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    Clinical Trial Results:
    A Phase 3, Randomized, Placebo-controlled, 12-week Double-blind Study, followed by a Non-Controlled Extension Treatment Period, to Assess the Efficacy and Safety of Fezolinetant in Women Suffering from Moderate to Severe Vasomotor Symptoms (Hot Flashes) Associated with Menopause

    Summary
    EudraCT number
    		 2018-003529-27
    Trial protocol
    		 GB   LV   CZ   HU  
    Global end of trial date
    23 Apr 2021

    Results information
    Results version number
    		 v3(current)
    This version publication date
    20 Jul 2022
    First version publication date
    18 Apr 2022
    Other versions
    		 v1 , v2
    Version creation reason
    • Correction of full data set
    Correct baseline severity data.

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    2693-CL-0302
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04003142
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Astellas Pharma Global Development, Inc
    Sponsor organisation address
    1 Astellas Way, Northbrook, IL, United States, 60062
    Public contact
    Clinical Trial Disclosure, Astellas Pharma Global Development, Inc, astellas.resultsdisclosure@astellas.com
    Scientific contact
    Clinical Trial Disclosure, Astellas Pharma Global Development, Inc, astellas.resultsdisclosure@astellas.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
    23 Apr 2021
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    23 Apr 2021
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this study is to evaluate the efficacy of fezolinetant vs placebo on the frequency and severity of moderate to severe VMS.
    Protection of trial subjects
    This clinical study was written, conducted and reported in accordance with the protocol, International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Good Clinical Practice (GCP) Guidelines, and applicable local regulations, including the European Directive 2001/20/EC, on the protection of human rights, and with the ethical principles that have their origin in the Declaration of Helsinki. Astellas ensures that the use and disclosure of protected health information (PHI) obtained during a research study complies with the federal, national and/or regional legislation related to the privacy and protection of personal information.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    10 Jul 2019
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Latvia: 14
    Country: Number of subjects enrolled
    Poland: 108
    Country: Number of subjects enrolled
    Canada: 33
    Country: Number of subjects enrolled
    United States: 323
    Country: Number of subjects enrolled
    Czechia: 14
    Country: Number of subjects enrolled
    Spain: 8
    Country: Number of subjects enrolled
    United Kingdom: 1
    Worldwide total number of subjects
    501
    EEA total number of subjects
    144
    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)
    496
    From 65 to 84 years
    5
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Postmenopausal women participants 40 to 65 years of age who had moderate to severe VMS & seeking treatment or relief for VMS associated with menopause, confirmed as menopausal, had to have 7 to 8 moderate to severe VMS per day within the 10 days prior to randomization & who met the inclusion criteria & none of the exclusion criteria were enrolled.

    Pre-assignment
    Screening details
    		 Prior to randomization, participants had a screening period during which a minimum 10-day collection of baseline VMS frequency and severity assessments were performed.

    Period 1
    Period 1 title
    Double-blind Period (DBP) (12 weeks)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Double-blind Period: Placebo
    Arm description
    		 Participants received fezolinetant matching placebo (two fezolinetant matching placebo tablets) orally, once daily (QD) up to week 12 during double-blind treatment period.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received fezolinetant matching placebo orally, QD.

    Arm title
    		 Double-blind Period: Fezolinetant 30 mg
    Arm description
    		 Participants received fezolinetant 30 mg (one 30 mg fezolinetant tablet and one placebo tablet) orally, QD up to week 12 during double-blind treatment period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Fezolinetant
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received fezolinetant 30 mg orally, QD.

    Arm title
    		 Double-blind Period: Fezolinetant 45 mg
    Arm description
    		 Participants received fezolinetant 45 mg (one 30 mg tablet and one 15 mg tablet) orally, QD up to week 12 during double-blind treatment period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Fezolinetant
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received fezolinetant 45 mg orally, QD.

    Number of subjects in period 1
    		Double-blind Period: Placebo Double-blind Period: Fezolinetant 30 mg Double-blind Period: Fezolinetant 45 mg
    Started
    168
    166
    167
    Treated
    167
    166
    167
    Completed
    151
    152
    155
    Not completed
    17
    14
    12
         Adverse event, non-fatal
    1
    1
    2
         Protocol Deviation
    1
    5
    -
         Miscellaneous
    2
    1
    2
         Lost to follow-up
    2
    1
    2
         Withdrawal by subject
    11
    6
    6
    Period 2
    Period 2 title
    Extension Period (EP) (40 weeks)
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    No

    Arm title
    		 Double-blind: Fezolinetant 30 mg/Extension: Fezolinetant 30 mg
    Arm description
    		 Participants received fezolinetant 30 mg (one 30 mg fezolinetant tablet and one placebo tablet) orally, QD up to week 12 during double-blind treatment period followed by fezolinetant 30 mg orally, QD from week 13 up to Week 52 during extension treatment period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Fezolinetant
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received fezolinetant 30 mg orally, QD.

    Arm title
    		 Double-blind: Fezolinetant 45 mg/Extension: Fezolinetant 45 mg
    Arm description
    		 Participants received fezolinetant 45 mg (one 30 mg tablet and one 15 mg tablet) orally, QD up to week 12 during double-blind treatment period followed by fezolinetant 45 mg orally, QD from week 13 up to Week 52 during extension treatment period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Fezolinetant
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received fezolinetant 45 mg orally, QD

    Arm title
    		 Double-blind Period:Placebo/Extension Period:Fezolinetant 30mg
    Arm description
    		 Participants who received placebo during double-blind treatment period were re-randomized to receive fezolinetant 30 mg orally, QD from week 13 up to week 52 during extension treatment period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Fezolinetant
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received fezolinetant 30 mg orally, QD.

    Arm title
    		 Double-blind Period:Placebo/Extension Period:Fezolinetant 45mg
    Arm description
    		 Participants who received placebo during double-blind treatment period were re-randomized to receive fezolinetant 45 mg orally, QD from week 13 up to week 52 during extension treatment period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Fezolinetant
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received fezolinetant 45 mg orally, QD

    Number of subjects in period 2
    		Double-blind: Fezolinetant 30 mg/Extension: Fezolinetant 30 mg Double-blind: Fezolinetant 45 mg/Extension: Fezolinetant 45 mg Double-blind Period:Placebo/Extension Period:Fezolinetant 30mg Double-blind Period:Placebo/Extension Period:Fezolinetant 45mg
    Started
    152
    154
    76
    75
    Completed
    125
    132
    63
    63
    Not completed
    27
    22
    13
    12
         Adverse event, serious fatal
    -
    -
    -
    1
         Adverse event, non-fatal
    4
    4
    2
    3
         Protocol Deviation
    -
    2
    -
    -
         Miscellaneous
    4
    1
    -
    2
         Lost to follow-up
    2
    1
    2
    1
         Withdrawal by subject
    17
    14
    9
    5

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Double-blind Period: Placebo
    Reporting group description
    		 Participants received fezolinetant matching placebo (two fezolinetant matching placebo tablets) orally, once daily (QD) up to week 12 during double-blind treatment period.

    Reporting group title
    Double-blind Period: Fezolinetant 30 mg
    Reporting group description
    		 Participants received fezolinetant 30 mg (one 30 mg fezolinetant tablet and one placebo tablet) orally, QD up to week 12 during double-blind treatment period.

    Reporting group title
    Double-blind Period: Fezolinetant 45 mg
    Reporting group description
    		 Participants received fezolinetant 45 mg (one 30 mg tablet and one 15 mg tablet) orally, QD up to week 12 during double-blind treatment period.

    Reporting group values
    		 Double-blind Period: Placebo Double-blind Period: Fezolinetant 30 mg Double-blind Period: Fezolinetant 45 mg Total
    Number of subjects
    		 168 166 167 501
    Age categorical
    Units:
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 54.6 ( 4.6 ) 53.9 ( 4.9 ) 54.3 ( 5.4 ) -
    Sex: Female, Male
    Units: Participants
        Female
    		 168 166 167 501
        Male
    		 0 0 0 0
    Race
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 1 1
        Asian
    		 1 0 0 1
        Native Hawaiian or Other Pacific Islander
    		 0 0 0 0
        Black or African American
    		 31 35 33 99
        White
    		 135 131 132 398
        More than one race
    		 1 0 1 2
        Unknown or Not Reported
    		 0 0 0 0
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 33 34 41 108
        Not Hispanic or Latino
    		 134 132 126 392
        Unknown or Not Reported
    		 1 0 0 1
    Severity of Moderate and Severe VMS per 24 hours
    Severity of moderate to severe VMS per day was calculated as follows: [(number of moderate VMS × 2) + (number of severe VMS × 3)]/number of daily moderate/severe VMS. Higher score indicates greater severity. Baseline was the weighted average of moderate to severe VMS per 24 hours based on the non-missing values in the 10 days immediately prior to randomization. Full analysis set (FAS) consisted of all randomized participants who took at least 1 dose of study intervention.)
    Units: Score on a scale
        arithmetic mean (standard deviation)
    		 2.41 ( 0.32 ) 2.44 ( 0.33 ) 2.41 ( 0.34 ) -
    Frequency of Moderate and Severe VMS per 24 hours
    The frequency of moderate to severe VMS was the number of moderate to severe VMS per 24 hours. Baseline was the average number of moderate to severe VMS per 24 hours based on the non-missing values in the 10 days immediately prior to randomization. FAS Population.
    Units: VMS per day
        arithmetic mean (standard deviation)
    		 11.59 ( 5.02 ) 11.23 ( 4.88 ) 11.79 ( 8.26 ) -

    End points

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    End points reporting groups
    Reporting group title
    Double-blind Period: Placebo
    Reporting group description
    		 Participants received fezolinetant matching placebo (two fezolinetant matching placebo tablets) orally, once daily (QD) up to week 12 during double-blind treatment period.

    Reporting group title
    Double-blind Period: Fezolinetant 30 mg
    Reporting group description
    		 Participants received fezolinetant 30 mg (one 30 mg fezolinetant tablet and one placebo tablet) orally, QD up to week 12 during double-blind treatment period.

    Reporting group title
    Double-blind Period: Fezolinetant 45 mg
    Reporting group description
    		 Participants received fezolinetant 45 mg (one 30 mg tablet and one 15 mg tablet) orally, QD up to week 12 during double-blind treatment period.
    Reporting group title
    Double-blind: Fezolinetant 30 mg/Extension: Fezolinetant 30 mg
    Reporting group description
    		 Participants received fezolinetant 30 mg (one 30 mg fezolinetant tablet and one placebo tablet) orally, QD up to week 12 during double-blind treatment period followed by fezolinetant 30 mg orally, QD from week 13 up to Week 52 during extension treatment period.

    Reporting group title
    Double-blind: Fezolinetant 45 mg/Extension: Fezolinetant 45 mg
    Reporting group description
    		 Participants received fezolinetant 45 mg (one 30 mg tablet and one 15 mg tablet) orally, QD up to week 12 during double-blind treatment period followed by fezolinetant 45 mg orally, QD from week 13 up to Week 52 during extension treatment period.

    Reporting group title
    Double-blind Period:Placebo/Extension Period:Fezolinetant 30mg
    Reporting group description
    		 Participants who received placebo during double-blind treatment period were re-randomized to receive fezolinetant 30 mg orally, QD from week 13 up to week 52 during extension treatment period.

