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Clinical Trial Results:
Pilot/Phase IIa Trial to Investigate the Effect of ESN364 in Early Postmenopausal Women Suffering From Hot Flashes

Summary
EudraCT number	2015-002578-20
Trial protocol	BE
Global end of trial date	06 Oct 2016

Results information
Results version number	v2(current)
This version publication date	18 Nov 2023
First version publication date	15 Nov 2017
Other versions	v1
Version creation reason

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

ESN364-HF-204

ISRCTN number

US NCT number

NCT05419908

WHO universal trial number (UTN)

Sponsor organisation name

Ogeda S.A.

Sponsor organisation address

47 Rue Adrienne Bolland, Gosselies, Belgium, 6047

Public contact

Clinical Trial Disclosure, Ogeda S.A., astellas.resultsdisclosure@astellas.com

Scientific contact

Clinical Trial Disclosure, Ogeda S.A., 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

06 Oct 2016

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

06 Oct 2016

Was the trial ended prematurely?

Main objective of the trial

The primary objective of the study was to evaluate the effect of ESN364 on the severity and frequency of hot flashes (HF) in early postmenopausal women suffering from HF, in terms of changes in weekly Hot Flash Score (HFS) from baseline to Week 12.

Protection of trial subjects

This study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and the International Conference on Harmonization (ICH) Note for Guidance on Good Clinical Practice (GCP) (CPMP/ICH/135/95) and with applicable local requirements.

Background therapy

Evidence for comparator

Actual start date of recruitment

21 Sep 2015

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Belgium: 87

Worldwide total number of subjects

EEA total number of subjects

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)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Postmenopausal women participants between 40 to 65 years of age who had hot flashes (HF) and who met the inclusion criteria and none of the exclusion criteria were enrolled in this study.

Screening details

Prior to randomization, participants had a screening period during which a minimum 7-day collection of baseline HF frequency and severity assessments were performed.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Carer, Data analyst, Assessor

Are arms mutually exclusive

Yes

Placebo

Arm description

Participants received fezolinetant matching placebo capsules orally, twice daily (BID) for a period of 12 weeks.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Participants received 90 mg of placebo orally twice a day for 12 weeks.

Fezolinetant

Arm description

Participants received 90 milligrams (mg) fezolinetant capsules orally, BID for a period of 12 weeks.

Arm type

Experimental

Investigational medicinal product name

ESN364

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Participants received 90 mg of ESN364 orally twice a day for 12 weeks.

Number of subjects in period 1	Placebo	Fezolinetant
Started	44	43
Completed	40	40
Not completed	4	3
Consent withdrawn by subject	2	-
Miscellaneous	1	1
Subject didn't Fulfill all Eligibility Criteria	1	-
Serious Adverse Event	-	2

Baseline characteristics

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Reporting group title

Placebo

Reporting group description

Participants received fezolinetant matching placebo capsules orally, twice daily (BID) for a period of 12 weeks.

Reporting group title

Fezolinetant

Reporting group description

Participants received 90 milligrams (mg) fezolinetant capsules orally, BID for a period of 12 weeks.

Reporting group values	Placebo	Fezolinetant	Total
Number of subjects	44	43	87
Age categorical
Units: Subjects
Age Continuous
Units: Years
arithmetic mean (standard deviation)	53.7 ( 4.25 )	53.3 ( 4.03 )	-
Sex: Female, Male
Units: Subjects
Female	44	43	87
Male	0	0	0
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	0	0	0
Asian	0	0	0
Native Hawaiian or Other Pacific Islander	0	0	0
Black or African American	0	0	0
White	44	42	86
More than one race	0	1	1
Unknown or Not Reported	0	0	0
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	1	1	2
Not Hispanic or Latino	42	42	84
Unknown or Not Reported	1	0	1
Weekly General Hot Flash Score
The HF Score was calculated as follows (number of mild HF/day × 1) + (number of moderate HF/day × 2) + (number of severe HF/day × 3). Higher scores indicate worse symptoms. There is no maximum score since the score was participant-dependent for both number and severity.
Units: Score on a scale
arithmetic mean (standard deviation)	25.76 ( 10.26 )	28.76 ( 13.39 )	-

End points

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Reporting group title

Placebo

Reporting group description

Participants received fezolinetant matching placebo capsules orally, twice daily (BID) for a period of 12 weeks.

Reporting group title

Fezolinetant

Reporting group description

Participants received 90 milligrams (mg) fezolinetant capsules orally, BID for a period of 12 weeks.

Primary: Change From Baseline to Week 12 in The Weekly General Hot Flash Score

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End point title

Change From Baseline to Week 12 in The Weekly General Hot Flash Score

End point description

The HF score (based on severity and frequency) was calculated as: (number of mild HF/day × 1) + (number of moderate HF/day × 2) + (number of severe HF/day × 3) Severity of HFs is clinically defined as follows: Mild: sensation of heat without sweating/dampness. If at night, participant didn’t wake up but later notices damp sheets or clothing. Moderate: Sensation of heat with sweating/dampness, but was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets. Severe: Sensation of intense heat with sweating, causing disruption of activity. If at night, participant woke up hot and was sweating and needed to take action (e.g., removing layers of clothes, open the window, or get out of bed). Higher scores indicate worse symptoms. There is no maximum score since the score was participant dependent for both number and severity.

End point type

Primary

End point timeframe

Baseline and Week 12 Intent-to-treat (ITT) population (included all randomized participants who received at least one dose of the study medication and who had post-baseline efficacy data) with available data at specified time point.

End point values	Placebo	Fezolinetant
Number of subjects analysed	40	40
Units: score on a scale
arithmetic mean (confidence interval 95%)	-12.19 (-16.55 to -7.83)	-26.51 (-30.83 to -22.18)

Statisticial Analysis 1

Statistical analysis description

analysis of covariance (ANCOVA)

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[1]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-12.34

Confidence interval

level

95%

sides

2-sided

lower limit

-16.89

upper limit

-7.79

Notes
[1] - Least square (LS) mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline weekly hot flash score as covariate. P-value of the t-statistic testing whether there is a treatment difference.

Secondary: Change From Baseline in The Weekly Hot Flash Severity Score at Weeks 4, 8 and 12 (Method 1)

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End point title

Change From Baseline in The Weekly Hot Flash Severity Score at Weeks 4, 8 and 12 (Method 1)

End point description

HF Severity Score by method 1 takes into account the number and severity of moderate and severe HF occurred during a given time period & was calculated as follows HF Severity score = [(No. of moderate HF/day × 2) + (No. of severe HF/day × 3)]/(number of moderate HF + No. of severe HF). Severity of HFs was clinically defined as follows: Moderate: Sensation of heat with sweating/dampness, but was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets. Severe: Sensation of intense heat with sweating, causing disruption of activity. If at night, participant woke up hot & was sweating and needed to take action (e.g. removing layers of clothes, open the window, or get out of bed). Higher scores indicate worse symptoms. There is no maximum score since the score was participant-dependent for both number & severity. ITT population with available data at specified time point.

End point type

Secondary

End point timeframe

Baseline and weeks 4, 8 and 12

End point values	Placebo	Fezolinetant
Number of subjects analysed	44	41
Units: score on a scale
arithmetic mean (confidence interval 95%)
Week 4 (n=44, n=41)	-0.294 (-0.473 to -0.116)	-1.428 (-1.718 to -1.138)
Week 8 (n=41, n-40)	-0.608 (-0.899 to -0.318)	-1.557 (-1.858 to -1.257)
Week 12 (n=40, n=40)	-0.534 (-0.798 to -0.270)	-1.656 (-1.937 to -1.376)

Statistical Analysis 1

Statistical analysis description

Week 4

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[2]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-1.134

Confidence interval

level

95%

sides

2-sided

lower limit

-1.466

upper limit

-0.802

Notes
[2] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline weekly hot flash score as covariate. P-value of the t-statistic testing whether there is a treatment difference.

Statistical Analysis 3

Statistical analysis description

Week 12

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[3]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-1.122

Confidence interval

level

95%

sides

2-sided

lower limit

-1.504

upper limit

-0.741

Notes
[3] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline weekly hot flash score as covariate. P-value of the t-statistic testing whether there is a treatment difference.

Statistical Analysis 2

Statistical analysis description

Week 8

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[4]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-0.948

Confidence interval

level

95%

sides

2-sided

lower limit

-1.362

upper limit

-0.535

Notes
[4] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline weekly hot flash score as covariate. P-value of the t-statistic testing whether there is a treatment difference.

Secondary: Change From Baseline in The Weekly Hot Flash Severity Score at Weeks 4, 8 and 12 (Method 2)

Top of page

End point title

Change From Baseline in The Weekly Hot Flash Severity Score at Weeks 4, 8 and 12 (Method 2)

End point description

The HF Severity Score by method 2 takes into account moderate and severe HF during a given time period and was calculated as follows HF Severity score = [(number of moderate HF/day × 2) + (number of severe HF/day × 3)] The severity of HFs was clinically defined as follows: - Moderate: Sensation of heat with sweating/dampness, but was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets. - Severe: Sensation of intense heat with sweating, causing disruption of activity. If at night, participant woke up hot and was sweating and needed to take action (e.g., removing layers of clothes, open the window, or get out of bed). Higher scores indicate worse symptoms. There is no maximum score since the score was participant-dependent for both number and severity. ITT population with available data at specified time point.

End point type

Secondary

End point timeframe

Baseline and weeks 4, 8 and 12

End point values	Placebo	Fezolinetant
Number of subjects analysed	44	41
Units: score on a scale
arithmetic mean (confidence interval 95%)
Week 4 (n=44, n=41)	-9.55 (-12.73 to -6.36)	-25.26 (-29.64 to -20.89)
Week 8 (n=41. n=41)	-11.91 (-15.72 to -8.10)	-25.71 (-30.15 to -21.27)
Week 12 (n=40, n=40)	-12.14 (-16.62 to -7.65)	-26.61 (-31.06 to -22.17)

Statistical Analysis 1

Statistical analysis description

Week 4

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[5]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-13.28

Confidence interval

level

95%

sides

2-sided

lower limit

-17.02

upper limit

-9.54

Notes
[5] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline weekly hot flash score as covariate. P-value of the t-statistic testing whether there is a treatment difference.

