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Clinical Trial Results:
A Double-Blind, Randomised, Placebo Controlled, Adaptive Design Study of the Efficacy, Safety and Pharmacokinetics of NT-814 in Female Subjects With Moderate to Severe Vasomotor Symptoms Associated With the Menopause

Summary
EudraCT number	2018-002763-26
Trial protocol	GB
Global end of trial date	21 Nov 2019

Results information
Results version number	v1
This version publication date	05 Dec 2020
First version publication date	05 Dec 2020
Other versions	v2

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

BAY3427080/21686

ISRCTN number

US NCT number

NCT03596762

WHO universal trial number (UTN)

Sponsor organisation name

Bayer AG

Sponsor organisation address

Kaiser Wilhelm Allee, Leverkusen, Germany,

Public contact

Therapeutic Area Head, Bayer AG, clinical-trials-contact@bayer.com

Scientific contact

Therapeutic Area Head, Bayer AG, clinical-trials-contact@bayer.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

21 Nov 2019

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

21 Nov 2019

Was the trial ended prematurely?

Main objective of the trial

Primary Objectives: - To evaluate the efficacy of once daily doses of 40 mg, 80 mg, 120 mg and 160 mg BAY3427080 (NT-814), compared with placebo, in reducing the frequency and severity of hot flashes. - To assess the safety and tolerability of once daily doses of 40 mg, 80 mg, 120 mg and 160 mg BAY3427080 (NT-814), compared with placebo, in subjects with post-menopausal symptoms.

Protection of trial subjects

The conduct of this clinical study met all local legal and regulatory requirements. The study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and the International Conference on Harmonization guideline E6: Good Clinical Practice. Only after the subject voluntarily signed the informed consent form was he/she able to enter the study. If the subject was not capable of providing a signature, an oral statement of consent could have been given in the presence of a witness. Each subject was assured of the right to withdraw from the study at any time without any disadvantage and without having to provide a reason for this decision. Only investigators qualified by training and experience were selected as appropriate experts to investigate the study drug.

Background therapy

Evidence for comparator

Actual start date of recruitment

20 Nov 2018

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Canada: 33

Country: Number of subjects enrolled

United Kingdom: 95

Country: Number of subjects enrolled

United States: 71

Worldwide total number of subjects

199

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)

198

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

The study was conducted between 20 November 2018 (first subject, first visit) and 21 November 2019 (last subject, last visit) at 11 sites in the USA, nine sites in the UK, and five sites in Canada.

Screening details

A total of 760 subjects were screened, of whom 199 completed screening and were randomised. Not meeting the eligibility criteria was the reason provided for all screening failures (561). A total of 47 subjects were randomised to placebo and 152 subjects to BAY3427080 (NT-814).

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

Subjects received four placebo capsules orally once daily in the evening before bedtime.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule, soft

Routes of administration

Oral use

Dosage and administration details

4 x placebo capsules

40 mg BAY3427080

Arm description

Subjects received one 40 mg BAY3427080 capsule and 3 placebo capsules.

Arm type

Experimental

Investigational medicinal product name

BAY3427080

Investigational medicinal product code

Other name

NT-814

Pharmaceutical forms

Capsule, soft

Routes of administration

Oral use

Dosage and administration details

one capsule of 40 mg BAY3427080 once daily in the evening before bedtime.

80 mg BAY3427080

Arm description

subjects received 2x40 mg BAY3427080 capsules and 2 placebo capsules.

Arm type

Experimental

Investigational medicinal product name

BAY3427080

Investigational medicinal product code

Other name

NT-814

Pharmaceutical forms

Capsule, soft

Routes of administration

Oral use

Dosage and administration details

Two capsules of 40 mg BAY3427080 once daily in the evening before bedtime.

120 mg BAY3427080

Arm description

Subjects received 3x40 mg BAY3427080 capsules and 1 placebo capsule.

Arm type

Experimental

Investigational medicinal product name

BAY3427080

Investigational medicinal product code

Other name

NT-814

Pharmaceutical forms

Capsule, soft

Routes of administration

Oral use

Dosage and administration details

Three capsules of 40 mg BAY3427080 once daily in the evening before bedtime.

160 mg BAY3427080

Arm description

Subjects received 4x40 mg BAY3427080 capsules.

Arm type

Experimental

Investigational medicinal product name

BAY3427080

Investigational medicinal product code

Other name

NT-814

Pharmaceutical forms

Capsule, soft

Routes of administration

Oral use

Dosage and administration details

Four capsules of 40 mg BAY3427080 once daily in the evening before bedtime.

Number of subjects in period 1	Placebo	40 mg BAY3427080	80 mg BAY3427080	120 mg BAY3427080	160 mg BAY3427080
Started	47	31	17	52	52
Completed	43	30	16	51	45
Not completed	4	1	1	1	7
Consent withdrawn by subject	2	1	-	1	1
Adverse event, non-fatal	2	-	1	-	5
Protocol deviation	-	-	-	-	1

Baseline characteristics

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Reporting group title

Placebo

Reporting group description

Subjects received four placebo capsules orally once daily in the evening before bedtime.

Reporting group title

40 mg BAY3427080

Reporting group description

Subjects received one 40 mg BAY3427080 capsule and 3 placebo capsules.

Reporting group title

80 mg BAY3427080

Reporting group description

subjects received 2x40 mg BAY3427080 capsules and 2 placebo capsules.

Reporting group title

120 mg BAY3427080

Reporting group description

Subjects received 3x40 mg BAY3427080 capsules and 1 placebo capsule.

Reporting group title

160 mg BAY3427080

Reporting group description

Subjects received 4x40 mg BAY3427080 capsules.

Reporting group values	Placebo	40 mg BAY3427080	80 mg BAY3427080	120 mg BAY3427080	160 mg BAY3427080	Total
Number of subjects	47	31	17	52	52	199
Age Categorical
Units: Subjects
In utero
Preterm newborn infants (gestational age < 37 wks)
Newborns (0-27 days)
Infants and toddlers (28 days-23 months)
Children (2-11 years)
Adolescents (12-17 years)
Adults (18-64 years)
From 65-84 years
85 years and over
Age Continuous
Units: years
arithmetic mean (standard deviation)	55.6 ± 4.1	55.4 ± 4.0	55.9 ± 4.2	54.8 ± 4.4	55.0 ± 3.8	-
Gender Categorical
Units: Subjects
Female	47	31	17	52	52	199
Male	0	0	0	0	0	0
Race
Units: Subjects
Asian	2	0	0	1	1	4
Black or African American	6	5	3	13	11	38
White	38	24	13	37	40	152
Other	1	2	1	1	0	5
Ethnicity
Units: Subjects
Hispanic or Latino	2	2	1	2	6	13
Not Hispanic or Latino	45	29	16	50	46	186

End points

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Reporting group title

Placebo

Reporting group description

Subjects received four placebo capsules orally once daily in the evening before bedtime.

Reporting group title

40 mg BAY3427080

Reporting group description

Subjects received one 40 mg BAY3427080 capsule and 3 placebo capsules.

Reporting group title

80 mg BAY3427080

Reporting group description

subjects received 2x40 mg BAY3427080 capsules and 2 placebo capsules.

Reporting group title

120 mg BAY3427080

Reporting group description

Subjects received 3x40 mg BAY3427080 capsules and 1 placebo capsule.

Reporting group title

160 mg BAY3427080

Reporting group description

Subjects received 4x40 mg BAY3427080 capsules.

Subject analysis set title

Safety Analysis Set

Subject analysis set type

Safety analysis

Subject analysis set description

All subjects who received at least one dose of double-blind study drug, irrespective of treatment received. Subjects were analysed according to treatment received.

Subject analysis set title

Full Analysis Set (FAS)

Subject analysis set type

Full analysis

Subject analysis set description

All randomised subjects who received at least one dose of double-blind study drug, irrespective of treatment received, and had hot flush data for at least 7 days’ worth of post-treatment assessments (i.e. requirement for primary efficacy endpoint). Subjects were analysed according to randomised treatment.

Subject analysis set title

Per Protocol (PP) Set

Subject analysis set type

Per protocol

Subject analysis set description

All subjects in the FAS who completed the 12-week treatment period excluding those identified as having relevant protocol deviations.

Primary: Mean change from baseline in mean daily frequency of moderate and severe hot flushes from baseline to Week 4

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End point title

Mean change from baseline in mean daily frequency of moderate and severe hot flushes from baseline to Week 4

End point description

Subjects recorded daily in their electronic diary (eDiary) the frequency and severity of hot flushes during the treatment period. The baseline assessment for hot flushes was calculated using the last 7 days (not necessarily consecutive days) with an available data in the evening and/or the morning of the baseline diary completion period. A diary day was comprised of the evening entry of this day and the morning entry of the following day, in that order. Mean daily frequency = Sum of number of hot flushes filled in the diary during the last 7 diary days (with at least one available data in the evening and/or morning) divided by 7. Moderate: Sensation of heat with sweating, but able to continue activity. Severe: Sensation of heat with sweating, causing cessation (stopping) of activity. In categories the number of subjects analyzed (N) at week 4 is mentioned for each reporting group respectively.

End point type

Primary

End point timeframe

From baseline to week 4

End point values	Placebo	40 mg BAY3427080	80 mg BAY3427080	120 mg BAY3427080	160 mg BAY3427080
Number of subjects analysed	47	31	17	52	52
Units: Hot Flushes
arithmetic mean (standard deviation)
Baseline	11.82 ± 4.42	12.13 ± 8.81	14.55 ± 5.87	13.54 ± 7.17	12.92 ± 6.90
Week 4: Change from baseline (N= 45,31,17,52,47)	-2.45 ± 3.65	-4.19 ± 5.78	-4.30 ± 6.45	-6.76 ± 5.85	-5.42 ± 5.36

40 mg BAY3427080 versus placebo

Comparison groups

Placebo v 40 mg BAY3427080

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1946

Method

Mixed-Effect Model Repeated Measures

Parameter type

Difference in LS means

Point estimate

-1.52

Confidence interval

level

95%

sides

2-sided

lower limit

-3.83

upper limit

0.78

80 mg BAY3427080 versus placebo

Comparison groups

Placebo v 80 mg BAY3427080

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3682

Method

Mixed-Effect Model Repeated Measures

Parameter type

Difference in LS means

Point estimate

1.29

Confidence interval

level

95%

sides

2-sided

lower limit

-4.11

upper limit

1.53

120 mg BAY3427080 versus placebo

Comparison groups

Placebo v 120 mg BAY3427080

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0002

Method

Mixed-Effect Model Repeated Measures

Parameter type

Difference in LS means

Point estimate

-3.93

Confidence interval

level

95%

sides

2-sided

lower limit

-5.94

upper limit

-1.92

160 mg BAY3427080 versus placebo

Comparison groups

Placebo v 160 mg BAY3427080

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0115

Method

Mixed-Effect Model Repeated Measures

Parameter type

Difference in LS means

Point estimate

-2.63

Confidence interval

level

95%

sides

2-sided

lower limit

-4.66

upper limit

-0.6

Primary: Mean change from baseline in mean daily frequency of moderate and severe hot flushes from baseline to Week 12

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End point title

Mean change from baseline in mean daily frequency of moderate and severe hot flushes from baseline to Week 12

End point description

Subjects recorded daily in their electronic diary (eDiary) the frequency and severity of hot flushes during the treatment period. The baseline assessment for hot flushes was calculated using the last 7 days (not necessarily consecutive days) with an available data in the evening and/or the morning of the baseline diary completion period. A diary day was comprised of the evening entry of this day and the morning entry of the following day, in that order. Mean daily frequency = Sum of number of hot flushes filled in the diary during the last 7 diary days (with at least one available data in the evening and/or morning) divided by 7. Moderate: Sensation of heat with sweating, but able to continue activity. Severe: Sensation of heat with sweating, causing cessation (stopping) of activity. In categories the number of subjects analyzed (N) at week 12 is mentioned for each reporting group respectively.

End point type

Primary

End point timeframe

Week 12

End point values	Placebo	40 mg BAY3427080	80 mg BAY3427080	120 mg BAY3427080	160 mg BAY3427080
Number of subjects analysed	47	31	17	52	52
Units: Hot Flushes
arithmetic mean (standard deviation)
Baseline	11.82 ± 4.42	12.13 ± 8.81	14.55 ± 5.87	13.54 ± 7.17	12.92 ± 6.90
Week 12: Change from baseline (N=44,30,16,51,43)	-4.49 ± 4.29	-6.48 ± 7.82	-5.49 ± 5.31	-7.91 ± 6.66	-6.57 ± 5.83

40 mg BAY3427080 versus placebo

Comparison groups

Placebo v 40 mg BAY3427080

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2097

Method

Mixed-Effect Model Repeated Measures

Parameter type

Difference in LS means

Point estimate

-1.67

Confidence interval

level

95%

sides

2-sided

lower limit

-4.28

upper limit

-0.95

80 mg BAY3427080 versus placebo

Comparison groups

Placebo v 80 mg BAY3427080

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6369

Method

Mixed-Effect Model Repeated Measures

Parameter type

Difference in LS means

Point estimate

-0.77

Confidence interval

level

95%

sides

2-sided

lower limit

-3.97

upper limit

2.44

120 mg BAY3427080 versus placebo

Comparison groups

Placebo v 120 mg BAY3427080

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0116

Method

Mixed-Effect Model Repeated Measures

Parameter type

Difference in LS means

Point estimate

-2.95

Confidence interval

level

95%

sides

2-sided

lower limit

-5.22

upper limit

-0.67

160 mg BAY3427080 versus placebo

Comparison groups

Placebo v 160 mg BAY3427080

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1346

Method

Mixed-Effect Model Repeated Measures

Parameter type

Difference in LS means

Point estimate

-1.78

Confidence interval

level

95%

sides

2-sided

lower limit

-4.12

upper limit

0.56

Primary: Mean change from baseline in mean severity of moderate and severe hot flushes from baseline to Week 4

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End point title

Mean change from baseline in mean severity of moderate and severe hot flushes from baseline to Week 4

End point description

Subjects recorded daily in their eDiary the frequency and severity of hot flushes during the treatment period. Mean weekly severity = (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3] / (total number of moderate to severe hot flushes over 7 days). Severity is graded by the women from 1 to 3 (1 = mild; 2 = moderate; 3 = severe). In categories the number of subjects analyzed (N) at week 4 is mentioned for each reporting group respectively.

