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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	2018-003528-35
Trial protocol	GB ES CZ HU
Global end of trial date	11 Aug 2021

Results information
Results version number	v1(current)
This version publication date	29 Jul 2022
First version publication date	29 Jul 2022
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

2693-CL-0301

ISRCTN number

US NCT number

NCT04003155

WHO universal trial number (UTN)

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

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

11 Aug 2021

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

11 Aug 2021

Was the trial ended prematurely?

Main objective of the trial

The primary objective of this study was 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

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Canada: 27

Country: Number of subjects enrolled

Czechia: 9

Country: Number of subjects enrolled

Hungary: 30

Country: Number of subjects enrolled

Poland: 121

Country: Number of subjects enrolled

Spain: 5

Country: Number of subjects enrolled

United Kingdom: 11

Country: Number of subjects enrolled

United States: 324

Worldwide total number of subjects

527

EEA total number of subjects

165

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

518

From 65 to 84 years

85 years and over

Subject disposition

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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 minimum average of 7 to 8 moderate to severe VMS per day within 10 days prior to randomization & who met inclusion & none of exclusion criteria were enrolled.

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 title

Double-Blind Period (12 weeks)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Investigator, Subject

Are arms mutually exclusive

Yes

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.

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

Fezolinetnat

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.

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	175	176	176
Full Analysis Set	175	173	174
Safety Analysis Set	175	174	173
Treated	175	173	174
Completed	152	142	161
Not completed	23	34	15
Consent withdrawn by subject	9	12	4
Adverse event, non-fatal	9	8	5
Miscellaneous	1	7	3
Lost to follow-up	3	4	-
Protocol deviation	1	3	3

Period 2 title

Extension Period (40 weeks)

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

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.

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.

Double-blind: Placebo/Extension Fezolinetant 30 mg

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.

Double-blind Placebo/Extension: Fezolinetant 45 mg

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 ^[1]	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
Started	142	158	76	76
Completed	124	143	62	67
Not completed	18	15	14	9
Consent withdrawn by subject	12	7	9	5
Adverse event, non-fatal	5	4	2	2
Miscellaneous	-	1	2	1
Lost to follow-up	1	3	1	1

Notes
[1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: Participants who received placebo in double-blind period were moved to fezolinetant 30/45 mg arms in extension treatment period

Baseline characteristics

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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	175	176	176	527
Age categorical
Units: Subjects
Age Continuous
Units: Years
arithmetic mean (standard deviation)	54.7 ( 4.8 )	54.1 ( 4.9 )	54.3 ( 5.2 )	-
Sex: Female, Male
Units:
Female	175	176	176	527
Male	0	0	0	0
Race/Ethnicity, Customized
Units: Subjects
Race: White	142	150	143	435
Race: Black or African American	28	21	27	76
Race: American Indian or Alaska Native	2	0	1	3
Race: Asian	3	3	3	9
Race: Pacific Islander	0	0	1	1
Race: More Than One Race	0	1	1	2
Race: Unknown	0	1	0	1
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	46	43	48	137
Not Hispanic or Latino	128	133	128	389
Unknown or Not Reported	1	0	0	1
Frequency of Moderate and Severe Vasomotor Symptoms 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. Analysis population description (APD): FAS Population
Units: VMS per day
arithmetic mean (standard deviation)	10.51 ( 3.79 )	10.65 ( 4.73 )	10.44 ( 3.92 )	-
Severity of Moderate and Severe Vasomotor Symptoms 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. APD: FAS Population
Units: Score on a scale
arithmetic mean (standard deviation)	2.43 ( 0.35 )	2.39 ( 0.34 )	2.40 ( 0.35 )	-

End points

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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

Reporting group title

Double-blind: Fezolinetant 45 mg/Extension: Fezolinetant 45 mg

Reporting group description

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.

Subject analysis set title

Double-blind: Fezolinetant 30 mg/Extension: Fezolinetant 30 mg

Subject analysis set type

Full analysis

Subject analysis set description

Subject analysis set title

Double-blind: Fezolinetant 45 mg/Extension: Fezolinetant 45 mg

Subject analysis set type

Full analysis

Subject analysis set description

Subject analysis set title

Full Analysis Set (FAS)

Subject analysis set type

Full analysis

Subject analysis set description

Full analysis set (FAS) consisted of all participants who were randomized and received at least 1 dose of study intervention. The randomized treatment for each participant was used for summaries by treatment group based on the FAS, even if a participant erroneously received a different treatment.

Subject analysis set title

Safety Analysis Set

Subject analysis set type

Safety analysis

Subject analysis set description

Safety population included all randomized participants who took at least 1 dose of study intervention. A participant erroneously receiving a treatment different from their randomized treatment was assigned to the treatment group that the participant received as first dose.

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 participant 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. APD: 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	166	157	164
Units: VMS per day
least squares mean (standard error)	-3.32 ( 0.29 )	-5.19 ( 0.30 )	-5.39 ( 0.30 )

Statistical Analysis 1

Statistical analysis description

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)

Comparison groups

Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg

Number of subjects included in analysis

323

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001 ^[1]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-1.87

Confidence interval

level

95%

sides

2-sided

lower limit

-2.69

upper limit

-1.05

Variability estimate

Standard error of the mean

Dispersion value

0.42

Notes
[1] - 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 2

Comparison groups

Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg

Number of subjects included in analysis

330

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[2]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-2.07

Confidence interval

level

95%

sides

2-sided

lower limit

-2.89

upper limit

-1.25

Variability estimate

Standard error of the mean

Dispersion value

0.42

Notes
[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 3

Comparison groups

Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg

Number of subjects included in analysis

323

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.012

Method

Hochberg

Confidence interval

Statistical Analysis 4

Comparison groups

Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg

Number of subjects included in analysis

330

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.007

Method

Hochberg

Confidence interval

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

Top of page

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 participant 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. APD: 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	139	131	146
Units: VMS per day
least squares mean (standard error)	-3.90 ( 0.31 )	-6.28 ( 0.32 )	-6.44 ( 0.31 )

Statistical Analysis 1

Comparison groups

Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg

Number of subjects included in analysis

270

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[3]

Method

MMRM

Parameter type

LSMean difference

Point estimate

-2.39

Confidence interval

level

95%

sides

2-sided

lower limit

-3.25

upper limit

-1.52

Variability estimate

Standard error of the mean

Dispersion value

0.44

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.