Statistical Analysis 3

Statistical analysis description

Week 12

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[6]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-12.42

Confidence interval

level

95%

sides

2-sided

lower limit

-17

upper limit

-7.83

Notes
[6] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline weekly hot flash score as covariate. P-value of the t-statistic testing whether there is a treatment difference.

Statistical Analysis 2

Statistical analysis description

Week 8

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[7]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-11.78

Confidence interval

level

95%

sides

2-sided

lower limit

-16.3

upper limit

-7.27

Notes
[7] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline weekly hot flash score as covariate. P-value of the t-statistic testing whether there is a treatment difference.

Secondary: Change From Baseline in The Weekly Mild, Moderate and Severe Hot Flash Frequency at Weeks 4, 8 and 12

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End point title

Change From Baseline in The Weekly Mild, Moderate and Severe Hot Flash Frequency at Weeks 4, 8 and 12

End point description

The weekly HF frequency was calculated as number of mild, moderate and severe hot flashes over the week. - Mild: sensation of heat without sweating/dampness. If at night, participant didn’t wake up but later notices damp sheets or clothing. - Moderate: Sensation of heat with sweating/dampness, but was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets. - Severe: Sensation of intense heat with sweating, causing disruption of activity. If at night, participant woke up hot and was sweating and needed to take action (e.g., removing layers of clothes, open the window, or get out of bed). Higher number of hot flashes is worse. ITT population with available data at specified time point.

End point type

Secondary

End point timeframe

Baseline and weeks 4, 8 and 12

End point values	Placebo	Fezolinetant
Number of subjects analysed	44	41
Units: HF's per day
arithmetic mean (confidence interval 95%)
Week 4 (n=44, n=41)	-26.4 (-35.2 to -17.5)	-72.3 (-82.7 to -61.8)
Week 8 (n=41, n=40)	-32.9 (-43.2 to -22.7)	-73.3 (-83.8 to -62.8)
Week 12 (n=40, n=40)	-35.6 (-46.7 to -24.5)	-75.3 (-86.4 to -64.3)

Statistical Analysis 1

Statistical analysis description

Week 4

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[8]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-39.8

Confidence interval

level

95%

sides

2-sided

lower limit

-50.5

upper limit

-29.1

Notes
[8] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as factor. P-value of the t-statistic testing whether there is a treatment difference.

Statistical Analysis 2

Statistical analysis description

Week 8

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[9]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-35.5

Confidence interval

level

95%

sides

2-sided

lower limit

-47.9

upper limit

-23

Notes
[9] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as factor. P-value of the t-statistic testing whether there is a treatment difference.

Statistical Analysis 3

Statistical analysis description

Week 12

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[10]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-35

Confidence interval

level

95%

sides

2-sided

lower limit

-47.9

upper limit

-22.1

Notes
[10] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as factor. P-value of the t-statistic testing whether there is a treatment difference.

Secondary: Percentage of Participants With >=70% Reduction in the Weekly Hot Flash Score From Baseline to Weeks 4, 8 and 12

Top of page

End point title

Percentage of Participants With >=70% Reduction in the Weekly Hot Flash Score From Baseline to Weeks 4, 8 and 12

End point description

HF score (based on severity and frequency) was calculated as: (No. of mild HF/day × 1) + (No. of moderate HF/day × 2) + (No. of severe HF/day × 3) Severity of HFs is clinically defined as follows: Mild: sensation of heat without sweating/dampness. If at night, participant didn’t wake up but later notices damp sheets or clothing. Moderate: Sensation of heat with sweating/dampness, but was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets. Severe: Sensation of intense heat with sweating, causing disruption of activity. If at night, participant woke up hot and was sweating and needed to take action (e.g. removing layers of clothes, open the window, or get out of bed). Higher scores indicate worse symptoms. There is no maximum score since the score was participant-dependent for both number and severity. ITT population with available data at specified time point.

End point type

Secondary

End point timeframe

Baseline and weeks 4, 8 and 12

End point values	Placebo	Fezolinetant
Number of subjects analysed	44	41
Units: percentage of participants
number (confidence interval 95%)
Week 4 (n=44, n=41)	22.7 (10.34 to 35.11)	87.8 (77.79 to 97.82)
Week 8 (n=41, n=40)	39.0 (24.09 to 53.96)	87.5 (77.25 to 97.75)
Week 12 (n=40, n=40)	42.5 (27.18 to 57.82)	95.0 (88.25 to 100.00)

Statistical Analysis 1

Statistical analysis description

Week 4

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[11]

Method

Likelihood-Ratio Chi-Square Test

Parameter type

Percentage Difference

Point estimate

65.1

Confidence interval

level

95%

sides

2-sided

lower limit

49.15

upper limit

Notes
[11] - Likelihood-ratio test based 95% confidence interval of the percentage difference.

Statistical Analysis 3

Statistical analysis description

Week 12

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[12]

Method

Likelihood-Ratio Chi-Square Test

Parameter type

Percentage Difference

Point estimate

52.5

Confidence interval

level

95%

sides

2-sided

lower limit

35.76

upper limit

69.24

Notes
[12] - Likelihood-ratio test based 95% confidence interval of the percentage difference.

Statistical Analysis 2

Statistical analysis description

Week 8

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[13]

Method

Likelihood-Ratio Chi-Square Test

Parameter type

Percentage Difference

Point estimate

48.5

Confidence interval

level

95%

sides

2-sided

lower limit

30.37

upper limit

66.59

Notes
[13] - Likelihood-ratio test based 95% confidence interval of the percentage difference.

Secondary: Percentage of Participants With >=80% Reduction in the Weekly Hot Flash Score From Baseline to Weeks 4, 8 and 12

Top of page

End point title

Percentage of Participants With >=80% Reduction in the Weekly Hot Flash Score From Baseline to Weeks 4, 8 and 12

End point description

End point type

Secondary

End point timeframe

Baseline and weeks 4, 8 and 12

End point values	Placebo	Fezolinetant
Number of subjects analysed	44	41
Units: percentage of participants
number (confidence interval 95%)
Week 4 (n=44, n=41)	9.1 (0.60 to 17.59)	78.0 (65.38 to 90.72)
Week 8 (n=41, n=40)	26.8 (13.27 to 40.39)	77.5 (64.56 to 90.44)
Week 12 (n=40, n=40)	30.0 (15.80 to 44.20)	87.5 (77.25 to 97.75)

Statistical Analysis 1

Statistical analysis description

Week 4

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001 ^[14]

Method

Likelihood-Ratio Chi-Square Test

Parameter type

Percentage Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

53.7

upper limit

84.21

Notes
[14] - Likelihood-ratio test based 95% confidence interval of the percentage difference.

Statistical Analysis 2

Statistical analysis description

Week 8

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[15]

Method

Likelihood-Ratio Chi-Square Test

Parameter type

Percentage Difference

Point estimate

50.7

Confidence interval

level

95%

sides

2-sided

lower limit

31.93

upper limit

69.42

Notes
[15] - Likelihood-ratio test based 95% confidence interval of the percentage difference

Statistical Analysis 3

Statistical analysis description

Week 12

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[16]

Method

Likelihood-Ratio Chi-Square Test

Parameter type

Percentage Difference

Point estimate

57.5

Confidence interval

level

95%

sides

2-sided

lower limit

39.99

upper limit

75.01

Notes
[16] - Likelihood-ratio test based 95% confidence interval of the percentage difference

Secondary: Percentage of Participants With >=90% Reduction in the Weekly Hot Flash Score From Baseline to Weeks 4, 8 and 12

Top of page

End point title

Percentage of Participants With >=90% Reduction in the Weekly Hot Flash Score From Baseline to Weeks 4, 8 and 12

End point description

End point type

Secondary

End point timeframe

Baseline and weeks 4, 8 and 12

End point values	Placebo	Fezolinetant
Number of subjects analysed	44	41
Units: percentage of participants
number (confidence interval 95%)
Week 4 (n=44, n=41)	6.8 (0.00 to 14.27)	61.0 (46.04 to 75.91)
Week 8 (n=41, n=40)	12.2 (2.18 to 22.21)	60.0 (44.82 to 75.18)
Week 12 (n=40, n=40)	15.0 (3.93 to 26.07)	62.5 (47.50 to 77.50)

Statistical Analysis 1

Statistical analysis description

Week 4

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[17]

Method

Likelihood-Ratio Chi-Square Test

Parameter type

Percentage Difference

Point estimate

54.2

Confidence interval

level

95%

sides

2-sided

lower limit

37.47

upper limit

70.84

Notes
[17] - Likelihood-ratio test based 95% confidence interval of the percentage difference.

Statistical Analysis 3

Statistical analysis description

Week 12

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[18]

Method

Likelihood-Ratio Chi-Square Test

Parameter type

Percentage Difference

Point estimate

47.5

Confidence interval

level

95%

sides

2-sided

lower limit

28.86

upper limit

66.14

Notes
[18] - Likelihood-ratio test based 95% confidence interval of the percentage difference.

Statistical Analysis 2

Statistical analysis description

Week 8

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[19]

Method

Likelihood-Ratio Chi-Square Test

Parameter type

Percentage Difference

Point estimate

47.8

Confidence interval

level

95%

sides

2-sided

lower limit

29.62

upper limit

65.99

Notes
[19] - Likelihood-ratio test based 95% confidence interval of the percentage difference.

Secondary: Percentage of Participants With >=50% Reduction in the Weekly Frequency of Moderate and severe HF From Baseline to Weeks 4, 8 and 12

Top of page

End point title

Percentage of Participants With >=50% Reduction in the Weekly Frequency of Moderate and severe HF From Baseline to Weeks 4, 8 and 12

End point description

The weekly HF frequency of moderate and severe HF was calculated as number of moderate and severe HF over the week. - Moderate: Sensation of heat with sweating/dampness, but was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets. - Severe: Sensation of intense heat with sweating, causing disruption of activity. If at night, participant woke up hot and was sweating and needed to take action (e.g., removing layers of clothes, open the window, or get out of bed). Higher number of HF indicates worse symptoms. ITT population with available data at specified time point.