End point type

Primary

End point timeframe

From baseline to week 4

End point values	Placebo	40 mg BAY3427080	80 mg BAY3427080	120 mg BAY3427080	160 mg BAY3427080
Number of subjects analysed	47	31	17	52	52
Units: Hot Flushes
arithmetic mean (standard deviation)
Baseline	2.54 ± 0.20	2.51 ± 0.26	2.63 ± 0.24	2.54 ± 0.24	2.54 ± 0.26
Week 4: Change from baseline (N=45,31,17,50,45)	-0.31 ± 0.41	-0.38 ± 0.54	-0.44 ± 0.56	-0.52 ± 0.58	-0.55 ± 0.68

40 mg BAY3427080 versus placebo

Comparison groups

Placebo v 40 mg BAY3427080

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7033

Method

Mixed-Effect Model Repeated Measures

Parameter type

Difference in LS means

Point estimate

-0.05

Confidence interval

level

95%

sides

2-sided

lower limit

-0.3

upper limit

0.2

80 mg BAY3427080 versus placebo

Comparison groups

Placebo v 80 mg BAY3427080

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3724

Method

Mixed-Effect Model Repeated Measures

Parameter type

Difference in LS means

Point estimate

-0.14

Confidence interval

level

95%

sides

2-sided

lower limit

-0.45

upper limit

0.17

120 mg BAY3427080 versus placebo

Comparison groups

Placebo v 120 mg BAY3427080

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0896

Method

Mixed-Effect Model Repeated Measures

Parameter type

Difference in LS means

Point estimate

-0.19

Confidence interval

level

95%

sides

2-sided

lower limit

-0.41

upper limit

0.03

160 mg BAY3427080 versus placebo

Comparison groups

Placebo v 160 mg BAY3427080

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.09

Method

Mixed-Effect Model Repeated Measures

Parameter type

Difference in LS means

Point estimate

-0.19

Confidence interval

level

95%

sides

2-sided

lower limit

-0.41

upper limit

0.03

Primary: Mean change from baseline in mean severity of moderate and severe hot flushes from baseline to Week 12

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End point title

Mean change from baseline in mean severity of moderate and severe hot flushes from baseline to Week 12

End point description

Subjects recorded daily in their eDiary the frequency and severity of hot flushes during the treatment period. Mean weekly severity = (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3] / (total number of moderate to severe hot flushes over 7 days). Severity was graded by the women from 1 to 3 (1 = mild; 2 = moderate; 3 = severe). In categories the number of subjects analyzed (N) at week 12 is mentioned for each reporting group respectively.

End point type

Primary

End point timeframe

Week 12

End point values	Placebo	40 mg BAY3427080	80 mg BAY3427080	120 mg BAY3427080	160 mg BAY3427080
Number of subjects analysed	47	31	17	52	52
Units: Hot Flushes
arithmetic mean (standard deviation)
Baseline	2.54 ± 0.20	2.51 ± 0.26	2.63 ± 0.24	2.54 ± 0.24	2.54 ± 0.26
Week 12: Change from baseline (N=44,30,16,49,41)	-0.41 ± 0.50	-0.53 ± 0.64	-0.26 ± 0.45	-0.56 ± 0.68	-0.73 ± 0.78

40 mg BAY3427080 versus placebo

Comparison groups

Placebo v 40 mg BAY3427080

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5511

Method

Mixed-Effect Model Repeated Measures

Parameter type

Difference in LS means

Point estimate

-0.09

Confidence interval

level

95%

sides

2-sided

lower limit

-0.39

upper limit

0.21

80 mg BAY3427080 versus placebo

Comparison groups

Placebo v 80 mg BAY3427080

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3822

Method

Mixed-Effect Model Repeated Measures

Parameter type

Difference in LS means

Point estimate

0.16

Confidence interval

level

95%

sides

2-sided

lower limit

-0.2

upper limit

0.52

120 mg BAY3427080 versus placebo

Comparison groups

Placebo v 120 mg BAY3427080

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2606

Method

Mixed-Effect Model Repeated Measures

Parameter type

Difference in LS means

Point estimate

-0.15

Confidence interval

level

95%

sides

2-sided

lower limit

-0.41

upper limit

0.11

160 mg BAY3427080 versus placebo

Comparison groups

Placebo v 160 mg BAY3427080

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0479

Method

Mixed-Effect Model Repeated Measures

Parameter type

Difference in LS means

Point estimate

-0.27

Confidence interval

level

95%

sides

2-sided

lower limit

-0.53

upper limit

Secondary: Mean change from baseline in frequency of mean daily moderate and severe hot flushes from baseline to Weeks 1, 2, 8 and 16

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End point title

Mean change from baseline in frequency of mean daily moderate and severe hot flushes from baseline to Weeks 1, 2, 8 and 16

End point description

Subjects recorded daily in their electronic diary (eDiary) the frequency and severity of hot flushes during the treatment period. The baseline assessment for hot flushes was calculated using the last 7 days (not necessarily consecutive days) with an available data in the evening and/or the morning of the baseline diary completion period. A diary day was comprised of the evening entry of this day and the morning entry of the following day, in that order. Mean daily frequency = Sum of number of hot flushes filled in the diary during the last 7 diary days (with at least one available data in the evening and/or morning) divided by 7. Moderate: Sensation of heat with sweating, but able to continue activity. Severe: Sensation of heat with sweating, causing cessation (stopping) of activity In categories the number of subjects analyzed (N) for each week is mentioned for each reporting group respectively.

End point type

Secondary

End point timeframe

From baseline to Weeks 1, 2, 8 and 16

End point values	Placebo	40 mg BAY3427080	80 mg BAY3427080	120 mg BAY3427080	160 mg BAY3427080
Number of subjects analysed	47	31	17	52	52
Units: Hot Flushes
arithmetic mean (standard deviation)
Baseline	11.82 ± 4.42	12.13 ± 8.81	14.55 ± 5.87	13.54 ± 7.17	12.92 ± 6.90
Week 1: Change from baseline (N=47,31,17,52,52)	-1.22 ± 3.07	-1.61 ± 3.05	-1.63 ± 3.56	-3.22 ± 3.43	-3.09 ± 3.76
Week 2: Change from baseline (N=45,31,17,52,51)	-2.19 ± 4.01	-3.03 ± 3.95	-3.47 ± 4.37	-4.58 ± 4.70	-3.78 ± 4.48
Week 8: Change from baseline (N=44,31,17,51,44)	-4.33 ± 4.79	-5.72 ± 6.18	-5.94 ± 5.26	-7.84 ± 5.95	-5.58 ± 6.00
Week 16: Change from baseline (N=43,30,16,51,42)	-3.95 ± 4.85	-5.74 ± 9.45	-2.01 ± 4.99	-5.95 ± 6.95	-2.78 ± 6.54

No statistical analyses for this end point

Secondary: Mean change from baseline in mean severity of moderate and severe hot flushes from baseline to Weeks 1, 2, 8 and 16

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End point title

Mean change from baseline in mean severity of moderate and severe hot flushes from baseline to Weeks 1, 2, 8 and 16

End point description

Subjects recorded daily in their diary the frequency and severity of hot flushes during the treatment period. Mean weekly severity = (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3] / (total number of moderate to severe hot flushes over 7 days). Severity is graded by the women from 1 to 3 (1 = mild; 2 = moderate; 3 = severe). In categories the number of subjects analyzed (N) for each week is mentioned for each reporting group respectively.

End point type

Secondary

End point timeframe

From baseline to Weeks 1, 2, 8 and 16

End point values	Placebo	40 mg BAY3427080	80 mg BAY3427080	120 mg BAY3427080	160 mg BAY3427080
Number of subjects analysed	47	31	17	50	50
Units: Hot Flushes
arithmetic mean (standard deviation)
Baseline (N=47,31,17,50,50)	2.54 ± 0.20	2.51 ± 0.26	2.63 ± 0.24	2.54 ± 0.24	2.55 ± 0.26
Week 1: Change from baseline (N=47,31,17,50,50)	-0.24 ± 0.30	-0.21 ± 0.20	-0.22 ± 0.21	-0.25 ± 0.28	-0.26 ± 0.26
Week 2: Change from baseline (N=45,31,17,50,49)	-0.30 ± 0.39	-0.32 ± 0.32	-0.42 ± 0.58	-0.37 ± 0.46	-0.40 ± 0.55
Week 8: Change from baseline (N=44,31,17,50,42)	-0.45 ± 0.58	-0.48 ± 0.54	-0.40 ± 0.61	-0.51 ± 0.54	-0.65 ± 0.73
Week 16: Change from baseline (N=43,30,16,49,41)	2.15 ± 0.65	2.03 ± 0.56	2.50 ± 0.46	2.13 ± 0.71	2.08 ± 0.62

No statistical analyses for this end point

Secondary: Mean change from baseline in mean daily frequency of all hot flushes from baseline to Weeks 1, 2, 4, 8, 12 and 16

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End point title

Mean change from baseline in mean daily frequency of all hot flushes from baseline to Weeks 1, 2, 4, 8, 12 and 16

End point description

Subjects recorded daily in their electronic diary (eDiary) the frequency and severity of hot flushes during the treatment period. The baseline assessment for hot flushes was calculated using the last 7 days (not necessarily consecutive days) with an available data in the evening and/or the morning of the baseline diary completion period. A diary day was comprised of the evening entry of this day and the morning entry of the following day, in that order. Mean daily frequency = Sum of number of hot flushes filled in the diary during the last 7 diary days (with at least one available data in the evening and/or morning) divided by 7. Moderate: Sensation of heat with sweating, but able to continue activity. Severe: Sensation of heat with sweating, causing cessation (stopping) of activity. *In categories the number of subjects analyzed (N) for each week is mentioned for each reporting group respectively.

End point type

Secondary

End point timeframe

From baseline to Weeks 1, 2, 4, 8, 12 and 16

End point values	Placebo	40 mg BAY3427080	80 mg BAY3427080	120 mg BAY3427080	160 mg BAY3427080
Number of subjects analysed	47	31	17	52	52
Units: Hot Flushes
arithmetic mean (standard deviation)
Baseline (N=47,31,17,52,52)	14.04 ± 5.57	14.19 ± 11.01	16.55 ± 6.89	15.39 ± 7.91	15.78 ± 9.62
Week 1 (N=47,31,17,52,52)	-1.36 ± 3.03	-1.72 ± 3.27	-1.33 ± 5.68	-3.30 ± 3.99	-3.69 ± 4.81
Week 2 (N=45,31,17,52,51)	-2.35 ± 4.60	-2.99 ± 4.90	-2.74 ± 5.97	-4.57 ± 5.48	-4.43 ± 5.68
Week 4 (N=45,31,17,52,47)	-2.67 ± 4.09	-4.11 ± 6.31	-3.45 ± 8.54	-6.70 ± 6.16	-5.79 ± 6.09
Week 8 (N=44,31,17,51,44)	-4.74 ± 5.57	-5.65 ± 6.55	-5.45 ± 6.56	-7.96 ± 6.16	-6.03 ± 6.43
Week 12 (N=44,30,16,51,43)	-5.07 ± 5.48	-6.50 ± 8.67	-5.11 ± 8.41	-7.94 ± 6.74	-7.47 ± 7.13
Week 16 (N=43,30,16,51,42)	-4.60 ± 6.17	-5.83 ± 10.86	-1.76 ± 7.50	-6.19 ± 7.68	-3.11 ± 6.71

No statistical analyses for this end point

Secondary: Mean change from baseline in mean severity of all hot flushes from baseline to Weeks 1, 2, 4, 8, 12 and 16

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End point title

Mean change from baseline in mean severity of all hot flushes from baseline to Weeks 1, 2, 4, 8, 12 and 16

End point description

End point type

Secondary

End point timeframe

From baseline to Weeks 1, 2, 4, 8, 12 and 16

End point values	Placebo	40 mg BAY3427080	80 mg BAY3427080	120 mg BAY3427080	160 mg BAY3427080
Number of subjects analysed	47	31	17	52	52
Units: Hot Flushes
arithmetic mean (standard deviation)
Baseline	2.34 ± 0.32	2.34 ± 0.35	2.46 ± 0.37	2.38 ± 0.34	2.35 ± 0.39
Week 1: Change from baseline (N=47,31,17,52,52)	-0.04 ± 0.23	-0.04 ± 0.18	-0.05 ± 0.12	-0.09 ± 0.25	-0.07 ± 0.18
Week 2: Change from baseline (N=45,31,17,52,51)	-0.10 ± 0.32	-0.15 ± 0.27	-0.25 ± 0.52	-0.21 ± 0.46	-0.20 ± 0.50
Week 4: Change from baseline (N=45,31,17,52,47)	-0.11 ± 0.36	-0.21 ± 0.47	-0.27 ± 0.49	-0.35 ± 0.60	-0.34 ± 0.63
Week 8: Change from baseline (N=44,31,17,51,44)	-0.25 ± 0.54	-0.31 ± 0.47	-0.23 ± 0.52	-0.35 ± 0.55	-0.44 ± 0.72
Week 12: Change from baseline (N=44,30,16,51,43)	-0.21 ± 0.44	-0.35 ± 0.57	-0.08 ± 0.41	-0.41 ± 0.62	-0.52 ± 0.79
Week 16: Change from baseline (N=43,30,16,51,42)	-0.21 ± 0.49	-0.30 ± 0.52	0.05 ± 0.34	-0.26 ± 0.56	-0.24 ± 0.54

No statistical analyses for this end point

Secondary: Mean change from baseline in the mean daily hot flush score (frequency x severity) at Weeks 1, 2, 4, 8, 12 and 16

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End point title

Mean change from baseline in the mean daily hot flush score (frequency x severity) at Weeks 1, 2, 4, 8, 12 and 16

End point description

Mean daily Hot Flushes score = Sum of (frequency x severity) filled in the diary during the last 7 days (with at least one available data in the evening and/or morning) divided by 7. Severity is graded by the women from 1 to 3 (1 = mild; 2 = moderate; 3 = severe). In categories the number of subjects analyzed (N) for each week is mentioned for each reporting group respectively.