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 ^[4]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-2.55

Confidence interval

level

95%

sides

2-sided

lower limit

-3.4

upper limit

-1.7

Variability estimate

Standard error of the mean

Dispersion value

0.43

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 3

Comparison groups

Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg

Number of subjects included in analysis

270

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.012

Method

Hochberg

Confidence interval

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

= 0.007

Method

Hochberg

Confidence interval

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

Top of page

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 participant 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. APD: 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	166	157	164
Units: Score on a scale
least squares mean (standard error)	-0.27 ( 0.04 )	-0.42 ( 0.04 )	-0.46 ( 0.04 )

Statistical Analysis 1

Comparison groups

Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg

Number of subjects included in analysis

323

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.012 ^[5]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-0.15

Confidence interval

level

95%

sides

2-sided

lower limit

-0.27

upper limit

-0.03

Variability estimate

Standard error of the mean

Dispersion value

0.06

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.

Statistical Analysis 2

Comparison groups

Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg

Number of subjects included in analysis

330

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.002 ^[6]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-0.19

Confidence interval

level

95%

sides

2-sided

lower limit

-0.3

upper limit

-0.07

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 3

Comparison groups

Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg

Number of subjects included in analysis

330

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.012

Method

Hochberg

Confidence interval

Statistical Analysis 4

Comparison groups

Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg

Number of subjects included in analysis

330

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.007

Method

Hochberg

Confidence interval

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

Top of page

End point title

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

End point description

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	139	131	146
Units: Score on a scale
least squares mean (standard error)	-0.37 ( 0.05 )	-0.60 ( 0.05 )	-0.57 ( 0.05 )

Statistical Analysis 1

Comparison groups

Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg

Number of subjects included in analysis

270

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.002 ^[7]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-0.24

Confidence interval

level

95%

sides

2-sided

lower limit

-0.39

upper limit

-0.09

Variability estimate

Standard error of the mean

Dispersion value

0.08

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.

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

= 0.007 ^[8]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.35

upper limit

-0.06

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 3

Comparison groups

Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg

Number of subjects included in analysis

270

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.012

Method

Hochberg

Confidence interval

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

= 0.007

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

Top of page

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. APD: 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	148	133	156
Units: Score on a scale
least squares mean (standard error)	-3.2 ( 0.5 )	-3.7 ( 0.6 )	-4.2 ( 0.5 )

Statistical Analysis 1

Comparison groups

Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg

Number of subjects included in analysis

281

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.489 ^[9]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-2

upper limit

Variability estimate

Standard error of the mean

Dispersion value

0.8

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 2

Comparison groups

Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg

Number of subjects included in analysis

304

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.155 ^[10]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-1.1

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

0.4

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.

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

Top of page

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 participant 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. APD: 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 and 11

End point values	Double-blind Period: Placebo	Double-blind Period: Fezolinetant 30 mg	Double-blind Period: Fezolinetant 45 mg
Number of subjects analysed	174	169	166
Units: VMS per day
least squares mean (standard error)
Week 1	-1.82 ( 0.26 )	-3.63 ( 0.26 )	-3.07 ( 0.26 )
Week 2	-2.76 ( 0.28 )	-4.73 ( 0.28 )	-4.58 ( 0.28 )
Week 3	-3.15 ( 0.28 )	-5.14 ( 0.29 )	-5.25 ( 0.29 )
Week 5	-3.49 ( 0.28 )	-5.56 ( 0.29 )	-5.67 ( 0.29 )
Week 6	-3.58 ( 0.29 )	-5.70 ( 0.30 )	-5.97 ( 0.29 )
Week 7	-3.71 ( 0.30 )	-5.80 ( 0.31 )	-5.97 ( 0.30 )
Week 8	-3.71 ( 0.30 )	-6.10 ( 0.31 )	-6.10 ( 0.30 )
Week 9	-4.09 ( 0.30 )	-6.16 ( 0.31 )	-6.24 ( 0.30 )
Week 10	-4.09 ( 0.30 )	-6.30 ( 0.31 )	-6.25 ( 0.30 )
Week 11	-3.89 ( 0.31 )	-6.37 ( 0.31 )	-6.34 ( 0.30 )

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

343

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[11]

Method

MMRM

Parameter type

LSMean difference

Point estimate

-1.81

Confidence interval

level

95%

sides

2-sided

lower limit

-2.53

upper limit

-1.09

Variability estimate

Standard error of the mean

Dispersion value

0.37

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.

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

340

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[12]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-1.25

Confidence interval

level

95%

sides

2-sided

lower limit

-1.97

upper limit

-0.53

Variability estimate

Standard error of the mean

Dispersion value

0.37

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 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

343

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[13]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-1.97

Confidence interval

level

95%

sides

2-sided

lower limit

-2.75

upper limit

-1.19

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 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

340

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[14]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-1.83

Confidence interval

level

95%

sides

2-sided

lower limit

-2.6

upper limit

-1.05

Variability estimate

Standard error of the mean

Dispersion value

0.39

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 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

343

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[15]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-1.99

Confidence interval

level

95%

sides

2-sided

lower limit

-2.79

upper limit

-1.19

Variability estimate

Standard error of the mean

Dispersion value

0.41

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 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

340

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[16]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-2.1

Confidence interval

level

95%

sides

2-sided

lower limit

-2.9

upper limit

-1.31

Variability estimate

Standard error of the mean

Dispersion value

0.4

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 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

343

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[17]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-2.07

Confidence interval

level

95%

sides

2-sided

lower limit

-2.87

upper limit

-1.27

Variability estimate

Standard error of the mean

Dispersion value

0.41

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 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

340

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[18]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-2.18

Confidence interval

level

95%

sides

2-sided

lower limit

-2.98

upper limit

-1.39

Variability estimate

Standard error of the mean

Dispersion value

0.4

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 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

343

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[19]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-2.11

Confidence interval

level

95%

sides

2-sided

lower limit

-2.92

upper limit

-1.3

Variability estimate

Standard error of the mean

Dispersion value

0.41

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 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

340

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[20]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-2.39

Confidence interval

level

95%

sides

2-sided

lower limit

-3.19

upper limit

-1.59

Variability estimate

Standard error of the mean

Dispersion value

0.41

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 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

343

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[21]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-2.1

Confidence interval

level

95%

sides

2-sided

lower limit

-2.95

upper limit

-1.25

Variability estimate

Standard error of the mean

Dispersion value

0.43

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 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

340

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[22]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-2.27

Confidence interval

level

95%

sides

2-sided

lower limit

-3.11

upper limit

-1.42

Variability estimate

Standard error of the mean

Dispersion value

0.43

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 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

343

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[23]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-2.39

Confidence interval

level

95%

sides

2-sided

lower limit

-3.25

upper limit

-1.54

Variability estimate

Standard error of the mean

Dispersion value

0.43

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 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

340

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[24]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-2.39

Confidence interval

level

95%

sides

2-sided

lower limit

-3.23

upper limit

-1.55

Variability estimate

Standard error of the mean

Dispersion value

0.43

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 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

343

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[25]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-2.08

Confidence interval

level

95%

sides

2-sided

lower limit

-2.93

upper limit

-1.22

Variability estimate

Standard error of the mean

Dispersion value

0.43

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 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

340

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[26]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-2.16

Confidence interval

level

95%

sides

2-sided

lower limit

-3

upper limit

-1.31

Variability estimate

Standard error of the mean

Dispersion value

0.43

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 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

340

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[27]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-2.16

Confidence interval

level

95%

sides

2-sided

lower limit

-2.98

upper limit

-1.33

Variability estimate

Standard error of the mean

Dispersion value

0.42

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 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

343

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[28]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-2.21

Confidence interval

level

95%

sides

2-sided

lower limit

-3.05

upper limit

-1.37

Variability estimate

Standard error of the mean

Dispersion value

0.43

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 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

343

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[29]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-2.48

Confidence interval

level

95%

sides

2-sided

lower limit

-3.34

upper limit

-1.62

Variability estimate

Standard error of the mean

Dispersion value

0.44

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 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

340

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[30]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-2.45

Confidence interval

level

95%

sides

2-sided

lower limit

-3.3

upper limit

-1.6

Variability estimate

Standard error of the mean

Dispersion value

0.43

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.

