week 11 DCS Total Score: 20 mg gefapixant v PBO
    Statistical analysis description
    Week 11 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0828
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.3
         upper limit
    		 0.1
    Statistical analysis title
    		 Week 11 DCS Total Score: 50 mg gefapixant v PBO
    Statistical analysis description
    Week 11 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    118
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0575
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.4
         upper limit
    		 0

    Secondary: Change from Baseline in Weekly Mean DCS at Week 12

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    End point title
    		 Change from Baseline in Weekly Mean DCS at Week 12
    End point description
    The DCS has a score ranging from 0 (best) to 10 (worst). Weekly mean daily score was defined as the average of the daily scores for each week. Baseline was defined as the average DCS score collected during the week prior to Day 1 (Day -7 to Day -1). Participants rated the severity of their cough using the DCS each day. LS mean change from baseline with associated SE reported for each treatment group. All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period were analysed.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12
    End point values
    		 Placebo Gefapixant 7.5 mg Gefapixant 20 mg Gefapixant 50 mg
    Number of subjects analysed
    61
    59
    59
    57
    Units: score on a scale
        least squares mean (standard error)
    -1.5 ± 0.26
    -1.8 ± 0.26
    -2.2 ± 0.26
    -2.2 ± 0.27
    Statistical analysis title
    		 Week 12 DCS Total Score: 7.5 mg gefapixant v PBO
    Statistical analysis description
    Week 12 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.4163
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1
         upper limit
    		 0.4
    Statistical analysis title
    		 Week 12 DCS Total Score: 20 mg gefapixant v PBO
    Statistical analysis description
    Week 12 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0882
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.3
         upper limit
    		 0.1
    Statistical analysis title
    		 Week 12 DCS Total Score: 50 mg gefapixant v PBO
    Statistical analysis description
    Week 12 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    118
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0961
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.4
         upper limit
    		 0.1

    Secondary: Change from Baseline in Leicester Cough Questionnaire (LCQ) Total Score after 4 Weeks of Treatment (Day 28)

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    End point title
    		 Change from Baseline in Leicester Cough Questionnaire (LCQ) Total Score after 4 Weeks of Treatment (Day 28)
    End point description
    The LCQ instrument is designed to assess the impact of cough on various aspects of a participant’s life over the preceding 2 weeks. It consists of 19 items which are divided over 3 domains: Physical (items 1, 2, 3, 9, 10, 11, 14 and 15), Psychological (4, 5, 6, 12, 13, 16, and 17), and Social (7, 8, 18, 19). A 7-point Likert scale is used to rate each item. For each domain, the domain score (range 1-7) is the sum of the individual item scores within the domain divided by the number of items in the domain. The total score is the sum of the three domain scores and ranges from 3-21; a higher score corresponds to a better health status. Baseline LCQ was defined as the LCQ collected at Baseline (Study Day -1). LS mean change from baseline with associated SE reported for each treatment group. All randomized participants who had taken ≥1 dose of study medication and provided ≥1 baseline and at least one post baseline endpoint observation during the treatment period were analysed.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 28
    End point values
    		 Placebo Gefapixant 7.5 mg Gefapixant 20 mg Gefapixant 50 mg
    Number of subjects analysed
    61
    59
    59
    57
    Units: score on a scale
        least squares mean (standard error)
    2.1 ± 0.40
    2.9 ± 0.40
    2.3 ± 0.40
    4.2 ± 0.4
    Statistical analysis title
    		 Day 28 LCQ Total Score: 7.5 mg gefapixant v PBO
    Statistical analysis description
    Day 28 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.163
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.3
         upper limit
    		 1.9
    Statistical analysis title
    		 Day 28 LCQ Total Score: 20 mg gefapixant v PBO
    Statistical analysis description
    Day 28 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.7601
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1
         upper limit
    		 1.3
    Statistical analysis title
    		 Day 28 LCQ Total Score: 50 mg gefapixant v PBO
    Statistical analysis description
    Day 28 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    118
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0004
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    2.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.9
         upper limit
    		 3.2

    Secondary: Change from Baseline in Leicester Cough Questionnaire (LCQ) Total Score after 8 Weeks of Treatment (Day 56)