End point type

Secondary

End point timeframe

From baseline to Weeks 1, 2, 4, 8, 12 and 16

End point values	Placebo	40 mg BAY3427080	80 mg BAY3427080	120 mg BAY3427080	160 mg BAY3427080
Number of subjects analysed	47	31	17	52	52
Units: Scores on scale
arithmetic mean (standard deviation)
Baseline (N=47,31,17,52,52)	32.35 ± 12.24	32.84 ± 24.82	40.76 ± 17.08	36.59 ± 19.88	35.73 ± 19.75
Week 1: Change from baseline (N=47,31,17,52,52)	-3.09 ± 8.16	-4.26 ± 7.93	-4.18 ± 11.27	-8.44 ± 8.98	-8.67 ± 10.53
Week 2: Change from baseline (N=45,31,17,52,51)	-5.62 ± 11.00	-7.88 ± 10.77	-9.08 ± 13.09	-11.98 ± 12.39	-10.51 ± 12.47
Week 4: Change from baseline (N=45,31,17,52,47)	-6.62 ± 9.79	-10.68 ± 15.26	-11.39 ± 18.82	-17.54 ± 15.50	-14.20 ± 14.30
Week 8: Change from baseline (N=44,31,17,51,44)	-11.63 ± 12.51	-14.64 ± 16.33	-16.17 ± 15.32	-20.54 ± 15.80	-14.89 ± 15.36
Week 12: Change from baseline (N=44,30,16,51,43)	-12.33 ± 11.96	-16.71 ± 20.60	-14.93 ± 16.83	-20.72 ± 17.81	-17.70 ± 15.38
Week 16: Change from baseline (N=43,30,16,51,42)	-10.89 ± 13.45	-14.93 ± 25.48	-4.97 ± 14.35	-15.60 ± 19.03	-7.50 ± 16.55

No statistical analyses for this end point

Secondary: Number of subjects with ≥50% and ≥80% reduction from baseline in mean daily hot flushes frequency at Week 12

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End point title

Number of subjects with ≥50% and ≥80% reduction from baseline in mean daily hot flushes frequency at Week 12

End point description

Proportion of responder is number of subjects with >=50 (80)% reduction from baseline in the number of moderate and severe hot flushes.

End point type

Secondary

End point timeframe

Week 12

End point values	Placebo	40 mg BAY3427080	80 mg BAY3427080	120 mg BAY3427080	160 mg BAY3427080
Number of subjects analysed	47	31	17	52	52
Units: Subjects
>= 50% reduction	17	20	5	32	30
>=80% reduction	8	6	0	16	18

No statistical analyses for this end point

Secondary: Mean change from baseline in number of all night-time awakenings (NTA) at Weeks 1, 2, 4, 8, 12 and 16

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End point title

Mean change from baseline in number of all night-time awakenings (NTA) at Weeks 1, 2, 4, 8, 12 and 16

End point description

Subjects were provided with an eDiary to document the number of night-time awakenings (NTA). Each evening, subjects recorded the total number of hot flushes of each severity experienced that day since waking. Each morning upon waking, subjects recorded the number of times they woke up in the night and the total number of hot flashes of each severity experienced during the night. In categories the number of subjects analyzed (N) at each week is mentioned for each reporting group respectively.

End point type

Secondary

End point timeframe

From baseline to weeks 1, 2, 4, 8, 12 and 16

End point values	Placebo	40 mg BAY3427080	80 mg BAY3427080	120 mg BAY3427080	160 mg BAY3427080
Number of subjects analysed	47	31	17	51	51
Units: Night-time awakenings
arithmetic mean (standard deviation)
Baseline	3.86 ± 2.06	3.44 ± 1.82	5.00 ± 1.76	3.80 ± 2.20	3.85 ± 2.57
Week 1: Change from baseline (N=47,31,17,52,52)	-0.65 ± 1.08	-0.70 ± 1.24	-0.57 ± 1.57	-0.91 ± 1.06	-0.86 ± 1.93
Week 2: Change from baseline (N=45,31,17,52,51)	-0.62 ± 1.54	-0.70 ± 1.20	-1.09 ± 1.84	-1.10 ± 1.34	-1.00 ± 2.10
Week 4: Change from baseline (N=45,31,17,52, 47)	-0.86 ± 1.40	-1.05 ± 1.43	-0.99 ± 2.96	-1.49 ± 1.43	-1.03 ± 2.22
Week 8: Change from baseline (N=44,31,17,51,44)	-0.99 ± 1.31	-1.66 ± 1.77	-1.30 ± 2.15	-1.79 ± 1.47	-1.17 ± 2.51
Week 12: Change from baseline (N=44,30,16,51,43)	-1.28 ± 1.44	-1.53 ± 1.89	-1.61 ± 2.46	-1.60 ± 1.38	-1.40 ± 2.40
Week 16: Change from baseline (N=43,30,16,51,42)	-1.08 ± 1.30	-0.96 ± 1.91	-0.31 ± 2.90	-1.05 ± 1.30	-0.32 ± 2.10

No statistical analyses for this end point

Secondary: Mean change from baseline in mean daily number of NTAs secondary to hot flushes at Weeks 1, 2, 4, 8, 12 and 16

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End point title

Mean change from baseline in mean daily number of NTAs secondary to hot flushes at Weeks 1, 2, 4, 8, 12 and 16

End point description

Subjects were provided with an eDiary to document the number of night-time awakenings (NTA). Each evening, subjects recorded the total number of hot flashes of each severity experienced that day since waking. Each morning upon waking, subjects recorded the number of times they woke up in the night and the total number of hot flushes of each severity experienced during the night. Night-time awakenings secondary to hot flashes corresponded to severe hot flash recorded on the morning diary, and all NTAs corresponded to the data recorded in the “Total number of times you woke up last night?” field from the eDiary recorded in the morning. Number of NTAs secondary to hot flushes could not be higher than the number of all NTAs.

End point type

Secondary

End point timeframe

From baseline to Weeks 1, 2, 4, 8, 12 and 16

End point values	Placebo	40 mg BAY3427080	80 mg BAY3427080	120 mg BAY3427080	160 mg BAY3427080
Number of subjects analysed	47	31	17	52	52
Units: Night-time awakenings
arithmetic mean (standard deviation)
Baseline	2.90 ± 1.64	2.41 ± 1.57	4.05 ± 1.86	2.76 ± 1.71	2.57 ± 1.54
Week 1: Change from baseline (N=47,31,17,52,52)	-0.57 ± 0.96	-0.52 ± 1.07	-0.63 ± 1.53	-0.90 ± 1.03	-0.68 ± 1.14
Week 2: Change from baseline (N=45,31,17,52,51)	-0.69 ± 1.03	-0.75 ± 1.18	-1.13 ± 1.89	-1.18 ± 1.27	-0.92 ± 1.38
Week 4: Change from baseline (N=45,31,17,52,47)	-0.89 ± 1.08	-0.91 ± 1.26	-1.33 ± 2.27	-1.53 ± 1.19	-1.01 ± 1.62
Week 8: Change from baseline (N=44,31,17,51,44)	-1.09 ± 1.36	-1.50 ± 1.40	-1.69 ± 2.21	-1.79 ± 1.35	-1.13 ± 1.86
Week 12: Change from baseline (N=44,30,16,51,43)	-1.31 ± 1.39	-1.63 ± 1.46	-1.70 ± 2.53	-1.67 ± 1.27	-1.32 ± 1.75
Week 16: Change from baseline (N=43,30,16,51,42)	-1.05 ± 1.19	-1.29 ± 1.63	-0.45 ± 2.05	-1.19 ± 1.23	-0.44 ± 1.62

No statistical analyses for this end point

Secondary: Change from baseline in the global and individual domain scores of the Pittsburgh Sleep Quality Index (PSQI) at Weeks 4, 8, 12 and 16

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End point title

Change from baseline in the global and individual domain scores of the Pittsburgh Sleep Quality Index (PSQI) at Weeks 4, 8, 12 and 16

End point description

The PSQI is a self-rated questionnaire which assesses sleep quality and disturbances over a 1-month time interval. Nineteen individual items generate seven “component” scores: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. The sum of scores for these seven components yields one global score. In categories the number of subjects analyzed (N) for each week is mentioned for each reporting group respectively.

End point type

Secondary

End point timeframe

From baseline to Weeks 4, 8, 12 and 16

End point values	Placebo	40 mg BAY3427080	80 mg BAY3427080	120 mg BAY3427080	160 mg BAY3427080
Number of subjects analysed	47	31	17	52	52
Units: Scores on scale
arithmetic mean (standard deviation)
Baseline (N=45,31,17,51,50)	10.80 ± 2.39	11.94 ± 3.11	11.35 ± 3.66	10.80 ± 3.00	11.44 ± 3.14
Week 4: Change from baseline (N=41,31,17,50,45)	-0.63 ± 2.02	-1.87 ± 2.93	-1.94 ± 2.68	-2.70 ± 3.11	-2.80 ± 2.84
Week 8: Change from baseline (N=42,31,16,51,43)	-1.36 ± 2.90	-2.39 ± 3.63	-2.38 ± 3.30	-3.00 ± 3.23	-3.14 ± 3.37
Week 12: Change from baseline (N=41,30,16,49,41)	-1.15 ± 2.95	-2.47 ± 3.82	-2.81 ± 2.97	-3.39 ± 3.12	-3.54 ± 4.12
Week 16: Change from baseline (N=41,30,16,50,42)	-1.85 ± 2.46	-2.10 ± 3.53	-1.38 ± 3.26	-2.24 ± 3.12	-1.79 ± 2.69

No statistical analyses for this end point

Secondary: Change from baseline in the Insomnia Severity Index (ISI) score at Weeks 4, 8, 12 and 16

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End point title

Change from baseline in the Insomnia Severity Index (ISI) score at Weeks 4, 8, 12 and 16

End point description

The ISI is a brief self-report questionnaire assessing the nature, severity, and impact of insomnia. The ISI comprises seven items assessing the perceived severity of difficulties initiating sleep, staying asleep, and early morning awakenings, satisfaction with current sleep pattern, interference with daily functioning, noticeability of impairment attributed to the sleep problem, and degree of distress or concern caused by the sleep problem. Subjects rated each item on a scale of 0 to 4, yielding a total score ranging from 0 to 28. In categories the number of subjects analyzed (N) for each week is mentioned for each reporting group respectively.

End point type

Secondary

End point timeframe

From baseline to Weeks 4, 8, 12 and 16

End point values	Placebo	40 mg BAY3427080	80 mg BAY3427080	120 mg BAY3427080	160 mg BAY3427080
Number of subjects analysed	47	31	17	52	52
Units: Scores on scale
arithmetic mean (standard deviation)
Baseline (N=44,31,17,51,50)	12.43 ± 5.09	13.23 ± 5.36	13.24 ± 8.04	12.63 ± 5.66	13.74 ± 5.89
Week 4: Change from Baseline (N=40,31,17,50,45)	-1.60 ± 2.98	-2.74 ± 4.91	-3.65 ± 6.03	-5.14 ± 5.51	-5.42 ± 5.42
Week 8: Change from Baseline (N=41,31,16,51,43)	-1.51 ± 3.64	-3.74 ± 5.63	-4.44 ± 6.17	-6.20 ± 4.93	-5.72 ± 5.14
Week 12: Change from Baseline (N=40,30,16, 49,41)	-1.95 ± 4.70	-3.80 ± 5.45	-5.81 ± 5.86	-6.12 ± 5.41	-7.39 ± 5.82
Week 16: Change from Baseline (N=40,30,16,50,42)	-2.65 ± 4.32	-3.73 ± 6.02	-3.00 ± 3.72	-4.34 ± 5.58	-4.00 ± 5.49

No statistical analyses for this end point

Secondary: Change from baseline in the hot flush related daily interference scale (HFRDIS) scores at Weeks 2, 4, 8, 12 and 16

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End point title

Change from baseline in the hot flush related daily interference scale (HFRDIS) scores at Weeks 2, 4, 8, 12 and 16

End point description

The HFRDIS is a 10-item, self-report questionnaire assessing the impact of hot flashes on a woman’s life during the past week. For each of the 10 items, subjects rated how much hot flushes had interfered with that aspect of their life on a scale of 0 (not at all) to 10 (very much so). In categories the number of subjects analyzed (N) for each week is mentioned for each reporting group respectively.