    Reporting group title
    Double-blind Period:Placebo/Extension Period:Fezolinetant 45mg
    Reporting group description
    		 Participants who received placebo during double-blind treatment period were re-randomized to receive fezolinetant 45 mg orally, QD from week 13 up to week 52 during extension treatment period.

    Subject analysis set title
    Double-blind: Fezolinetant 30 mg/Extension: Fezolinetant 30 mg
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Participants received fezolinetant 30 mg (one 30 mg fezolinetant tablet and one placebo tablet) orally, QD up to week 12 during double-blind treatment period followed by fezolinetant 30 mg orally, QD from week 13 up to Week 52 during extension treatment period.

    Subject analysis set title
    Double-blind: Fezolinetant 45 mg/Extension: Fezolinetant 45 mg
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Participants received fezolinetant 45 mg (one 30 mg tablet and one 15 mg tablet) orally, QD up to week 12 during double-blind treatment period followed by fezolinetant 45 mg orally, QD from week 13 up to Week 52 during extension treatment period.

    Primary: Change From Baseline in The Mean Frequency of Moderate to Severe VMS at Week 4

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    End point title
    		 Change From Baseline in The Mean Frequency of Moderate to Severe VMS at Week 4
    End point description
    The frequency of moderate to severe VMS was the number of moderate to severe VMS per 24 hours. A daily frequency per week was derived by taking the mean of the data over 7 days. Moderate VMS was defined as sensation of heat with sweating/dampness, but was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets. Severe VMS was defined as sensation of intense heat with sweating, caused disruption of activity. If at night, participant woke up hot and was sweating and needed to take action (e.g., remove layers of clothes, open the window, or get out of bed). Baseline was the average number of moderate to severe VMS per 24 hours based on the non-missing values in the 10 days immediately prior to randomization.
    End point type
    Primary
    End point timeframe
    Baseline and week 4 Analysis Population: Full analysis set (FAS) (consisted of all randomized participants who took at least 1 dose of study intervention) with available data at specified time point.
    End point values
    		 Double-blind Period: Placebo Double-blind Period: Fezolinetant 30 mg Double-blind Period: Fezolinetant 45 mg
    Number of subjects analysed
    151
    155
    155
    Units: VMS per day
        least squares mean (standard error)
    -3.72 ( 0.33 )
    -5.53 ( 0.33 )
    -6.26 ( 0.33 )
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg
    Number of subjects included in analysis
    306
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [1]
    P-value
    		 < 0.001 [2]
    Method
    		 MMRM
    Parameter type
    		 Least squares (LS) Mean difference
    Point estimate
    -1.82
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.73
         upper limit
    		 -0.91
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.46
    Notes
    [1] - Least squares Mean (LSM), Standard error (SE), Confidence interval (CI), Mixed model repeated measures (MMRM), Change from Baseline (CFB), Dependent variable (dv), Treatment (tr), Week (wk), Baseline (bl), Weight (wt)
    [2] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 3
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg
    Number of subjects included in analysis
    306
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.049
    Method
    		 Hochberg
    Confidence interval
    Statistical analysis title
    		 Statistical Analysis 4
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg
    Number of subjects included in analysis
    306
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Hochberg
    Confidence interval
    Statistical analysis title
    		 Statistical Analysis 2
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg
    Number of subjects included in analysis
    306
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [3]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -2.55
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.45
         upper limit
    		 -1.64
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.46
    Notes
    [3] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.

    Primary: Change From Baseline in The Mean Frequency of Moderate to Severe VMS at Week 12

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    End point title
    		 Change From Baseline in The Mean Frequency of Moderate to Severe VMS at Week 12
    End point description
    The frequency of moderate to severe VMS was the number of moderate to severe VMS per 24 hours. A daily frequency per week was derived by taking the mean of the data over 7 days. Moderate VMS was defined as sensation of heat with sweating/dampness, but was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets. Severe VMS was defined as sensation of intense heat with sweating, caused disruption of activity. If at night, participant woke up hot and was sweating and needed to take action (e.g., remove layers of clothes, open the window, or get out of bed). Baseline was the average number of moderate to severe VMS per 24 hours based on the non-missing values in the 10 days immediately prior to randomization. Analysis Population: FAS population with available data at specified time point.
    End point type
    Primary
    End point timeframe
    Baseline and week 12
    End point values
    		 Double-blind Period: Placebo Double-blind Period: Fezolinetant 30 mg Double-blind Period: Fezolinetant 45 mg
    Number of subjects analysed
    140
    133
    145
    Units: VMS per day
        least squares mean (standard error)
    -4.97 ( 0.39 )
    -6.83 ( 0.39 )
    -7.50 ( 0.39 )
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg
    Number of subjects included in analysis
    273
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [4]
    Method
    		 MMRM
    Parameter type
    		 LSMean Difference
    Point estimate
    -1.86
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.94
         upper limit
    		 -0.78
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.55
    Notes
    [4] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 3
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg
    Number of subjects included in analysis
    273
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.049
    Method
    		 Hochberg
    Confidence interval
    Statistical analysis title
    		 Statistical Analysis 4
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg
    Number of subjects included in analysis
    285
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Hochberg
    Confidence interval
    Statistical analysis title
    		 Statistical Analysis 2
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg
    Number of subjects included in analysis
    285
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [5]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -2.53
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.6
         upper limit
    		 -1.46
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.55
    Notes
    [5] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.

    Primary: Change From Baseline in The Mean Severity of Moderate to Severe VMS at Week 4

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    End point title
    		 Change From Baseline in The Mean Severity of Moderate to Severe VMS at Week 4
    End point description
    Severity of moderate to severe VMS per day at post baseline visit was calculated as follows: [(number of mild hot flashes per day x 1) + (number of moderate hot flashes per day x 2) + (number of severe hot flashes per day x 3)]/Total number of daily mild/moderate/severe hot flashes Moderate VMS was defined as sensation of heat with sweating/dampness, but was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets. Severe VMS was defined as sensation of intense heat with sweating, caused disruption of activity. If at night, participant woke up hot and was sweating and needed to take action (e.g., remove layers of clothes, open the window, or get out of bed). Severity was zero for participants that had no mild or moderate or severe VMS. Higher scores indicates greater severity. Analysis Population: FAS population with available data at specified time point.
    End point type
    Primary
    End point timeframe
    Baseline and week 4
    End point values
    		 Double-blind Period: Placebo Double-blind Period: Fezolinetant 30 mg Double-blind Period: Fezolinetant 45 mg
    Number of subjects analysed
    151
    155
    155
    Units: Score on a scale
        least squares mean (standard error)
    -0.32 ( 0.05 )
    -0.47 ( 0.05 )
    -0.61 ( 0.05 )
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg
    Number of subjects included in analysis
    306
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.021 [6]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -0.15
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.27
         upper limit
    		 -0.02
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.06
    Notes
    [6] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 3
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg
    Number of subjects included in analysis
    306
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.049
    Method
    		 Hochberg
    Confidence interval
    Statistical analysis title
    		 Statistical Analysis 4
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg
    Number of subjects included in analysis
    306
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Hochberg
    Confidence interval
    Statistical analysis title
    		 Statistical Analysis 2
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg
    Number of subjects included in analysis
    306
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [7]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -0.29
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.41
         upper limit
    		 -0.16
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.06
    Notes
    [7] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.

    Primary: Change From Baseline in The Mean Severity of Moderate to Severe VMS at Week 12

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    End point title
    		 Change From Baseline in The Mean Severity of Moderate to Severe VMS at Week 12
    End point description
    Severity of moderate to severe VMS per day at post baseline visit was calculated as follows: [(number of mild hot flashes per day x 1) + (number of moderate hot flashes per day x 2) + (number of severe hot flashes per day x 3)]/Total number of daily mild/moderate/severe hot flashes Moderate VMS was defined as sensation of heat with sweating/dampness, but was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets. Severe VMS was defined as sensation of intense heat with sweating, caused disruption of activity. If at night, participant woke up hot and was sweating and needed to take action (e.g., remove layers of clothes, open the window, or get out of bed). Severity was zero for participants that had no mild or moderate or severe VMS. Higher scores indicates greater severity. Analysis Population: FAS population with available data at specified time point.
    End point type
    Primary
    End point timeframe
    Baseline and week 12
    End point values
    		 Double-blind Period: Placebo Double-blind Period: Fezolinetant 30 mg Double-blind Period: Fezolinetant 45 mg
    Number of subjects analysed
    140
    133
    145
    Units: Score on a scale
        least squares mean (standard error)
    -0.48 ( 0.06 )
    -0.64 ( 0.06 )
    -0.77 ( 0.06 )
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg
    Number of subjects included in analysis
    273
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.049 [8]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -0.16
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.33
         upper limit
    		 0
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.08
    Notes
    [8] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 2
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg
    Number of subjects included in analysis
    285
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [9]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -0.29
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.45
         upper limit
    		 -0.13
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.08
    Notes
    [9] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 3
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg
    Number of subjects included in analysis
    273
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.049
    Method
    		 Hochberg
    Confidence interval
    Statistical analysis title
    		 Statistical Analysis 4
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg
    Number of subjects included in analysis
    285
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Hochberg
    Confidence interval

    Secondary: Change From Baseline in The Mean Patient-reported Outcomes Measurement Information System Sleep Disturbance – Short Form 8b (PROMIS SD SF 8b) Total Score at Week 12

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    End point title
    		 Change From Baseline in The Mean Patient-reported Outcomes Measurement Information System Sleep Disturbance – Short Form 8b (PROMIS SD SF 8b) Total Score at Week 12
    End point description
    The PROMIS SD SF 8b assesses self-reported sleep disturbance over the past 7 days and includes perceptions of restless sleep; satisfaction with sleep; refreshing sleep; difficulties sleeping, getting to sleep or staying asleep; amount of sleep; and sleep quality. Because it assesses the participants experience of sleep disturbance, the measure does not focus on specific sleep-disorder symptoms or ask patients to report objective measures of sleep (e.g., total amount of sleep, time to fall asleep and amount of wakefulness during sleep). Responses to each of the 8 items range from 1 (no disturbed sleep) to 5 (disturbed sleep), and the range of possible summed raw scores is 8 to 40. Higher scores on the PROMIS SD SF 8b indicate more of the disturbed sleep. Analysis Population: FAS population with available data at specified time point.
    End point type
    Secondary
    End point timeframe
    Baseline and week 12
    End point values
    		 Double-blind Period: Placebo Double-blind Period: Fezolinetant 30 mg Double-blind Period: Fezolinetant 45 mg
    Number of subjects analysed
    143
    139
    145
    Units: Score on a scale
        least squares mean (standard error)
    -3.4 ( 0.5 )
    -4.1 ( 0.5 )
    -5.5 ( 0.5 )
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg
    Number of subjects included in analysis
    282
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.381 [10]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -0.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.1
         upper limit
    		 0.8
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.7
    Notes
    [10] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 2
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg
    Number of subjects included in analysis
    288
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.007 [11]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.5
         upper limit
    		 -0.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.7
    Notes
    [11] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.