End point type

Secondary

End point timeframe

Baseline and weeks 4, 8 and 12

End point values	Placebo	Fezolinetant
Number of subjects analysed	44	41
Units: percentage of participants
number (confidence interval 95%)
Week 4 (n=44, n=41)	45.5 (30.74 to 60.17)	95.1 (88.53 to 100.00)
Week 8 (n=41, n=40)	53.7 (38.39 to 68.92)	97.5 (92.66 to 100.00)
Week 12 (n=40, n=40)	55.0 (39.58 to 70.42)	97.5 (92.66 to 100.00)

Statistical Analysis 1

Statistical analysis description

Week 4

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[20]

Method

Likelihood-Ratio Chi-Square Test

Parameter type

Percentage Difference

Point estimate

49.7

Confidence interval

level

95%

sides

2-sided

lower limit

33.54

upper limit

65.79

Notes
[20] - Likelihood-ratio test based 95% confidence interval of the percentage difference.

Statistical Analysis 3

Statistical analysis description

Week 12

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[21]

Method

Likelihood-Ratio Chi-Square Test

Parameter type

Percentage Difference

Point estimate

42.5

Confidence interval

level

95%

sides

2-sided

lower limit

26.34

upper limit

58.66

Notes
[21] - Likelihood-ratio test based 95% confidence interval of the percentage difference.

Statistical Analysis 2

Statistical analysis description

Week 8

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[22]

Method

Likelihood-Ratio Chi-Square Test

Parameter type

Percentage Difference

Point estimate

43.8

Confidence interval

level

95%

sides

2-sided

lower limit

27.83

upper limit

59.85

Notes
[22] - Likelihood-ratio test based 95% confidence interval of the percentage difference.

Secondary: Percentage of Participants With >=70% Reduction in the Weekly Frequency of Moderate and severe HF From Baseline to Weeks 4, 8 and 12

Top of page

End point title

Percentage of Participants With >=70% Reduction in the Weekly Frequency of Moderate and severe HF From Baseline to Weeks 4, 8 and 12

End point description

End point type

Secondary

End point timeframe

Baseline and weeks 4, 8 and 12

End point values	Placebo	Fezolinetant
Number of subjects analysed	44	41
Units: percentage of participants
number (confidence interval 95%)
Week 4 (n=44, n=41)	25.0 (12.21 to 37.79)	87.8 (77.79 to 97.82)
Week 8 (n=41, n=40)	46.3 (31.08 to 61.61)	92.5 (84.34 to 100.00)
Week 12 (n=40, n=40)	40.0 (24.82 to 55.18)	97.5 (92.66 to 100.00)

Statistical Analysis 1

Statistical analysis description

Week 4

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[23]

Method

Likelihood-Ratio Chi-Square Test

Parameter type

Percentage Difference

Point estimate

62.8

Confidence interval

level

95%

sides

2-sided

lower limit

46.56

upper limit

79.05

Notes
[23] - Likelihood-ratio test based 95% confidence interval of the percentage difference.

Statistical Analysis 3

Statistical analysis description

Week 12

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[24]

Method

Likelihood-Ratio Chi-Square Test

Parameter type

Percentage Difference

Point estimate

57.5

Confidence interval

level

95%

sides

2-sided

lower limit

41.57

upper limit

73.43

Notes
[24] - Likelihood-ratio test based 95% confidence interval of the percentage difference.

Statistical Analysis 2

Statistical analysis description

Week 8

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[25]

Method

Likelihood-Ratio Chi-Square Test

Parameter type

Percentage Difference

Point estimate

46.2

Confidence interval

level

95%

sides

2-sided

lower limit

28.85

upper limit

63.47

Notes
[25] - Likelihood-ratio test based 95% confidence interval of the percentage difference.

Secondary: Percentage of Participants With >=90% Reduction in the Weekly Frequency of Moderate and severe HF From Baseline to Weeks 4, 8 and 12

Top of page

End point title

Percentage of Participants With >=90% Reduction in the Weekly Frequency of Moderate and severe HF From Baseline to Weeks 4, 8 and 12

End point description

End point type

Secondary

End point timeframe

Baseline and weeks 4, 8 and 12

End point values	Placebo	Fezolinetant
Number of subjects analysed	44	41
Units: percentage of participants
number (confidence interval 95%)
Week 4 (n=44, n=41)	6.8 (0.00 to 14.27)	68.3 (54.05 to 82.54)
Week 8 (n=41, n=40)	24.4 (11.25 to 37.54)	67.5 (52.99 to 82.01)
Week 12 (n=40, n=40)	20.0 (7.60 to 32.40)	72.5 (58.66 to 86.34)

Statistical Analysis 1

Statistical analysis description

Week 4

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[26]

Method

Likelihood-Ratio Chi-Square Test

Parameter type

Percentage Difference

Point estimate

61.5

Confidence interval

level

95%

sides

2-sided

lower limit

45.4

upper limit

77.55

Notes
[26] - Likelihood-ratio test based 95% confidence interval of the percentage difference.

Statistical Analysis 3

Statistical analysis description

Week 12

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[27]

Method

Likelihood-Ratio Chi-Square Test

Parameter type

Percentage Difference

Point estimate

52.5

Confidence interval

level

95%

sides

2-sided

lower limit

33.92

upper limit

71.08

Notes
[27] - Likelihood-ratio test based 95% confidence interval of the percentage difference.

Statistical Analysis 2

Statistical analysis description

Week 8

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[28]

Method

Likelihood-Ratio Chi-Square Test

Parameter type

Percentage Difference

Point estimate

43.1

Confidence interval

level

95%

sides

2-sided

lower limit

23.53

upper limit

62.69

Notes
[28] - Likelihood-ratio test based 95% confidence interval of the percentage difference.

Secondary: Change From Baseline in Hot Flash Related Daily Interference Scale (HFRDIS) Score at Weeks 4, 8 and 12

Top of page

End point title

Change From Baseline in Hot Flash Related Daily Interference Scale (HFRDIS) Score at Weeks 4, 8 and 12

End point description

The HFRDIS was a 10-item scale which measured a woman’s perceptions of the degree to which HF interfere with 9 daily life activities (work, social activities, leisure, sleep, mood, concentration, relations with others, sexuality, enjoying life); the 10th item measures interference with overall quality of life. This scale was modeled after items on the Brief Pain Inventory and Brief Fatigue Inventory both of which assessed the extent to which pain or fatigue interfere with daily life. Participants were asked to rate the extent to which HF had interfered with each item during the previous 4-week time interval using a 0 (do not interfere) to 10 (completely interfere) scale. Overall mean score was calculated as sum of items/number of available items. Higher score indicate a higher interference. ITT population with available data at specified time point.

End point type

Secondary

End point timeframe

Baseline and weeks 4, 8 and 12

End point values	Placebo	Fezolinetant
Number of subjects analysed	42	41
Units: score on a scale
arithmetic mean (standard deviation)
Week 4: Work (n=42, n=41)	-1.7 ( 2.93 )	-4.6 ( 2.65 )
Week 8: Work (n=39, n=39)	-2.4 ( 2.80 )	-5.0 ( 2.38 )
Week 12: Work (n=39, n=39)	-2.3 ( 2.58 )	-4.6 ( 2.68 )
Week 4: Social Activities (n=42, n=41)	-1.6 ( 2.53 )	-4.3 ( 2.48 )
Week 8: Social Activities (n=39, n=39)	-1.9 ( 2.85 )	-4.7 ( 2.37 )
Week 12: Social Activities (n=39, n=39)	-1.8 ( 2.51 )	-4.3 ( 2.35 )
Week 4: Leisure Activities (n=42, n=41)	-1.6 ( 2.63 )	-4.0 ( 2.51 )
Week 8: Leisure Activities (n=39, n=39)	-1.7 ( 2.72 )	-4.2 ( 2.50 )
Week 12: Leisure Activities (n=39, n=39)	-2.0 ( 2.52 )	-3.8 ( 3.08 )
Week 4: Sleep (n=42, n=41)	-2.5 ( 2.93 )	-5.2 ( 2.77 )
Week 8: Sleep (n=39, n=39)	-3.2 ( 3.29 )	-5.7 ( 2.37 )
Week 12: Sleep (n=39, n=39)	-3.3 ( 3.01 )	-5.8 ( 2.43 )
Week 4: Mood (n=42, n=41)	-2.3 ( 2.49 )	-4.0 ( 2.85 )
Week 8: Mood (n=39, n=39)	-2.3 ( 2.86 )	-4.4 ( 2.84 )
Week 12: Mood (n=39, n=39)	-2.5 ( 2.56 )	-4.3 ( 2.64 )
Week 4: Concentration (n=42, n=41)	-1.6 ( 2.68 )	-3.9 ( 2.57 )
Week 8: Concentration (n=39, n=39)	-1.6 ( 3.06 )	-4.1 ( 2.59 )
Week 12: Concentration (n=39, n=39)	-1.9 ( 3.17 )	-4.0 ( 2.47 )
Week 4: Relations With Others (n=42, n=41)	-2.1 ( 2.93 )	-3.3 ( 2.45 )
Week 8: Relations With Others (n=39, n=39)	-1.8 ( 3.02 )	-3.5 ( 2.70 )
Week 12: Relations With Others (n=39, n=39)	-1.8 ( 3.16 )	-3.3 ( 2.67 )
Week 4: Sexuality (n=42, n=41)	-1.9 ( 2.88 )	-3.0 ( 3.49 )
Week 8: Sexuality (n=39, n=39)	-1.8 ( 3.48 )	-3.2 ( 3.76 )
Week 12: Sexuality (n=39, n=39)	-1.7 ( 2.84 )	-3.4 ( 3.86 )
Week 4: Enjoyment of Life (n=42, n=41)	-1.6 ( 2.86 )	-3.6 ( 2.65 )
Week 8: Enjoyment of Life (n=39, n=39)	-1.5 ( 3.15 )	-3.9 ( 2.59 )
Week 12: Enjoyment of Life (n=39, n=39)	-1.6 ( 3.38 )	-3.7 ( 2.42 )
Week 4: Overall Quality of Life (n=42, n=41)	-1.4 ( 2.43 )	-3.8 ( 2.87 )
Week 8: Overall Quality of Life (n=39, n=39)	-1.5 ( 3.01 )	-4.5 ( 1.92 )
Week 12: Overall Quality of Life (n=39, n=39)	-1.6 ( 3.05 )	-4.6 ( 2.16 )
Week 4: Overall Mean Score (n=42, n=41)	-1.84 ( 1.922 )	-3.97 ( 2.141 )
Week 8: Overall Mean Score (n=39, n=39)	-1.98 ( 2.439 )	-4.33 ( 1.945 )
Week 12: Overall Mean Score (n=39, n=39)	-2.05 ( 2.326 )	-4.17 ( 2.067 )

Statistical Analysis 1

Statistical analysis description

Week 4: Work

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[29]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-2.53

Confidence interval

level

95%

sides

2-sided

lower limit

-3.45

upper limit

-1.6

Notes
[29] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline weekly HFRDIS as covariate.