End point type

Secondary

End point timeframe

From baseline to Weeks 2, 4, 8, 12 and 16

End point values	Placebo	40 mg BAY3427080	80 mg BAY3427080	120 mg BAY3427080	160 mg BAY3427080
Number of subjects analysed	47	31	17	52	52
Units: Scores on scale
arithmetic mean (standard deviation)
Baseline (N=45,31,17,51,50)	52.93 ± 18.40	52.74 ± 20.33	50.29 ± 21.45	53.86 ± 23.42	55.36 ± 19.71
Week 2: Change from baseline (N=42,31,17,51,48)	-4.00 ± 20.28	-5.39 ± 21.99	-11.12 ± 28.14	-13.75 ± 29.66	-10.90 ± 21.31
Week 4: Change from baseline (N=43,31,17,50,45)	-9.98 ± 20.84	-13.00 ± 22.53	-15.06 ± 24.02	-23.04 ± 28.32	-18.44 ± 23.37
Week 8: Change from baseline (N=42,31,16,51,43)	-15.48 ± 21.07	-16.26 ± 23.71	-17.88 ± 27.15	-26.39 ± 24.90	-24.09 ± 25.51
Week 12: Change from baseline (N=41,30,16,49,41)	-19.37 ± 20.20	-21.30 ± 22.89	-15.56 ± 28.70	-28.33 ± 25.36	-27.83 ± 24.64
Week 16: Change from baseline (N=41,30,16,50,42)	-15.22 ± 21.72	-10.73 ± 24.87	-16.69 ± 24.15	-19.16 ± 22.43	-12.07 ± 25.94

No statistical analyses for this end point

Secondary: Change from baseline in the Menopause-specific Quality-of-Life questionnaire Intervention Version (MenQoL-I) scores at Weeks 4, 8, 12 and 16

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End point title

Change from baseline in the Menopause-specific Quality-of-Life questionnaire Intervention Version (MenQoL-I) scores at Weeks 4, 8, 12 and 16

End point description

The MenQoL-I is a validated questionnaire used to measure condition-specific quality of life in menopausal women. It is composed of 32 items across four domains (physical, vasomotor, psychosocial and sexual). For each item, subjects recorded whether they had experienced the problem in the past month, and if so, they rated how bothered they were by the problem on a scale of 0 (not at all bothered) to 6 (extremely bothered). The item responses were then converted into analysis scores and an overall questionnaire score. In categories the number of subjects analyzed (N) for each week is mentioned for each reporting group respectively.

End point type

Secondary

End point timeframe

From baseline to Weeks 4, 8, 12 and 16;

End point values	Placebo	40 mg BAY3427080	80 mg BAY3427080	120 mg BAY3427080	160 mg BAY3427080
Number of subjects analysed	47	31	17	52	52
Units: Scores on scale
arithmetic mean (standard deviation)
Baseline (N=46,31,17,51,51)	4.00 ± 1.06	4.38 ± 1.16	4.47 ± 1.25	4.17 ± 1.13	4.50 ± 1.23
Week 4: Change from baseline (N=42,31,17,50,46)	-0.33 ± 0.90	-0.62 ± 1.30	-0.56 ± 0.87	-1.29 ± 1.14	-1.13 ± 1.09
Week 8: Change from baseline (N=43,31,16,51,43)	-0.62 ± 1.10	-0.87 ± 1.25	-0.91 ± 1.06	-1.45 ± 1.18	-1.50 ± 0.99
Week 12: Change from baseline (N=42,30,16,49,41)	-0.70 ± 1.03	-0.81 ± 1.44	-1.09 ± 0.76	-1.54 ± 1.34	-1.72 ± 1.32
Week 16: Change from baseline (N=42,30,16,50,42)	-0.68 ± 1.01	-0.76 ± 1.33	-0.69 ± 0.93	-1.18 ± 1.13	-1.00 ± 1.36

No statistical analyses for this end point

Secondary: Change from baseline in the Beck Depression Inventory II (BDI-II) scores at Weeks 2, 4, 8, 12 and 16.

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End point title

Change from baseline in the Beck Depression Inventory II (BDI-II) scores at Weeks 2, 4, 8, 12 and 16.

End point description

The BDI-II is a 21-item questionnaire assessing the intensity of depressive symptoms over the past 2 weeks. It is composed of items relating to symptoms of depression such as hopelessness and irritability, cognitions such as guilt or feelings of being punished, as well as physical symptoms such as fatigue, weight loss, and lack of interest in sex. Subjects rated each item on a scale of 0 to 3 to give a total score ranging from 0 to 63, with a higher score suggesting more severe depressive symptoms. In categories the number of subjects analyzed (N) for each week is mentioned for each reporting group respectively.

End point type

Secondary

End point timeframe

From baseline to weeks 2, 4, 8, 12 and 16

End point values	Placebo	40 mg BAY3427080	80 mg BAY3427080	120 mg BAY3427080	160 mg BAY3427080
Number of subjects analysed	47	31	17	52	52
Units: Scores on scale
arithmetic mean (standard deviation)
Baseline (N=44,31,17,51,50)	11.18 ± 8.74	14.29 ± 11.36	10.47 ± 7.01	9.92 ± 8.62	11.48 ± 9.30
Week 2: Change from baseline (N=41,31,17,51,48)	-1.90 ± 5.29	-2.23 ± 9.27	-3.06 ± 7.34	-3.65 ± 6.95	-2.71 ± 6.08
Week 4: Change from baseline (N=42,31,17,50,45)	-1.55 ± 5.14	-4.23 ± 9.82	-2.35 ± 5.16	-4.08 ± 6.39	-4.13 ± 6.63
Week 8: Change from baseline (N=41,31,16,51,43)	-2.24 ± 5.26	-5.32 ± 10.13	-2.00 ± 8.22	-4.73 ± 6.34	-5.51 ± 7.14
Week 12: Change from baseline (N=40,30,16,49,41)	-1.30 ± 7.22	-5.00 ± 3.80	-1.69 ± 7.65	-4.29 ± 6.56	-5.73 ± 7.39
Week 16: Change from baseline (N=40,30,16,50,42)	-2.43 ± 6.08	-5.10 ± 11.62	-0.75 ± 6.71	-4.04 ± 6.12	-2.36 ± 8.05

No statistical analyses for this end point

Secondary: Plasma BAY3427080 Concentrations at Weeks 2, 4, 8 ,12

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End point title

Plasma BAY3427080 Concentrations at Weeks 2, 4, 8 ,12 ^[1]

End point description

Blood samples for analysis of plasma BAY3427080 concentrations were collected at Weeks 2, 4, 8, and 12. A small number of subjects had NT-814 concentrations below the LOQ for the assay (1.5 ng/mL) at two or more visits (three subjects in each of the 40 mg, 120 mg, and 160 mg groups, four in 80 mg group), indicating that these subjects were non compliant with treatment.

End point type

Secondary

End point timeframe

At weeks 2, 4, 8 ,12

Notes
[1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: PK samples were collected for placebo subjects but not analyzed. Only subjects who received the active study drug and for whom valid PK data were available were included in the pharmacokinetic analysis.

End point values	40 mg BAY3427080	80 mg BAY3427080	120 mg BAY3427080	160 mg BAY3427080
Number of subjects analysed	31 ^[2]	17 ^[3]	52 ^[4]	52 ^[5]
Units: ng/ml
geometric mean (geometric coefficient of variation)
Week 2	64.254 ± 75.681	157.207 ± 93.120	292.929 ± 100.381	319.552 ± 170.571
Week 4	78.946 ± 78.892	118.554 ± 175.865	253.800 ± 142.944	398.389 ± 91.644
Week 8	87.985 ± 68.277	138.795 ± 72.619	226.121 ± 79.171	341.673 ± 145.535
Week 12	70.138 ± 66.542	130.729 ± 414.199	197.041 ± 231.390	298.896 ± 220.963

Notes
[2] - Safety Analysis Set
[3] - Safety Analysis Set
[4] - Safety Analysis Set
[5] - Safety Analysis Set

No statistical analyses for this end point

Secondary: Nature and severity of adverse events

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End point title

Nature and severity of adverse events

End point description

A Treatment-Emergent Adverse Events (TEAE) is defined as any adverse event (serious and non-serious) with the onset date on or after the date of first dosing with study treatment. Safety Analysis Set.

End point type

Secondary

End point timeframe

Up to Week 16

End point values	Placebo	40 mg BAY3427080	80 mg BAY3427080	120 mg BAY3427080	160 mg BAY3427080
Number of subjects analysed	47	31	17	52	52
Units: Subjects
Number of TEAEs	28	17	14	34	38
Number of TEAEs related to IMP	7	7	8	8	12
Number of Serious TEAEs	2	0	1	1	1
Number of TEAEs leading to death	0	0	0	0	0
Number of Severe TEAEs	2	0	1	3	2

No statistical analyses for this end point

Secondary: Withdrawals due to an adverse event

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End point title

Withdrawals due to an adverse event

End point description

A Treatment-Emergent Adverse Events (TEAE) is defined as any adverse event (serious and non-serious) with the onset date on or after the date of first dosing with study treatment.

End point type

Secondary

End point timeframe

Up to Week 16

End point values	Placebo	40 mg BAY3427080	80 mg BAY3427080	120 mg BAY3427080	160 mg BAY3427080
Number of subjects analysed	47	31	17	52	52
Units: Subjects
TEAEs leading to treatment discontinuation	1	0	2	0	5
TEAEs leading to study discontinuation	1	0	1	0	4

No statistical analyses for this end point

Secondary: Number of subjects used concomitant medications

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End point title

Number of subjects used concomitant medications

End point description

A concomitant medication is defined as any medication used on or after date and time of first randomised treatment. All concomitant medications taken during the study were recorded in the eCRF. Any medication that was not specifically prohibited was allowed. (1) Antidiarrheals, intestinal antiinflammatory/antiinfective agents;

End point type

Secondary

End point timeframe

Up to week 16

End point values	Placebo	40 mg BAY3427080	80 mg BAY3427080	120 mg BAY3427080	160 mg BAY3427080
Number of subjects analysed	47	31	17	52	52
Units: Subjects
Analgesics	18	8	9	12	16
Antiinflammatory and antirheumatic products	14	7	5	12	13
Vitamins	14	6	6	9	14
Drugs for acid related disorders	13	7	2	10	10
Psychoanaleptics	6	5	4	10	9
Psycholeptics	3	7	5	7	7
Antibacterials for systemic use	9	5	2	5	7
Drugs for obstructive airway diseases	7	3	3	4	9
Lipid modifying agents	3	3	4	8	4
Agents acting on the renin-angiotensin system	7	4	0	11	3
Thyroid therapy	4	3	3	7	5
Antihistamines for systemic use	5	4	3	6	3
Antithrombotic agents	2	4	2	6	4
Nasal preparations	2	4	1	1	7
Diuretics	1	2	0	5	5
Antianemic preparations	5	2	2	5	2
Mineral supplements	2	2	3	3	3
Calcium channel blockers	3	0	1	6	3
Drugs used in diabetes	3	2	0	1	6
Beta blocking agents	1	2	0	5	1
Ophthalmologicals	1	1	2	3	1
Urologicals	1	1	1	3	1
Antidiarrheals, intestinal agents (1)	2	2	0	0	3
Antivirals for systemic use	1	3	1	1	0
Corticosteroids for systemic use	1	1	0	1	3
Drugs for constipation	2	0	1	3	1
Anesthetics	0	1	0	3	0
Antiemetics and antinauseants	2	0	1	1	2
Drugs for functional gastrointestinal disorders	3	1	0	1	2
General nutrients	1	1	0	1	2
Topical products for joint and muscular pain	1	2	0	0	2
Antifungals for dermatological use	0	1	1	0	1
Antiobesity preparations, excl. Diet products	0	0	0	2	1
Corticosteroids, dermatological preparations	1	2	0	1	0
Cough and cold preparations	3	1	0	2	0
Other nervous system drugs	1	1	0	1	1
Unspecified herbal and traditional medicine	1	0	1	1	1
All other therapeutic products	0	1	0	1	0
Anti-acne preparations	0	1	0	1	0
Other alimentary tract and metabolism products	1	1	0	1	0
Throat preparations	0	1	0	0	1
Vaccines	0	1	0	1	0
Antiepileptics	0	0	1	0	0
Antihemorrhagics	0	0	0	0	1
Antihypertensives	0	0	1	0	0
Antiprotozoals	0	0	0	0	1
Antipruritics, incl. antihistamines, anesthetics	0	0	0	0	1
Antipsoriatics	0	0	0	0	1
Bile and liver therapy	0	0	0	1	0
Drugs for treatment of bone diseases	0	0	1	0	0
Gynecological antiinfectives and antiseptics	0	0	0	1	0
Immunosuppressants	0	0	0	1	0
Other respiratory system products	0	0	0	0	1
Stomatological preparations	0	0	0	0	1
Tonics	0	0	0	1	0
Muscle relaxants	2	0	1	1	2
Antibiotics,chemotherapeutics (dermatological use)	1	0	0	1	0
Antimycotics for systemic use	1	0	0	0	0

No statistical analyses for this end point

Secondary: Change from baseline in vital signs (systolic blood pressure) at Weeks 2, 4, 8, 12 and 16

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End point title

Change from baseline in vital signs (systolic blood pressure) at Weeks 2, 4, 8, 12 and 16

End point description

Vital signs, including systolic and diastolic blood pressure, pulse rate, temperature, weight, waist circumference, and height, were measured at the time points and recorded in the eCRF. All vital signs were reviewed by the Investigator or delegated physician. In categories the number of subjects analyzed (N) for each week is mentioned for each reporting group respectively.