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

Top of page

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

End point type

Secondary

End point timeframe

Baseline and weeks 1, 2, 3, 5, 6, 7, 8, 9, 10 and 11

End point values	Double-blind Period: Placebo	Double-blind Period: Fezolinetant 30 mg	Double-blind Period: Fezolinetant 45 mg
Number of subjects analysed	175	173	174
Units: Score on a scale
least squares mean (standard error)
Week 1	-0.15 ( 0.03 )	-0.25 ( 0.03 )	-0.25 ( 0.03 )
Week 2	-0.21 ( 0.03 )	-0.35 ( 0.04 )	-0.36 ( 0.03 )
Week 3	-0.27 ( 0.04 )	-0.43 ( 0.04 )	-0.43 ( 0.04 )
Week 5	-0.29 ( 0.04 )	-0.46 ( 0.04 )	-0.46 ( 0.04 )
Week 6	-0.30 ( 0.05 )	-0.50 ( 0.05 )	-0.55 ( 0.05 )
Week 7	-0.28 ( 0.05 )	-0.52 ( 0.05 )	-0.54 ( 0.05 )
Week 8	-0.29 ( 0.05 )	-0.57 ( 0.05 )	-0.53 ( 0.05 )
Week 9	-0.35 ( 0.05 )	-0.62 ( 0.05 )	-0.56 ( 0.05 )
Week 10	-0.34 ( 0.05 )	-0.62 ( 0.05 )	-0.57 ( 0.05 )
Week 11	-0.37 ( 0.06 )	-0.64 ( 0.06 )	-0.61 ( 0.06 )

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

348

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.006 ^[31]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.17

upper limit

-0.03

Variability estimate

Standard error of the mean

Dispersion value

0.04

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.

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

349

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.006 ^[32]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.17

upper limit

-0.03

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 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

348

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.003 ^[33]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-0.15

Confidence interval

level

95%

sides

2-sided

lower limit

-0.24

upper limit

-0.05

Variability estimate

Standard error of the mean

Dispersion value

0.05

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 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

349

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.002 ^[34]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-0.15

Confidence interval

level

95%

sides

2-sided

lower limit

-0.25

upper limit

-0.06

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 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

348

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.004 ^[35]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-0.16

Confidence interval

level

95%

sides

2-sided

lower limit

-0.27

upper limit

-0.05

Variability estimate

Standard error of the mean

Dispersion value

0.06

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 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

349

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.003 ^[36]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-0.17

Confidence interval

level

95%

sides

2-sided

lower limit

-0.28

upper limit

-0.06

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 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

348

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.006 ^[37]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-0.17

Confidence interval

level

95%

sides

2-sided

lower limit

-0.29

upper limit

-0.05

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 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

349

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.004 ^[38]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-0.17

Confidence interval

level

95%

sides

2-sided

lower limit

-0.29

upper limit

-0.06

Variability estimate

Standard error of the mean

Dispersion value

0.06

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 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

348

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.003 ^[39]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.33

upper limit

-0.07

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 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

349

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[40]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-0.25

Confidence interval

level

95%

sides

2-sided

lower limit

-0.38

upper limit

-0.13

Variability estimate

Standard error of the mean

Dispersion value

0.06

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 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

348

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[41]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-0.24

Confidence interval

level

95%

sides

2-sided

lower limit

-0.37

upper limit

-0.11

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 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

349

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[42]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-0.26

Confidence interval

level

95%

sides

2-sided

lower limit

-0.39

upper limit

-0.13

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 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

348

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

-0.41

upper limit

-0.15

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 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

349

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[44]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-0.24

Confidence interval

level

95%

sides

2-sided

lower limit

-0.37

upper limit

-0.11

Variability estimate

Standard error of the mean

Dispersion value

0.07

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 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

348

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[45]

Method

MMRM

Parameter type

MMRM

Point estimate

-0.26

Confidence interval

level

95%

sides

2-sided

lower limit

-0.41

upper limit

-0.12

Variability estimate

Standard error of the mean

Dispersion value

0.07

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 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

349

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.004 ^[46]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-0.21

Confidence interval

level

95%

sides

2-sided

lower limit

-0.35

upper limit

-0.06

Variability estimate

Standard error of the mean

Dispersion value

0.07

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 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

348

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

-0.13

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 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

349

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.002 ^[48]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-0.23

Confidence interval

level

95%

sides

2-sided

lower limit

-0.37

upper limit

-0.08

Variability estimate

Standard error of the mean

Dispersion value

0.07

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 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

348

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[49]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-0.27

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
[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 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

349

Analysis specification

Pre-specified

Analysis type

P-value

= 0.002 ^[50]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-0.24

Confidence interval

level

95%

sides

2-sided

lower limit

-0.4

upper limit

-0.09

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.

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

Top of page

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 participant 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. APD: 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	175	173	174
Units: Percent change
least squares mean (standard error)
Week 1	-16.63 ( 2.31 )	-32.15 ( 2.34 )	-28.84 ( 2.35 )
Week 2	-25.08 ( 2.50 )	-42.37 ( 2.55 )	-43.37 ( 2.54 )
Week 3	-28.81 ( 2.54 )	-46.94 ( 2.59 )	-50.00 ( 2.57 )
Week 4	-30.59 ( 2.67 )	-47.34 ( 2.72 )	-51.65 ( 2.69 )
Week 5	-32.55 ( 2.65 )	-50.12 ( 2.71 )	-54.33 ( 2.67 )
Week 6	-33.35 ( 2.72 )	-51.74 ( 2.78 )	-57.18 ( 2.73 )
Week 7	-34.85 ( 2.86 )	-53.14 ( 2.93 )	-56.26 ( 2.85 )
Week 8	-35.71 ( 2.83 )	-55.88 ( 2.90 )	-56.89 ( 2.83 )
Week 9	-39.64 ( 2.87 )	-56.31 ( 2.93 )	-58.54 ( 2.85 )
Week 10	-39.51 ( 2.81 )	-57.39 ( 2.87 )	-59.01 ( 2.79 )
Week 11	-38.05 ( 2.84 )	-58.37 ( 2.90 )	-60.18 ( 2.82 )
Week 12	-37.06 ( 2.89 )	-57.13 ( 2.95 )	-61.24 ( 2.86 )

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

348

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[51]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-15.52

Confidence interval

level

95%

sides

2-sided

lower limit

-21.99

upper limit

-9.06

Variability estimate

Standard error of the mean

Dispersion value

3.29

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.