    Secondary: Change from Baseline in The Mean Frequency of Moderate, and Severe VMS to Each Study Week Up to Week 12

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    End point title
    		 Change from Baseline in The Mean Frequency of Moderate, and Severe VMS to Each Study Week Up to Week 12
    End point description
    The frequency of moderate to severe VMS was the number of moderate to severe VMS per 24 hours. A daily frequency per week was derived by taking the mean of the data over 7 days. Moderate VMS was defined as sensation of heat with sweating/dampness, but was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets. Severe VMS was defined as sensation of intense heat with sweating, caused disruption of activity. If at night, participant woke up hot and was sweating and needed to take action (e.g., remove layers of clothes, open the window, or get out of bed). Baseline was the average number of moderate to severe VMS per 24 hours based on the non-missing values in the 10 days immediately prior to randomization. Analysis Population: FAS population with available data at specified time point.
    End point type
    Secondary
    End point timeframe
    Baseline and weeks 1, 2, 3, 5, 6, 7, 8, 9, 10, 11
    End point values
    		 Double-blind Period: Placebo Double-blind Period: Fezolinetant 30 mg Double-blind Period: Fezolinetant 45 mg
    Number of subjects analysed
    166
    164
    158
    Units: VMS per day
    least squares mean (standard error)
        Week 1 (n = 166, 164, 158)
    -2.32 ( 0.28 )
    -3.62 ( 0.29 )
    -4.03 ( 0.29 )
        Week 2 (n = 159, 160, 156)
    -3.06 ( 0.32 )
    -4.82 ( 0.32 )
    -5.03 ( 0.32 )
        Week 3 (n = 156, 157, 156)
    -3.56 ( 0.32 )
    -5.29 ( 0.32 )
    -5.95 ( 0.32 )
        Week 5 (n = 152, 152, 154)
    -4.05 ( 0.34 )
    -5.89 ( 0.34 )
    -6.71 ( 0.34 )
        Week 6 (n = 152, 146, 149)
    -4.25 ( 0.33 )
    -6.03 ( 0.33 )
    -6.91 ( 0.33 )
        Week 7 (n = 149, 143, 147)
    -4.44 ( 0.35 )
    -6.24 ( 0.35 )
    -6.78 ( 0.35 )
        Week 8 (n = 148, 143, 154)
    -4.48 ( 0.37 )
    -6.25 ( 0.37 )
    -6.86 ( 0.37 )
        Week 9 (n = 145, 140, 148)
    -4.88 ( 0.38 )
    -6.54 ( 0.38 )
    -7.39 ( 0.38 )
        Week 10 (n = 139, 138, 149)
    -4.83 ( 0.38 )
    -6.74 ( 0.38 )
    -7.47 ( 0.38 )
        Week 11 (n = 138, 142, 149)
    -4.90 ( 0.38 )
    -6.76 ( 0.38 )
    -7.46 ( 0.37 )
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Week 1
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg
    Number of subjects included in analysis
    330
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.001 [12]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -1.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.09
         upper limit
    		 -0.51
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.4
    Notes
    [12] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Week 1
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg
    Number of subjects included in analysis
    324
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [13]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -1.71
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.51
         upper limit
    		 -0.91
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.4
    Notes
    [13] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 3
    Statistical analysis description
    Week 2
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg
    Number of subjects included in analysis
    330
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [14]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -1.76
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.65
         upper limit
    		 -0.87
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.45
    Notes
    [14] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 4
    Statistical analysis description
    Week 2
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg
    Number of subjects included in analysis
    324
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [15]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -1.97
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.86
         upper limit
    		 -1.08
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.45
    Notes
    [15] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 5
    Statistical analysis description
    Week 3
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg
    Number of subjects included in analysis
    330
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [16]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -1.74
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.63
         upper limit
    		 -0.84
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.46
    Notes
    [16] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 6
    Statistical analysis description
    Week 3
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg
    Number of subjects included in analysis
    324
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [17]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -2.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.29
         upper limit
    		 -1.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.46
    Notes
    [17] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 7
    Statistical analysis description
    Week 5
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg
    Number of subjects included in analysis
    330
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [18]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -1.84
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.79
         upper limit
    		 -0.9
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.48
    Notes
    [18] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 8
    Statistical analysis description
    Week 5
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg
    Number of subjects included in analysis
    324
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [19]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -2.66
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.61
         upper limit
    		 -1.72
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.48
    Notes
    [19] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 9
    Statistical analysis description
    Week 6
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg
    Number of subjects included in analysis
    330
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [20]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -1.78
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.71
         upper limit
    		 -0.85
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.47
    Notes
    [20] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 11
    Statistical analysis description
    Week 7
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg
    Number of subjects included in analysis
    330
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [21]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -1.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.77
         upper limit
    		 -0.83
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.49
    Notes
    [21] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 10
    Statistical analysis description
    Week 6
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg
    Number of subjects included in analysis
    324
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [22]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -2.66
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.59
         upper limit
    		 -1.73
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.47
    Notes
    [22] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 12
    Statistical analysis description
    Week 7
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg
    Number of subjects included in analysis
    324
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [23]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -2.34
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.3
         upper limit
    		 -1.37
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.49
    Notes
    [23] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 13
    Statistical analysis description
    Week 8
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg
    Number of subjects included in analysis
    330
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [24]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -1.76
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.79
         upper limit
    		 -0.74
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.52
    Notes
    [24] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 14
    Statistical analysis description
    Week 8
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg
    Number of subjects included in analysis
    324
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [25]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -2.38
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.4
         upper limit
    		 -1.35
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.52
    Notes
    [25] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 15
    Statistical analysis description
    Week 9
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg
    Number of subjects included in analysis
    330
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.002 [26]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -1.65
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.71
         upper limit
    		 -0.59
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.54
    Notes
    [26] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 16
    Statistical analysis description
    Week 9
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg
    Number of subjects included in analysis
    324
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [27]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -2.51
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.57
         upper limit
    		 -1.45
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.54
    Notes
    [27] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 17
    Statistical analysis description
    Week 10
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg
    Number of subjects included in analysis
    330
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [28]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -1.91
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.96
         upper limit
    		 -0.86
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.54
    Notes
    [28] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 18
    Statistical analysis description
    Week 10
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg
    Number of subjects included in analysis
    324
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [29]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -2.65
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.69
         upper limit
    		 -1.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.53
    Notes
    [29] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 19
    Statistical analysis description
    Week 11
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg
    Number of subjects included in analysis
    330
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [30]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -1.86
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.91
         upper limit
    		 -0.81
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.53
    Notes
    [30] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 20
    Statistical analysis description
    Week 11
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg
    Number of subjects included in analysis
    324
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [31]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -2.56
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.61
         upper limit
    		 -1.52
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.53
    Notes
    [31] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.

    Secondary: Change from Baseline in The Mean Severity of Moderate, and Severe VMS to Each Study Week Up to Week 12

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    End point title
    		 Change from Baseline in The Mean Severity of Moderate, and Severe VMS to Each Study Week Up to Week 12
    End point description
    Severity of moderate to severe VMS per day at post baseline visit was calculated as follows: [(number of mild hot flashes per day x 1) + (number of moderate hot flashes per day x 2) + (number of severe hot flashes per day x 3)]/Total number of daily mild/moderate/severe hot flashes Moderate VMS was defined as sensation of heat with sweating/dampness, but was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets. Severe VMS was defined as sensation of intense heat with sweating, caused disruption of activity. If at night, participant woke up hot and was sweating and needed to take action (e.g., remove layers of clothes, open the window, or get out of bed). Severity was zero for participants that had no mild or moderate or severe VMS. Higher scores indicates greater severity. Analysis Population: FAS population with available data at specified time point.
    End point type
    Secondary
    End point timeframe
    Baseline and weeks 1, 2, 3, 5, 6, 7, 8, 9, 10, 11
    End point values
    		 Double-blind Period: Placebo Double-blind Period: Fezolinetant 30 mg Double-blind Period: Fezolinetant 45 mg
    Number of subjects analysed
    166
    164
    158
    Units: Score on a scale
    least squares mean (standard error)
        Week 1 (n = 166, 164, 158)
    -0.18 ( 0.03 )
    -0.32 ( 0.03 )
    -0.34 ( 0.03 )
        Week 2 (n = 159, 160, 156)
    -0.24 ( 0.04 )
    -0.41 ( 0.04 )
    -0.42 ( 0.04 )
        Week 3 (n = 156, 157, 156)
    -0.31 ( 0.04 )
    -0.42 ( 0.04 )
    -0.54 ( 0.04 )
        Week 5 (n = 152, 152, 154)
    -0.37 ( 0.05 )
    -0.53 ( 0.05 )
    -0.66 ( 0.05 )
        Week 6 (n = 152, 146, 149)
    -0.37 ( 0.05 )
    -0.55 ( 0.05 )
    -0.65 ( 0.05 )
        Week 7 (n = 149, 143, 147)
    -0.42 ( 0.05 )
    -0.58 ( 0.05 )
    -0.70 ( 0.05 )
        Week 8 (n = 148, 143, 154)
    -0.43 ( 0.05 )
    -0.56 ( 0.05 )
    -0.69 ( 0.05 )
        Week 9 (n = 145, 140, 148)
    -0.46 ( 0.06 )
    -0.59 ( 0.06 )
    -0.74 ( 0.06 )
        Week 10 (n = 139, 138, 149)
    -0.45 ( 0.06 )
    -0.64 ( 0.06 )
    -0.76 ( 0.06 )
        Week 11 (n = 138, 142, 149)
    -0.46 ( 0.06 )
    -0.67 ( 0.06 )
    -0.77 ( 0.06 )
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Week 1
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg
    Number of subjects included in analysis
    330
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.001 [32]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -0.13
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.21
         upper limit
    		 -0.05
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.04
    Notes
    [32] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Week 1
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg
    Number of subjects included in analysis
    324
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [33]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -0.16
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.24
         upper limit
    		 -0.08
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.04
    Notes
    [33] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 3
    Statistical analysis description
    Week 2
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg
    Number of subjects included in analysis
    330
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.001 [34]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -0.17
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.28
         upper limit
    		 -0.07
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.05
    Notes
    [34] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 4
    Statistical analysis description
    Week 2
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg
    Number of subjects included in analysis
    324
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.001 [35]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -0.18
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.28
         upper limit
    		 -0.07
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.05
    Notes
    [35] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 5
    Statistical analysis description
    Week 3
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg
    Number of subjects included in analysis
    330
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.067 [36]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -0.11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.23
         upper limit
    		 0.01
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.06
    Notes
    [36] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 6
    Statistical analysis description
    Week 3
    Comparison groups
    Double-blind Period: Fezolinetant 45 mg v Double-blind Period: Placebo
    Number of subjects included in analysis
    324
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [37]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -0.23
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.35
         upper limit
    		 -0.11
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.06
    Notes
    [37] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 7
    Statistical analysis description
    Week 5
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg
    Number of subjects included in analysis
    330
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.02 [38]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -0.16
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.3
         upper limit
    		 -0.03
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.07
    Notes
    [38] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 8
    Statistical analysis description
    Week 5
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg
    Number of subjects included in analysis
    324
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [39]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -0.29
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.43
         upper limit
    		 -0.16
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.07
    Notes
    [39] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 9
    Statistical analysis description
    Week 6
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg
    Number of subjects included in analysis
    330
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.012 [40]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -0.18
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.32
         upper limit
    		 -0.04
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.07
    Notes
    [40] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 10
    Statistical analysis description
    Week 6
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg
    Number of subjects included in analysis
    324
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [41]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -0.28
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.42
         upper limit
    		 -0.14
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.07
    Notes
    [41] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 11
    Statistical analysis description
    Week 7
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg
    Number of subjects included in analysis
    330
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.03 [42]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -0.16
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.31
         upper limit
    		 -0.02
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.07
    Notes
    [42] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 12
    Statistical analysis description
    Week 7
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg
    Number of subjects included in analysis
    324
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [43]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -0.28
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.43
         upper limit
    		 -0.14
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.07
    Notes
    [43] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 13
    Statistical analysis description
    Week 8
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg
    Number of subjects included in analysis
    330
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.095 [44]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -0.13
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.28
         upper limit
    		 0.02
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.08
    Notes
    [44] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 14
    Statistical analysis description
    Week 8
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg
    Number of subjects included in analysis
    324
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [45]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -0.26
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.41
         upper limit
    		 -0.11
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.08
    Notes
    [45] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 15
    Statistical analysis description
    Week 9
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg
    Number of subjects included in analysis
    330
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.109 [46]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -0.13
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.28
         upper limit
    		 0.03
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.08
    Notes
    [46] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 16
    Statistical analysis description
    Week 9
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg
    Number of subjects included in analysis
    324
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [47]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -0.28
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.43
         upper limit
    		 -0.12
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.08
    Notes
    [47] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 17
    Statistical analysis description
    Week 10
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg
    Number of subjects included in analysis
    330
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.02 [48]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -0.19
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.35
         upper limit
    		 -0.03
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.08
    Notes
    [48] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 18
    Statistical analysis description
    Week 10
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg
    Number of subjects included in analysis
    324
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [49]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -0.31
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.47
         upper limit
    		 -0.15
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.08
    Notes
    [49] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 19
    Statistical analysis description
    Week 11
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg
    Number of subjects included in analysis
    330
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.012 [50]
    Method
    		 MMRM
    Parameter type
    		 LSMean diferrence
    Point estimate
    -0.21
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.37
         upper limit
    		 -0.05
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.08
    Notes
    [50] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 20
    Statistical analysis description
    Week 11
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg
    Number of subjects included in analysis
    324
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [51]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -0.31
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.47
         upper limit
    		 -0.15
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.08
    Notes
    [51] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.