End point type

Secondary

End point timeframe

From baseline to Weeks 2, 4, 8, 12 and 16

End point values	Placebo	40 mg BAY3427080	80 mg BAY3427080	120 mg BAY3427080	160 mg BAY3427080
Number of subjects analysed	47	31	17	52	52
Units: mmHg
arithmetic mean (standard deviation)
Baseline (N=47,31,17,52,52)	123.2 ± 10.4	124.2 ± 10.1	128.9 ± 9.8	124.6 ± 10.9	124.0 ± 12.9
Week 2: Change from baseline (N=44,31,17,52,51)	0.3 ± 12.5	-0.2 ± 9.0	-1.5 ± 12.5	-2.9 ± 9.3	-0.8 ± 9.2
Week 4: Change from baseline (N=45,31,17,51,48)	1.7 ± 12.4	0.1 ± 11.9	-3.1 ± 9.4	-4.7 ± 10.7	-1.3 ± 10.8
Week 8: Change from baseline (N=44,31,16,52,46)	0.5 ± 10.8	0.5 ± 12.5	-2.1 ± 10.1	-1.3 ± 10.0	-3.8 ± 10.5
Week 12: Change from baseline (N=44,30,16,50,45)	-0.6 ± 12.2	-2.1 ± 10.9	-5.9 ± 11.3	-1.1 ± 10.2	-1.3 ± 12.8
Week 16: Change from baseline (N=43,30,16,51,45)	3.8 ± 13.3	-0.9 ± 11.7	-6.4 ± 11.1	-1.4 ± 10.8	2.1 ± 9.4

No statistical analyses for this end point

Secondary: Change from baseline in vital signs (pulse rate) at Weeks 2, 4, 8, 12 and 16

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End point title

Change from baseline in vital signs (pulse rate) at Weeks 2, 4, 8, 12 and 16

End point description

End point type

Secondary

End point timeframe

From baseline to Weeks 2, 4, 8, 12 and 16

End point values	Placebo	40 mg BAY3427080	80 mg BAY3427080	120 mg BAY3427080	160 mg BAY3427080
Number of subjects analysed	47	31	17	52	52
Units: beats/min
arithmetic mean (standard deviation)
Baseline (N=47,31,17,52,52)	69.7 ± 7.8	71.4 ± 10.3	70.6 ± 8.7	70.1 ± 10.2	69.7 ± 10.2
Week 2: Change from baseline (N=44,31,17,52,51)	-0.1 ± 8.1	-0.3 ± 7.3	-0.7 ± 9.9	-3.1 ± 9.7	2.1 ± 9.4
Week 4: Change from baseline (N=45,31,17,51,48)	-0.6 ± 6.9	0.5 ± 7.6	-2.8 ± 8.9	-1.8 ± 6.4	0.9 ± 7.7
Week 8: Change from baseline (N=44,31,16,52,46)	0.4 ± 7.7	-0.5 ± 8.1	-3.1 ± 9.8	-2.8 ± 7.9	0.3 ± 8.1
Week 12: Change from baseline (N=44,30,16,50,45)	0.1 ± 9.2	0.3 ± 8.4	0.9 ± 8.8	-1.4 ± 8.8	0.9 ± 7.4
Week 16: Change from baseline (N=43,30,16,51,45)	3.2 ± 10.6	3.3 ± 10.5	0.0 ± 11.3	-0.7 ± 8.5	0.3 ± 8.4

No statistical analyses for this end point

Secondary: Change from baseline in vital signs (temperature) at Weeks 2, 4, 8, 12 and 16

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End point title

Change from baseline in vital signs (temperature) at Weeks 2, 4, 8, 12 and 16

End point description

End point type

Secondary

End point timeframe

From baseline to Weeks 2, 4, 8, 12 and 16

End point values	Placebo	40 mg BAY3427080	80 mg BAY3427080	120 mg BAY3427080	160 mg BAY3427080
Number of subjects analysed	47	31	17	52	52
Units: Celsius (C)
arithmetic mean (standard deviation)
Baseline (N=47,31,17,52,52)	36.69 ± 0.43	36.62 ± 0.32	36.73 ± 0.30	36.52 ± 0.46	36.68 ± 0.39
Week 2: Change from baseline (N=44,31,17,52,51)	-0.09 ± 0.40	-0.04 ± 0.28	0.04 ± 0.26	0.12 ± 0.50	-0.01 ± 0.43
Week 4: Change from baseline (N=45,31,17,50,48)	-0.15 ± 0.47	-0.06 ± 0.34	0.01 ± 0.41	0.12 ± 0.46	-0.06 ± 0.32
Week 8: Change from baseline (N=44,31,16, 52,46)	-0.09 ± 0.38	-0.01 ± 0.35	0.00 ± 0.31	0.11 ± 0.49	-0.01 ± 0.42
Week 12: Change from baseline (N=44,30,16,50,45)	-0.12 ± 0.44	-0.12 ± 0.31	-0.03 ± 0.38	0.04 ± 0.46	-0.08 ± 0.36
Week 16: Change from baseline (N=43,30,16,51,45)	-0.07 ± 0.50	-0.03 ± 0.30	-0.04 ± 0.32	0.08 ± 0.41	-0.09 ± 0.41

No statistical analyses for this end point

Secondary: Change from baseline in vital signs (weight) at Weeks 2, 4, 8, 12 and 16

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End point title

Change from baseline in vital signs (weight) at Weeks 2, 4, 8, 12 and 16

End point description

End point type

Secondary

End point timeframe

From baseline to Weeks 2, 4, 8, 12 and 16

End point values	Placebo	40 mg BAY3427080	80 mg BAY3427080	120 mg BAY3427080	160 mg BAY3427080
Number of subjects analysed	47	31	17	52	52
Units: Kilogram (Kg)
arithmetic mean (standard deviation)
Baseline (N=47,31,17,52,52)	75.85 ± 13.13	72.65 ± 14.76	78.14 ± 15.75	72.36 ± 15.26	74.11 ± 15.02
Week 2: Change from baseline (N=44,31,17,52,51)	0.20 ± 1.07	0.30 ± 1.03	0.13 ± 1.32	-0.13 ± 1.19	0.04 ± 0.84
Week 4: Change from baseline (N=45,31,17,51,48)	0.23 ± 1.51	0.08 ± 1.11	0.12 ± 1.88	-0.31 ± 1.26	0.00 ± 1.35
Week 8: Change from baseline (N=44,31,16,52,46)	0.16 ± 1.98	0.26 ± 1.59	-0.11 ± 1.79	-0.18 ± 1.78	-0.25 ± 2.32
Week 12: Change from baseline (N=44,30,16,50,45)	-0.02 ± 2.34	0.58 ± 2.46	-0.14 ± 2.03	-0.08 ± 1.93	-0.48 ± 2.62
Week 16: Change from baseline (N=43,30,16,51,45)	0.17 ± 2.48	0.39 ± 2.81	-0.13 ± 2.59	-0.20 ± 2.13	-0.34 ± 2.82

No statistical analyses for this end point

Secondary: Change from baseline in vital signs (Body Mass Index ) at Weeks 2, 4, 8, 12 and 16

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End point title

Change from baseline in vital signs (Body Mass Index ) at Weeks 2, 4, 8, 12 and 16

End point description

End point type

Secondary

End point timeframe

From baseline to Weeks 2, 4, 8, 12 and 16

End point values	Placebo	40 mg BAY3427080	80 mg BAY3427080	120 mg BAY3427080	160 mg BAY3427080
Number of subjects analysed	47	31	17	52	52
Units: kg/m2
arithmetic mean (standard deviation)
Baseline (N=47,31,17,52,52)	28.59 ± 3.81	27.69 ± 4.97	29.81 ± 4.93	27.26 ± 4.85	27.72 ± 4.74
Week 2: Change from baseline (N=44,31,17,52,51)	0.07 ± 0.41	0.11 ± 0.39	0.06 ± 0.5	-0.04 ± 0.45	0.01 ± 0.33
Week 4: Change from baseline (N=45,31,17,51,48)	0.07 ± 0.58	0.02 ± 0.42	0.06 ± 0.75	-0.11 ± 0.49	0.00 ± 0.53
Week 8: Change from baseline (N=44,31,16,52,46)	0.04 ± 0.75	0.09 ± 0.59	-0.04 ± 0.69	-0.06 ± 0.66	-0.09 ± 0.88
Week 12: Change from baseline (N=44,30,16,50,45)	-0.03 ± 0.87	0.21 ± 0.87	-0.05 ± 0.79	-0.02 ± 0.73	-0.18 ± 0.99
Week 16: Change from baseline (N=43,30,16,51,45)	0.04 ± 0.96	0.13 ± 1.01	-0.04 ± 1.01	-0.07 ± 0.79	-0.13 ± 1.07

No statistical analyses for this end point

Secondary: Change from baseline in vital signs (waist circumference) at Weeks 2, 4, 8, 12 and 16

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End point title

Change from baseline in vital signs (waist circumference) at Weeks 2, 4, 8, 12 and 16

End point description

End point type

Secondary

End point timeframe

From baseline to Weeks 2, 4, 8, 12 and 16

End point values	Placebo	40 mg BAY3427080	80 mg BAY3427080	120 mg BAY3427080	160 mg BAY3427080
Number of subjects analysed	47	31	17	52	52
Units: cm
arithmetic mean (standard deviation)
Baseline (N=46,31,17,50,52)	95.47 ± 11.69	93.61 ± 13.10	97.59 ± 13.15	91.12 ± 13.03	92.42 ± 12.36
Week 2: Change from baseline (N=43,31,17,49,51)	0.26 ± 3.99	0.79 ± 3.55	-0.91 ± 2.15	0.13 ± 3.72	-0.18 ± 3.90
Week 4: Change from baseline (N=44,31,17,48,48)	0.17 ± 4.99	-0.07 ± 4.23	-1.26 ± 3.00	0.05 ± 3.84	-0.09 ± 3.97
Week 8: Change from baseline (N=43,31,16,50,45)	-0.14 ± 4.45	-0.11 ± 4.30	0.04 ± 2.77	-0.76 ± 4.10	-0.08 ± 4.71
Week 12: Change from baseline (N=43,30,16,48,45)	-1.72 ± 5.25	-1.16 ± 4.87	0.60 ± 2.81	-0.25 ± 3.97	-0.39 ± 4.42
Week 16: Change from baseline (N=42,30,16, 49,44)	-0.80 ± 5.46	-0.99 ± 5.18	4.33 ± 12.90	0.02 ± 4.58	-0.24 ± 4.41

No statistical analyses for this end point

Secondary: Number of subjects with normal electrocardiogram (ECG) findings at each visit

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End point title

Number of subjects with normal electrocardiogram (ECG) findings at each visit

End point description

All ECGs were performed after the subject had rested for 5 minutes in a semi-recumbent position. All ECG reports were reviewed, signed and dated by the Investigator or delegated physician. The Investigator commented on all abnormal findings and determined whether they were Normal, Abnormal not clinically significant, Abnormal clinically significant. In categories the number of subjects analyzed (N) for each week is mentioned for each reporting group respectively.

End point type

Secondary

End point timeframe

At Weeks 2, 4, 8, 12 and 16

End point values	Placebo	40 mg BAY3427080	80 mg BAY3427080	120 mg BAY3427080	160 mg BAY3427080
Number of subjects analysed	47	31	17	52	52
Units: Subjects
Baseline (N=47,31,17,52,52)	38	24	11	31	34
Week 2 (N= 44,31,17,52,51)	33	23	12	34	27
Week 4 (N=45,31,17,51,48)	32	23	10	28	31
Week 8 (N=44,31,17,52,46)	29	21	12	30	27
Week 12 (N=44,30,16,50,45)	30	22	11	31	31
Week 16 (N=43,30,16,51,45)	27	26	14	31	28

No statistical analyses for this end point

Secondary: Change from baseline in vital signs (diastolic blood pressure) at Weeks 2, 4, 8, 12 and 16

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End point title

Change from baseline in vital signs (diastolic blood pressure) at Weeks 2, 4, 8, 12 and 16

End point description

Vital signs, including systolic and diastolic blood pressure were measured at the time points and recorded in the eCRF. All vital signs were reviewed by the Investigator or delegated physician. In categories the number of subjects analyzed (N) for each week is mentioned for each reporting group respectively.