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

349

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[52]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-12.22

Confidence interval

level

95%

sides

2-sided

lower limit

-18.69

upper limit

-5.74

Variability estimate

Standard error of the mean

Dispersion value

3.3

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 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

348

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[53]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-17.3

Confidence interval

level

95%

sides

2-sided

lower limit

-24.32

upper limit

-10.27

Variability estimate

Standard error of the mean

Dispersion value

3.57

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 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

349

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[54]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-18.29

Confidence interval

level

95%

sides

2-sided

lower limit

-25.3

upper limit

-11.29

Variability estimate

Standard error of the mean

Dispersion value

3.57

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 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

348

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[55]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-18.13

Confidence interval

level

95%

sides

2-sided

lower limit

-25.25

upper limit

-11

Variability estimate

Standard error of the mean

Dispersion value

3.63

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 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

349

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[56]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-21.19

Confidence interval

level

95%

sides

2-sided

lower limit

-28.29

upper limit

-14.09

Variability estimate

Standard error of the mean

Dispersion value

3.61

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 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

348

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[57]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-16.75

Confidence interval

level

95%

sides

2-sided

lower limit

-24.24

upper limit

-9.26

Variability estimate

Standard error of the mean

Dispersion value

3.81

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 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

349

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[58]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-21.05

Confidence interval

level

95%

sides

2-sided

lower limit

-28.5

upper limit

-13.61

Variability estimate

Standard error of the mean

Dispersion value

3.79

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 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

348

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[59]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-17.57

Confidence interval

level

95%

sides

2-sided

lower limit

-25.02

upper limit

-10.12

Variability estimate

Standard error of the mean

Dispersion value

3.79

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 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

349

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[60]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-21.78

Confidence interval

level

95%

sides

2-sided

lower limit

-29.18

upper limit

-14.39

Variability estimate

Standard error of the mean

Dispersion value

3.76

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 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

348

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[61]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-18.39

Confidence interval

level

95%

sides

2-sided

lower limit

-26.03

upper limit

-10.75

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 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

349

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[62]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-23.83

Confidence interval

level

95%

sides

2-sided

lower limit

-31.39

upper limit

-16.27

Variability estimate

Standard error of the mean

Dispersion value

3.85

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 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

348

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[63]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-18.29

Confidence interval

level

95%

sides

2-sided

lower limit

-26.33

upper limit

-10.25

Variability estimate

Standard error of the mean

Dispersion value

4.09

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 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

349

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[64]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-21.41

Confidence interval

level

95%

sides

2-sided

lower limit

-29.35

upper limit

-13.48

Variability estimate

Standard error of the mean

Dispersion value

4.04

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 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

348

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[65]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-20.16

Confidence interval

level

95%

sides

2-sided

lower limit

-28.14

upper limit

-12.19

Variability estimate

Standard error of the mean

Dispersion value

4.06

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 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

349

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001 ^[66]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-21.17

Confidence interval

level

95%

sides

2-sided

lower limit

-29.04

upper limit

-13.3

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 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

348

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001 ^[67]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-16.67

Confidence interval

level

95%

sides

2-sided

lower limit

-24.73

upper limit

-8.61

Variability estimate

Standard error of the mean

Dispersion value

4.1

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 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

349

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[68]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-18.89

Confidence interval

level

95%

sides

2-sided

lower limit

-26.84

upper limit

-10.94

Variability estimate

Standard error of the mean

Dispersion value

4.05

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 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

348

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[69]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-17.88

Confidence interval

level

95%

sides

2-sided

lower limit

-25.77

upper limit

-9.99

Variability estimate

Standard error of the mean

Dispersion value

4.01

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 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

349

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[70]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-19.5

Confidence interval

level

95%

sides

2-sided

lower limit

-27.28

upper limit

-11.72

Variability estimate

Standard error of the mean

Dispersion value

3.96

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 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

348

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[71]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-20.32

Confidence interval

level

95%

sides

2-sided

lower limit

-28.3

upper limit

-12.35

Variability estimate

Standard error of the mean

Dispersion value

4.06

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 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

349

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[72]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-22.14

Confidence interval

level

95%

sides

2-sided

lower limit

-30

upper limit

-14.28

Variability estimate

Standard error of the mean

Dispersion value

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 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

348

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[73]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-20.08

Confidence interval

level

95%

sides

2-sided

lower limit

-28.19

upper limit

-11.96

Variability estimate

Standard error of the mean

Dispersion value

4.13

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 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

349

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[74]

Method

MMRM

Parameter type

LSMean Difference

Point estimate

-24.18

Confidence interval

level

95%

sides

2-sided

lower limit

-32.16

upper limit

-16.2

Variability estimate

Standard error of the mean

Dispersion value

4.06

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.

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

Top of page

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 participant 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. APD: FAS Population

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	175	173	174
Units: Participants
Week 1	18	47	44
Week 2	37	64	75
Week 3	42	69	89
Week 4	49	77	94
Week 5	47	76	94
Week 6	50	78	96
Week 7	52	79	98
Week 8	52	93	87
Week 9	56	85	97
Week 10	45	84	100
Week 11	55	85	100
Week 12	52	77	99

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

348

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.001 ^[75]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.187

Confidence interval

level

95%

sides

2-sided

lower limit

1.363

upper limit

3.549

Notes
[75] - 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 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

348

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[76]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.245

Confidence interval

level

95%

sides

2-sided

lower limit

1.823

upper limit

5.999

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 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

349

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[77]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.964

Confidence interval

level

95%

sides

2-sided

lower limit

1.658

upper limit

5.497

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 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

348

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.002 ^[78]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.096

Confidence interval

level

95%

sides

2-sided

lower limit

1.326

upper limit

3.345

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 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

349

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[79]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.847

Confidence interval

level

95%

sides

2-sided

lower limit

1.786

upper limit

4.601

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 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

349

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[80]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.025

Confidence interval

level

95%

sides

2-sided

lower limit

1.947

upper limit

4.746

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 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

348

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.001 ^[81]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.061

Confidence interval

level

95%

sides

2-sided

lower limit

1.323

upper limit

3.233

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 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

349

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[82]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.333

Confidence interval

level

95%

sides

2-sided

lower limit

2.121

upper limit

5.302

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 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