Statistical Analysis 5

Statistical analysis description

Week 8: Social Activties

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[30]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-2.34

Confidence interval

level

95%

sides

2-sided

lower limit

-3.21

upper limit

-1.47

Notes
[30] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline weekly HFRDIS as covariate.

Statistical Analysis 4

Statistical analysis description

Week 4: Social Activities

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[31]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-2.33

Confidence interval

level

95%

sides

2-sided

lower limit

-3.19

upper limit

-1.46

Notes
[31] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline weekly HFRDIS as covariate.

Statistical Analysis 2

Statistical analysis description

Week 8: Work

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[32]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-2.29

Confidence interval

level

95%

sides

2-sided

lower limit

-3.15

upper limit

-1.42

Notes
[32] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline weekly HFRDIS as covariate.

Statistical Analysis 7

Statistical analysis description

Week 4: Leisure Activities

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[33]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-2.15

Confidence interval

level

95%

sides

2-sided

lower limit

-2.99

upper limit

-1.31

Notes
[33] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline weekly HFRDIS as covariate.

Statistical Analysis 8

Statistical analysis description

Week 8: Leisure Activties

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[34]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-2.37

Confidence interval

level

95%

sides

2-sided

lower limit

-3.19

upper limit

-1.55

Notes
[34] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline weekly HFRDIS as covariate.

Statistical Analysis 9

Statistical analysis description

Week 12: Leisure Activties

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.002 ^[35]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-1.64

Confidence interval

level

95%

sides

2-sided

lower limit

-2.66

upper limit

-0.62

Notes
[35] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline weekly HFRDIS as covariate.

Statistical Analysis 10

Statistical analysis description

Week 4: Sleep

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[36]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-2.93

Confidence interval

level

95%

sides

2-sided

lower limit

-4.08

upper limit

-1.78

Notes
[36] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline weekly HFRDIS as covariate.

Statistical Analysis 6

Statistical analysis description

Week 12: Social Activties

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[37]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-2.19

Confidence interval

level

95%

sides

2-sided

lower limit

-3.09

upper limit

-1.29

Notes
[37] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline weekly HFRDIS as covariate.

Statistical Analysis 3

Statistical analysis description

Week 12: Work

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[38]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-2.11

Confidence interval

level

95%

sides

2-sided

lower limit

-3.03

upper limit

-1.2

Notes
[38] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline weekly HFRDIS as covariate.

Statistical Analysis 17

Statistical analysis description

Week 8: Concentration

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[39]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-2.23

Confidence interval

level

94%

sides

2-sided

lower limit

-3.21

upper limit

-1.25

Notes
[39] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline weekly HFRDIS as covariate.

Statistical Analysis 16

Statistical analysis description

Week 4: Concentration

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[40]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-1.92

Confidence interval

level

95%

sides

2-sided

lower limit

-2.86

upper limit

-0.97

Notes
[40] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline weekly HFRDIS as covariate.

Statistical Analysis 13

Statistical analysis description

Week 4: Mood

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[41]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-1.74

Confidence interval

level

95%

sides

2-sided

lower limit

-2.67

upper limit

-0.81

Notes
[41] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline weekly HFRDIS as covariate.

Statistical Analysis 12

Statistical analysis description

Week 12: Sleep

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[42]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-2.61

Confidence interval

level

95%

sides

2-sided

lower limit

-3.67

upper limit

-1.54

Notes
[42] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline weekly HFRDIS as covariate.

Statistical Analysis 11

Statistical analysis description

Week 8: Sleep

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[43]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-2.71

Confidence interval

level

95%

sides

2-sided

lower limit

-3.86

upper limit

-1.57

Notes
[43] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline weekly HFRDIS as covariate.

Statistical Analysis 14

Statistical analysis description

Week 8: Mood

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[44]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-2.12

Confidence interval

level

95%

sides

2-sided

lower limit

-3.09

upper limit

-1.16

Notes
[44] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline weekly HFRDIS as covariate.

Statistical Analysis 15

Statistical analysis description

Week 12: Mood

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[45]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-1.79

Confidence interval

level

95%

sides

2-sided

lower limit

-2.69

upper limit

-0.88

Notes
[45] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline weekly HFRDIS as covariate.

Statistical Analysis 20

Statistical analysis description

Week 8: Relations With others

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[46]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-1.85

Confidence interval

level

95%

sides

2-sided

lower limit

-2.8

upper limit

-0.9

Notes
[46] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline weekly HFRDIS as covariate.

Statistical Analysis 18

Statistical analysis description

Week 12: Concentration

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[47]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-1.9

Confidence interval

level

95%

sides

2-sided

lower limit

-2.91

upper limit

-0.88

Notes
[47] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline weekly HFRDIS as covariate.

Statistical Analysis 22

Statistical analysis description

Week 4: Sexuality

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.081 ^[48]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-1.06

Confidence interval

level

95%

sides

2-sided

lower limit

-2.25

upper limit

0.13

Notes
[48] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline weekly HFRDIS as covariate.

Statistical Analysis 23

Statistical analysis description

Week 8: Sexuality

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.05 ^[49]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-1.4

Confidence interval

level

95%

sides

2-sided

lower limit

-2.8

upper limit

Notes
[49] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline weekly HFRDIS as covariate.

Statistical Analysis 24

Statistical analysis description

Week 12: Sexuality

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.026 ^[50]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-1.51

Confidence interval

level

95%

sides

2-sided

lower limit

-2.84

upper limit

-0.19

Notes
[50] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline weekly HFRDIS as covariate.

Statistical Analysis 25

Statistical analysis description

Week 4: Enjoyment of Life

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[51]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-1.65

Confidence interval

level

95%

sides

2-sided

lower limit

-2.51

upper limit

-0.79

Notes
[51] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline weekly HFRDIS as covariate.

Statistical Analysis 26

Statistical analysis description

Week 8: Enjoyment of Life

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[52]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-2.07

Confidence interval

level

95%

sides

2-sided

lower limit

-2.97

upper limit

-1.18

Notes
[52] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline weekly HFRDIS as covariate.

Statistical Analysis 27

Statistical analysis description

Week 12: Enjoyment of Life

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[53]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-1.83

Confidence interval

level

95%

sides

2-sided

lower limit

-2.88

upper limit

-0.78

Notes
[53] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline weekly HFRDIS as covariate.

Statistical Analysis 21

Statistical analysis description

Week 12: Relations With Others

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[54]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-1.72

Confidence interval

level

95%

sides

2-sided

lower limit

-2.66

upper limit

-0.77

Notes
[54] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline weekly HFRDIS as covariate.

Statistical Analysis 19

Statistical analysis description

Week 4: Relations With Others

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.003 ^[55]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-1.33

Confidence interval

level

95%

sides

2-sided

lower limit

-2.2

upper limit

-0.46

Notes
[55] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline weekly HFRDIS as covariate.

Statistical Analysis 30

Statistical analysis description

Week 12: Overall Quality of Life

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[56]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-2.36

Confidence interval

level

95%

sides

2-sided

lower limit

-3.31

upper limit

-1.41

Notes
[56] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline weekly HFRDIS as covariate.

Statistical Analysis 31

Statistical analysis description

Week 4: Overall Mean Score

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[57]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-1.98

Confidence interval

level

95%

sides

2-sided

lower limit

-2.73

upper limit

-1.23

Notes
[57] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline weekly HFRDIS as covariate.

Statistical Analysis 32

Statistical analysis description

Week 8: Overall Mean Score

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[58]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-2.21

Confidence interval

level

95%

sides

2-sided

lower limit

-3.02

upper limit

-1.4

Notes
[58] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline weekly HFRDIS as covariate.

Statistical Analysis 33

Statistical analysis description

Week 12: Overall Mean Score

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[59]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-1.98

Confidence interval

level

95%

sides

2-sided

lower limit

-2.83

upper limit

-1.13

Notes
[59] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline weekly HFRDIS as covariate.

Statistical Analysis 29

Statistical analysis description

Week 8: Overall Quality of Life

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[60]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-2.51

Confidence interval

level

95%

sides

2-sided

lower limit

-3.41

upper limit

-1.61

Notes
[60] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline weekly HFRDIS as covariate.

Statistical Analysis 28

Statistical analysis description

Week 4: Overall Quality of Life

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[61]

Method

ANCOVA

Parameter type

LS Mean difference

Point estimate

-1.92

Confidence interval

level

95%

sides

2-sided

lower limit

-2.86

upper limit

-0.97

Notes
[61] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline weekly HFRDIS as covariate.