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    End point title
    		 Change from Baseline in Leicester Cough Questionnaire (LCQ) Total Score after 8 Weeks of Treatment (Day 56)
    End point description
    The LCQ instrument is designed to assess the impact of cough on various aspects of a participant’s life over the preceding 2 weeks. It consists of 19 items which are divided over 3 domains: Physical (items 1, 2, 3, 9, 10, 11, 14 and 15), Psychological (4, 5, 6, 12, 13, 16, and 17), and Social (7, 8, 18, 19). A 7-point Likert scale is used to rate each item. For each domain, the domain score (range 1-7) is the sum of the individual item scores within the domain divided by the number of items in the domain. The total score is the sum of the three domain scores and ranges from 3-21; a higher score corresponds to a better health status. Baseline LCQ was defined as the LCQ collected at Baseline (Study Day -1). LS mean change from baseline with associated SE reported for each treatment group. All randomized participants who had taken ≥1 dose of study medication and provided ≥1 baseline and at least one post baseline endpoint observation during the treatment period were analysed.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 56
    End point values
    		 Placebo Gefapixant 7.5 mg Gefapixant 20 mg Gefapixant 50 mg
    Number of subjects analysed
    61
    59
    59
    57
    Units: score on a scale
        least squares mean (standard error)
    2.0 ± 0.4
    3.1 ± 0.4
    3.0 ± 0.4
    3.5 ± 0.5
    Statistical analysis title
    		 Day 56 LCQ Total Score: 7.5 mg gefapixant v PBO
    Statistical analysis description
    Day 56 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0941
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.2
         upper limit
    		 2.3
    Statistical analysis title
    		 Day 56 LCQ Total Score: 20 mg gefapixant v PBO
    Statistical analysis description
    Day 56 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1321
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.3
         upper limit
    		 2.2
    Statistical analysis title
    		 Day 56 LCQ Total Score: 50 mg gefapixant v PBO
    Statistical analysis description
    Day 56 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    118
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0192
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    1.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.2
         upper limit
    		 2.7

    Secondary: Change from Baseline in Leicester Cough Questionnaire (LCQ) Total Score At Day 85/Early Termination

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    End point title
    		 Change from Baseline in Leicester Cough Questionnaire (LCQ) Total Score At Day 85/Early Termination
    End point description
    The LCQ instrument is designed to assess the impact of cough on various aspects of a participant’s life over the preceding 2 weeks. It consists of 19 items which are divided over 3 domains: Physical (items 1, 2, 3, 9, 10, 11, 14 and 15), Psychological (4, 5, 6, 12, 13, 16, and 17), and Social (7, 8, 18, 19). A 7-point Likert scale is used to rate each item. For each domain, the domain score (range 1-7) is the sum of the individual item scores within the domain divided by the number of items in the domain. The total score is the sum of the three domain scores and ranges from 3-21; a higher score corresponds to a better health status. Baseline LCQ was defined as the LCQ collected at Baseline (Study Day -1). LS mean change from baseline with associated SE reported for each treatment group. All randomized participants who had taken ≥1 dose of study medication and provided ≥1 baseline and at least one post baseline endpoint observation during the treatment period were analysed.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 85/Early Termination
    End point values
    		 Placebo Gefapixant 7.5 mg Gefapixant 20 mg Gefapixant 50 mg
    Number of subjects analysed
    61
    59
    59
    57
    Units: score on a scale
        least squares mean (standard error)
    2.1 ± 0.4
    3.3 ± 0.4
    3.2 ± 0.4
    4.0 ± 0.5
    Statistical analysis title
    		 Day 85 LCQ Total Score: 7.5 mg gefapixant v PBO
    Statistical analysis description
    Day 85/Early Termination estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0626
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    1.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.1
         upper limit
    		 2.4
    Statistical analysis title
    		 Day 85 LCQ Total Score: 20 mg gefapixant v PBO
    Statistical analysis description
    Day 85/Early Termination estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0967
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.2
         upper limit
    		 2.3
    Statistical analysis title
    		 Day 85 LCQ Total Score: 50 mg gefapixant v PBO
    Statistical analysis description
    Day 85/Early Termination estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    118
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0028
    Method
    		 Mixed Effect Repeated Measures model
    Parameter type
    		 LS Mean Difference
    Point estimate
    1.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.7
         upper limit
    		 3.1

    Secondary: Percentage of Participants Reporting “Very Much Improved” or “Much Improved” According to the Patient’s Global Impression of Change (PGIC) after 4 Weeks of Treatment (Day 28)