348

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.002 ^[83]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.049

Confidence interval

level

95%

sides

2-sided

lower limit

1.317

upper limit

3.21

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 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

348

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001 ^[84]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.13

Confidence interval

level

95%

sides

2-sided

lower limit

1.363

upper limit

3.357

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 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

349

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[85]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.223

Confidence interval

level

95%

sides

2-sided

lower limit

2.067

upper limit

5.08

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 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

348

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.002 ^[86]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.984

Confidence interval

level

95%

sides

2-sided

lower limit

1.28

upper limit

3.097

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 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

349

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[87]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.097

Confidence interval

level

95%

sides

2-sided

lower limit

1.994

upper limit

4.858

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 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

349

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[88]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.062

Confidence interval

level

95%

sides

2-sided

lower limit

1.977

upper limit

4.788

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 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

348

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[89]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.748

Confidence interval

level

95%

sides

2-sided

lower limit

1.774

upper limit

4.294

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 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

349

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001 ^[90]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.379

Confidence interval

level

95%

sides

2-sided

lower limit

1.536

upper limit

3.712

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 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

348

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[91]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.725

Confidence interval

level

95%

sides

2-sided

lower limit

1.742

upper limit

4.306

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 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

348

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.001 ^[92]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.051

Confidence interval

level

95%

sides

2-sided

lower limit

1.329

upper limit

3.186

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 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

349

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[93]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.701

Confidence interval

level

95%

sides

2-sided

lower limit

1.75

upper limit

4.204

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 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

348

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[94]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.104

Confidence interval

level

95%

sides

2-sided

lower limit

1.363

upper limit

3.27

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 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

349

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001 ^[95]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.921

Confidence interval

level

95%

sides

2-sided

lower limit

2.505

upper limit

6.214

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 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

349

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[96]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.953

Confidence interval

level

95%

sides

2-sided

lower limit

1.912

upper limit

4.602

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 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

348

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.005 ^[97]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.894

Confidence interval

level

95%

sides

2-sided

lower limit

1.22

upper limit

2.961

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 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

349

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[98]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.156

Confidence interval

level

95%

sides

2-sided

lower limit

2.035

upper limit

4.944

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.

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

Top of page

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 participant 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. APD: FAS Population

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	175	173	174
Units: Participants
Week 1	0	0	0
Week 2	1	3	4
Week 3	1	6	5
Week 4	5	6	8
Week 5	2	10	6
Week 6	2	8	10
Week 7	2	13	13
Week 8	2	10	14
Week 9	5	15	16
Week 10	7	17	18
Week 11	10	16	19
Week 12	6	12	18

Statistical Analysis 1

Statistical analysis description

Week 2

Comparison groups

Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg

Number of subjects included in analysis

348

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.322 ^[99]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.158

Confidence interval

level

95%

sides

2-sided

lower limit

0.398

upper limit

64.304

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.

Statistical Analysis 2

Statistical analysis description

Week 2

Comparison groups

Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.225 ^[100]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.925

Confidence interval

level

95%

sides

2-sided

lower limit

0.569

upper limit

77.353

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 3

Statistical analysis description

Week 3

Comparison groups

Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg

Number of subjects included in analysis

348

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.089 ^[101]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

6.334

Confidence interval

level

95%

sides

2-sided

lower limit

1.064

upper limit

120.422

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 4

Statistical analysis description

Week 3

Comparison groups

Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.143 ^[102]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

5.026

Confidence interval

level

95%

sides

2-sided

lower limit

0.797

upper limit

96.916

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 5

Statistical analysis description

Week 4

Comparison groups

Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg

Number of subjects included in analysis

348

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.711 ^[103]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.257

Confidence interval

level

95%

sides

2-sided

lower limit

0.37

upper limit

4.468

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 6

Statistical analysis description

Week 4

Comparison groups

Double-blind Period: Placebo v Double-blind Period: Fezolinetant 45 mg

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.441 ^[104]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.57

Confidence interval

level

95%

sides

2-sided

lower limit

0.508

upper limit

5.328

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 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

348

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.032 ^[105]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

5.351

Confidence interval

level

95%

sides

2-sided

lower limit

1.383

upper limit

35.172

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 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

349

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.175 ^[106]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.059

Confidence interval

level

95%

sides

2-sided

lower limit

0.693

upper limit

21.086

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 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

348

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.071 ^[107]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

4.225

Confidence interval

level

95%

sides

2-sided

lower limit

1.039

upper limit

28.29

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 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

349

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.035 ^[108]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

5.22

Confidence interval

level

95%

sides

2-sided

lower limit

1.348

upper limit

34.323

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 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

348

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.011 ^[109]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

7.064

Confidence interval

level

95%

sides

2-sided

lower limit

1.912

upper limit

45.64

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 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

349

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.012 ^[110]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

6.949

Confidence interval

level

95%

sides

2-sided

lower limit

1.881

upper limit

44.892

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 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

348

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.032 ^[111]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

5.344

Confidence interval

level

95%

sides

2-sided

lower limit

1.381

upper limit

35.134

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 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

349

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.008 ^[112]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

7.514

Confidence interval

level

95%

sides

2-sided

lower limit

2.055

upper limit

48.354

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 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

348

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.026 ^[113]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.238

Confidence interval

level

95%

sides

2-sided

lower limit

1.222

upper limit

10.148

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 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

349

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.019 ^[114]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.438

Confidence interval

level

95%

sides

2-sided

lower limit

1.311

upper limit

10.714

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 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

348

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.037 ^[115]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.626

Confidence interval

level

95%

sides

2-sided

lower limit

1.101

upper limit

6.951

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 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

349

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.027 ^[116]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.758

Confidence interval

level

95%

sides

2-sided

lower limit

1.167

upper limit

7.263

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 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

348

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.21 ^[117]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.69

Confidence interval

level

95%

sides

2-sided

lower limit

0.753

upper limit

3.968

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 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

349

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.087 ^[118]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.01

Confidence interval

level

95%

sides

2-sided

lower limit

0.923

upper limit

4.634

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 21

Statistical analysis description

Week 12

Comparison groups

Double-blind Period: Placebo v Double-blind Period: Fezolinetant 30 mg

Number of subjects included in analysis

348

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.148 ^[119]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.1

Confidence interval

level

95%

sides

2-sided

lower limit

0.795

upper limit

6.157

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 22

Statistical analysis description

Week 12

Comparison groups

Double-blind Period: Fezolinetant 45 mg v Double-blind Period: Placebo

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.015 ^[120]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.262

Confidence interval

level

95%

sides

2-sided

lower limit

1.329

upper limit

9.194

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.