    Secondary: Mean Percent Change in The Frequency of Moderate And Severe VMS From Baseline to Each Study Week Up to Week 12

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    End point title
    		 Mean Percent Change in The Frequency of Moderate And Severe VMS From Baseline to Each Study Week Up to Week 12
    End point description
    The frequency of moderate to severe VMS was the number of moderate to severe VMS per 24 hours. A daily frequency per week was derived by taking the mean of the data over 7 days. Moderate VMS was defined as sensation of heat with sweating/dampness, but was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets. Severe VMS was defined as sensation of intense heat with sweating, caused disruption of activity. If at night, participant woke up hot and was sweating and needed to take action (e.g., remove layers of clothes, open the window, or get out of bed). Baseline was the average number of moderate to severe VMS per 24 hours based on the non-missing values in the 10 days immediately prior to randomization. Analysis Population: FAS population with available data at specified time point.
    End point type
    Secondary
    End point timeframe
    Baseline and weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12
    End point values
    		 Double-blind Period: Placebo Double-blind Period: Fezolinetant 30 mg Double-blind Period: Fezolinetant 45 mg
    Number of subjects analysed
    166
    164
    158
    Units: Percent change
    least squares mean (standard error)
        Week 1 (n = 166, 164, 158)
    -20.82 ( 2.42 )
    -32.98 ( 2.43 )
    -36.50 ( 2.45 )
        Week 2 (n = 159, 160, 156)
    -29.21 ( 2.69 )
    -43.82 ( 2.69 )
    -45.16 ( 2.71 )
        Week 3 (n = 156, 157, 156)
    -33.17 ( 2.76 )
    -48.68 ( 2.75 )
    -53.42 ( 2.76 )
        Week 4 (n = 151, 155, 155)
    -34.72 ( 2.78 )
    -51.06 ( 2.77 )
    -56.37 ( 2.77 )
        Week 5 (n = 152, 152, 154)
    -37.88 ( 2.75 )
    -53.50 ( 2.75 )
    -60.76 ( 2.74 )
        Week 6 (n = 152, 146, 149)
    -39.64 ( 2.73 )
    -54.42 ( 2.73 )
    -62.30 ( 2.73 )
        Week 7 (n = 149, 143, 147)
    -40.91 ( 2.84 )
    -55.88 ( 2.84 )
    -62.38 ( 2.83 )
        Week 8 (n = 148, 143, 154)
    -41.84 ( 2.86 )
    -56.22 ( 2.86 )
    -62.42 ( 2.84 )
        Week 9 (n = 145, 140, 148)
    -45.87 ( 2.88 )
    -58.01 ( 2.88 )
    -65.60 ( 2.86 )
        Week 10 (n = 139, 138, 149)
    -45.58 ( 2.83 )
    -59.98 ( 2.82 )
    -65.68 ( 2.81 )
        Week 11 (n = 138, 142, 149)
    -45.41 ( 2.88 )
    -60.37 ( 2.87 )
    -65.56 ( 2.86 )
        Week 12 (n = 140, 133, 145)
    -46.91 ( 2.87 )
    -60.55 ( 2.87 )
    -65.85 ( 2.85 )
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Week 1
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg
    Number of subjects included in analysis
    330
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [52]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -12.16
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -18.9
         upper limit
    		 -5.43
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.43
    Notes
    [52] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 3
    Statistical analysis description
    Week 2
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg
    Number of subjects included in analysis
    330
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [53]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -14.61
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -22.09
         upper limit
    		 -7.13
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.81
    Notes
    [53] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Week 1
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg
    Number of subjects included in analysis
    324
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [54]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -15.68
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -22.44
         upper limit
    		 -8.91
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.44
    Notes
    [54] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 5
    Statistical analysis description
    Week 3
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg
    Number of subjects included in analysis
    330
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [55]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -15.51
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -23.16
         upper limit
    		 -7.86
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.89
    Notes
    [55] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 4
    Statistical analysis description
    Week 2
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg
    Number of subjects included in analysis
    324
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [56]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -15.95
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -23.45
         upper limit
    		 -8.45
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.82
    Notes
    [56] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 7
    Statistical analysis description
    Week 4
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg
    Number of subjects included in analysis
    330
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [57]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -16.34
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -24.04
         upper limit
    		 -8.63
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.92
    Notes
    [57] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 6
    Statistical analysis description
    Week 3
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg
    Number of subjects included in analysis
    324
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [58]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -20.25
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -27.91
         upper limit
    		 -12.59
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.9
    Notes
    [58] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 8
    Statistical analysis description
    Week 4
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg
    Number of subjects included in analysis
    324
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [59]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -21.65
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -29.36
         upper limit
    		 -13.94
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.92
    Notes
    [59] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 9
    Statistical analysis description
    Week 5
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg
    Number of subjects included in analysis
    330
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [60]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -15.62
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -23.27
         upper limit
    		 -7.98
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.89
    Notes
    [60] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 10
    Statistical analysis description
    Week 5
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg
    Number of subjects included in analysis
    324
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [61]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -22.88
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -30.52
         upper limit
    		 -15.24
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.89
    Notes
    [61] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 11
    Statistical analysis description
    Week 6
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg
    Number of subjects included in analysis
    330
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [62]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -14.78
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -22.38
         upper limit
    		 -7.19
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.87
    Notes
    [62] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 12
    Statistical analysis description
    Week 6
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg
    Number of subjects included in analysis
    324
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [63]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -22.66
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -30.25
         upper limit
    		 -15.07
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.86
    Notes
    [63] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 13
    Statistical analysis description
    Week 7
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg
    Number of subjects included in analysis
    330
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [64]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -14.97
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -22.86
         upper limit
    		 -7.09
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.01
    Notes
    [64] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 15
    Statistical analysis description
    Week 8
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg
    Number of subjects included in analysis
    330
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [65]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -14.38
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -22.33
         upper limit
    		 -6.43
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.05
    Notes
    [65] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 14
    Statistical analysis description
    Week 7
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg
    Number of subjects included in analysis
    324
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [66]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -21.47
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -29.34
         upper limit
    		 -13.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.01
    Notes
    [66] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 16
    Statistical analysis description
    Week 8
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg
    Number of subjects included in analysis
    324
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [67]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -20.57
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -28.5
         upper limit
    		 -12.65
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.03
    Notes
    [67] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 17
    Statistical analysis description
    Week 9
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg
    Number of subjects included in analysis
    330
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.003 [68]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -12.14
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -20.14
         upper limit
    		 -4.14
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.07
    Notes
    [68] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 19
    Statistical analysis description
    Week 10
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg
    Number of subjects included in analysis
    330
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [69]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -14.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -22.25
         upper limit
    		 -6.54
    Variability estimate
    Standard error of the mean
    Dispersion value
    4
    Notes
    [69] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 18
    Statistical analysis description
    Week 9
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg
    Number of subjects included in analysis
    324
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [70]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -19.73
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -27.71
         upper limit
    		 -11.755
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.06
    Notes
    [70] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 20
    Statistical analysis description
    Week 10
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg
    Number of subjects included in analysis
    324
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [71]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -20.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -27.93
         upper limit
    		 -12.27
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.98
    Notes
    [71] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 22
    Statistical analysis description
    Week 11
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg
    Number of subjects included in analysis
    324
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [72]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -20.15
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -28.13
         upper limit
    		 -12.18
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.06
    Notes
    [72] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 21
    Statistical analysis description
    Week 11
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg
    Number of subjects included in analysis
    330
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [73]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -14.96
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -22.96
         upper limit
    		 -6.96
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.07
    Notes
    [73] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 23
    Statistical analysis description
    Week 12
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg
    Number of subjects included in analysis
    330
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [74]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -13.64
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -21.62
         upper limit
    		 -5.65
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.07
    Notes
    [74] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.
    Statistical analysis title
    		 Statistical Analysis 24
    Statistical analysis description
    Week 12
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg
    Number of subjects included in analysis
    324
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [75]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -18.94
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -26.89
         upper limit
    		 -10.98
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.05
    Notes
    [75] - LSM, SE, CI, & p-values come from MMRM analysis of covariance model with CFB as dv & trt group, wk & smoking status as factors, with bl measurement & bl wt as covariates, as well as an interaction of trt by wk & interaction of bl measurement by wk.