End point type

Secondary

End point timeframe

From baseline to Weeks 2, 4, 8, 12 and 16

End point values	Placebo	40 mg BAY3427080	80 mg BAY3427080	120 mg BAY3427080	160 mg BAY3427080
Number of subjects analysed	47	31	17	52	52
Units: mmHg
arithmetic mean (standard deviation)
Baseline (N=47,31,17,52,52)	80.1 ± 8.0	78.7 ± 8.5	79.9 ± 9.1	78.1 ± 7.6	78.7 ± 10.1
Week 2: Change from baseline (N=44,31,16,52,51)	-0.7 ± 6.6	-1.1 ± 8.4	-0.8 ± 8.7	-3.1 ± 7.6	-0.4 ± 7.6
Week 4: Change from baseline (N=45,31,17,51,48)	-0.2 ± 7.4	1.2 ± 7.8	-2.1 ± 6.5	-2.8 ± 9.1	-2.3 ± 8.0
Week 8: Change from baseline (N=44,31,16,52,46)	0.2 ± 6.7	-0.5 ± 6.8	-3.6 ± 6.9	-0.6 ± 8.4	-1.6 ± 7.5
Week 12: Change from baseline (N=44,30,16,50,45)	-0.5 ± 9.6	-2.8 ± 9.9	-2.2 ± 7.1	-1.8 ± 10.3	-1.0 ± 9.3
Week 16: Change from baseline (N=43,30,16,51,45)	1.6 ± 7.6	-1.2 ± 8.3	-3.8 ± 9.7	-1.9 ± 9.1	0.6 ± 7.2

No statistical analyses for this end point

Secondary: Number of subjects with abnormal not clinically significant ECG findings at each visit

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End point title

Number of subjects with abnormal not clinically significant ECG findings at each visit

End point description

End point type

Secondary

End point timeframe

At Weeks 2, 4, 8, 12 and 16

End point values	Placebo	40 mg BAY3427080	80 mg BAY3427080	120 mg BAY3427080	160 mg BAY3427080
Number of subjects analysed	47	31	17	52	52
Units: Subjects
Baseline (N=47,31,17,52,52)	9	7	6	21	18
Week 2 (N=44,31,17,52,51)	11	8	5	18	24
Week 4 (N=45,31,17,51,48)	13	8	6	23	17
Week 8 (N=44,31,17,52,46)	15	10	5	21	19
Week 12 (N=44,30,16,50,45)	14	8	5	19	14
Week 16 (N=43,30,16,51,45)	16	4	2	20	17

No statistical analyses for this end point

Secondary: Number of subjects with abnormal clinically significant ECG findings at each visit

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End point title

Number of subjects with abnormal clinically significant ECG findings at each visit

End point description

End point type

Secondary

End point timeframe

At Weeks 2, 4, 8, 12 and 16

End point values	Placebo	40 mg BAY3427080	80 mg BAY3427080	120 mg BAY3427080	160 mg BAY3427080
Number of subjects analysed	47	31	17	52	52
Units: Subjects
Baseline (N=47,31,17,52,52)	0	0	0	0	0
Week 2 (N= 44,31,17,52,51)	0	0	0	0	0
Week 4 (N=45,31,17,51,48)	0	0	1	0	0
Week 8 (N=44,31,17,52,46)	0	0	0	1	0
Week 12 (N=44,30,16,50,45)	0	0	0	0	0
Week 16 (N=43,30,16,51,45)	0	0	0	0	0

No statistical analyses for this end point

Secondary: Change from baseline at Weeks 2, 4, 8, 12 and 16 in ECG intervals (RR)

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End point title

Change from baseline at Weeks 2, 4, 8, 12 and 16 in ECG intervals (RR)

End point description

All ECGs were performed after the subject had rested for 5 minutes in a semi-recumbent position. The same model of ECG recorder was used throughout the study for any given subject wherever possible. All ECG reports were reviewed, signed and dated by the Investigator or delegated physician. Reports were then filed with the subject’s medical record. In categories the number of subjects analyzed (N) for each week is mentioned for each reporting group respectively.

End point type

Secondary

End point timeframe

At Weeks 2, 4, 8, 12 and 16

End point values	Placebo	40 mg BAY3427080	80 mg BAY3427080	120 mg BAY3427080	160 mg BAY3427080
Number of subjects analysed	47	31	17	52	52
Units: mSec
arithmetic mean (standard deviation)
Baseline	913.5 ± 128.5	891.4 ± 145.6	934.3 ± 120.3	927.8 ± 135.5	935.9 ± 151.2
Week 2: Change from baseline (N=44,31,17,52,51)	17.3 ± 84.2	23.0 ± 101.7	-12.6 ± 99.7	27.3 ± 94.7	-2.6 ± 137.7
Week 4: Change from baseline (N=45,31,17,51,48)	1.6 ± 82.8	24.8 ± 101.9	20.5 ± 108.5	27.3 ± 92.6	4.5 ± 108.0
Week 8: Change from baseline (N=44,31,17,52,46)	35.8 ± 108.7	24.8 ± 104.6	19.0 ± 128.6	22.3 ± 109.2	-22.6 ± 90.1
Week 12: Change from baseline (N=44,30,16,50,45)	25.5 ± 143.4	18.0 ± 110.9	-23.3 ± 105.1	27.2 ± 95.9	-1.4 ± 107.9
Week 16: Change from baseline (N=43,30,16,51,45)	-22.4 ± 135.5	2.4 ± 138.5	-25.4 ± 149.6	5.9 ± 110.8	-8.0 ± 110.3

No statistical analyses for this end point

Secondary: Change from baseline at Weeks 2, 4, 8, 12 and 16 in ECG intervals (PR)

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End point title

Change from baseline at Weeks 2, 4, 8, 12 and 16 in ECG intervals (PR)

End point description

End point type

Secondary

End point timeframe

At Weeks 2, 4, 8, 12 and 16

End point values	Placebo	40 mg BAY3427080	80 mg BAY3427080	120 mg BAY3427080	160 mg BAY3427080
Number of subjects analysed	47	31	17	52	52
Units: mSec
arithmetic mean (standard deviation)
Baseline	162.6 ± 21.8	167.8 ± 16.5	162.9 ± 21.7	157.2 ± 21.7	164.2 ± 25.8
Week 2: Change from baseline (N=44,31,17,52,51)	1.2 ± 9.7	4.6 ± 11.7	5.2 ± 11.8	3.0 ± 10.2	-2.2 ± 16.3
Week 4: Change from baseline (N=45,31,17,51,48)	0.0 ± 11.2	5.9 ± 12.3	2.9 ± 12.1	3.8 ± 17.7	1.8 ± 13.8
Week 8: Change from baseline (N=44,31,17,52,46)	1.5 ± 15.1	3.6 ± 10.4	-0.1 ± 12.3	4.3 ± 10.3	-1.1 ± 14.5
Week 12: Change from baseline (N=44,30,16,50,45)	1.6 ± 11.5	3.9 ± 11.7	0.7 ± 16.2	1.9 ± 11.4	-1.5 ± 16.9
Week 16: Change from baseline (N=43,30,16,51,45)	0.4 ± 11.3	2.2 ± 13.3	2.4 ± 16.0	2.8 ± 11.1	-0.4 ± 13.3

No statistical analyses for this end point

Secondary: Change from baseline at Weeks 2, 4, 8, 12 and 16 in ECG intervals (QT)

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End point title

Change from baseline at Weeks 2, 4, 8, 12 and 16 in ECG intervals (QT)

End point description

End point type

Secondary

End point timeframe

At Weeks 2, 4, 8, 12 and 16

End point values	Placebo	40 mg BAY3427080	80 mg BAY3427080	120 mg BAY3427080	160 mg BAY3427080
Number of subjects analysed	47	31	17	52	52
Units: mSec
arithmetic mean (standard deviation)
Baseline	394.5 ± 31.2	397.2 ± 28.7	403.5 ± 26.9	402.3 ± 40.3	401.2 ± 28.0
Week 2: Change from baseline (N=44,31,17,52,51)	3.6 ± 18.0	0.2 ± 17.8	1.1 ± 21.7	-0.9 ± 35.6	-3.2 ± 25.2
Week 4: Change from baseline (N=45,31,17,51,48)	4.7 ± 18.5	-0.1 ± 18.5	4.8 ± 35.2	0.2 ± 28.1	0.8 ± 21.5
Week 8: Change from baseline (N=44,31,17,52,46)	2.0 ± 19.0	1.5 ± 17.2	6.5 ± 28.4	0.5 ± 34.6	-4.0 ± 20.3
Week 12: Change from baseline (N=44,30,16,50,45)	1.4 ± 25.1	0.8 ± 21.6	-8.9 ± 20.6	-1.1 ± 32.9	1.0 ± 19.5
Week 16: Change from baseline (N=43,30,16,51,45)	-1.7 ± 23.3	-4.7 ± 24.4	-3.2 ± 27.6	-4.1 ± 38.1	-2.4 ± 25.5

No statistical analyses for this end point

Secondary: Change from baseline at Weeks 2, 4, 8, 12 and 16 in ECG intervals (QTc)

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End point title

Change from baseline at Weeks 2, 4, 8, 12 and 16 in ECG intervals (QTc)

End point description

All ECGs were performed after the subject had rested for 5 minutes in a semi-recumbent position. The same model of ECG recorder was used throughout the study for any given subject wherever possible. All ECG reports were reviewed, signed and dated by the Investigator or delegated physician. Reports were then filed with the subject’s medical record. QTc: QT corrected interval. In categories the number of subjects analyzed (N) for each week is mentioned for each reporting group respectively.

End point type

Secondary

End point timeframe

At Weeks 2, 4, 8, 12 and 16

End point values	Placebo	40 mg BAY3427080	80 mg BAY3427080	120 mg BAY3427080	160 mg BAY3427080
Number of subjects analysed	47	31	17	52	52
Units: mSec
arithmetic mean (standard deviation)
Baseline	410.6 ± 20.9	417.9 ± 21.4	416.4 ± 14.1	415.9 ± 29.3	415.2 ± 22.1
Week 2: Change from baseline (N=44,31,17,52,51)	1.6 ± 14.3	-2.4 ± 11.2	2.9 ± 14.7	-4.9 ± 28.2	-2.1 ± 15.4
Week 4: Change from baseline (N=45,31,17,51,48)	5.6 ± 16.1	-5.4 ± 11.8	1.7 ± 19.9	-2.9 ± 24.5	0.2 ± 16.3
Week 8: Change from baseline (N=44,31,17,52,46)	-3.9 ± 18.5	-3.8 ± 12.3	2.3 ± 10.8	-2.2 ± 27.5	1.2 ± 14.7
Week 12: Change from baseline (N=44,30,16,50,45)	-2.4 ± 20.8	-3.2 ± 14.9	-3.1 ± 14.4	-4.7 ± 31.3	0.5 ± 14.4
Week 16: Change from baseline (N=43,30,16,51,45)	2.8 ± 14.9	-4.8 ± 13.6	4.3 ± 17.5	-4.5 ± 31.2	-1.6 ± 13.6

No statistical analyses for this end point

Secondary: Change from baseline at Weeks 2, 4, 8, 12 and 16 in ECG intervals (QTcF)

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End point title

Change from baseline at Weeks 2, 4, 8, 12 and 16 in ECG intervals (QTcF)

End point description

All ECGs were performed after the subject had rested for 5 minutes in a semi-recumbent position. The same model of ECG recorder was used throughout the study for any given subject wherever possible. All ECG reports were reviewed, signed and dated by the Investigator or delegated physician. Reports were then filed with the subject’s medical record. QTcF: QT interval with Fridericia’s correction. In categories the number of subjects analyzed (N) for each week is mentioned for each reporting group respectively.

End point type

Secondary

End point timeframe

At Weeks 2, 4, 8, 12 and 16

End point values	Placebo	40 mg BAY3427080	80 mg BAY3427080	120 mg BAY3427080	160 mg BAY3427080
Number of subjects analysed	47	31	17	52	52
Units: mSec
arithmetic mean (standard deviation)
Baseline	407.2 ± 20.6	413.8 ± 19.9	413.2 ± 14.3	413.1 ± 30.7	411.4 ± 18.6
Week 2: Change from baseline (N=44,31,17,52,51)	1.2 ± 13.7	-3.5 ± 10.2	3.4 ± 13.4	-4.8 ± 29.5	-2.5 ± 15.7
Week 4: Change from baseline (N=45,31,17,51,48)	4.8 ± 16.4	-4.2 ± 11.5	2.1 ± 23.4	-3.5 ± 24.7	0.4 ± 15.4
Week 8: Change from baseline (N=44,31,17,52,46)	-2.8 ± 15.9	-2.7 ± 10.9	4.0 ± 13.2	-2.6 ± 28.7	-0.4 ± 16.1
Week 12: Change from baseline (N=44,30,16,50,45)	-1.7 ± 18.5	-1.9 ± 13.9	-5.1 ± 13.2	-5.1 ± 30.8	1.1 ± 14.6
Week 16: Change from baseline (N=43,30,16,51,45)	2.6 ± 15.1	-5.6 ± 14.2	1.5 ± 14.5	-4.8 ± 32.7	-1.3 ± 16.4

No statistical analyses for this end point

Secondary: Number of subjects with absolute QTcF values by category at each visit: ≤450, >450 to ≤480, >480 to ≤500, >500 msec

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End point title

Number of subjects with absolute QTcF values by category at each visit: ≤450, >450 to ≤480, >480 to ≤500, >500 msec

End point description

Absolute QTcF values reported. Number of subjects analyzed at for each reporting group respectively was as follow: Baseline N=47, 31, 17, 52, 52; Week 1 N=44, 31, 17, 52, 52; Week 4 N=45, 31, 17, 51, 48; Week 8 N=44, 31, 17, 52, 46; Week 12 N=44, 30, 16, 50, 45; Week 16 N=43, 30, 16, 51, 45.