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 ^[121]

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. 99999 denotes "NA". APD: 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, 48, 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
[121] - 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: Placebo/Extension Fezolinetant 30 mg	Double-blind Placebo/Extension: Fezolinetant 45 mg	Double-blind: Fezolinetant 30 mg/Extension: Fezolinetant 30 mg	Double-blind: Fezolinetant 45 mg/Extension: Fezolinetant 45 mg
Number of subjects analysed	160	68	70	150	160
Units: Participants
Week 4: Much better (N=160,0,1,150,160)	32	0	1	50	72
Week 4: Moderately better (N=160,0,1,150,160)	21	0	0	33	24
Week 4: A little better (N=160,0,1,150,160)	44	0	0	42	35
Week 4: No change (N=160,0,1,150,160)	55	0	0	23	28
Week 4: A little worse (N=160,0,1,150,160)	1	0	0	1	0
Week 4: Moderately worse (N=160,0,1,150,160)	1	0	0	1	1
Week 4: Much worse (N=160,0,1,150,160)	6	0	0	0	0
Week 12: Much better (N=149,68,70,136,157)	35	31	44	50	74
Week 12: Moderately better (N=149,68,70,136,157)	24	14	16	24	30
Week 12: A little better (N=149,68,70,136,157)	40	16	8	41	35
Week 12: No change (N=149,68,70,136,157)	37	4	2	19	11
Week 12: A little worse (N=149,68,70,136,157)	6	1	0	1	2
Week 12: Moderately worse (N=149,68,70,136,157)	4	2	0	1	4
Week 12: Much worse (N=149,68,70,149,136)	3	0	0	0	1
Week 16: Much better (N=0,1,0,5,4)	99999	0	99999	1	2
Week 16: Moderately better (N=0,1,0,5,4)	99999	0	99999	2	1
Week 16: A little better (N=0,1,0,5,4)	99999	1	99999	1	1
Week 16: No change (N=0,1,0,5,4)	99999	0	99999	1	0
Week 16: A little worse (N=0,1,0,5,4)	99999	0	99999	0	0
Week 16: Moderately worse (N=0,1,0,5,4)	99999	0	99999	0	0
Week 16: Much worse (N=0,1,0,5,4)	99999	0	99999	0	0
Week 20: Much better (N=0,0,0,3,4)	99999	99999	99999	1	1
Week 20: Moderately better (N=0,0,0,3,4)	99999	99999	99999	1	0
Week 20: A little better (N=0,0,0,3,4)	99999	99999	99999	0	2
Week 20: No change (N=0,0,0,3,4)	99999	99999	99999	1	1
Week 20: A little worse (N=0,0,0,3,4)	99999	99999	99999	0	0
Week 20: Moderately worse (N=0,0,0,3,4)	99999	99999	99999	0	0
Week 20: Much worse (N=0,0,0,3,4)	99999	99999	99999	0	0
Week 24: Much better (N=0,0,0,127,148)	99999	99999	99999	55	81
Week 24: Moderately better (N=0,0,0,127,148)	99999	99999	99999	27	30
Week 24: A little better (N=0,0,0,127,148)	99999	99999	99999	34	27
Week 24: No change (N=0,0,0,127,148)	99999	99999	99999	10	6
Week 24: A little worse (N=0,0,0,127,148)	99999	99999	99999	0	1
Week 24: Moderately worse (N=0,0,0,127,148)	99999	99999	99999	1	2
Week 24: Much worse (N=0,0,0,127,148)	99999	99999	99999	0	1
Week 28: Much better (N=0,0,0,1,1)	99999	99999	99999	0	1
Week 28: Moderately better (N=0,0,0,1,1)	99999	99999	99999	0	0
Week 28: A little better (N=0,0,0,1,1)	99999	99999	99999	0	0
Week 28: No change (N=0,0,0,1,1)	99999	99999	99999	0	0
Week 28: A little worse (N=0,0,0,1,1)	99999	99999	99999	0	0
Week 28: Moderately worse (N=0,0,0,1,1)	99999	99999	99999	0	0
Week 28: Much worse (N=0,0,0,1,1)	99999	99999	99999	0	0
Week 32: Much better (N=0,0,0,0,1)	99999	99999	99999	99999	0
Week 32: Moderately better (N=0,0,0,0,1)	99999	99999	99999	99999	1
Week 32: A little better (N=0,0,0,0,1)	99999	99999	99999	99999	0
Week 32: No change (N=0,0,0,0,1)	99999	99999	99999	99999	0
Week 32: A little worse (N=0,0,0,0,1)	99999	99999	99999	99999	0
Week 32: Moderately worse (N=0,0,0,0,1)	99999	99999	99999	99999	0
Week 32: Much worse (N=0,0,0,0,1)	99999	99999	99999	99999	0
Week 36: Much better (N=0,1,0,0,1)	99999	0	99999	0	0
Week 36: Moderately better (N=0,1,0,0,1)	99999	1	99999	99999	1
Week 36: A little better (N=0,1,0,0,1)	99999	0	99999	99999	0
Week 36: No change (N=0,1,0,0,1)	99999	0	99999	99999	0
Week 36: A little worse (N=0,1,0,0,1)	99999	0	99999	99999	0
Week 36: Moderately worse (N=0,1,0,0,1)	99999	0	99999	99999	0
Week 36: Much worse (N=0,1,0,0,1)	99999	0	99999	99999	0
Week 40: Much better (N=0,55,63,2,0)	99999	33	39	0	99999
Week 40: Moderately better (N=0,55,63,2,0)	99999	8	12	2	99999
Week 40: A little better (N=0,55,63,2,0)	99999	6	10	0	99999
Week 40: No change (N=0,55,63,2,0)	99999	6	1	0	99999
Week 40: A little worse (N=0,55,63,2,0)	99999	2	1	0	99999
Week 40: Moderately worse (N=0,55,63,2,0)	99999	0	0	0	99999
Week 40: Much worse (N=0,55,63,2,0)	99999	0	0	0	99999
Week 48: Much better (N=0,0,0,2,0)	99999	99999	99999	0	99999
Week 48: Moderately better (N=0,0,0,2,0)	99999	99999	99999	1	99999
Week 48: A little better (N=0,0,0,2,0)	99999	99999	99999	1	99999
Week 48: No change (N=0,0,0,2,0)	99999	99999	99999	0	99999
Week 48: A little worse (N=0,0,0,2,0)	99999	99999	99999	0	99999
Week 48: Moderately worse (N=0,0,0,2,0)	99999	99999	99999	0	99999
Week 48: Much worse (N=0,0,0,2,0)	99999	99999	99999	0	99999
Week 52: Much better (N=0,0,0,111,127)	99999	99999	99999	56	71
Week 52: Moderately better (N=0,0,0,111,127)	99999	99999	99999	26	30
Week 52: A little better (N=0,0,0,111,127)	99999	99999	99999	23	15
Week 52: No change (N=0,0,0,111,127)	99999	99999	99999	6	8
Week 52: A little worse (N=0,0,0,111,127)	99999	99999	99999	0	1
Week 52: Moderately worse (N=0,0,0,111,127)	99999	99999	99999	0	1
Week 52: Much worse (N=0,0,0,111,127)	99999	99999	99999	0	1