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    End point title
    		 Percentage of Participants Reporting “Very Much Improved” or “Much Improved” According to the Patient’s Global Impression of Change (PGIC) after 4 Weeks of Treatment (Day 28)
    End point description
    The self-reported measure Patient’s Global Impression of Change (PGIC) reflects a participant’s belief about the efficacy of treatment. PGIC is a 7-point scale depicting a patient's rating of overall improvement. Participants rate their change as “very much improved,” “much improved,” “minimally improved,” “no change,” “minimally worse,” “much worse,” or “very much worse.” The counts and percentages of ordered responses to the participant’s global perception of change were computed for each treatment group on Day 28 and the percentage of participants with improvements (either "very much improved" or "much improved" on the PGIC scale) was reported for each treatment group. All randomised participants who had taken at least 1 dose of study medication and provided at least 1 baseline and 1 Day 28 PGIC observation during the treatment period were analysed.
    End point type
    Secondary
    End point timeframe
    Day 28
    End point values
    		 Placebo Gefapixant 7.5 mg Gefapixant 20 mg Gefapixant 50 mg
    Number of subjects analysed
    60
    58
    59
    56
    Units: percentage of participants
        number (not applicable)
    30.0
    37.9
    35.6
    46.4
    Statistical analysis title
    		 Day 28 PGIC: 7.5 mg gefapixant v PBO
    Statistical analysis description
    The distribution of responses were compared between each of the gefapixant treatment groups and placebo using the stratified CMH test (stratified by country). P-values calculated using CMH test.
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    118
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.3182
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 28 PGIC: 20 mg gefapixant v PBO
    Statistical analysis description
    The distribution of responses were compared between each of the gefapixant treatment groups and placebo using the stratified CMH test (stratified by country). P-values calculated using CMH test.
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    119
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.5021
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 28 PGIC: 50 mg gefapixant v PBO
    Statistical analysis description
    The distribution of responses were compared between each of the gefapixant treatment groups and placebo using the stratified CMH test (stratified by country). P-values calculated using CMH test.
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    116
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0665
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval

    Secondary: Percentage of Participants Reporting “Very Much Improved” or “Much Improved” According to the PGIC after 8 Weeks of Treatment (Day 56)

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    End point title
    		 Percentage of Participants Reporting “Very Much Improved” or “Much Improved” According to the PGIC after 8 Weeks of Treatment (Day 56)
    End point description
    The self-reported measure Patient’s Global Impression of Change (PGIC) reflects a participant’s belief about the efficacy of treatment. PGIC is a 7-point scale depicting a patient's rating of overall improvement. Participants rate their change as “very much improved,” “much improved,” “minimally improved,” “no change,” “minimally worse,” “much worse,” or “very much worse.” The counts and percentages of ordered responses to the participant’s global perception of change were computed for each treatment group on Day 28 and the percentage of participants with improvements (either "very much improved" or "much improved" on the PGIC scale) was reported for each treatment group. All randomised participants who had taken at least 1 dose of study medication and provided at least 1 baseline and 1 Day 56 PGIC observation during the treatment period were analysed.
    End point type
    Secondary
    End point timeframe
    Day 56
    End point values
    		 Placebo Gefapixant 7.5 mg Gefapixant 20 mg Gefapixant 50 mg
    Number of subjects analysed
    58
    58
    59
    51
    Units: percentage of participants
        number (not applicable)
    29.3
    44.8
    44.1
    60.8
    Statistical analysis title
    		 Day 56 PGIC: 7.5 mg gefapixant v PBO
    Statistical analysis description
    The distribution of responses were compared between each of the gefapixant treatment groups and placebo using the stratified CMH test (stratified by country). P-values calculated using CMH test.
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    116
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0872
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 56 PGIC: 20 mg gefapixant v PBO
    Statistical analysis description
    The distribution of responses were compared between each of the gefapixant treatment groups and placebo using the stratified CMH test (stratified by country). P-values calculated using CMH test.
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    117
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0994
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 56 PGIC: 50 mg gefapixant v PBO
    Statistical analysis description
    The distribution of responses were compared between each of the gefapixant treatment groups and placebo using the stratified CMH test (stratified by country). P-values calculated using CMH test.
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    109
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0009
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval

    Secondary: Percentage of Participants Reporting “Very Much Improved” or “Much Improved” According to the PGIC at Day 85/Early Termination

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    End point title
    		 Percentage of Participants Reporting “Very Much Improved” or “Much Improved” According to the PGIC at Day 85/Early Termination
    End point description
    The self-reported measure Patient’s Global Impression of Change (PGIC) reflects a participant’s belief about the efficacy of treatment. PGIC is a 7-point scale depicting a patient's rating of overall improvement. Participants rate their change as “very much improved,” “much improved,” “minimally improved,” “no change,” “minimally worse,” “much worse,” or “very much worse.” The counts and percentages of ordered responses to the participant’s global perception of change were computed for each treatment group on Day 28 and the percentage of participants with improvements (either "very much improved" or "much improved" on the PGIC scale) was reported for each treatment group. All randomised participants who had taken at least 1 dose of study medication and provided at least 1 baseline and 1 Day 85 PGIC observation during the treatment period were analysed.
    End point type
    Secondary
    End point timeframe
    Day 85/Early Termination
    End point values
    		 Placebo Gefapixant 7.5 mg Gefapixant 20 mg Gefapixant 50 mg
    Number of subjects analysed
    60
    58
    59
    57
    Units: percentage of participants
        number (not applicable)
    28.3
    53.4
    49.2
    64.9
    Statistical analysis title
    		 Day 85 PGIC: 7.5 mg gefapixant v PBO
    Statistical analysis description
    The distribution of responses were compared between each of the gefapixant treatment groups and placebo using the stratified CMH test (stratified by country). P-values calculated using CMH test.
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    118
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0037
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 85 PGIC: 20 mg gefapixant v PBO
    Statistical analysis description
    The distribution of responses were compared between each of the gefapixant treatment groups and placebo using the stratified CMH test (stratified by country). P-values calculated using CMH test.
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    119
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0166
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 85: 50 mg gefapixant v PBO
    Statistical analysis description
    The distribution of responses were compared between each of the gefapixant treatment groups and placebo using the stratified CMH test (stratified by country). P-values calculated using CMH test.
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    117
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.0001
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval

    Secondary: Percentage of Participants Rated as “Very Much Improved” or “Much Improved” by Clinicians according to the Clinician’s Global Impression of Change (CGIC) at Day 85/Early Termination

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    End point title
    		 Percentage of Participants Rated as “Very Much Improved” or “Much Improved” by Clinicians according to the Clinician’s Global Impression of Change (CGIC) at Day 85/Early Termination
    End point description
    The Clinician’s Global Impression of Change (CGIC) reflects a clinician's belief about the efficacy of treatment. CGIC is a 7-point scale depicting a clinician’s rating of a participant’s overall improvement. Clinicians rated the participant’s change at Week 12 (Day 85) as “very much improved,” “much improved,” “minimally improved,” “no change,” “minimally worse,” “much worse,” or “very much worse.” The counts and percentages of ordered responses to the clinician’s global perception of change were computed for each treatment group, and the percentage of participants rated by clinicians as having improvement (either "very much improved" or "much improved" on the CGIC scale) was reported for each treatment group. All randomised participants who had taken at least 1 dose of study medication and provided at least 1 baseline and 1 Day 85 CGIC observation during the treatment period were analysed.
    End point type
    Secondary
    End point timeframe
    Day 85/Early Termination
    End point values
    		 Placebo Gefapixant 7.5 mg Gefapixant 20 mg Gefapixant 50 mg
    Number of subjects analysed
    60
    58
    59
    57
    Units: percentage of participants
        number (not applicable)
    35.0
    53.4
    50.8
    64.9
    Statistical analysis title
    		 Day 85 CGIC: 7.5 mg gefapixant v PBO
    Statistical analysis description
    The distribution of responses were compared between each of the gefapixant treatment groups and placebo using the stratified CMH test (stratified by country). P-values calculated using CMH test.
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    118
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0396
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 85 CGIC: 20 mg gefapixant v PBO
    Statistical analysis description
    The distribution of responses were compared between each of the gefapixant treatment groups and placebo using the stratified CMH test (stratified by country). P-values calculated using CMH test.
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    119
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0751
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Day 85 CGIC: 50 mg gefapixant v PBO
    Statistical analysis description
    The distribution of responses were compared between each of the gefapixant treatment groups and placebo using the stratified CMH test (stratified by country). P-values calculated using CMH test.
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    117
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval

    Secondary: Acceptability Questionnaire: Percentage of Participants That Were Likely to Take Study Medication For At Least One Year

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    End point title
    		 Acceptability Questionnaire: Percentage of Participants That Were Likely to Take Study Medication For At Least One Year
    End point description
    At the end of the treatment period (Day 85), participants were asked “How likely would you be to take this medication?” This question was asked in reference to the time frame of “At least one year”. The counts and percentages of ordered categorical responses to this question were computed for each treatment group. All randomised participants who had taken at least 1 dose of study medication and had available Acceptability Questionnaire data at Day 85 were analysed.
    End point type
    Secondary
    End point timeframe
    Day 85/Early Termination
    End point values
    		 Placebo Gefapixant 7.5 mg Gefapixant 20 mg Gefapixant 50 mg
    Number of subjects analysed
    60
    58
    58
    57
    Units: percentage of participants
    number (not applicable)
        Extremely unlikely
    3.3
    6.9
    5.2
    1.8
        Unlikely
    3.3
    1.7
    3.4
    12.3
        Neither likely or unlikely
    5.0
    5.2
    12.1
    1.8
        Likely
    30.0
    15.5
    13.8
    29.8
        Extremely likely
    58.3
    70.7
    65.5
    54.4
    Statistical analysis title
    		 1 Year Acceptability: 7.5 mg gefapixant v PBO
    Statistical analysis description
    The distribution of “Extremely likely” responses was compared between each of the gefapixant treatment groups and placebo using the stratified CMH test (stratified by country). P-values calculated for the gefapixant vs. placebo using CMH test.
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    118
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.8464
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 1 Year Acceptability: 50 mg gefapixant v PBO
    Statistical analysis description
    The distribution of “Extremely likely” responses was compared between each of the gefapixant treatment groups and placebo using the stratified CMH test (stratified by country). P-values calculated for gefapixant vs. placebo using CMH test.
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    117
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.4364
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 1 Year Acceptability: 20 mg gefapixant v PBO
    Statistical analysis description
    The distribution of “Extremely likely” responses was compared between each of the gefapixant treatment groups and placebo using the stratified CMH test (stratified by country). P-values calculated for gefapixant vs. placebo using CMH test.
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    118
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.7687
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval

    Secondary: Acceptability Questionnaire: Percentage of Participants That Were Likely to Take Study Medication For At Least Six Months

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    End point title
    		 Acceptability Questionnaire: Percentage of Participants That Were Likely to Take Study Medication For At Least Six Months
    End point description
    At the end of the treatment period (Day 85), participants were asked “How likely would you be to take this medication?” This question was asked in reference to the time frame of “At least six months”. The counts and percentages of ordered categorical responses to this question were computed for each treatment group. All randomised participants who had taken at least 1 dose of study medication and had available Acceptability Questionnaire data at Day 85 were analysed.
    End point type
    Secondary
    End point timeframe
    Day 85/Early Termination
    End point values
    		 Placebo Gefapixant 7.5 mg Gefapixant 20 mg Gefapixant 50 mg
    Number of subjects analysed
    60
    57
    58
    57
    Units: percentage of participants
    number (not applicable)
        Extremely unlikely
    3.3
    5.3
    5.2
    1.8
        Unlikely
    1.7
    3.5
    3.4
    10.5
        Neither likely or unlikely
    6.7
    3.5
    6.9
    3.5
        Likely
    21.7
    14.0
    17.2
    29.8
        Extremely likely
    66.7
    73.7
    67.2
    54.4
    Statistical analysis title
    		 6 Month Acceptability: 7.5 mg gefapixant v PBO
    Statistical analysis description
    The distribution of “Extremely likely” responses were compared between each of the gefapixant treatment groups and placebo using the stratified CMH test (stratified by country). P-values calculated for gefapixant vs. placebo using CMH test.
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    117
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.9966
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 6 Month Acceptability: 50 mg gefapixant v PBO
    Statistical analysis description
    The distribution of “Extremely likely” responses were compared between each of the gefapixant treatment groups and placebo using the stratified CMH test (stratified by country). P-values calculated for gefapixant vs. placebo using CMH test.
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    117
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.2155
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 6 Month Acceptability: 20 mg gefapixant v PBO
    Statistical analysis description
    The distribution of “Extremely likely” responses were compared between each of the gefapixant treatment groups and placebo using the stratified CMH test (stratified by country). P-values calculated for gefapixant vs. placebo using CMH test.
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    118
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.6372
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval

    Secondary: Acceptability Questionnaire: Percentage of Participants That Were Likely to Take Study Medication For At Least Four Weeks

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    End point title
    		 Acceptability Questionnaire: Percentage of Participants That Were Likely to Take Study Medication For At Least Four Weeks
    End point description
    At the end of the treatment period (Day 85), participants were asked “How likely would you be to take this medication?” This question was asked in reference to the time frame of “At least four weeks”. The counts and percentages of ordered categorical responses to this question were computed for each treatment group. All randomised participants who had taken at least 1 dose of study medication and had available Acceptability Questionnaire data at Day 85 were analysed.
    End point type
    Secondary
    End point timeframe
    Day 85/Early Termination
    End point values
    		 Placebo Gefapixant 7.5 mg Gefapixant 20 mg Gefapixant 50 mg
    Number of subjects analysed
    60
    58
    58
    57
    Units: percentage of participants
    number (not applicable)
        Extremely unlikely
    3.3
    5.2
    5.2
    0.0
        Unlikely
    1.7
    1.7
    1.7
    5.3
        Neither likely or unlikely
    3.3
    1.7
    6.9
    8.8
        Likely
    18.3
    19.0
    15.5
    26.3
        Extremely likely
    73.3
    72.4
    70.7
    59.6
    Statistical analysis title
    		 4 Week Acceptability: 7.5 mg gefapixant v PBO
    Statistical analysis description
    The distribution of “Extremely likely” responses were compared between each of the gefapixant treatment groups and placebo using the stratified CMH test (stratified by country). P-values calculated for gefapixant vs. placebo using CMH test.
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    118
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.7559
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 4 Week Acceptability: 50 mg gefapixant v PBO
    Statistical analysis description
    The distribution of “Extremely likely” responses were compared between each of the gefapixant treatment groups and placebo using the stratified CMH test (stratified by country). P-values calculated for gefapixant vs. placebo using CMH test.
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    117
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.279
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 4 Week Acceptability: 20 mg gefapixant v PBO
    Statistical analysis description
    The distribution of “Extremely likely” responses were compared between each of the gefapixant treatment groups and placebo using the stratified CMH test (stratified by country). P-values calculated for gefapixant vs. placebo using CMH test.
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    118
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.5091
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval

    Secondary: Acceptability Questionnaire: Percentage of Participants That Were Likely to Take Study Medication Twice Daily

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    End point title
    		 Acceptability Questionnaire: Percentage of Participants That Were Likely to Take Study Medication Twice Daily
    End point description
    At the end of the treatment period (Day 85), participants were asked “How likely would you be to take this medication?” This question was asked in reference to the time frame of “Twice daily”. The counts and percentages of ordered categorical responses to this question were computed for each treatment group. All randomised participants who had taken at least 1 dose of study medication and had available Acceptability Questionnaire data at Day 85 were analysed.
    End point type
    Secondary
    End point timeframe
    Day 85/Early Termination
    End point values
    		 Placebo Gefapixant 7.5 mg Gefapixant 20 mg Gefapixant 50 mg
    Number of subjects analysed
    60
    57
    57
    56
    Units: percentage of participants
    number (not applicable)
        Extremely unlikely
    3.3
    7.0
    5.3
    1.8
        Unlikely
    0.0
    0.0
    3.5
    5.4
        Neither likely or unlikely
    3.3
    5.3
    3.5
    8.9
        Likely
    20.0
    15.8
    22.8
    30.4
        Extremely likely
    73.3
    71.9
    64.9
    53.6
    Statistical analysis title
    		 Twice Daily Acceptability: 7.5 mg gefapixant v PBO
    Statistical analysis description
    The distribution of “Extremely likely” responses were compared between each of the gefapixant treatment groups and placebo using the stratified CMH test (stratified by country). P-values calculated for gefapixant vs. placebo using CMH test.
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    117
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.3887
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Twice Daily Acceptability: 20 mg gefapixant v PBO
    Statistical analysis description
    The distribution of “Extremely likely” responses were compared between each of the gefapixant treatment groups and placebo using the stratified CMH test (stratified by country). P-values calculated for gefapixant vs. placebo using CMH test.
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    117
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.2333
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Twice Daily Acceptability: 50 mg gefapixant v PBO
    Statistical analysis description
    The distribution of “Extremely likely” responses were compared between each of the gefapixant treatment groups and placebo using the stratified CMH test (stratified by country). P-values calculated for gefapixant vs. placebo using CMH test.
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    116
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0534
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval

    Secondary: Taste Questionnaire: Percentage of Participants That Experienced Taste Effect After Taking Medication by Frequency after 12 Weeks of Treatment (Day 84)

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    End point title
    		 Taste Questionnaire: Percentage of Participants That Experienced Taste Effect After Taking Medication by Frequency after 12 Weeks of Treatment (Day 84)
    End point description
    The tolerance to taste-related adverse events (AEs) was evaluated at the end of the study (Day 84) and a structured taste questionnaire was administered to participants experiencing a taste-related AE. Participants were asked to indicate the frequency that they experienced the taste effect by answering the question “How frequently do you experience the taste effect after taking each dose of medication?” The counts and percentages of categorical frequency responses to the individual items were computed for each treatment group. All randomised participants who had taken at least 1 dose of study medication, who had experienced a taste-related AE, and who had Day 84 taste questionnaire data available were analysed.
    End point type
    Secondary
    End point timeframe
    Day 84
    End point values
    		 Placebo Gefapixant 7.5 mg Gefapixant 20 mg Gefapixant 50 mg
    Number of subjects analysed
    57
    56
    57
    51
    Units: percentage of participants
    number (not applicable)
        No Taste Effect Noted
    96.5
    96.4
    61.4
    35.3
        Never
    1.8
    0.0
    0.0
    0.0
        Occasionally
    1.8
    1.8
    8.8
    0.0
        Often
    0.0
    1.8
    7.0
    3.9
        Almost Always
    0.0
    0.0
    7.0
    9.8
        Always
    0.0
    0.0
    15.8
    51.0
        No Taste Effect Noted + Never
    98.2
    96.4
    61.4
    35.3
    Statistical analysis title
    		 Taste Effect Frequency: 7.5 mg gefapixant v PBO
    Statistical analysis description
    The distribution of “No Taste Effect Noted” or “Never” responses were compared between each of the gefapixant treatment groups and placebo using the stratified CMH test (stratified by country). P-values calculated for gefapixant vs. placebo using CMH test.
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    113
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.6115
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Taste Effect Frequency: 20 mg gefapixant v PBO
    Statistical analysis description
    The distribution of “No Taste Effect Noted” or “Never” responses were compared between each of the gefapixant treatment groups and placebo using the stratified CMH test (stratified by country). P-values calculated for gefapixant vs. placebo using CMH test.
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    114
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.0001
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Taste Effect Frequency: 50 mg gefapixant v PBO
    Statistical analysis description
    The distribution of “No Taste Effect Noted” or “Never” responses were compared between each of the gefapixant treatment groups and placebo using the stratified CMH test (stratified by country). P-values calculated for gefapixant vs. placebo using CMH test.
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    108
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.0001
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval

    Secondary: Taste Questionnaire: Percentage of Participants That Found Taste Effect of Study Medication Bothersome after 12 Weeks of Treatment (Day 84)

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    End point title
    		 Taste Questionnaire: Percentage of Participants That Found Taste Effect of Study Medication Bothersome after 12 Weeks of Treatment (Day 84)
    End point description
    The tolerance to taste-related adverse events (AEs) was evaluated at the end of the study (Day 84) and a structured taste questionnaire was administered to participants experiencing a taste-related AE to determine what degree the participant found the taste effect bothersome by answering the question “How bothersome is the taste effect of the medication? The counts and percentages of categorical responses to the individual items were computed for each treatment group. All randomised participants who had taken at least 1 dose of study medication, who had experienced a taste-related AE, and who had Day 84 taste questionnaire data available were analysed.
    End point type
    Secondary
    End point timeframe
    Day 84
    End point values
    		 Placebo Gefapixant 7.5 mg Gefapixant 20 mg Gefapixant 50 mg
    Number of subjects analysed
    57
    56
    57
    51
    Units: percentage of participants
    number (not applicable)
        No Taste Effect Noted
    96.5
    96.4
    61.4
    35.3
        Not At All
    3.5
    3.6
    7.0
    5.9
        A Little
    0.0
    0.0
    8.8
    3.9
        Somewhat
    0.0
    0.0
    17.5
    13.7
        Very
    0.0
    0.0
    5.3
    29.4
        Extremely
    0.0
    0.0
    0.0
    11.8
        No Taste Effect Noted + Not At All
    100.0
    100.0
    68.4
    41.2
    Statistical analysis title
    		 Taste Effect Frequency: 7.5 mg gefapixant v PBO
    Statistical analysis description
    The distribution of “No Taste Effect Noted” or “Not at All” responses were compared between each of the gefapixant treatment groups and placebo using the stratified CMH test (stratified by country). P-values calculated for gefapixant vs. placebo using CMH test.
    Comparison groups
    Placebo v Gefapixant 7.5 mg
    Number of subjects included in analysis
    113
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0 [1]
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Notes
    [1] - A p-value of zero was calculated if all participants (100%) had “No Taste Effect Noted” or “Not at All” responses in both comparison groups.
    Statistical analysis title
    		 Taste Effect Frequency: 20 mg gefapixant v PBO
    Statistical analysis description
    The distribution of “No Taste Effect Noted” or “Not at All” responses were compared between each of the gefapixant treatment groups and placebo using the stratified CMH test (stratified by country). P-values calculated for gefapixant vs. placebo using CMH test.
    Comparison groups
    Placebo v Gefapixant 20 mg
    Number of subjects included in analysis
    114
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.0001
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Taste Effect Frequency: 50 mg gefapixant v PBO
    Statistical analysis description
    The distribution of “No Taste Effect Noted” or “Not at All” responses were compared between each of the gefapixant treatment groups and placebo using the stratified CMH test (stratified by country). P-values calculated for gefapixant vs. placebo using CMH test.
    Comparison groups
    Placebo v Gefapixant 50 mg
    Number of subjects included in analysis
    108
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.0001
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Up to ~14 weeks (Day 99)
    Adverse event reporting additional description
    All randomised participants who received at least 1 dose of study drug. One participant randomised to receive 7.5 mg gefapixant was discontinued before receiving treatment.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    17.0
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.

    Reporting group title
    Gefapixant 20 mg
    Reporting group description
    		 Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.

    Reporting group title
    Gefapixant 7.5 mg
    Reporting group description
    		 Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.

    Reporting group title
    Gefapixant 50 mg
    Reporting group description
    		 Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.