End point type

Secondary

End point timeframe

From baseline to Weeks 2, 4, 8, 12 and 16

End point values	Placebo	40 mg BAY3427080	80 mg BAY3427080	120 mg BAY3427080	160 mg BAY3427080
Number of subjects analysed	47	31	17	52	52
Units: Subjects
Baseline: <=450 msec	46	30	16	51	50
Baseline: >450 to <=480 msec	1	1	1	0	2
Baseline: >480 to <=500 msec	0	0	0	0	0
Baseline: >500 msec	0	0	0	1	0
Week 2: <=450 msec	44	30	16	52	50
Week 2: >450 to <=480 msec	0	1	1	0	1
Week 2: >480 to <=500 msec	0	0	0	0	0
Week 2: >500 msec	0	0	0	0	0
Week 4: <=450 msec	44	30	16	51	47
Week 4: >450 to <=480 msec	1	1	0	0	1
Week 4: >480 to <=500 msec	0	0	0	0	0
Week 4: >500 msec	0	0	1	0	0
Week 8: <=450 msec	44	30	17	52	46
Week 8: >450 to <=480 msec	0	1	0	0	0
Week 8: >480 to <=500 msec	0	0	0	0	0
Week 8: >500 msec	0	0	0	0	0
Week 12: <=450 msec	44	30	16	50	45
Week 12: >450 to <=480 msec	0	0	0	0	0
Week 12: >480 to <=500 msec	0	0	0	0	0
Week 12: >500 msec	0	0	0	0	0
Week 16: <=450 msec	42	30	15	51	44
Week 16: >450 to <=480 msec	1	0	1	0	1
Week 16: >480 to <=500 msec	0	0	0	0	0
Week 16: >500 msec	0	0	0	0	0

No statistical analyses for this end point

Secondary: Number of subjects with change from baseline in ECG QTcF values by category at Weeks 2, 4, 8, 12 and 16: ≤0, >0 to ≤30, >30 to ≤60, >60 msec

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End point title

Number of subjects with change from baseline in ECG QTcF values by category at Weeks 2, 4, 8, 12 and 16: ≤0, >0 to ≤30, >30 to ≤60, >60 msec

End point description

Increase from Baseline overtime was reported. Number of subjects analyzed at for each reporting group respectively was as follow: Baseline N=47, 31, 17, 52, 52; Week 1 N=44, 31, 17, 52, 52; Week 4 N=45, 31, 17, 51, 48; Week 8 N=44, 31, 17, 52, 46; Week 12 N=44, 30, 16, 50, 45; Week 16 N=43, 30, 16, 51, 45.

End point type

Secondary

End point timeframe

From baseline to Weeks 2, 4, 8, 12 and 16

End point values	Placebo	40 mg BAY3427080	80 mg BAY3427080	120 mg BAY3427080	160 mg BAY3427080
Number of subjects analysed	47	31	17	52	52
Units: Subjects
Week 2: <=0 msec	19	21	8	27	29
Week 2: >0 to <=30 msec	25	10	8	24	22
Week 2: >30 to <=60 msec	0	0	1	1	0
Week 2: >60 msec	0	0	0	0	0
Week 4: <=0 msec	20	20	8	27	24
Week 4: >0 to <=30 msec	23	11	8	24	22
Week 4: >30 to <=60 msec	2	0	0	0	2
Week 4: >60 msec	0	0	1	0	0
Week 8: <=0 msec	24	20	8	25	19
Week 8: >0 to <=30 msec	20	11	9	26	26
Week 8: >30 to <=60 msec	0	0	0	1	1
Week 8: >60 msec	0	0	0	0	0
Week 12: <=0 msec	24	15	10	29	22
Week 12: >0 to <=30 msec	19	15	6	21	22
Week 12: >30 to <=60 msec	1	0	0	0	1
Week 12: >60 msec	0	0	0	0	0
Week 16: <=0 msec	18	18	7	26	24
Week 16: >0 to <=30 msec	23	12	9	24	20
Week 16: >30 to <=60 msec	2	0	0	1	1
Week 16: >60 msec	0	0	0	0	0

No statistical analyses for this end point

Secondary: Change from baseline in the electronic Columbia Suicide Severity Rating Scale (eC-SSRS) at Weeks 4, 12 and 16

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End point title

Change from baseline in the electronic Columbia Suicide Severity Rating Scale (eC-SSRS) at Weeks 4, 12 and 16

End point description

The Columbia Suicide Severity Rating Scale (C-SSRS) is a rating scale created to evaluate suicidality in adults and children over the age of 12. It rates an individual's degree of suicidal ideation on a scale, ranging from "wish to be dead" to "active suicidal ideation with specific plan and intent." The version used was the eC-SSRS, which is a subject-reported version of the scale. Shifts from baseline versus post-baseline to demonstrate changes in categories (cat) were reported using cat 1 (No Suicidal Ideation or Behaviour), cat 2 (Suicidal Ideation) and cat 3 (Suicidal Behaviour).

End point type

Secondary

End point timeframe

Baseline to Weeks 4, 12 and 16

End point values	Placebo	40 mg BAY3427080	80 mg BAY3427080	120 mg BAY3427080	160 mg BAY3427080
Number of subjects analysed	42 ^[6]	26 ^[7]	16 ^[8]	44 ^[9]	46 ^[10]
Units: Subjects
Week 4: shift from cat 1 to cat 1	34	14	13	38	38
Week 4: shift from cat 1 to cat 2	1	0	0	0	0
Week 4: shift from cat 1 to cat 3	0	0	0	0	0
Week 4: shift from cat 2 to cat 1	5	7	2	4	7
Week 4: shift from cat 2 to cat 2	1	0	0	0	0
Week 4: shift from cat 2 to cat 3	0	0	0	0	0
Week 4: shift from cat 3 to cat 1	1	5	1	2	1
Week 4: shift from cat 3 to cat 2	0	0	0	0	0
Week 4: shift from cat 3 to cat 3	0	0	0	0	0
Week 12: shift from cat 1 to cat 1	34	14	12	40	33
Week 12: shift from cat 1 to cat 2	0	0	0	0	0
Week 12: shift from cat 1 to cat 3	0	0	0	0	0
Week 12: shift from cat 2 to cat 1	7	5	3	2	7
Week 12: shift from cat 2 to cat 2	0	2	0	1	0
Week 12: shift from cat 2 to cat 3	0	0	0	0	0
Week 12: shift from cat 3 to cat 1	1	5	1	2	1
Week 12: shift from cat 3 to cat 2	0	0	0	0	0
Week 12: shift from cat 3 to cat 3	0	0	0	0	0
Week 16: shift from cat 1 to cat 1	33	15	12	40	33
Week 16: shift from cat 1 to cat 2	0	0	0	0	0
Week 16: shift from cat 1 to cat 3	0	0	0	0	0
Week 16: shift from cat 2 to cat 1	6	6	3	4	7
Week 16: shift from cat 2 to cat 2	1	1	0	0	0
Week 16: shift from cat 2 to cat 3	0	0	0	0	0
Week 16: shift from cat 3 to cat 1	1	5	1	2	1
Week 16: shift from cat 3 to cat 2	0	0	0	0	0
Week 16: shift from cat 3 to cat 3	0	0	0	0	0

Notes
[6] - Week 16 N=41
[7] - Week 16 N=27
[8] - Week 12 N=45; Week 16 N=46
[9] - Week 12 N=45; Week 16 N=46
[10] - Weeks 12 and 16 N=41