Secondary: Change From Baseline in Leeds Sleep Evaluation Questionnaire (LSEQ) at Weeks 4, 8 and 12

Top of page

End point title

Change From Baseline in Leeds Sleep Evaluation Questionnaire (LSEQ) at Weeks 4, 8 and 12

End point description

The LSEQ was a 10-item self-rated questionnaire which assessed participants aspects of sleep and early morning behavior. The questions were grouped into 4 chronological areas: the ease of getting to sleep, the perceived quality of sleep, the ease of awaking from sleep, and the integrity of early morning behavior following wakefulness. The LSEQ was a visual analogue scale which requires respondents to place marks on a group of 10 cm lines. representing the changes they have experienced in a variety of symptoms since the beginning of treatment. Lines extends between extremes like “more difficult than usual” and “easier than usual”. Responses are measured using a 100-mm scale and are averaged to provide a score for each domain. ITT population with available data at specified time point.

End point type

Secondary

End point timeframe

Baseline and weeks 4, 8 and 12

End point values	Placebo	Fezolinetant
Number of subjects analysed	43	41
Units: millimeter (mm)
arithmetic mean (standard deviation)
Week 4: Getting to Sleep (n=43, n=41)	1.017 ( 1.9195 )	2.283 ( 2.7364 )
Week 8: Getting to Sleep (n=40, n=40)	1.145 ( 1.7931 )	2.248 ( 2.5233 )
Week 12: Getting to Sleep (n=39, n=39)	1.282 ( 1.7761 )	2.094 ( 2.4419 )
Week 4: Quality of Sleep (n=43, n=41)	2.145 ( 2.6443 )	4.437 ( 4.0768 )
Week 8: Quality of Sleep (n=39, n=40)	2.378 ( 2.8160 )	4.703 ( 3.1971 )
Week 12: Quality of Sleep (n=39, n=39)	1.904 ( 2.7872 )	4.385 ( 3.4477 )
Week 4: Awake Following Sleep (n=43, n=40)	0.642 ( 2.0739 )	2.180 ( 3.0579 )
Week 8: Awake Following Sleep (n=40, n=40)	0.653 ( 2.5019 )	2.920 ( 3.0219 )
Week 12: Awake Following Sleep (n=39, n=39)	1.024 ( 2.6114 )	2.887 ( 3.1333 )
Week 4: Behavior Following Wakening (n=43, n=41)	1.173 ( 2.1743 )	2.513 ( 2.7919 )
Week 8: Behavior Following Wakening (n=40, n=40)	0.750 ( 2.6371 )	2.539 ( 2.7742 )
Week 12: Behavior Following Wakening (n=39, n=39)	1.203 ( 2.5185 )	2.233 ( 2.8190 )

Statistical Analysis 1

Statistical analysis description

Week 4: Getting to Sleep

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[62]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

1.375

Confidence interval

level

95%

sides

2-sided

lower limit

0.651

upper limit

2.1

Notes
[62] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline LSEQ as covariate.

Statistical Analysis 2

Statistical analysis description

Week 8: Getting to Sleep

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[63]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

1.166

Confidence interval

level

95%

sides

2-sided

lower limit

0.505

upper limit

1.827

Notes
[63] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline LSEQ as covariate.

Statistical Analysis 3

Statistical analysis description

Week 12: Getting to Sleep

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.014 ^[64]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

0.895

Confidence interval

level

95%

sides

2-sided

lower limit

0.19

upper limit

1.599

Notes
[64] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline LSEQ as covariate.

Statistical Analysis 4

Statistical analysis description

Week 4: Quality of Sleep

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[65]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

2.423

Confidence interval

level

95%

sides

2-sided

lower limit

1.308

upper limit

3.539

Notes
[65] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline LSEQ as covariate.

Statistical Analysis 5

Statistical analysis description

Week 8: Quality of Sleep

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[66]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

2.291

Confidence interval

level

95%

sides

2-sided

lower limit

1.31

upper limit

3.251

Notes
[66] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline LSEQ as covariate.

Statistical Analysis 6

Statistical analysis description

Week 12: Quality of Sleep

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[67]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

2.433

Confidence interval

level

95%

sides

2-sided

lower limit

1.334

upper limit

3.532

Notes
[67] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline LSEQ as covariate.

Statistical Analysis 7

Statistical analysis description

Week 4: Awake Following Sleep

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.059 ^[68]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

0.877

Confidence interval

level

95%

sides

2-sided

lower limit

-0.034

upper limit

1.789

Notes
[68] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline LSEQ as covariate.

Statistical Analysis 8

Statistical analysis description

Week 8: Awake Following Sleep

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.001 ^[69]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

1.457

Confidence interval

level

95%

sides

2-sided

lower limit

0.579

upper limit

2.335

Notes
[69] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline LSEQ as covariate.

Statistical Analysis 9

Statistical analysis description

Week 12: Awake Following Sleep

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.031 ^[70]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

1.113

Confidence interval

level

95%

sides

2-sided

lower limit

0.107

upper limit

2.12

Notes
[70] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline LSEQ as covariate.

Statistical Analysis 10

Statistical analysis description

Week 4: Behaviour Following Wakening

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.008 ^[71]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

1.203

Confidence interval

level

95%

sides

2-sided

lower limit

0.317

upper limit

2.088

Notes
[71] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline LSEQ as covariate.

Statistical Analysis 11

Statistical analysis description

Week 8: Behaviour Following Wakening

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.001 ^[72]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

1.597

Confidence interval

level

95%

sides

2-sided

lower limit

0.639

upper limit

2.556

Notes
[72] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline LSEQ as covariate.

Statistical Analysis 12

Statistical analysis description

Week 12: Behaviour Following Sleep

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.084 ^[73]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

0.842

Confidence interval

level

95%

sides

2-sided

lower limit

-0.116

upper limit

1.8

Notes
[73] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline LSEQ as covariate.

Secondary: Change From Baseline in Greene Climacteric Scale (GCS) at Weeks 4, 8 and 12

Top of page

End point title

Change From Baseline in Greene Climacteric Scale (GCS) at Weeks 4, 8 and 12

End point description

The GCS was a 21-item scale which provides a brief but comprehensive and valid measure of climacteric symptomatology. Each item was rated by the participant according to its severity using a four-point rating scale from 0 (none) to 3 (severe). The first 20 items of the scale combine into three main independent symptom measures: psychological symptoms (items 1 to 11; score 0 to 33), physical symptoms (items 12 to 18; score 0 to 21), and vasomotor symptoms (items 19 to 20; score 0 to 6), by summing up the individual item scores. Item 21 is a probe for sexual dysfunction (Loss of interest in sex). The total score ranges from 0 to 63. Higher scores indicate worse symptoms. ITT population with available data at specified time point.

End point type

Secondary

End point timeframe

Baseline and weeks 4, 8 and 12

End point values	Placebo	Fezolinetant
Number of subjects analysed	43	40
Units: score on a scale
arithmetic mean (standard deviation)
Week 4: Loss of Interest in Sex (n=41, n=40)	-0.4 ( 0.67 )	-0.5 ( 0.88 )
Week 8: Loss of interest in Sex (n=39, n=39)	-0.5 ( 0.85 )	-0.7 ( 1.15 )
Week 12: Loss of Interest in Sex (n=39, n=39)	-0.4 ( 0.75 )	-0.6 ( 1.14 )
Week 4: Psychological (n=41, n=39)	-2.3 ( 5.22 )	-5.3 ( 5.97 )
Week 8: Psychological (n=39, n=38)	-2.6 ( 5.31 )	-6.7 ( 6.49 )
Week 12: Psychological (n=38, n=39)	-2.9 ( 5.14 )	-6.6 ( 6.03 )
Week 4: Physical (n=39, n=38)	-2.1 ( 3.68 )	-1.2 ( 2.71 )
Week 8: Physical (n=37, n=38)	-1.9 ( 3.46 )	-1.9 ( 3.09 )
Week 12: Physical (n=38, n=37)	-2.4 ( 3.80 )	-1.9 ( 3.32 )
Week 4: Vasomotor (n=43, n=40)	-1.1 ( 1.79 )	-3.3 ( 1.83 )
Week 8: Vasomotor (n=39, n=39)	-1.7 ( 2.23 )	-3.6 ( 1.48 )
Week 12: Vasomotor (n=40, n=39)	-1.5 ( 2.31 )	-3.6 ( 1.37 )
Week 4: Total Symptom Score (n=37, n=35)	-5.5 ( 9.33 )	-9.9 ( 9.24 )
Week 8: Total Symptom Score (n=34, n=35)	-5.8 ( 8.89 )	-13.1 ( 10.68 )
Week 12: Total Symptom Score (n=36, n=35)	-6.3 ( 8.87 )	-13.1 ( 10.04 )

Statistical Analysis 1

Statistical analysis description

Week 4: Loss of Interest in Sex

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.881 ^[74]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.3

upper limit

0.3

Notes
[74] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline GCS as covariate.

Statistical Analysis 3

Statistical analysis description

Week 12: Loss of Interest in Sex

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.301 ^[75]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.6

upper limit

0.2

Notes
[75] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline GCS as covariate.

Statistical Analysis 2

Statistical analysis description

Week 8: Loss of Interest in Sex

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.383 ^[76]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.6

upper limit

0.2

Notes
[76] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline GCS as covariate.

Statistical Analysis 7

Statistical analysis description

Week 4: Physical

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.732 ^[77]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-1.2

upper limit

0.9

Notes
[77] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline GCS as covariate.

Statistical Analysis 6

Statistical analysis description

Week 12: Psychological

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.005 ^[78]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-3.1

Confidence interval

level

95%

sides

2-sided

lower limit

-5.2

upper limit

-1

Notes
[78] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline GCS as covariate.

Statistical Analysis 5

Statistical analysis description

Week 8: Psychological

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.003 ^[79]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-3.3

Confidence interval

level

95%

sides

2-sided

lower limit

-5.4

upper limit

-1.2

Notes
[79] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline GCS as covariate.

Statistical Analysis 4

Statistical analysis description

Week 4: Psychological

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.02 ^[80]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-2.5

Confidence interval

level

95%

sides

2-sided

lower limit

-4.5

upper limit

-0.4

Notes
[80] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline GCS as covariate.

Statistical Analysis 8

Statistical analysis description

Week 8: Physical

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.282 ^[81]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

0.6

Notes
[81] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline GCS as covariate.