    Serious adverse events
    		 Placebo Gefapixant 20 mg Gefapixant 7.5 mg Gefapixant 50 mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 63 (0.00%)
    0 / 63 (0.00%)
    1 / 63 (1.59%)
         number of deaths (all causes)
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    Injury, poisoning and procedural complications
    Frostbite
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 63 (0.00%)
    0 / 63 (0.00%)
    1 / 63 (1.59%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Placebo Gefapixant 20 mg Gefapixant 7.5 mg Gefapixant 50 mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    21 / 63 (33.33%)
    45 / 63 (71.43%)
    26 / 63 (41.27%)
    52 / 63 (82.54%)
    Investigations
    Blood creatine phosphokinase increased
         subjects affected / exposed
    0 / 63 (0.00%)
    2 / 63 (3.17%)
    5 / 63 (7.94%)
    0 / 63 (0.00%)
         occurrences all number
    0
    2
    5
    0
    Nervous system disorders
    Ageusia
         subjects affected / exposed
    1 / 63 (1.59%)
    3 / 63 (4.76%)
    0 / 63 (0.00%)
    13 / 63 (20.63%)
         occurrences all number
    1
    3
    0
    14
    Dysgeusia
         subjects affected / exposed
    3 / 63 (4.76%)
    21 / 63 (33.33%)
    6 / 63 (9.52%)
    30 / 63 (47.62%)
         occurrences all number
    4
    26
    7
    39
    Headache
         subjects affected / exposed
    3 / 63 (4.76%)
    12 / 63 (19.05%)
    4 / 63 (6.35%)
    4 / 63 (6.35%)
         occurrences all number
    4
    16
    4
    4
    Hypogeusia
         subjects affected / exposed
    1 / 63 (1.59%)
    11 / 63 (17.46%)
    0 / 63 (0.00%)
    15 / 63 (23.81%)
         occurrences all number
    1
    12
    0
    18
    Gastrointestinal disorders
    Dry mouth
         subjects affected / exposed
    6 / 63 (9.52%)
    3 / 63 (4.76%)
    2 / 63 (3.17%)
    3 / 63 (4.76%)
         occurrences all number
    7
    3
    2
    3
    Hypoaesthesia oral
         subjects affected / exposed
    3 / 63 (4.76%)
    4 / 63 (6.35%)
    2 / 63 (3.17%)
    5 / 63 (7.94%)
         occurrences all number
    4
    4
    2
    5
    Nausea
         subjects affected / exposed
    0 / 63 (0.00%)
    4 / 63 (6.35%)
    0 / 63 (0.00%)
    6 / 63 (9.52%)
         occurrences all number
    0
    4
    0
    6
    Paraesthesia oral
         subjects affected / exposed
    5 / 63 (7.94%)
    5 / 63 (7.94%)
    4 / 63 (6.35%)
    4 / 63 (6.35%)
         occurrences all number
    8
    5
    6
    4
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    2 / 63 (3.17%)
    5 / 63 (7.94%)
    2 / 63 (3.17%)
    5 / 63 (7.94%)
         occurrences all number
    2
    5
    3
    5
    Oropharyngeal pain
         subjects affected / exposed
    2 / 63 (3.17%)
    0 / 63 (0.00%)
    1 / 63 (1.59%)
    4 / 63 (6.35%)
         occurrences all number
    2
    0
    1
    4
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    2 / 63 (3.17%)
    4 / 63 (6.35%)
    0 / 63 (0.00%)
    0 / 63 (0.00%)
         occurrences all number
    3
    4
    0
    0
    Upper respiratory tract infection
         subjects affected / exposed
    2 / 63 (3.17%)
    9 / 63 (14.29%)
    5 / 63 (7.94%)
    6 / 63 (9.52%)
         occurrences all number
    2
    9
    5
    6
    Urinary tract infection
         subjects affected / exposed
    2 / 63 (3.17%)
    5 / 63 (7.94%)
    3 / 63 (4.76%)
    2 / 63 (3.17%)
         occurrences all number
    2
    6
    3
    3

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    22 Dec 2015
    Amendment 1 (AM1) included revisions to inclusion and exclusion criteria, revisions to Subject Discontinuation criteria, and addition of Interactive Web Response System (IWRS) as a randomization method. AM1 also revised the selection and timing of dose for each subject, revised the primary endpoint to specify “after 4 weeks (Day 28)”, and removed the safety assessment for renal/urological AEs.
    11 Mar 2016
    AM2 included revisions to inclusion and exclusion criteria and to the Prohibited Concomitant Therapy section, and updated the Independent Data Monitoring Committee section of the protocol.
    04 Nov 2016
    AM3 removed the Week 4 timepoint from the primary objective and primary endpoint, and moved this timepoint to the Secondary Objectives/Endpoints. AM3 also revised the Secondary Objectives and divided the Secondary Endpoints into “key” and “other” categories. The statistical sections were also updated to reflect the changes made to the primary endpoint and primary analysis. This protocol amendment aligned key aspects of the statistical section of the study protocol with the statistical analysis plan. These revisions to the protocol, which provided additional detail and specificity of the planned analyses in order to facilitate the validity of the conclusions from the trial, were finalized after Last Subject Last Visit (LSLV) but prior to database lock, as was the statistical analysis plan. These changes did not result in any changes to the conduct of the trial. AM3 was approved on 15 December 2016, but due to system limitations, the Global End of Trial Date (LSLV) was imputed as the Amendment Date.

    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
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