    Secondary: Number of Participants With Percent Reduction of >=50% in the Mean Frequency of Moderate and Severe VMS From Baseline to Each Study Week Up to Week 12

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    End point title
    		 Number of Participants With Percent Reduction of >=50% in the Mean Frequency of Moderate and Severe VMS From Baseline to Each Study Week Up to Week 12
    End point description
    The frequency of moderate to severe VMS was the number of moderate to severe VMS per 24 hours. A daily frequency per week was derived by taking the mean of the data over 7 days. Moderate VMS was defined as sensation of heat with sweating/dampness, but was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets. Severe VMS was defined as sensation of intense heat with sweating, caused disruption of activity. If at night, participant woke up hot and was sweating and needed to take action (e.g., remove layers of clothes, open the window, or get out of bed). Baseline was the average number of moderate to severe VMS per 24 hours based on the non-missing values in the 10 days immediately prior to randomization. Participant has >=50% reduction from baseline to each post baseline week for the frequency of moderate to severe VMS.
    End point type
    Secondary
    End point timeframe
    Baseline and weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 Analysis Population: FAS population with available data at specified time point.
    End point values
    		 Double-blind Period: Placebo Double-blind Period: Fezolinetant 30 mg Double-blind Period: Fezolinetant 45 mg
    Number of subjects analysed
    167
    166
    167
    Units: Participants
        Week 1
    28
    46
    58
        Week 2
    39
    71
    71
        Week 3
    48
    81
    89
        Week 4
    44
    84
    88
        Week 5
    54
    84
    98
        Week 6
    53
    81
    95
        Week 7
    55
    84
    92
        Week 8
    56
    81
    103
        Week 9
    64
    84
    98
        Week 10
    62
    85
    103
        Week 11
    60
    94
    105
        Week 12
    71
    84
    101
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Week 1
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg
    Number of subjects included in analysis
    333
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.02 [76]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.881
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.11
         upper limit
    		 3.233
    Notes
    [76] - Based on logistic regression with treatment group and smoking status (current vs former/never) as factors and mean frequency of vasomotor symptoms at baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Week 1
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg
    Number of subjects included in analysis
    334
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [77]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.645
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.585
         upper limit
    		 4.498
    Notes
    [77] - Based on logistic regression with treatment group and smoking status (current vs former/never) as factors and mean frequency of vasomotor symptoms at baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 3
    Statistical analysis description
    Week 2
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg
    Number of subjects included in analysis
    333
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [78]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.464
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.535
         upper limit
    		 4.001
    Notes
    [78] - Based on logistic regression with treatment group and smoking status (current vs former/never) as factors and mean frequency of vasomotor symptoms at baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 4
    Statistical analysis description
    Week 2
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg
    Number of subjects included in analysis
    334
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [79]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.464
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.534
         upper limit
    		 4.004
    Notes
    [79] - Based on logistic regression with treatment group and smoking status (current vs former/never) as factors and mean frequency of vasomotor symptoms at baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 5
    Statistical analysis description
    Week 3
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg
    Number of subjects included in analysis
    333
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [80]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.367
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.502
         upper limit
    		 3.762
    Notes
    [80] - Based on logistic regression with treatment group and smoking status (current vs former/never) as factors and mean frequency of vasomotor symptoms at baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 6
    Statistical analysis description
    Week 3
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg
    Number of subjects included in analysis
    334
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [81]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.894
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.835
         upper limit
    		 4.609
    Notes
    [81] - Based on logistic regression with treatment group and smoking status (current vs former/never) as factors and mean frequency of vasomotor symptoms at baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 8
    Statistical analysis description
    Week 4
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg
    Number of subjects included in analysis
    334
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [82]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    3.218
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.025
         upper limit
    		 5.172
    Notes
    [82] - Based on logistic regression with treatment group and smoking status (current vs former/never) as factors and mean frequency of vasomotor symptoms at baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 7
    Statistical analysis description
    Week 4
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg
    Number of subjects included in analysis
    333
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [83]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.902
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.829
         upper limit
    		 4.657
    Notes
    [83] - Based on logistic regression with treatment group and smoking status (current vs former/never) as factors and mean frequency of vasomotor symptoms at baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 10
    Statistical analysis description
    Week 5
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg
    Number of subjects included in analysis
    334
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [84]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    3.074
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.957
         upper limit
    		 4.878
    Notes
    [84] - Based on logistic regression with treatment group and smoking status (current vs former/never) as factors and mean frequency of vasomotor symptoms at baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 9
    Statistical analysis description
    Week 5
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg
    Number of subjects included in analysis
    333
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [85]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.153
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.375
         upper limit
    		 3.394
    Notes
    [85] - Based on logistic regression with treatment group and smoking status (current vs former/never) as factors and mean frequency of vasomotor symptoms at baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 11
    Statistical analysis description
    Week 6
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg
    Number of subjects included in analysis
    333
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.002 [86]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.05
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.31
         upper limit
    		 3.228
    Notes
    [86] - Based on logistic regression with treatment group and smoking status (current vs former/never) as factors and mean frequency of vasomotor symptoms at baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 12
    Statistical analysis description
    Week 6
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg
    Number of subjects included in analysis
    334
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [87]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.908
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.856
         upper limit
    		 4.599
    Notes
    [87] - Based on logistic regression with treatment group and smoking status (current vs former/never) as factors and mean frequency of vasomotor symptoms at baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 13
    Statistical analysis description
    Week 7
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg
    Number of subjects included in analysis
    333
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.001 [88]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.113
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.349
         upper limit
    		 3.332
    Notes
    [88] - Based on logistic regression with treatment group and smoking status (current vs former/never) as factors and mean frequency of vasomotor symptoms at baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 14
    Statistical analysis description
    Week 7
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg
    Number of subjects included in analysis
    334
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [89]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.594
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.653
         upper limit
    		 4.104
    Notes
    [89] - Based on logistic regression with treatment group and smoking status (current vs former/never) as factors and mean frequency of vasomotor symptoms at baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 15
    Statistical analysis description
    Week 8
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg
    Number of subjects included in analysis
    333
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.005 [90]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.891
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.21
         upper limit
    		 2.973
    Notes
    [90] - Based on logistic regression with treatment group and smoking status (current vs former/never) as factors and mean frequency of vasomotor symptoms at baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 16
    Statistical analysis description
    Week 8
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg
    Number of subjects included in analysis
    334
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [91]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    3.314
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.108
         upper limit
    		 5.265
    Notes
    [91] - Based on logistic regression with treatment group and smoking status (current vs former/never) as factors and mean frequency of vasomotor symptoms at baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 17
    Statistical analysis description
    Week 9
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg
    Number of subjects included in analysis
    333
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.027 [92]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.646
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.06
         upper limit
    		 2.566
    Notes
    [92] - Based on logistic regression with treatment group and smoking status (current vs former/never) as factors and mean frequency of vasomotor symptoms at baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 18
    Statistical analysis description
    Week 9
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg
    Number of subjects included in analysis
    334
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [93]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.347
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.507
         upper limit
    		 3.683
    Notes
    [93] - Based on logistic regression with treatment group and smoking status (current vs former/never) as factors and mean frequency of vasomotor symptoms at baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 19
    Statistical analysis description
    Week 10
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg
    Number of subjects included in analysis
    333
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.01 [94]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.792
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.153
         upper limit
    		 2.799
    Notes
    [94] - Based on logistic regression with treatment group and smoking status (current vs former/never) as factors and mean frequency of vasomotor symptoms at baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 20
    Statistical analysis description
    Week 10
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg
    Number of subjects included in analysis
    334
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [95]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.819
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.805
         upper limit
    		 4.441
    Notes
    [95] - Based on logistic regression with treatment group and smoking status (current vs former/never) as factors and mean frequency of vasomotor symptoms at baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 21
    Statistical analysis description
    Week 11
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg
    Number of subjects included in analysis
    333
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [96]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.357
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.513
         upper limit
    		 3.699
    Notes
    [96] - Based on logistic regression with treatment group and smoking status (current vs former/never) as factors and mean frequency of vasomotor symptoms at baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 22
    Statistical analysis description
    Week 11
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg
    Number of subjects included in analysis
    334
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [97]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    3.131
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.999
         upper limit
    		 4.95
    Notes
    [97] - Based on logistic regression with treatment group and smoking status (current vs former/never) as factors and mean frequency of vasomotor symptoms at baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 23
    Statistical analysis description
    Week 12
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg
    Number of subjects included in analysis
    333
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.152 [98]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.373
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.891
         upper limit
    		 2.122
    Notes
    [98] - Based on logistic regression with treatment group and smoking status (current vs former/never) as factors and mean frequency of vasomotor symptoms at baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 24
    Statistical analysis description
    Week 12
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg
    Number of subjects included in analysis
    334
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [99]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.09
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.351
         upper limit
    		 3.252
    Notes
    [99] - Based on logistic regression with treatment group and smoking status (current vs former/never) as factors and mean frequency of vasomotor symptoms at baseline as a covariate.

    Secondary: Number of Participants With Mean Percent Reduction of 100% in The Mean Frequency of Moderate, and Severe VMS From Baseline to Each Study Week Up to Week 12