No statistical analyses for this end point

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 participant 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. APD: 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/Fezolinetanat 30 mg and Placebo/Fezolinetant 45 mg)

End point values	Double-blind: Placebo/Extension Fezolinetant 30 mg	Double-blind Placebo/Extension: Fezolinetant 45 mg	Double-blind: Fezolinetant 30 mg/Extension: Fezolinetant 30 mg	Double-blind: Fezolinetant 45 mg/Extension: Fezolinetant 45 mg
Number of subjects analysed	60	62	121	138
Units: VMS per day
arithmetic mean (standard deviation)	-6.89 ( 3.67 )	-7.32 ( 4.53 )	-7.15 ( 6.02 )	-7.32 ( 4.58 )

No statistical analyses for this end point

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

Top of page

End point title

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

End point description

End point type

Secondary

End point timeframe

Baseline and 24 weeks of fezolinetant exposure (week 36 for arms Placebo/Fezolinetanat 30 mg and Placebo/Fezolinetant 45 mg)

End point values	Double-blind: Placebo/Extension Fezolinetant 30 mg	Double-blind Placebo/Extension: Fezolinetant 45 mg	Double-blind: Fezolinetant 30 mg/Extension: Fezolinetant 30 mg	Double-blind: Fezolinetant 45 mg/Extension: Fezolinetant 45 mg
Number of subjects analysed	60	62	121	138
Units: Score on a scale
arithmetic mean (standard deviation)	-0.78 ( 0.80 )	-0.76 ( 0.89 )	-0.75 ( 0.82 )	-0.77 ( 0.90 )

No statistical analyses for this end point

Secondary: Number of Participants With Adverse Events

Top of page

End point title

Number of Participants With Adverse Events ^[122]

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)

Notes
[122] - 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: Placebo/Extension Fezolinetant 30 mg	Double-blind Placebo/Extension: Fezolinetant 45 mg	Double-blind: Fezolinetant 30 mg/Extension: Fezolinetant 30 mg	Double-blind: Fezolinetant 45 mg/Extension: Fezolinetant 45 mg
Number of subjects analysed	175	76	76	174	173
Units: Participants
TEAE	78	48	37	108	115
Drug-Related TEAE	22	6	2	20	21
Serious TEAE	1	3	2	7	8
Drug-Related Serious TEAE	0	0	0	2	0
TEAE Leading to Death	0	0	0	0	0
Drug-Related TEAE Leading to Death	0	0	0	0	0
TEAE Leading to Withdrawal of treatment (trt)	9	2	1	13	8
Drug-Related TEAE Leading to Withdrawal of trt	7	0	1	7	5
Death	0	0	0	0	0

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

From first dose date up to 21 days after last dose (up to 55 weeks)

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

v23.0

Reporting group title

Double-blind Period: Placebo

Reporting group description

Participants received fezolinetant matching placebo (two fezolinetant matching placebo tablets) 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

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: Fezolinetant 45 mg/Extension: Fezolinetant 45 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

Placebo/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: Fezolinetant 45 mg/Extension: Fezolinetant 45 mg	Placebo/Fezolinetant 45 mg
Total subjects affected by serious adverse events
subjects affected / exposed	1 / 175 (0.57%)	7 / 174 (4.02%)	8 / 173 (4.62%)	3 / 76 (3.95%)	2 / 76 (2.63%)
number of deaths (all causes)	0	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0	0
Investigations
Blood pressure increased
subjects affected / exposed	0 / 175 (0.00%)	0 / 174 (0.00%)	1 / 173 (0.58%)	0 / 76 (0.00%)	0 / 76 (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
Liver function test increased
subjects affected / exposed	0 / 175 (0.00%)	1 / 174 (0.57%)	0 / 173 (0.00%)	1 / 76 (1.32%)	0 / 76 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Transaminases increased
subjects affected / exposed	0 / 175 (0.00%)	1 / 174 (0.57%)	0 / 173 (0.00%)	0 / 76 (0.00%)	0 / 76 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Apocrine breast carcinoma
subjects affected / exposed	0 / 175 (0.00%)	0 / 174 (0.00%)	0 / 173 (0.00%)	0 / 76 (0.00%)	1 / 76 (1.32%)
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
Benign lung neoplasm
subjects affected / exposed	0 / 175 (0.00%)	0 / 174 (0.00%)	1 / 173 (0.58%)	0 / 76 (0.00%)	0 / 76 (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
Haemangioma of liver
subjects affected / exposed	0 / 175 (0.00%)	0 / 174 (0.00%)	1 / 173 (0.58%)	0 / 76 (0.00%)	0 / 76 (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
Lung neoplasm
subjects affected / exposed	0 / 175 (0.00%)	0 / 174 (0.00%)	1 / 173 (0.58%)	0 / 76 (0.00%)	0 / 76 (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
Squamous cell carcinoma of skin
subjects affected / exposed	0 / 175 (0.00%)	0 / 174 (0.00%)	0 / 173 (0.00%)	1 / 76 (1.32%)	0 / 76 (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
Injury, poisoning and procedural complications
Ankle fracture
subjects affected / exposed	0 / 175 (0.00%)	1 / 174 (0.57%)	0 / 173 (0.00%)	0 / 76 (0.00%)	0 / 76 (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
Foot fracture
subjects affected / exposed	0 / 175 (0.00%)	0 / 174 (0.00%)	0 / 173 (0.00%)	1 / 76 (1.32%)	0 / 76 (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
Vascular disorders
Varicose vein
subjects affected / exposed	0 / 175 (0.00%)	0 / 174 (0.00%)	1 / 173 (0.58%)	0 / 76 (0.00%)	0 / 76 (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
Nervous system disorders
Paraesthesia
subjects affected / exposed	0 / 175 (0.00%)	0 / 174 (0.00%)	1 / 173 (0.58%)	0 / 76 (0.00%)	0 / 76 (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
General disorders and administration site conditions
Chest pain
subjects affected / exposed	0 / 175 (0.00%)	0 / 174 (0.00%)	1 / 173 (0.58%)	0 / 76 (0.00%)	0 / 76 (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
Reproductive system and breast disorders
Pelvic pain
subjects affected / exposed	0 / 175 (0.00%)	0 / 174 (0.00%)	0 / 173 (0.00%)	0 / 76 (0.00%)	1 / 76 (1.32%)
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
Uterine haemorrhage
subjects affected / exposed	0 / 175 (0.00%)	1 / 174 (0.57%)	0 / 173 (0.00%)	0 / 76 (0.00%)	0 / 76 (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
Hepatobiliary disorders
Cholelithiasis
subjects affected / exposed	1 / 175 (0.57%)	0 / 174 (0.00%)	1 / 173 (0.58%)	0 / 76 (0.00%)	0 / 76 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Anxiety
subjects affected / exposed	0 / 175 (0.00%)	1 / 174 (0.57%)	0 / 173 (0.00%)	0 / 76 (0.00%)	0 / 76 (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
Renal and urinary disorders
Renal colic
subjects affected / exposed	0 / 175 (0.00%)	0 / 174 (0.00%)	1 / 173 (0.58%)	0 / 76 (0.00%)	0 / 76 (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
Ureteric stenosis
subjects affected / exposed	0 / 175 (0.00%)	0 / 174 (0.00%)	1 / 173 (0.58%)	0 / 76 (0.00%)	0 / 76 (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
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
subjects affected / exposed	0 / 175 (0.00%)	1 / 174 (0.57%)	0 / 173 (0.00%)	0 / 76 (0.00%)	0 / 76 (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
Rhabdomyolysis
subjects affected / exposed	0 / 175 (0.00%)	1 / 174 (0.57%)	0 / 173 (0.00%)	0 / 76 (0.00%)	0 / 76 (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
Infections and infestations
COVID-19 pneumonia
subjects affected / exposed	0 / 175 (0.00%)	0 / 174 (0.00%)	1 / 173 (0.58%)	0 / 76 (0.00%)	0 / 76 (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