Statistical Analysis 13

Statistical analysis description

Week 4: Total Symptom Score

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.013 ^[82]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-4.6

Confidence interval

level

95%

sides

2-sided

lower limit

-8.2

upper limit

-1

Notes
[82] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline GCS as covariate.

Statistical Analysis 9

Statistical analysis description

Week 12: Physical

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.254 ^[83]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-1.7

upper limit

0.5

Notes
[83] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline GCS as covariate.

Statistical Analysis 10

Statistical analysis description

Week 4: Vasomotor

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[84]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-2

Confidence interval

level

95%

sides

2-sided

lower limit

-2.7

upper limit

-1.4

Notes
[84] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline GCS as covariate.

Statistical Analysis 11

Statistical analysis description

Week 8: Vasomotor

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[85]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-1.8

Confidence interval

level

95%

sides

2-sided

lower limit

-2.4

upper limit

-1.1

Notes
[85] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline GCS as covariate.

Statistical Analysis 12

Statistical analysis description

Week 12: Vasomotor

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[86]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-2

Confidence interval

level

95%

sides

2-sided

lower limit

-2.6

upper limit

-1.3

Notes
[86] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline GCS as covariate.

Statistical Analysis 14

Statistical analysis description

Week 8: Total Symptom Score

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[87]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-6.9

Confidence interval

level

95%

sides

2-sided

lower limit

-10.7

upper limit

-3.1

Notes
[87] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline GCS as covariate.

Statistical Analysis 15

Statistical analysis description

Week 12: Total Symptom Score

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[88]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-6.3

Confidence interval

level

95%

sides

2-sided

lower limit

-9.9

upper limit

-2.8

Notes
[88] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline GCS as covariate.

Secondary: Change From Baseline in Sheehan Disability Scale (SDS) at Weeks 4, 8 and 12

Top of page

End point title

Change From Baseline in Sheehan Disability Scale (SDS) at Weeks 4, 8 and 12

End point description

The SDS was a composite of 3 self-rated items designed to measure the extent to which 3 major sectors in a participant’s life are impaired by panic, anxiety, phobic, or depressive symptoms. The participant rates the extent to which his/her 1- work/school, 2- social life, and 3- family life are impaired by his/her symptoms on a 10-point visual analog scale. The 3 items could be summed into a single dimensional measure of global functional impairment that ranges from 0 (unimpaired) to 30 (highly impaired).Higher scores indicate significant functional impairment. ITT population with available data at specified time point.

End point type

Secondary

End point timeframe

Baseline and weeks 4, 8 and 12

End point values	Placebo	Fezolinetant
Number of subjects analysed	42	40
Units: score on a scale
arithmetic mean (standard deviation)
Week (Wk) 4: Work/School (n=35, n=38)	-1.3 ( 2.43 )	-3.6 ( 2.78 )
Week 8: Work/School (n=34, n=35)	-1.7 ( 2.56 )	-4.4 ( 2.43 )
Week 12: Work/School (n=35, n=36)	-1.8 ( 2.76 )	-4.3 ( 2.47 )
Week 4: Social Life (n=42, n=40)	-1.2 ( 2.35 )	-3.3 ( 2.60 )
Week 8: Social Life (n=39, n=40)	-1.3 ( 2.57 )	-3.8 ( 2.79 )
Week 12: Social Life (n=40, n=40)	-1.5 ( 2.55 )	-3.6 ( 2.51 )
Wk 4:Family Life/Home Responsibilities(n=42,n=40)	-1.5 ( 2.70 )	-3.3 ( 2.97 )
Wk 8:Family Life/Home Responsibilities(n=39,n=40)	-1.7 ( 2.64 )	-4.0 ( 2.83 )
Wk 12:Family Life/Home Responsibilities(n=40,n=40)	-1.7 ( 2.38 )	-3.7 ( 2.65 )
Week 4: Global Functional Impairment (n=35, n=38)	-3.7 ( 5.50 )	-9.6 ( 6.99 )
Week 8: Global Functional Impairment (n=34, n=35)	-4.5 ( 6.87 )	-12.3 ( 6.42 )
Week 12: Global Functional Impairment (n=35, n=36)	-4.8 ( 6.49 )	-11.8 ( 6.35 )

Statistical Analysis 1

Statistical analysis description

Week 4: Work/School

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[89]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-1.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.7

upper limit

-0.8

Notes
[89] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline SDS as covariate.

Statistical Analysis 2

Statistical analysis description

Week 8: Work/School

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[90]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-2

Confidence interval

level

95%

sides

2-sided

lower limit

-2.8

upper limit

-1.3

Notes
[90] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline SDS as covariate.

Statistical Analysis 5

Statistical analysis description

Week 8: Social Life

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[91]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-1.9

Confidence interval

level

95%

sides

2-sided

lower limit

-2.7

upper limit

-1.1

Notes
[91] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline SDS as covariate.

Statistical Analysis 4

Statistical analysis description

Week 4: Social Life

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[92]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-1.4

Confidence interval

level

95%

sides

2-sided

lower limit

-2.2

upper limit

-0.6

Notes
[92] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline SDS as covariate.

Statistical Analysis 3

Statistical analysis description

Week 12: Work/School

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[93]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-1.6

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

-0.8

Notes
[93] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline SDS as covariate.

Statistical Analysis 6

Statistical analysis description

Week 12: Social Life

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[94]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-1.6

Confidence interval

level

95%

sides

2-sided

lower limit

-2.4

upper limit

-0.7

Notes
[94] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline SDS as covariate.

Statistical Analysis 10

Statistical analysis description

Week 4: Global Functional Impairment

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[95]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-4.4

Confidence interval

level

95%

sides

2-sided

lower limit

-6.9

upper limit

-2

Notes
[95] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline SDS as covariate.

Statistical Analysis 7

Statistical analysis description

Week 4: Family Life/Home Responsibilities

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.005 ^[96]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-1.3

Confidence interval

level

95%

sides

2-sided

lower limit

-2.2

upper limit

-0.4

Notes
[96] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline SDS as covariate.

Statistical Analysis 8

Statistical analysis description

Week 8: Family Life/Home Responsibilities

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[97]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-1.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

-0.9

Notes
[97] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline SDS as covariate.

Statistical Analysis 9

Statistical analysis description

Week 12: Family Life/Home Responsibilities

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[98]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-1.6

Confidence interval

level

95%

sides

2-sided

lower limit

-2.4

upper limit

-0.7

Notes
[98] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline SDS as covariate.

Statistical Analysis 11

Statistical analysis description

Week 8: Global Functional Impairment

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[99]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-5.8

Confidence interval

level

95%

sides

2-sided

lower limit

-8

upper limit

-3.6

Notes
[99] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline SDS as covariate.

Statistical Analysis 12

Statistical analysis description

Week 12: Global Functional Impairment

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[100]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-5.3

Confidence interval

level

95%

sides

2-sided

lower limit

-7.8

upper limit

-2.8

Notes
[100] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline SDS as covariate.

Secondary: Change From Baseline in Sheehan Disability Scale (SDS) at Weeks 4, 8 and 12 (Days Lost and Days Unproductive)

Top of page

End point title

Change From Baseline in Sheehan Disability Scale (SDS) at Weeks 4, 8 and 12 (Days Lost and Days Unproductive)

End point description

The SDS was a composite of 3 self-rated items designed to measure the extent to which 3 major sectors in a participant’s life are impaired by panic, anxiety, phobic, or depressive symptoms. The participant rates the extent to which his/her 1- work/school, 2- social life, and 3- family life are impaired by his/her symptoms. In addition to the 3 items, the participants were asked two questions Days Lost: On how many days in the last week did your symptoms cause you to miss school or work or leave you unable to carry out your normal daily responsibilities? Day Unproductive: On how many days in the last week did you feel so impaired by your symptoms, that even though you went to school or work, your productivity was reduced? ITT population with available data at specified time point.

End point type

Secondary

End point timeframe

Baseline and weeks 4, 8 and 12

End point values	Placebo	Fezolinetant
Number of subjects analysed	29	28
Units: days
arithmetic mean (standard deviation)
Week 4: Days Lost (n=27, n=25)	-0.2 ( 1.27 )	0.0 ( 0.73 )
Week 8: Days Lost (n=29, n=27)	-0.3 ( 0.81 )	0.0 ( 0.00 )
Week 12: Days Lost (n=26, n=27)	-0.2 ( 1.18 )	0.0 ( 0.00 )
Week 4: Days Unproductive (n=27, n=26)	-0.8 ( 2.83 )	-1.7 ( 2.67 )
Week 8: Days Unproductive (n=29, n=28)	-1.2 ( 3.10 )	-2.0 ( 2.55 )
Week 12: Days Unproductive (n=26, n=28)	-1.4 ( 2.82 )	-2.2 ( 2.59 )

Statistical Analysis 1

Statistical analysis description

Week 4: Days Lost

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.936 ^[101]

Method

ANCOVA

Parameter type

LS Mean difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.5

upper limit

0.6

Notes
[101] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline SDS as covariate.

Statistical Analysis 2

Statistical analysis description

Week 8: Days Lost

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.884 ^[102]

Method

ANCOVA

Parameter type

LS Mean difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.1

upper limit

0.1

Notes
[102] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline SDS as covariate.

Statistical Analysis 6

Statistical analysis description

Week 12: Days Unproductive

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.049 ^[103]

Method

ANCOVA

Parameter type

LS Mean difference

Point estimate

-0.8

Confidence interval

level

95%

sides

2-sided

lower limit

-1.7

upper limit

Notes
[103] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline SDS as covariate.

Statistical Analysis 4

Statistical analysis description

Week 4: Days Unproductive

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.052 ^[104]

Method

ANCOVA

Parameter type

LS Mean difference

Point estimate

-0.9

Confidence interval

level

95%

sides

2-sided

lower limit

-1.8

upper limit

Notes
[104] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline SDS as covariate.

Statistical Analysis 5

Statistical analysis description

Week 8: Days Unproductive

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.06 ^[105]

Method

ANCOVA

Parameter type

LS Mean difference

Point estimate

-0.9

Confidence interval

level

95%

sides

2-sided

lower limit

-1.7

upper limit

Notes
[105] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline SDS as covariate.