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    End point title
    		 Number of Participants With Mean Percent Reduction of 100% in The Mean Frequency of Moderate, and Severe VMS From Baseline to Each Study Week Up to Week 12
    End point description
    The frequency of moderate to severe VMS was the number of moderate to severe VMS per 24 hours. A daily frequency per week was derived by taking the mean of the data over 7 days. Moderate VMS was defined as sensation of heat with sweating/dampness, but was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets. Severe VMS was defined as sensation of intense heat with sweating, caused disruption of activity. If at night, participant woke up hot and was sweating and needed to take action (e.g., remove layers of clothes, open the window, or get out of bed). Baseline was the average number of moderate to severe VMS per 24 hours based on the non-missing values in the 10 days immediately prior to randomization. Participant has 100% reduction from baseline to each post baseline week for the frequency of moderate to severe VMS.
    End point type
    Secondary
    End point timeframe
    Baseline and weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 Analysis Population: FAS population with available data at specified time point.
    End point values
    		 Double-blind Period: Placebo Double-blind Period: Fezolinetant 30 mg Double-blind Period: Fezolinetant 45 mg
    Number of subjects analysed
    167
    166
    167
    Units: Participants
        Week 1
    1
    1
    3
        Week 2
    3
    8
    4
        Week 3
    5
    4
    11
        Week 4
    3
    10
    17
        Week 5
    3
    12
    11
        Week 6
    9
    12
    17
        Week 7
    9
    13
    18
        Week 8
    10
    17
    22
        Week 9
    9
    14
    18
        Week 10
    11
    17
    25
        Week 11
    9
    15
    28
        Week 12
    9
    15
    25
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Week 1
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg
    Number of subjects included in analysis
    333
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.951 [100]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.915
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.036
         upper limit
    		 23.464
    Notes
    [100] - Based on logistic regression with treatment group and smoking status (current vs former/never) as factors and mean frequency of vasomotor symptoms at baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Week 1
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg
    Number of subjects included in analysis
    334
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.362 [101]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.889
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.364
         upper limit
    		 58.864
    Notes
    [101] - Based on logistic regression with treatment group and smoking status (current vs former/never) as factors and mean frequency of vasomotor symptoms at baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 3
    Statistical analysis description
    Week 2
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg
    Number of subjects included in analysis
    333
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.138 [102]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.775
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.785
         upper limit
    		 12.87
    Notes
    [102] - Based on logistic regression with treatment group and smoking status (current vs former/never) as factors and mean frequency of vasomotor symptoms at baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 4
    Statistical analysis description
    Week 2
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg
    Number of subjects included in analysis
    334
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.704 [103]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.342
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.291
         upper limit
    		 6.914
    Notes
    [103] - Based on logistic regression with treatment group and smoking status (current vs former/never) as factors and mean frequency of vasomotor symptoms at baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 5
    Statistical analysis description
    Week 3
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg
    Number of subjects included in analysis
    333
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.741 [104]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.798
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.194
         upper limit
    		 3.079
    Notes
    [104] - Based on logistic regression with treatment group and smoking status (current vs former/never) as factors and mean frequency of vasomotor symptoms at baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 6
    Statistical analysis description
    Week 3
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg
    Number of subjects included in analysis
    334
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.134 [105]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.292
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.809
         upper limit
    		 7.443
    Notes
    [105] - Based on logistic regression with treatment group and smoking status (current vs former/never) as factors and mean frequency of vasomotor symptoms at baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 7
    Statistical analysis description
    Week 4
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg
    Number of subjects included in analysis
    333
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.062 [106]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    3.474
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.039
         upper limit
    		 15.712
    Notes
    [106] - Based on logistic regression with treatment group and smoking status (current vs former/never) as factors and mean frequency of vasomotor symptoms at baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 8
    Statistical analysis description
    Week 4
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg
    Number of subjects included in analysis
    334
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.004 [107]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    6.184
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.025
         upper limit
    		 26.875
    Notes
    [107] - Based on logistic regression with treatment group and smoking status (current vs former/never) as factors and mean frequency of vasomotor symptoms at baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 9
    Statistical analysis description
    Week 5
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg
    Number of subjects included in analysis
    333
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.028 [108]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    4.217
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.305
         upper limit
    		 18.806
    Notes
    [108] - Based on logistic regression with treatment group and smoking status (current vs former/never) as factors and mean frequency of vasomotor symptoms at baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 10
    Statistical analysis description
    Week 5
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg
    Number of subjects included in analysis
    334
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.044 [109]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    3.802
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.157
         upper limit
    		 17.075
    Notes
    [109] - Based on logistic regression with treatment group and smoking status (current vs former/never) as factors and mean frequency of vasomotor symptoms at baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 11
    Statistical analysis description
    Week 6
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg
    Number of subjects included in analysis
    333
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.519 [110]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.342
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.551
         upper limit
    		 3.382
    Notes
    [110] - Based on logistic regression with treatment group and smoking status (current vs former/never) as factors and mean frequency of vasomotor symptoms at baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 12
    Statistical analysis description
    Week 6
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg
    Number of subjects included in analysis
    334
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.117 [111]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.961
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.863
         upper limit
    		 4.741
    Notes
    [111] - Based on logistic regression with treatment group and smoking status (current vs former/never) as factors and mean frequency of vasomotor symptoms at baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 13
    Statistical analysis description
    Week 7
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg
    Number of subjects included in analysis
    333
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.393 [112]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.471
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.612
         upper limit
    		 3.687
    Notes
    [112] - Based on logistic regression with treatment group and smoking status (current vs former/never) as factors and mean frequency of vasomotor symptoms at baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 14
    Statistical analysis description
    Week 7
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg
    Number of subjects included in analysis
    334
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.086 [113]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.087
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.923
         upper limit
    		 5.043
    Notes
    [113] - Based on logistic regression with treatment group and smoking status (current vs former/never) as factors and mean frequency of vasomotor symptoms at baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 15
    Statistical analysis description
    Week 8
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg
    Number of subjects included in analysis
    333
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.168 [114]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.774
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.798
         upper limit
    		 4.143
    Notes
    [114] - Based on logistic regression with treatment group and smoking status (current vs former/never) as factors and mean frequency of vasomotor symptoms at baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 16
    Statistical analysis description
    Week 8
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg
    Number of subjects included in analysis
    334
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.03 [115]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.374
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.112
         upper limit
    		 5.41
    Notes
    [115] - Based on logistic regression with treatment group and smoking status (current vs former/never) as factors and mean frequency of vasomotor symptoms at baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 17
    Statistical analysis description
    Week 9
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg
    Number of subjects included in analysis
    333
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.287 [116]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.605
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.681
         upper limit
    		 3.971
    Notes
    [116] - Based on logistic regression with treatment group and smoking status (current vs former/never) as factors and mean frequency of vasomotor symptoms at baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 18
    Statistical analysis description
    Week 9
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg
    Number of subjects included in analysis
    334
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.08 [117]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.108
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.936
         upper limit
    		 5.076
    Notes
    [117] - Based on logistic regression with treatment group and smoking status (current vs former/never) as factors and mean frequency of vasomotor symptoms at baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 19
    Statistical analysis description
    Week 10
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg
    Number of subjects included in analysis
    333
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.247 [118]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.599
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.73
         upper limit
    		 3.636
    Notes
    [118] - Based on logistic regression with treatment group and smoking status (current vs former/never) as factors and mean frequency of vasomotor symptoms at baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 20
    Statistical analysis description
    Week 10
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg
    Number of subjects included in analysis
    334
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.017 [119]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.481
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.201
         upper limit
    		 5.441
    Notes
    [119] - Based on logistic regression with treatment group and smoking status (current vs former/never) as factors and mean frequency of vasomotor symptoms at baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 21
    Statistical analysis description
    Week 11
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg
    Number of subjects included in analysis
    333
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.212 [120]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.728
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.744
         upper limit
    		 4.236
    Notes
    [120] - Based on logistic regression with treatment group and smoking status (current vs former/never) as factors and mean frequency of vasomotor symptoms at baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 22
    Statistical analysis description
    Week 11
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg
    Number of subjects included in analysis
    334
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.002 [121]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    3.536
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.666
         upper limit
    		 8.207
    Notes
    [121] - Based on logistic regression with treatment group and smoking status (current vs former/never) as factors and mean frequency of vasomotor symptoms at baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 23
    Statistical analysis description
    Week 12
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg
    Number of subjects included in analysis
    333
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.225 [122]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.701
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.733
         upper limit
    		 4.169
    Notes
    [122] - Based on logistic regression with treatment group and smoking status (current vs former/never) as factors and mean frequency of vasomotor symptoms at baseline as a covariate.
    Statistical analysis title
    		 Statistical Analysis 24
    Statistical analysis description
    Week 12
    Comparison groups
    Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg
    Number of subjects included in analysis
    334
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.006 [123]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    3.049
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.42
         upper limit
    		 7.125
    Notes
    [123] - Based on logistic regression with treatment group and smoking status (current vs former/never) as factors and mean frequency of vasomotor symptoms at baseline as a covariate.

    Secondary: Change from Baseline in The Mean Frequency of Moderate, and Severe VMS at Week 24

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    End point title
    		 Change from Baseline in The Mean Frequency of Moderate, and Severe VMS at Week 24
    End point description
    The frequency of moderate to severe VMS was the number of moderate to severe VMS per 24 hours. A daily frequency per week was derived by taking the mean of the data over 7 days. Moderate VMS was defined as sensation of heat with sweating/dampness, but was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets. Severe VMS was defined as sensation of intense heat with sweating, caused disruption of activity. If at night, participant woke up hot and was sweating and needed to take action (e.g., remove layers of clothes, open the window, or get out of bed). Baseline was the average number of moderate to severe VMS per 24 hours based on the non-missing values in the 10 days immediately prior to randomization. Analysis Population: FAS population with available data at specified time point.
    End point type
    Secondary
    End point timeframe
    Baseline and 24 weeks of fezolinetant exposure (week 36 for arms Placebo/Fezolinetant 30 mg and Placebo/Fezolinetant 45 mg)
    End point values
    		 Double-blind Period:Placebo/Extension Period:Fezolinetant 30mg Double-blind Period:Placebo/Extension Period:Fezolinetant 45mg Double-blind: Fezolinetant 30 mg/Extension: Fezolinetant 30 mg Double-blind: Fezolinetant 45 mg/Extension: Fezolinetant 45 mg
    Number of subjects analysed
    62
    60
    131
    134
    Units: VMS per day
        arithmetic mean (standard deviation)
    -9.01 ( 5.80 )
    -7.08 ( 5.40 )
    -7.86 ( 4.21 )
    -7.96 ( 4.53 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in The Mean Severity of Moderate, and Severe VMS at Week 24

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    End point title
    		 Change from Baseline in The Mean Severity of Moderate, and Severe VMS at Week 24
    End point description
    Severity of moderate to severe VMS per day at post baseline visit was calculated as follows: [(number of mild hot flashes per day x 1) + (number of moderate hot flashes per day x 2) + (number of severe hot flashes per day x 3)]/Total number of daily mild/moderate/severe hot flashes Moderate VMS was defined as sensation of heat with sweating/dampness, but was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets. Severe VMS was defined as sensation of intense heat with sweating, caused disruption of activity. If at night, participant woke up hot and was sweating and needed to take action (e.g., remove layers of clothes, open the window, or get out of bed). Severity was zero for participants that had no mild or moderate or severe VMS. Higher scores indicates greater severity. Analysis Population: FAS population with available data at specified time point.
    End point type
    Secondary
    End point timeframe
    Baseline and 24 weeks of fezolinetant exposure (week 36 for arms Placebo/Fezolinetant 30 mg and Placebo/Fezolinetant 45 mg)
    End point values
    		 Double-blind Period:Placebo/Extension Period:Fezolinetant 30mg Double-blind Period:Placebo/Extension Period:Fezolinetant 45mg Double-blind: Fezolinetant 30 mg/Extension: Fezolinetant 30 mg Double-blind: Fezolinetant 45 mg/Extension: Fezolinetant 45 mg
    Number of subjects analysed
    62
    60
    131
    134
    Units: Score on a scale
        arithmetic mean (standard deviation)
    -0.78 ( 0.85 )
    -0.95 ( 0.77 )
    -0.85 ( 0.88 )
    -0.90 ( 0.80 )
    No statistical analyses for this end point