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: Fezolinetant 45 mg/Extension: Fezolinetant 45 mg	Placebo/Fezolinetant 45 mg
Total subjects affected by non serious adverse events
subjects affected / exposed	24 / 175 (13.71%)	38 / 174 (21.84%)	45 / 173 (26.01%)	18 / 76 (23.68%)	14 / 76 (18.42%)
Investigations
Alanine aminotransferase increased
subjects affected / exposed	4 / 175 (2.29%)	8 / 174 (4.60%)	10 / 173 (5.78%)	2 / 76 (2.63%)	2 / 76 (2.63%)
occurrences all number	4	9	13	2	2
Blood alkaline phosphatase increased
subjects affected / exposed	6 / 175 (3.43%)	6 / 174 (3.45%)	5 / 173 (2.89%)	5 / 76 (6.58%)	1 / 76 (1.32%)
occurrences all number	6	6	8	11	1
Blood glucose increased
subjects affected / exposed	0 / 175 (0.00%)	10 / 174 (5.75%)	8 / 173 (4.62%)	2 / 76 (2.63%)	0 / 76 (0.00%)
occurrences all number	0	15	14	4	0
Gamma-glutamyltransferase increased
subjects affected / exposed	4 / 175 (2.29%)	6 / 174 (3.45%)	7 / 173 (4.05%)	4 / 76 (5.26%)	0 / 76 (0.00%)
occurrences all number	4	8	12	4	0
Nervous system disorders
Headache
subjects affected / exposed	13 / 175 (7.43%)	11 / 174 (6.32%)	14 / 173 (8.09%)	3 / 76 (3.95%)	5 / 76 (6.58%)
occurrences all number	14	17	15	5	11
Infections and infestations
COVID-19
subjects affected / exposed	0 / 175 (0.00%)	9 / 174 (5.17%)	11 / 173 (6.36%)	4 / 76 (5.26%)	6 / 76 (7.89%)
occurrences all number	0	9	11	4	6
Urinary tract infection
subjects affected / exposed	3 / 175 (1.71%)	3 / 174 (1.72%)	9 / 173 (5.20%)	2 / 76 (2.63%)	1 / 76 (1.32%)
occurrences all number	3	6	9	2	2

More information

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Were there any global substantial amendments to the protocol? Yes

17 May 2019

The study title was updated to convey that the second phase of the study was a non-controlled extension period. The number of participants to be enrolled was increased from 300 to 450, and the sample size justification parameters were updated to reflect a possible 20% discontinuation rate instead of a 32% rate. An additional treatment arm was added to include a 45 mg dose of fezolinetant. The schedule of assessments was updated to include a mammogram at week 52/end of treatment/early discontinuation and an endometrial biopsy following study discontinuation. The screening serology panel was updated to include testing for antibody against hepatitis B antigen and antibody to hepatitis B core antigen. The dose rationale was 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 was increased to within 12 months of trial enrollment. The schedule of assessments was updated to include 2 additional study visits (2b and 5b). The schedule of assessments and pharmacokinetics assessment sections were updated to include the addition of blood draws for pharmacokinetic analysis in participants with a signal of elevated transaminases who were returning for a repeat hepatic abnormality testing blood draw. Details were added for the reporting of drug-induced liver damage and it was clarified that such events were to be characterized as serious adverse events. The statistical analysis was updated to accommodate inclusion of a second dosing cohort.

01 Jul 2020

Inclusion criterion 4 was updated to remove with or without hysterectomy from the bilateral oophorectomy screening criteria. Inclusion criteria 8 and 10 were aligned to account for the exclusion of participants who had a hysterectomy. Inclusion criterion 9 was updated to specify that the endometrial biopsy obtained at screening must have been considered evaluable; this criterion was now required for all participants. Alternate measures that may be implemented due to site closures related to the COVID-19 pandemic were added to the protocol. These included telemedicine conferences (by telephone), home healthcare services and laboratory assessments performed at local laboratories. It was noted that participants who screen failed due to a COVID-19 pandemic study suspension and have had an evaluable endometrial biopsy would not require a repeat biopsy if they rescreened. Exclusion criteria 6 and 7 were updated so that they applied to all participants, not just participants with a uterus, and the exception for endometrial thickness less than 4 mm was removed from exclusion criterion 7. Exclusion criterion 20 was added to exclude participants who had partial or full hysterectomies. Language was added to specify that the screening endometrial biopsy must have been evaluable. Retest biopsies were only to be performed for insufficient material or unevaluable biopsies, and a maximum of 1 retest biopsy during screening was allowed. It was noted that participants would be allowed into the study based on the primary endometrial result/diagnosis, but a second and tertiary diagnosis would also be reported.

01 Jul 2020

Adverse events (AEs) of abuse liability, depression, wakefulness and effect on memory were added to the protocol as AEs of special interest. AEs of liver test elevation were clarified. Category 2 results of secondary or tertiary screening endometrial biopsy diagnosis were added to the list of reasons for participant discontinuation. The exploratory endpoint of “Mean score on the Patient Global Impression of Change (PGI-C) in VMS from baseline to each visit” was re-categorized as a secondary endpoint. Sections 7.4.2.2 Secondary Endpoints and 7.4.3 Exploratory Endpoints were updated to move the PGI-C analysis to Section 7.4.2.2. Language was added to instruct sites about daily diary compliance.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Secondary: Number of Participants With Adverse Events

Secondary: Number of Participants With Adverse Events

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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