Statistical Analysis 3

Statistical analysis description

Week 12: Days Lost

Comparison groups

Placebo v Fezolinetant

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.124 ^[106]

Method

ANCOVA

Parameter type

LS Mean difference

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.4

upper limit

0.1

Notes
[106] - Least square mean difference versus placebo, obtained from an ANCOVA model with treatment group as fixed effect and baseline SDS as covariate.

Secondary: Change From Baseline in Plasma Concentration of Luteinizing Hormone (LH)

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End point title

Change From Baseline in Plasma Concentration of Luteinizing Hormone (LH)

End point description

Change From baseline in plasma concentration of LH was reported. Safety population with available data at specified time point.

End point type

Secondary

End point timeframe

Baseline and week 4: pre-dose, week 8:pre-dose, week 12:pre-dose, week 12: 3h, follow-up (week 15)

End point values	Placebo	Fezolinetant
Number of subjects analysed	43	42
Units: international unit per liter (IU/L)
arithmetic mean (standard deviation)
Week 4: Pre-dose (n=43, n=42)	-2.34 ( 9.350 )	-8.84 ( 10.865 )
Week 8: Pre-dose (n=40, n=40)	-3.86 ( 9.838 )	-9.46 ( 13.647 )
Week 12: Pre-dose (n=40, n=40)	-4.61 ( 13.304 )	-9.72 ( 12.834 )
Week 12: 3 hours (h) (n=40, n=40)	-7.16 ( 13.009 )	-21.78 ( 11.923 )
Week 15 (n=43, n=42)	-6.16 ( 14.197 )	-3.33 ( 11.742 )

No statistical analyses for this end point

Secondary: Change From Baseline in Plasma Concentration of Follicle-Stimulating Hormone (FSH)

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End point title

Change From Baseline in Plasma Concentration of Follicle-Stimulating Hormone (FSH)

End point description

Change From baseline in plasma concentration of FSH was reported. Safety population with available data at specified time point.

End point type

Secondary

End point timeframe

Baseline and week 4: pre-dose, week 8:pre-dose, week 12:pre-dose, week 12:3h, follow-up (week 15)

End point values	Placebo	Fezolinetant
Number of subjects analysed	43	42
Units: IU/L
arithmetic mean (standard deviation)
Week 4: Pre-dose (n=43, n=41)	-5.80 ( 19.430 )	-3.44 ( 18.026 )
Week 8: Pre-dose (n=40, n=40)	-6.60 ( 20.086 )	-10.36 ( 23.943 )
Week 12: Pre-dose (n=40, n=40)	-7.05 ( 19.978 )	-10.51 ( 24.521 )
Week 12: 3h (n=40, n=40)	-8.47 ( 19.159 )	-19.48 ( 22.734 )
Week 15 (n=43, n=42)	-6.50 ( 21.011 )	-6.97 ( 22.273 )

No statistical analyses for this end point

Secondary: Change From Baseline in Plasma Concentration of Estradiol (E2)

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End point title

Change From Baseline in Plasma Concentration of Estradiol (E2)

End point description

Change From baseline in plasma concentration of E2 was reported. Safety population with available data at specified time point.

End point type

Secondary

End point timeframe

Baseline and week 4: pre-dose, week 8:pre-dose, week 12:pre-dose, week 12:3h, follow-up (week 15)

End point values	Placebo	Fezolinetant
Number of subjects analysed	43	42
Units: Picomoles per liter (pmol/L)
arithmetic mean (standard deviation)
Week 4: Pre-dose (n=43, n=42)	18.4 ( 140.36 )	-7.3 ( 75.13 )
Week 8: Pre-dose (n=40, n=40)	26.0 ( 157.18 )	1.0 ( 71.78 )
Week 12: Pre-dose (n=40, n=40)	32.3 ( 101.87 )	25.5 ( 108.27 )
Week 12: 3h (n=40, n=40)	26.0 ( 100.33 )	11.5 ( 77.68 )
Week 15 (n=43, n=42)	37.0 ( 167.37 )	27.9 ( 188.18 )

No statistical analyses for this end point

Secondary: Change From Baseline in Plasma Concentration of Sex Hormone-Binding Globulin (SHBG)

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End point title

Change From Baseline in Plasma Concentration of Sex Hormone-Binding Globulin (SHBG)

End point description

Change From baseline in plasma concentration of SHBG was reported. Safety population with available data at specified time point.

End point type

Secondary

End point timeframe

Baseline and week 4: pre-dose, week 8:pre-dose, week 12:pre-dose, week 12:3h, follow-up (week 15)

End point values	Placebo	Fezolinetant
Number of subjects analysed	43	42
Units: Nanomoles per liter (nmol/L)
arithmetic mean (standard deviation)
Week 4: Pre-dose (n=43, n=41)	0.61 ( 16.260 )	-0.47 ( 11.986 )
Week 8: Pre-dose (n=40, n=40)	5.10 ( 20.713 )	-1.37 ( 12.186 )
Week 12: Pre-dose (n=40, n=40)	1.75 ( 18.090 )	0.36 ( 15.165 )
Week 12: 3h (n=40, n=40)	1.56 ( 18.658 )	-1.49 ( 16.406 )
Week 15 (n=43, n=42)	1.92 ( 16.341 )	-0.86 ( 13.540 )

No statistical analyses for this end point

Secondary: Change From Baseline in Plasma Concentration of Leptin

Top of page

End point title

Change From Baseline in Plasma Concentration of Leptin

End point description

Change From baseline in plasma concentration of leptin was reported. Safety population with available data at specified time point.

End point type

Secondary

End point timeframe

Baseline and week 4: pre-dose, week 8:pre-dose, week 12:pre-dose, week 12:3h, follow-up (week 15)

End point values	Placebo	Fezolinetant
Number of subjects analysed	43	42
Units: nanogram per liter (ng/mL)
arithmetic mean (standard deviation)
Week 4: Pre-dose (n=42, n=40)	1.2436 ( 5.6269 )	-2.2185 ( 6.9522 )
Week 8: Pre-dose (n=40, n=40)	1.6225 ( 7.5029 )	-1.7090 ( 6.9716 )
Week 12: Pre-dose (n=40, n=40)	0.9668 ( 5.4301 )	-0.4183 ( 11.0737 )
Week 12: 3h (n=40, n=40)	-2.0755 ( 5.3193 )	-4.2085 ( 8.5335 )
Week 15 (n=43, n=42)	-0.9914 ( 14.6660 )	-0.6031 ( 8.2519 )

No statistical analyses for this end point

Secondary: Change From Baseline in Plasma Concentration of Insulin

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End point title

Change From Baseline in Plasma Concentration of Insulin

End point description

Change From baseline in plasma concentration of insulin was reported. Safety population with available data at specified time point.

End point type

Secondary

End point timeframe

Baseline and week 4: pre-dose, week 8:pre-dose, week 12:pre-dose, week 12:3h, follow-up (week 15)

End point values	Placebo	Fezolinetant
Number of subjects analysed	43	42
Units: micro units per milliliter (μU/mL)
arithmetic mean (standard deviation)
Week 4: Pre-dose (n=43, n=41)	-0.2767 ( 3.0971 )	-0.7512 ( 3.8798 )
Week 8: Pre-dose (n=40, nn=40)	0.3525 ( 4.0903 )	-0.5325 ( 3.6121 )
Week 12: Pre-dose (n=40, n=40)	-0.0825 ( 3.1593 )	0.1300 ( 4.7942 )
Week 12: 3h (n=40, n=40)	16.3225 ( 19.0210 )	14.4950 ( 19.2787 )
Week 15 (n=43, n=42)	0.3256 ( 4.1132 )	-0.1595 ( 3.1071 )

No statistical analyses for this end point

Secondary: Change From Baseline in Plasma Concentration of C-peptide

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End point title

Change From Baseline in Plasma Concentration of C-peptide

End point description

Change From baseline in plasma concentration of C-peptide was reported. Safety population with available data at specified time point.

End point type

Secondary

End point timeframe

Baseline and week 4: pre-dose, week 8:pre-dose, week 12:pre-dose, week 12:3h, follow-up (week 15)

End point values	Placebo	Fezolinetant
Number of subjects analysed	43	42
Units: ng/mL
arithmetic mean (standard deviation)
Week 4: Pre-dose (n=43, n=41)	-0.0465 ( 0.3978 )	-0.1463 ( 0.5134 )
Week 8: Pre-dose (n=40, n=40)	-0.0300 ( 0.5273 )	-0.1175 ( 0.4750 )
Week 12: Pre-dose (n=40, n=40)	-0.0750 ( 0.5212 )	-0.0425 ( 0.7154 )
Week 12: 3h (n=40, n=40)	2.1325 ( 1.9976 )	2.2875 ( 2.1811 )
Week 15 (n=43, n=42)	-0.0047 ( 0.6102 )	-0.0095 ( 0.4023 )

No statistical analyses for this end point

Secondary: Change From Baseline in Plasma Concentration of Glycated hemoglobin (HBA1c)

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End point title

Change From Baseline in Plasma Concentration of Glycated hemoglobin (HBA1c)

End point description

Change From baseline in plasma concentration of HBA1c was reported. Safety population with available data at specified time point.

End point type

Secondary

End point timeframe

Baseline and week 12

End point values	Placebo	Fezolinetant
Number of subjects analysed	40	39
Units: Percentage of HBA1c
arithmetic mean (standard deviation)	-0.00050000 ( 0.003162278 )	-0.002307692 ( 0.004845800 )

No statistical analyses for this end point

Secondary: Number of Participants with Adverse Events (AE's)

Top of page

End point title

Number of Participants with Adverse Events (AE's)

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 & 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 in participant 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: An AE observed from first dose date up to end of study. Safety population.