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

On or after first dosing with randomised study treatment up to Week 16

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

21.1

Reporting group title

Placebo

Reporting group description

Subjects received placebo

Reporting group title

40 mg BAY3427080

Reporting group description

Subjects received 40 mg BAY3427080

Reporting group title

80 mg BAY3427080

Reporting group description

Subjects received 80 mg BAY3427080

Reporting group title

120 mg BAY3427080

Reporting group description

Subjects received 120 mg BAY3427080

Reporting group title

160 mg BAY3427080

Reporting group description

Subjects received 160 mg BAY3427080

Serious adverse events	Placebo	40 mg BAY3427080	80 mg BAY3427080	120 mg BAY3427080	160 mg BAY3427080
Total subjects affected by serious adverse events
subjects affected / exposed	2 / 47 (4.26%)	0 / 31 (0.00%)	1 / 17 (5.88%)	1 / 52 (1.92%)	1 / 52 (1.92%)
number of deaths (all causes)	0	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0	0
Nervous system disorders
Migraine
subjects affected / exposed	0 / 47 (0.00%)	0 / 31 (0.00%)	0 / 17 (0.00%)	1 / 52 (1.92%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Nephrolithiasis
subjects affected / exposed	0 / 47 (0.00%)	0 / 31 (0.00%)	1 / 17 (5.88%)	0 / 52 (0.00%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Sepsis
subjects affected / exposed	1 / 47 (2.13%)	0 / 31 (0.00%)	0 / 17 (0.00%)	0 / 52 (0.00%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Tooth abscess
subjects affected / exposed	0 / 47 (0.00%)	0 / 31 (0.00%)	0 / 17 (0.00%)	0 / 52 (0.00%)	1 / 52 (1.92%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infective exacerbation of chronic obstructive airways disease
subjects affected / exposed	1 / 47 (2.13%)	0 / 31 (0.00%)	0 / 17 (0.00%)	0 / 52 (0.00%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	Placebo	40 mg BAY3427080	80 mg BAY3427080	120 mg BAY3427080	160 mg BAY3427080
Total subjects affected by non serious adverse events
subjects affected / exposed	18 / 47 (38.30%)	13 / 31 (41.94%)	14 / 17 (82.35%)	23 / 52 (44.23%)	23 / 52 (44.23%)
General disorders and administration site conditions
Fatigue
subjects affected / exposed	0 / 47 (0.00%)	3 / 31 (9.68%)	1 / 17 (5.88%)	1 / 52 (1.92%)	4 / 52 (7.69%)
occurrences all number	0	3	1	1	4
Non-cardiac chest pain
subjects affected / exposed	0 / 47 (0.00%)	0 / 31 (0.00%)	1 / 17 (5.88%)	0 / 52 (0.00%)	0 / 52 (0.00%)
occurrences all number	0	0	1	0	0
Reproductive system and breast disorders
Breast tenderness
subjects affected / exposed	1 / 47 (2.13%)	0 / 31 (0.00%)	1 / 17 (5.88%)	1 / 52 (1.92%)	0 / 52 (0.00%)
occurrences all number	1	0	1	1	0
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	2 / 47 (4.26%)	0 / 31 (0.00%)	1 / 17 (5.88%)	1 / 52 (1.92%)	0 / 52 (0.00%)
occurrences all number	2	0	1	1	0
Oropharyngeal pain
subjects affected / exposed	0 / 47 (0.00%)	2 / 31 (6.45%)	0 / 17 (0.00%)	0 / 52 (0.00%)	2 / 52 (3.85%)
occurrences all number	0	2	0	0	2
Psychiatric disorders
Depressed mood
subjects affected / exposed	0 / 47 (0.00%)	0 / 31 (0.00%)	1 / 17 (5.88%)	2 / 52 (3.85%)	0 / 52 (0.00%)
occurrences all number	0	0	1	2	0
Insomnia
subjects affected / exposed	1 / 47 (2.13%)	0 / 31 (0.00%)	1 / 17 (5.88%)	0 / 52 (0.00%)	1 / 52 (1.92%)
occurrences all number	1	0	1	0	1
Investigations
Aspartate aminotransferase increased
subjects affected / exposed	0 / 47 (0.00%)	0 / 31 (0.00%)	1 / 17 (5.88%)	1 / 52 (1.92%)	0 / 52 (0.00%)
occurrences all number	0	0	1	1	0
Blood creatine phosphokinase increased
subjects affected / exposed	1 / 47 (2.13%)	1 / 31 (3.23%)	1 / 17 (5.88%)	3 / 52 (5.77%)	1 / 52 (1.92%)
occurrences all number	1	1	2	3	1
Electrocardiogram QT prolonged
subjects affected / exposed	0 / 47 (0.00%)	0 / 31 (0.00%)	1 / 17 (5.88%)	0 / 52 (0.00%)	0 / 52 (0.00%)
occurrences all number	0	0	1	0	0
Liver function test increased
subjects affected / exposed	0 / 47 (0.00%)	0 / 31 (0.00%)	1 / 17 (5.88%)	0 / 52 (0.00%)	0 / 52 (0.00%)
occurrences all number	0	0	1	0	0
Injury, poisoning and procedural complications
Arthropod bite
subjects affected / exposed	1 / 47 (2.13%)	2 / 31 (6.45%)	0 / 17 (0.00%)	1 / 52 (1.92%)	1 / 52 (1.92%)
occurrences all number	1	2	0	1	1
Cardiac disorders
Bradycardia
subjects affected / exposed	0 / 47 (0.00%)	0 / 31 (0.00%)	1 / 17 (5.88%)	0 / 52 (0.00%)	0 / 52 (0.00%)
occurrences all number	0	0	1	0	0
Nervous system disorders
Dizziness
subjects affected / exposed	0 / 47 (0.00%)	0 / 31 (0.00%)	0 / 17 (0.00%)	3 / 52 (5.77%)	3 / 52 (5.77%)
occurrences all number	0	0	0	4	3
Headache
subjects affected / exposed	6 / 47 (12.77%)	3 / 31 (9.68%)	2 / 17 (11.76%)	6 / 52 (11.54%)	4 / 52 (7.69%)
occurrences all number	8	3	2	7	6
Somnolence
subjects affected / exposed	1 / 47 (2.13%)	3 / 31 (9.68%)	1 / 17 (5.88%)	2 / 52 (3.85%)	6 / 52 (11.54%)
occurrences all number	2	3	1	2	6
Gastrointestinal disorders
Abdominal pain upper
subjects affected / exposed	0 / 47 (0.00%)	0 / 31 (0.00%)	1 / 17 (5.88%)	1 / 52 (1.92%)	0 / 52 (0.00%)
occurrences all number	0	0	1	1	0
Diarrhoea
subjects affected / exposed	3 / 47 (6.38%)	2 / 31 (6.45%)	2 / 17 (11.76%)	3 / 52 (5.77%)	3 / 52 (5.77%)
occurrences all number	3	2	2	3	3
Flatulence
subjects affected / exposed	0 / 47 (0.00%)	0 / 31 (0.00%)	1 / 17 (5.88%)	0 / 52 (0.00%)	0 / 52 (0.00%)
occurrences all number	0	0	1	0	0
Nausea
subjects affected / exposed	2 / 47 (4.26%)	2 / 31 (6.45%)	2 / 17 (11.76%)	1 / 52 (1.92%)	2 / 52 (3.85%)
occurrences all number	2	4	2	1	2
Skin and subcutaneous tissue disorders
Rash
subjects affected / exposed	1 / 47 (2.13%)	0 / 31 (0.00%)	1 / 17 (5.88%)	1 / 52 (1.92%)	1 / 52 (1.92%)
occurrences all number	1	0	1	1	1
Renal and urinary disorders
Haematuria
subjects affected / exposed	0 / 47 (0.00%)	0 / 31 (0.00%)	1 / 17 (5.88%)	0 / 52 (0.00%)	0 / 52 (0.00%)
occurrences all number	0	0	1	0	0
Nephrolithiasis
subjects affected / exposed	0 / 47 (0.00%)	0 / 31 (0.00%)	1 / 17 (5.88%)	1 / 52 (1.92%)	0 / 52 (0.00%)
occurrences all number	0	0	2	1	0
Musculoskeletal and connective tissue disorders
Joint swelling
subjects affected / exposed	1 / 47 (2.13%)	0 / 31 (0.00%)	1 / 17 (5.88%)	0 / 52 (0.00%)	0 / 52 (0.00%)
occurrences all number	1	0	1	0	0
Infections and infestations
Herpes zoster
subjects affected / exposed	0 / 47 (0.00%)	0 / 31 (0.00%)	2 / 17 (11.76%)	0 / 52 (0.00%)	0 / 52 (0.00%)
occurrences all number	0	0	2	0	0
Nasopharyngitis
subjects affected / exposed	4 / 47 (8.51%)	1 / 31 (3.23%)	0 / 17 (0.00%)	3 / 52 (5.77%)	0 / 52 (0.00%)
occurrences all number	4	1	0	3	0
Urinary tract infection
subjects affected / exposed	1 / 47 (2.13%)	2 / 31 (6.45%)	0 / 17 (0.00%)	2 / 52 (3.85%)	2 / 52 (3.85%)
occurrences all number	1	2	0	2	2
Viral upper respiratory tract infection
subjects affected / exposed	0 / 47 (0.00%)	0 / 31 (0.00%)	1 / 17 (5.88%)	2 / 52 (3.85%)	0 / 52 (0.00%)
occurrences all number	0	0	1	2	0
Viral sinusitis
subjects affected / exposed	0 / 47 (0.00%)	0 / 31 (0.00%)	1 / 17 (5.88%)	0 / 52 (0.00%)	0 / 52 (0.00%)
occurrences all number	0	0	1	0	0

More information

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Were there any global substantial amendments to the protocol? Yes

07 Feb 2019

In addition to minor typographical and formatting corrections, the following changes were made: - Clinical Chemistry was added to Week 8 visit. - A footnote was added to Inclusion Criterion #3 to provide further clarity and guidance on the definition of post-menopausal status. - Haemoglobin A1c was added to the list of clinical chemistry parameters. - The CRO’s name was updated from Pharm Olam International to Pharm Olam.

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.

The secondary endpoint "change from baseline in clinical laboratory assessments" will be reported during the next update of the record.

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Clinical trials

Clinical Trial Results: A Double-Blind, Randomised, Placebo Controlled, Adaptive Design Study of the Efficacy, Safety and Pharmacokinetics of NT-814 in Female Subjects With Moderate to Severe Vasomotor Symptoms Associated With the Menopause

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Mean change from baseline in mean daily frequency of moderate and severe hot flushes from baseline to Week 4

Primary: Mean change from baseline in mean daily frequency of moderate and severe hot flushes from baseline to Week 4

Primary: Mean change from baseline in mean daily frequency of moderate and severe hot flushes from baseline to Week 12

Primary: Mean change from baseline in mean daily frequency of moderate and severe hot flushes from baseline to Week 12

Primary: Mean change from baseline in mean severity of moderate and severe hot flushes from baseline to Week 4

Primary: Mean change from baseline in mean severity of moderate and severe hot flushes from baseline to Week 4

Primary: Mean change from baseline in mean severity of moderate and severe hot flushes from baseline to Week 12

Primary: Mean change from baseline in mean severity of moderate and severe hot flushes from baseline to Week 12

Secondary: Mean change from baseline in frequency of mean daily moderate and severe hot flushes from baseline to Weeks 1, 2, 8 and 16

Secondary: Mean change from baseline in frequency of mean daily moderate and severe hot flushes from baseline to Weeks 1, 2, 8 and 16

Secondary: Mean change from baseline in mean severity of moderate and severe hot flushes from baseline to Weeks 1, 2, 8 and 16

Secondary: Mean change from baseline in mean severity of moderate and severe hot flushes from baseline to Weeks 1, 2, 8 and 16

Secondary: Mean change from baseline in mean daily frequency of all hot flushes from baseline to Weeks 1, 2, 4, 8, 12 and 16

Secondary: Mean change from baseline in mean daily frequency of all hot flushes from baseline to Weeks 1, 2, 4, 8, 12 and 16

Secondary: Mean change from baseline in mean severity of all hot flushes from baseline to Weeks 1, 2, 4, 8, 12 and 16

Secondary: Mean change from baseline in mean severity of all hot flushes from baseline to Weeks 1, 2, 4, 8, 12 and 16

Secondary: Mean change from baseline in the mean daily hot flush score (frequency x severity) at Weeks 1, 2, 4, 8, 12 and 16

Secondary: Mean change from baseline in the mean daily hot flush score (frequency x severity) at Weeks 1, 2, 4, 8, 12 and 16

Secondary: Number of subjects with ≥50% and ≥80% reduction from baseline in mean daily hot flushes frequency at Week 12

Secondary: Number of subjects with ≥50% and ≥80% reduction from baseline in mean daily hot flushes frequency at Week 12

Secondary: Mean change from baseline in number of all night-time awakenings (NTA) at Weeks 1, 2, 4, 8, 12 and 16

Secondary: Mean change from baseline in number of all night-time awakenings (NTA) at Weeks 1, 2, 4, 8, 12 and 16

Secondary: Mean change from baseline in mean daily number of NTAs secondary to hot flushes at Weeks 1, 2, 4, 8, 12 and 16

Secondary: Mean change from baseline in mean daily number of NTAs secondary to hot flushes at Weeks 1, 2, 4, 8, 12 and 16

Secondary: Change from baseline in the global and individual domain scores of the Pittsburgh Sleep Quality Index (PSQI) at Weeks 4, 8, 12 and 16

Secondary: Change from baseline in the global and individual domain scores of the Pittsburgh Sleep Quality Index (PSQI) at Weeks 4, 8, 12 and 16

Secondary: Change from baseline in the Insomnia Severity Index (ISI) score at Weeks 4, 8, 12 and 16

Secondary: Change from baseline in the Insomnia Severity Index (ISI) score at Weeks 4, 8, 12 and 16

Secondary: Change from baseline in the hot flush related daily interference scale (HFRDIS) scores at Weeks 2, 4, 8, 12 and 16

Secondary: Change from baseline in the hot flush related daily interference scale (HFRDIS) scores at Weeks 2, 4, 8, 12 and 16

Secondary: Change from baseline in the Menopause-specific Quality-of-Life questionnaire Intervention Version (MenQoL-I) scores at Weeks 4, 8, 12 and 16

Secondary: Change from baseline in the Menopause-specific Quality-of-Life questionnaire Intervention Version (MenQoL-I) scores at Weeks 4, 8, 12 and 16

Secondary: Change from baseline in the Beck Depression Inventory II (BDI-II) scores at Weeks 2, 4, 8, 12 and 16.

Secondary: Change from baseline in the Beck Depression Inventory II (BDI-II) scores at Weeks 2, 4, 8, 12 and 16.

Secondary: Plasma BAY3427080 Concentrations at Weeks 2, 4, 8 ,12

Secondary: Plasma BAY3427080 Concentrations at Weeks 2, 4, 8 ,12

Secondary: Nature and severity of adverse events

Secondary: Nature and severity of adverse events

Secondary: Withdrawals due to an adverse event

Secondary: Withdrawals due to an adverse event

Secondary: Number of subjects used concomitant medications

Secondary: Number of subjects used concomitant medications

Secondary: Change from baseline in vital signs (systolic blood pressure) at Weeks 2, 4, 8, 12 and 16

Secondary: Change from baseline in vital signs (systolic blood pressure) at Weeks 2, 4, 8, 12 and 16

Secondary: Change from baseline in vital signs (pulse rate) at Weeks 2, 4, 8, 12 and 16

Secondary: Change from baseline in vital signs (pulse rate) at Weeks 2, 4, 8, 12 and 16

Secondary: Change from baseline in vital signs (temperature) at Weeks 2, 4, 8, 12 and 16

Secondary: Change from baseline in vital signs (temperature) at Weeks 2, 4, 8, 12 and 16

Secondary: Change from baseline in vital signs (weight) at Weeks 2, 4, 8, 12 and 16

Secondary: Change from baseline in vital signs (weight) at Weeks 2, 4, 8, 12 and 16

Secondary: Change from baseline in vital signs (Body Mass Index ) at Weeks 2, 4, 8, 12 and 16

Secondary: Change from baseline in vital signs (Body Mass Index ) at Weeks 2, 4, 8, 12 and 16

Secondary: Change from baseline in vital signs (waist circumference) at Weeks 2, 4, 8, 12 and 16

Secondary: Change from baseline in vital signs (waist circumference) at Weeks 2, 4, 8, 12 and 16

Secondary: Number of subjects with normal electrocardiogram (ECG) findings at each visit

Secondary: Number of subjects with normal electrocardiogram (ECG) findings at each visit

Secondary: Change from baseline in vital signs (diastolic blood pressure) at Weeks 2, 4, 8, 12 and 16

Secondary: Change from baseline in vital signs (diastolic blood pressure) at Weeks 2, 4, 8, 12 and 16

Secondary: Number of subjects with abnormal not clinically significant ECG findings at each visit

Secondary: Number of subjects with abnormal not clinically significant ECG findings at each visit

Secondary: Number of subjects with abnormal clinically significant ECG findings at each visit

Secondary: Number of subjects with abnormal clinically significant ECG findings at each visit

Secondary: Change from baseline at Weeks 2, 4, 8, 12 and 16 in ECG intervals (RR)

Secondary: Change from baseline at Weeks 2, 4, 8, 12 and 16 in ECG intervals (RR)

Secondary: Change from baseline at Weeks 2, 4, 8, 12 and 16 in ECG intervals (PR)

Secondary: Change from baseline at Weeks 2, 4, 8, 12 and 16 in ECG intervals (PR)

Secondary: Change from baseline at Weeks 2, 4, 8, 12 and 16 in ECG intervals (QT)

Secondary: Change from baseline at Weeks 2, 4, 8, 12 and 16 in ECG intervals (QT)

Secondary: Change from baseline at Weeks 2, 4, 8, 12 and 16 in ECG intervals (QTc)

Secondary: Change from baseline at Weeks 2, 4, 8, 12 and 16 in ECG intervals (QTc)

Clinical Trial Results:
A Double-Blind, Randomised, Placebo Controlled, Adaptive Design Study of the Efficacy, Safety and Pharmacokinetics of NT-814 in Female Subjects With Moderate to Severe Vasomotor Symptoms Associated With the Menopause