    Secondary: Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit

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    End point title
    		 Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit [124]
    End point description
    The PGI is comprised of 2 companion 1-item PRO measures analogous to the Clinical Global Impression (CGI) scales. These measures provide brief, stand-alone global assessments prior to and after initiating a study medication. Patient-perceived change from the initiation of treatment (PGI-C)-VMS is used to evaluate meaningful within-person changes over time in VMS. This measure provides patient-perceived change from the initiation of treatment. The PGI-C VMS asks: “Compared to the beginning of this study, how would you rate your HFs/night sweats now?” Subject ratings range from (1) much better to (7) much worse. Participant ratings range from 1=much better, 2= moderately better, 3= a little better, 4= no change, 5= a little worse, 6= moderately worse, 7= much worse. Analysis Population: FAS population with available data at specified time point.
    End point type
    Secondary
    End point timeframe
    Weeks 4, 12, 16, 20, 24, 28, 32, 36, 40, 44, 52 of fezolinetant exposure (weeks 16, 24, 28, 32, 36, 40, 44, 48 and 52 for arms Placebo/Fezolinetant 30 mg and Placebo/Fezolinetant 45 mg)
    Notes
    [124] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: There was no pre-specified statistical analysis for this endpoint.
    End point values
    		 Double-blind Period: Placebo Double-blind Period:Placebo/Extension Period:Fezolinetant 30mg Double-blind Period:Placebo/Extension Period:Fezolinetant 45mg Double-blind: Fezolinetant 30 mg/Extension: Fezolinetant 30 mg Double-blind: Fezolinetant 45 mg/Extension: Fezolinetant 45 mg
    Number of subjects analysed
    151
    67
    69
    155
    150
    Units: Participants
        Week 4: Much better (n = 151, 0, 3, 155, 159)
    25
    0
    2
    61
    68
        Week 4:Moderately better(n=151, 0, 3, 155, 159)
    23
    0
    0
    21
    32
        Week 4:A little better(n=151, 0, 3, 155, 159)
    46
    0
    1
    42
    42
        Week 4:No change (n = 151, 0, 3, 155, 159)
    43
    0
    0
    29
    16
        Week 4:A little worse (n = 151, 0, 3, 155, 159)
    6
    0
    0
    2
    0
        Week 4:Moderately worse(n=151, 0, 3, 155, 159)
    6
    0
    0
    0
    0
        Week 4:Much worse (n = 151, 0, 3, 155, 159)
    2
    0
    0
    0
    1
        Week 12: Much better (n = 144, 67, 69, 145, 149)
    35
    40
    30
    68
    71
        Week 12:Moderately better(n=144, 67, 69, 145, 149)
    24
    11
    18
    25
    37
        Week 12:A little better(n=144, 67, 69, 145, 149)
    36
    11
    10
    29
    32
        Week 12: No change(n = 144, 67, 69, 145, 149)
    39
    4
    4
    19
    8
        Week 12:A little worse(n = 144, 67, 69, 145, 149)
    6
    1
    4
    1
    1
        Week 12:Moderately worse(n=144, 67, 69, 145, 149)
    2
    0
    1
    2
    0
        Week 12: Much worse(n=144, 67, 69, 145, 149)
    2
    0
    2
    1
    0
        Week 16: Much better(n =NA,0, 0, 1, 2, )
    99999
    0
    0
    0
    2
        Week 16:Moderately better(n =NA,0, 0, 1, 2, )
    99999
    0
    0
    0
    0
        Week 16: A little better(n =NA,0, 0, 1, 2, )
    99999
    0
    0
    0
    0
        Week 16: No change(n =NA,0, 0, 1, 2, )
    99999
    0
    0
    0
    0
        Week 16: A little worse(n =NA,0, 0, 1, 2, )
    99999
    0
    0
    0
    0
        Week 16:Moderately worse(n =NA,0, 0, 1, 2, )
    99999
    0
    0
    0
    0
        Week 16: Much worse(n =NA,0, 0, 1, 2, )
    99999
    0
    0
    0
    0
        Week 20: Much better (n =NA,0, 0,2,0)
    99999
    0
    0
    0
    0
        Week 20:Moderately better(n =NA,0, 0,2,0)
    99999
    0
    0
    0
    0
        Week 20: A little better (n =NA,0, 0,2,0)
    99999
    0
    0
    0
    0
        Week 20: No change (n =NA,0, 0,2,0)
    99999
    0
    0
    1
    0
        Week 20: A little worse (n =NA,0, 0,2,0)
    99999
    0
    0
    0
    0
        Week 20: Moderately worse(n =NA,0, 0,2,0)
    99999
    0
    0
    0
    0
        Week 20: Much worse (n =NA,0, 0,2,0)
    99999
    0
    0
    0
    0
        Week 24: Much better (n = NA,1, 0, 134, 139)
    99999
    0
    0
    68
    76
        Week 24:Moderately better(n = NA,1, 0, 134, 139)
    99999
    1
    0
    31
    33
        Week 24: A little better(n = NA,1, 0, 134, 139)
    99999
    0
    0
    22
    22
        Week 24: No change (n = NA,1, 0, 134, 139)
    99999
    0
    0
    9
    4
        Week 24: A little worse(n = NA,1, 0, 134, 139)
    99999
    0
    0
    1
    3
        Week 24:Moderately worse (n = NA,1, 0, 134, 139)
    99999
    0
    0
    2
    1
        Week 24: Much worse (n = NA,1, 0, 134, 139)
    99999
    0
    0
    1
    0
        Week 28: Much better (n = NA,1, 0,1,1)
    99999
    1
    0
    1
    0
        Week 28: Moderately better (n = NA,1, 0,1,1)
    99999
    0
    0
    0
    0
        Week 28: A little better (n = NA,1, 0,1,1)
    99999
    0
    0
    0
    0
        Week 28: No change (n = NA,1, 0,1,1)
    99999
    0
    0
    0
    0
        Week 28: A little worse (n = NA,1, 0,1,1)
    99999
    0
    0
    0
    0
        Week 28:Moderately worse (n = NA,1, 0,1,1)
    99999
    0
    0
    0
    0
        Week 28: Much worse (n = NA,1, 0,1,1)
    99999
    0
    0
    0
    1
        Week 32: Much better (n =NA, 0, 0,0,1)
    99999
    0
    0
    0
    1
        Week 32:Moderately better(n =NA, 0, 0,0,1)
    99999
    0
    0
    0
    0
        Week 32: A little better(n =NA, 0, 0,0,1)
    99999
    0
    0
    0
    0
        Week 32: No change(n =NA, 0, 0,0,1)
    99999
    0
    0
    0
    0
        Week 32: A little worse(n =NA, 0, 0,0,1)
    99999
    0
    0
    0
    0
        Week 32:Moderately worse(n =NA, 0, 0,0,1)
    99999
    0
    0
    0
    0
        Week 32: Much worse(n =NA, 0, 0,0,1)
    99999
    0
    0
    0
    0
        Week 36: Much better (n =NA, 0, 0,1, 0,)
    99999
    0
    0
    0
    0
        Week 36: Moderately better (n =NA, 0, 0,1, 0,)
    99999
    0
    0
    1
    0
        Week 36: A little better(n =NA, 0, 0,1, 0,)
    99999
    0
    0
    0
    0
        Week 36: No change(n =NA, 0, 0,1, 0,)
    99999
    0
    0
    0
    0
        Week 36: A little worse(n =NA, 0, 0,1, 0,)
    99999
    0
    0
    0
    0
        Week 36: Moderately worse(n =NA, 0, 0,1, 0,)
    99999
    0
    0
    0
    0
        Week 36: Much worse(n =NA, 0, 0,1, 0,)
    99999
    0
    0
    0
    0
        Week 40: Much better (n = NA,55, 54,0, 0)
    99999
    33
    31
    0
    0
        Week 40:Moderately better(n = NA,55, 54,0, 0)
    99999
    14
    13
    0
    0
        Week 40: A little better(n = NA,55, 54,0, 0)
    99999
    5
    8
    0
    0
        Week 40: No change(n = NA,55, 54,0, 0)
    99999
    3
    2
    0
    0
        Week 40: A little worse(n = NA,55, 54,0, 0)
    99999
    0
    0
    0
    0
        Week 40:Moderately worse(n = NA,55, 54,0, 0)
    99999
    0
    0
    0
    0
        Week 40: Much worse(n = NA,55, 54,0, 0)
    99999
    0
    0
    0
    0
        Week 44: Much better (n = NA, NA, NA,2, 0,)
    99999
    99999
    99999
    2
    0
        Week 44:Moderately better(n = NA, NA, NA,2, 0,)
    99999
    99999
    99999
    0
    0
        Week 44: A little better (n = NA, NA, NA,2, 0,)
    99999
    99999
    99999
    0
    0
        Week 44: No change(n = NA, NA, NA,2, 0,)
    99999
    99999
    99999
    0
    0
        Week 44: A little worse(n = NA, NA, NA,2, 0,)
    99999
    99999
    99999
    0
    0
        Week 44:Moderately worse(n = NA, NA, NA,2, 0,)
    99999
    99999
    99999
    0
    0
        Week 44: Much worse(n = NA, NA, NA,2, 0,)
    99999
    99999
    99999
    0
    0
        Week 52: Much better (n = NA, NA, NA,107, 116)
    99999
    99999
    99999
    60
    77
        Week 52:Moderately better(n = NA, NA, NA,107, 116)
    99999
    99999
    99999
    25
    22
        Week 52: A little better(n = NA, NA, NA,107, 116)
    99999
    99999
    99999
    14
    13
        Week 52: No change(n = NA, NA, NA,107, 116)
    99999
    99999
    99999
    4
    2
        Week 52: A little worse(n = NA, NA, NA,107, 116)
    99999
    99999
    99999
    1
    0
        Week 52:Moderately worse(n=NA, NA, NA,107,116)
    99999
    99999
    99999
    1
    0
        Week 52: Much worse(n = NA, NA, NA,107, 116)
    99999
    99999
    99999
    2
    2
    No statistical analyses for this end point

    Secondary: Number of Participants With Adverse Events

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    End point title
    		 Number of Participants With Adverse Events [125]
    End point description
    An AE is any untoward medical occurrence in a participant administered a study drug, & which does not necessarily have to have a causal relationship with treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with use of a medicinal product (mp) whether or not considered related to the mp. An AE is considered “serious” if it results in death, is life-threatening, results in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, Results in congenital anomaly or birth defect, requires inpatient hospitalization or leads to prolongation of hospitalization, hospitalization for treatment/observation/examination caused by AE is to be considered as serious, discontinuation due to increases in liver enzymes, other medically important events. TEAE was defined as an AE observed from first dose date up to 21 days after last dose.
    End point type
    Secondary
    End point timeframe
    From first dose date up to 21 days after last dose (to 55 weeks) Analysis Population: Safety analysis set consisted of all randomized participants who took at least 1 dose of study intervention.
    Notes
    [125] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: There was no pre-specified statistical analysis for this endpoint.
    End point values
    		 Double-blind Period: Placebo Double-blind Period:Placebo/Extension Period:Fezolinetant 30mg Double-blind Period:Placebo/Extension Period:Fezolinetant 45mg Double-blind: Fezolinetant 30 mg/Extension: Fezolinetant 30 mg Double-blind: Fezolinetant 45 mg/Extension: Fezolinetant 45 mg
    Number of subjects analysed
    167
    76
    75
    166
    167
    Units: Participants
        Treatment Emergent Adverse Events (TEAE)
    54
    43
    45
    107
    106
        Drug-related TEAE
    11
    8
    8
    33
    30
        Serious TEAE
    0
    2
    4
    9
    8
        Drug-related serious TEAE
    0
    0
    1
    0
    1
        TEAE leading to death
    0
    0
    1
    0
    0
        Drug-related TEAE leading to death
    0
    0
    0
    0
    0
        TEAE leading to withdrawal of treatment
    1
    2
    3
    4
    7
        Drug-related TEAE leading to withdrawal of trt
    0
    1
    2
    1
    6
        Death
    0
    0
    1
    0
    0
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From first dose date up to 21 days after last dose (to 55 weeks)
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    v23.0
    Reporting groups
    Reporting group title
    Double-blind Period: Placebo
    Reporting group description
    		 Participants received fezolinetant matching placebo (two fezolinetant matching placebo tablets) orally, once daily (QD) up to week 12 during double-blind treatment period.