End point type

Secondary

End point timeframe

From first dose of study drug until end of the study (Up to week 15) Treatment (trt)

End point values	Placebo	Fezolinetant
Number of subjects analysed	44	43
Units: participants
At least one TEAE	35	29
At least one serious TEAE	1	0
At least one TEAE leading to death	0	0
At least one severe TEAE	0	0
At least 1 TEAE for which trt permanently stopped	0	2
At least 1 TEAE that was considered trt related	11	13

No statistical analyses for this end point

Secondary: Change From Baseline in Plasma Concentration of Bone Alkaline Phosphatase (BALP) at Week 12

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End point title

Change From Baseline in Plasma Concentration of Bone Alkaline Phosphatase (BALP) at Week 12

End point description

Change from baseline in plasma concentration of BALP was reported. ITT population with available data at specified time point.

End point type

Secondary

End point timeframe

Baseline and week 12

End point values	Placebo	Fezolinetant
Number of subjects analysed	40	40
Units: microgram per milliliter (ug/mL)
arithmetic mean (standard deviation)	2.9 ( 5.43 )	1.7 ( 3.19 )

No statistical analyses for this end point

Secondary: Change From Baseline in Plasma Concentration of Carboxy-terminal Telopeptide of Type I Collagen (CTX) at Week 12

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End point title

Change From Baseline in Plasma Concentration of Carboxy-terminal Telopeptide of Type I Collagen (CTX) at Week 12

End point description

Change from baseline in plasma concentration of CTX was reported. ITT population with available data at specified time point.

End point type

Secondary

End point timeframe

Baseline and week 12

End point values	Placebo	Fezolinetant
Number of subjects analysed	40	40
Units: ug/mL
arithmetic mean (standard deviation)	-0.021 ( 0.1278 )	0.001 ( 0.1356 )

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

From first dose of study drug until end of the study (Up to week 15)

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

18.0

Reporting group title

Fezolinetant

Reporting group description

Participants received 90 mg fezolinetant capsules orally, BID for a period of 12 weeks.

Reporting group title

Placebo

Reporting group description

Participants received fezolinetant matching placebo capsules orally, BID for a period of 12 weeks.

Serious adverse events	Fezolinetant	Placebo
Total subjects affected by serious adverse events
subjects affected / exposed	0 / 43 (0.00%)	1 / 44 (2.27%)
number of deaths (all causes)	0	0
number of deaths resulting from adverse events
Injury, poisoning and procedural complications
Upper limb fracture
subjects affected / exposed	0 / 43 (0.00%)	1 / 44 (2.27%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Fezolinetant	Placebo
Total subjects affected by non serious adverse events
subjects affected / exposed	18 / 43 (41.86%)	18 / 44 (40.91%)
Cardiac disorders
Palpitations
subjects affected / exposed	3 / 43 (6.98%)	2 / 44 (4.55%)
occurrences all number	3	2
Nervous system disorders
Headache
subjects affected / exposed	7 / 43 (16.28%)	6 / 44 (13.64%)
occurrences all number	10	10
General disorders and administration site conditions
Fatigue
subjects affected / exposed	3 / 43 (6.98%)	0 / 44 (0.00%)
occurrences all number	3	0
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	3 / 43 (6.98%)	0 / 44 (0.00%)
occurrences all number	3	0
Musculoskeletal and connective tissue disorders
Arthritis
subjects affected / exposed	0 / 43 (0.00%)	3 / 44 (6.82%)
occurrences all number	0	3
Back pain
subjects affected / exposed	0 / 43 (0.00%)	3 / 44 (6.82%)
occurrences all number	0	3
Infections and infestations
Nasopharyngitis
subjects affected / exposed	2 / 43 (4.65%)	4 / 44 (9.09%)
occurrences all number	2	4
Influenza
subjects affected / exposed	3 / 43 (6.98%)	1 / 44 (2.27%)
occurrences all number	3	1

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Were there any global substantial amendments to the protocol? Yes

10 Dec 2015

The overall reason for the revision is to liberalize the participant selection criteria to facilitate recruitment, and to allow for a lower number of subjects to be included in the interim analysis. For a detailed overview of the changes, please refer to the Protocol Amendment section of the full CSR.

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.

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Clinical trials

Clinical Trial Results: Pilot/Phase IIa Trial to Investigate the Effect of ESN364 in Early Postmenopausal Women Suffering From Hot Flashes

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Change From Baseline to Week 12 in The Weekly General Hot Flash Score

Primary: Change From Baseline to Week 12 in The Weekly General Hot Flash Score

Secondary: Change From Baseline in The Weekly Hot Flash Severity Score at Weeks 4, 8 and 12 (Method 1)

Secondary: Change From Baseline in The Weekly Hot Flash Severity Score at Weeks 4, 8 and 12 (Method 1)

Secondary: Change From Baseline in The Weekly Hot Flash Severity Score at Weeks 4, 8 and 12 (Method 2)

Secondary: Change From Baseline in The Weekly Hot Flash Severity Score at Weeks 4, 8 and 12 (Method 2)

Secondary: Change From Baseline in The Weekly Mild, Moderate and Severe Hot Flash Frequency at Weeks 4, 8 and 12

Secondary: Change From Baseline in The Weekly Mild, Moderate and Severe Hot Flash Frequency at Weeks 4, 8 and 12

Secondary: Percentage of Participants With >=70% Reduction in the Weekly Hot Flash Score From Baseline to Weeks 4, 8 and 12

Secondary: Percentage of Participants With >=70% Reduction in the Weekly Hot Flash Score From Baseline to Weeks 4, 8 and 12

Secondary: Percentage of Participants With >=80% Reduction in the Weekly Hot Flash Score From Baseline to Weeks 4, 8 and 12

Secondary: Percentage of Participants With >=80% Reduction in the Weekly Hot Flash Score From Baseline to Weeks 4, 8 and 12

Secondary: Percentage of Participants With >=90% Reduction in the Weekly Hot Flash Score From Baseline to Weeks 4, 8 and 12

Secondary: Percentage of Participants With >=90% Reduction in the Weekly Hot Flash Score From Baseline to Weeks 4, 8 and 12

Secondary: Percentage of Participants With >=50% Reduction in the Weekly Frequency of Moderate and severe HF From Baseline to Weeks 4, 8 and 12

Secondary: Percentage of Participants With >=50% Reduction in the Weekly Frequency of Moderate and severe HF From Baseline to Weeks 4, 8 and 12

Secondary: Percentage of Participants With >=70% Reduction in the Weekly Frequency of Moderate and severe HF From Baseline to Weeks 4, 8 and 12

Secondary: Percentage of Participants With >=70% Reduction in the Weekly Frequency of Moderate and severe HF From Baseline to Weeks 4, 8 and 12

Secondary: Percentage of Participants With >=90% Reduction in the Weekly Frequency of Moderate and severe HF From Baseline to Weeks 4, 8 and 12

Secondary: Percentage of Participants With >=90% Reduction in the Weekly Frequency of Moderate and severe HF From Baseline to Weeks 4, 8 and 12

Secondary: Change From Baseline in Hot Flash Related Daily Interference Scale (HFRDIS) Score at Weeks 4, 8 and 12

Secondary: Change From Baseline in Hot Flash Related Daily Interference Scale (HFRDIS) Score at Weeks 4, 8 and 12

Secondary: Change From Baseline in Leeds Sleep Evaluation Questionnaire (LSEQ) at Weeks 4, 8 and 12

Secondary: Change From Baseline in Leeds Sleep Evaluation Questionnaire (LSEQ) at Weeks 4, 8 and 12

Secondary: Change From Baseline in Greene Climacteric Scale (GCS) at Weeks 4, 8 and 12

Secondary: Change From Baseline in Greene Climacteric Scale (GCS) at Weeks 4, 8 and 12

Secondary: Change From Baseline in Sheehan Disability Scale (SDS) at Weeks 4, 8 and 12

Secondary: Change From Baseline in Sheehan Disability Scale (SDS) at Weeks 4, 8 and 12

Secondary: Change From Baseline in Sheehan Disability Scale (SDS) at Weeks 4, 8 and 12 (Days Lost and Days Unproductive)

Secondary: Change From Baseline in Sheehan Disability Scale (SDS) at Weeks 4, 8 and 12 (Days Lost and Days Unproductive)

Secondary: Change From Baseline in Plasma Concentration of Luteinizing Hormone (LH)

Secondary: Change From Baseline in Plasma Concentration of Luteinizing Hormone (LH)

Secondary: Change From Baseline in Plasma Concentration of Follicle-Stimulating Hormone (FSH)

Secondary: Change From Baseline in Plasma Concentration of Follicle-Stimulating Hormone (FSH)

Secondary: Change From Baseline in Plasma Concentration of Estradiol (E2)

Secondary: Change From Baseline in Plasma Concentration of Estradiol (E2)

Secondary: Change From Baseline in Plasma Concentration of Sex Hormone-Binding Globulin (SHBG)

Secondary: Change From Baseline in Plasma Concentration of Sex Hormone-Binding Globulin (SHBG)

Secondary: Change From Baseline in Plasma Concentration of Leptin

Secondary: Change From Baseline in Plasma Concentration of Leptin

Secondary: Change From Baseline in Plasma Concentration of Insulin

Secondary: Change From Baseline in Plasma Concentration of Insulin

Secondary: Change From Baseline in Plasma Concentration of C-peptide

Secondary: Change From Baseline in Plasma Concentration of C-peptide

Secondary: Change From Baseline in Plasma Concentration of Glycated hemoglobin (HBA1c)

Secondary: Change From Baseline in Plasma Concentration of Glycated hemoglobin (HBA1c)

Secondary: Number of Participants with Adverse Events (AE's)

Secondary: Number of Participants with Adverse Events (AE's)

Secondary: Change From Baseline in Plasma Concentration of Bone Alkaline Phosphatase (BALP) at Week 12

Secondary: Change From Baseline in Plasma Concentration of Bone Alkaline Phosphatase (BALP) at Week 12

Secondary: Change From Baseline in Plasma Concentration of Carboxy-terminal Telopeptide of Type I Collagen (CTX) at Week 12

Secondary: Change From Baseline in Plasma Concentration of Carboxy-terminal Telopeptide of Type I Collagen (CTX) at Week 12

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical Trial Results:
Pilot/Phase IIa Trial to Investigate the Effect of ESN364 in Early Postmenopausal Women Suffering From Hot Flashes