    Reporting group title
    Double-blind: Fezolinetant 30 mg/Extension: Fezolinetant 30 mg
    Reporting group description
    		 Participants received fezolinetant 30 mg (one 30 mg fezolinetant tablet and one placebo tablet) orally, QD up to week 12 during double-blind treatment period followed by fezolinetant 30 mg orally, QD from week 13 up to Week 52 during extension treatment period.

    Reporting group title
    Double-blind: Fezolinetant 45 mg/Extension: Fezolinetant 45 mg
    Reporting group description
    		 Participants received fezolinetant 45 mg (one 30 mg tablet and one 15 mg tablet) orally, QD up to week 12 during double-blind treatment period followed by fezolinetant 45 mg (one 30 mg tablet and one 15 mg tablet) orally, QD from week 13 up to Week 52 during extension treatment period.

    Reporting group title
    Double-blind : Placebo/Extension : Fezolinetant 30 mg
    Reporting group description
    		 Participants who received placebo during double-blind treatment period were re-randomized to receive fezolinetant 30 mg orally, QD from week 13 up to week 52 during extension treatment period.

    Reporting group title
    Double-blind : Placebo/Extension : Fezolinetant 45 mg
    Reporting group description
    		 Participants who received placebo during double-blind treatment period were re-randomized to receive fezolinetant 45 mg orally, QD from week 13 up to week 52 during extension treatment period.

    Serious adverse events
    		 Double-blind Period: Placebo Double-blind: Fezolinetant 30 mg/Extension: Fezolinetant 30 mg Double-blind: Fezolinetant 45 mg/Extension: Fezolinetant 45 mg Double-blind : Placebo/Extension : Fezolinetant 30 mg Double-blind : Placebo/Extension : Fezolinetant 45 mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 167 (0.00%)
    9 / 166 (5.42%)
    8 / 167 (4.79%)
    2 / 76 (2.63%)
    4 / 75 (5.33%)
         number of deaths (all causes)
    0
    0
    0
    0
    1
         number of deaths resulting from adverse events
    0
    0
    0
    0
    1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Invasive breast carcinoma
         subjects affected / exposed
    0 / 167 (0.00%)
    0 / 166 (0.00%)
    0 / 167 (0.00%)
    1 / 76 (1.32%)
    0 / 75 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Squamous cell carcinoma of skin
         subjects affected / exposed
    0 / 167 (0.00%)
    0 / 166 (0.00%)
    1 / 167 (0.60%)
    0 / 76 (0.00%)
    0 / 75 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Keratoacanthoma
         subjects affected / exposed
    0 / 167 (0.00%)
    0 / 166 (0.00%)
    1 / 167 (0.60%)
    0 / 76 (0.00%)
    0 / 75 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Uterine leiomyoma
         subjects affected / exposed
    0 / 167 (0.00%)
    0 / 166 (0.00%)
    0 / 167 (0.00%)
    0 / 76 (0.00%)
    1 / 75 (1.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Foot fracture
         subjects affected / exposed
    0 / 167 (0.00%)
    0 / 166 (0.00%)
    0 / 167 (0.00%)
    0 / 76 (0.00%)
    1 / 75 (1.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Limb injury
         subjects affected / exposed
    0 / 167 (0.00%)
    0 / 166 (0.00%)
    1 / 167 (0.60%)
    0 / 76 (0.00%)
    0 / 75 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Multiple injuries
         subjects affected / exposed
    0 / 167 (0.00%)
    0 / 166 (0.00%)
    0 / 167 (0.00%)
    0 / 76 (0.00%)
    1 / 75 (1.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Limb traumatic amputation
         subjects affected / exposed
    0 / 167 (0.00%)
    1 / 166 (0.60%)
    0 / 167 (0.00%)
    0 / 76 (0.00%)
    0 / 75 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Posterior tibial nerve injury
         subjects affected / exposed
    0 / 167 (0.00%)
    0 / 166 (0.00%)
    1 / 167 (0.60%)
    0 / 76 (0.00%)
    0 / 75 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin laceration
         subjects affected / exposed
    0 / 167 (0.00%)
    0 / 166 (0.00%)
    1 / 167 (0.60%)
    0 / 76 (0.00%)
    0 / 75 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    0 / 167 (0.00%)
    1 / 166 (0.60%)
    0 / 167 (0.00%)
    1 / 76 (1.32%)
    0 / 75 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    0 / 167 (0.00%)
    1 / 166 (0.60%)
    0 / 167 (0.00%)
    0 / 76 (0.00%)
    0 / 75 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    0 / 167 (0.00%)
    0 / 166 (0.00%)
    1 / 167 (0.60%)
    0 / 76 (0.00%)
    0 / 75 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 167 (0.00%)
    1 / 166 (0.60%)
    0 / 167 (0.00%)
    0 / 76 (0.00%)
    0 / 75 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Postmenopausal haemorrhage
         subjects affected / exposed
    0 / 167 (0.00%)
    1 / 166 (0.60%)
    0 / 167 (0.00%)
    0 / 76 (0.00%)
    0 / 75 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vaginal haemorrhage
         subjects affected / exposed
    0 / 167 (0.00%)
    0 / 166 (0.00%)
    1 / 167 (0.60%)
    0 / 76 (0.00%)
    0 / 75 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Biliary dyskinesia
         subjects affected / exposed
    0 / 167 (0.00%)
    0 / 166 (0.00%)
    1 / 167 (0.60%)
    0 / 76 (0.00%)
    0 / 75 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis acute
         subjects affected / exposed
    0 / 167 (0.00%)
    1 / 166 (0.60%)
    0 / 167 (0.00%)
    0 / 76 (0.00%)
    0 / 75 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatotoxicity
         subjects affected / exposed
    0 / 167 (0.00%)
    0 / 166 (0.00%)
    0 / 167 (0.00%)
    0 / 76 (0.00%)
    1 / 75 (1.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Tendonitis
         subjects affected / exposed
    0 / 167 (0.00%)
    0 / 166 (0.00%)
    1 / 167 (0.60%)
    0 / 76 (0.00%)
    0 / 75 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    COVID-19
         subjects affected / exposed
    0 / 167 (0.00%)
    2 / 166 (1.20%)
    0 / 167 (0.00%)
    0 / 76 (0.00%)
    0 / 75 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tooth infection
         subjects affected / exposed
    0 / 167 (0.00%)
    1 / 166 (0.60%)
    0 / 167 (0.00%)
    0 / 76 (0.00%)
    0 / 75 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Double-blind Period: Placebo Double-blind: Fezolinetant 30 mg/Extension: Fezolinetant 30 mg Double-blind: Fezolinetant 45 mg/Extension: Fezolinetant 45 mg Double-blind : Placebo/Extension : Fezolinetant 30 mg Double-blind : Placebo/Extension : Fezolinetant 45 mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    6 / 167 (3.59%)
    20 / 166 (12.05%)
    34 / 167 (20.36%)
    10 / 76 (13.16%)
    12 / 75 (16.00%)
    Investigations
    Blood creatine phosphokinase increased
         subjects affected / exposed
    0 / 167 (0.00%)
    2 / 166 (1.20%)
    3 / 167 (1.80%)
    1 / 76 (1.32%)
    5 / 75 (6.67%)
         occurrences all number
    0
    2
    3
    1
    6
    Vascular disorders
    Hot flush
         subjects affected / exposed
    1 / 167 (0.60%)
    3 / 166 (1.81%)
    7 / 167 (4.19%)
    4 / 76 (5.26%)
    0 / 75 (0.00%)
         occurrences all number
    1
    3
    7
    4
    0
    Nervous system disorders
    Headache
         subjects affected / exposed
    4 / 167 (2.40%)
    8 / 166 (4.82%)
    12 / 167 (7.19%)
    1 / 76 (1.32%)
    4 / 75 (5.33%)
         occurrences all number
    4
    9
    14
    1
    5
    Infections and infestations
    COVID-19
         subjects affected / exposed
    1 / 167 (0.60%)
    8 / 166 (4.82%)
    15 / 167 (8.98%)
    4 / 76 (5.26%)
    3 / 75 (4.00%)
         occurrences all number
    1
    8
    15
    4
    3

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    17 May 2019
    The changed included: The study title is updated to convey that the second phase of the study is a non-controlled extension period. The number of subjects to be enrolled is increased from 300 to 450, and the sample size justification parameters are updated to reflect a possible 20% discontinuation rate instead of a 32% rate. An additional treatment arm is added to include a 45 mg dose of fezolinetant. The schedule of assessments is updated to include a mammogram at week 52/end of treatment/early discontinuation and an endometrial biopsy following study discontinuation. Further details are provided regarding the circumstances under which these procedures are performed. The screening serology panel is updated to include testing for antibody against hepatitis B antigen and antibody to hepatitis B core antigen. The dose rationale is updated with additional information about Study ESN364_HF_205 and results regarding the potential for drug-induced liver injury. The length of time prior to screening in which a normal/negative or not clinically significant mammogram may have been performed is increased to within 12 months of trial enrollment. The schedule of assessments is updated to include 2 additional study visits (2b and 5b). The schedule of assessments and pharmacokinetics assessment sections are updated to include the addition of blood draws for pharmacokinetic analysis in subjects with a signal of elevated transaminases who are returning for a repeat hepatic abnormality testing blood draw. Details are added for the reporting of drug-induced liver damage and it is clarified that such events are to be characterized as serious adverse events (SAEs). The statistical analysis is updated to accommodate inclusion of a second dosing cohort.
    01 Jul 2020
    The changes included: Inclusion criterion #4 was updated to remove with or without hysterectomy from the bilateral oophorectomy screening criteria. Inclusion criteria #8 and #10 are aligned to account for the exclusion of subjects who have had a hysterectomy. Inclusion criterion #9 is updated to specify that the endometrial biopsy obtained at screening must be considered evaluable; this criterion is now required for all subjects. Alternate measures that may be implemented due to site closures related to the COVID-19 pandemic are added to the protocol. These include telemedicine conferences (by telephone), home healthcare services, and laboratory assessments performed at local laboratories. It is noted that subjects who screen fail due to a COVID-19 pandemic study suspension and have an evaluable endometrial biopsy will not require a repeat biopsy if they rescreen. Exclusion criteria #6 and #7 are updated so that they apply to all subjects, not just subjects with a uterus, and the exception for endometrial thickness less than 4 mm is removed from exclusion criterion #7. Exclusion criterion #20 is added to exclude subjects who have had partial or full hysterectomies. Language is added to specify that the screening endometrial biopsy must be evaluable. Retest biopsies may only be performed for insufficient material or unevaluable biopsies, and a maximum of one retest biopsy during screening is allowed. It is noted that subjects will be allowed into the study based on the primary endometrial result/diagnosis, but a second and tertiary diagnosis will also be reported. Adverse events (AEs) of abuse liability, depression, wakefulness and effect on memory are added to the protocol as AEs of special interest. AEs of liver test elevation are clarified. Category 2 results of secondary or tertiary screening endometrial biopsy diagnosis are added to the list of reasons for subject discontinuation.
    01 Jul 2020
    The exploratory endpoint of “Mean score on the PGI-C in VMS from baseline to each visit” is re-categorized as a secondary endpoint. Language is added to instruct sites about daily diary compliance.

    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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