Trial Outcomes & Findings for Assess Safety and Efficacy of Vilaprisan in Subjects With Endometriosis (NCT NCT03573336)

Last Updated: 2022-05-04

Results Overview

Pain intensity was assessed on 11-point (0-10) NRS by ESD item 1. In ESD item 1, participants were asked to rate the worst pain in the target area during the past 24 hours, where 0= no pain and 10= worst imaginable pain and responses were recorded in ESD. Mean 'worst pelvic pain' was calculated as the sum of the participant's daily assessments of the ESD item 1 ("worst pain" during the last 24 hours) during a study period divided by number of days with pain assessment in that study period. This was summarized by study period. No inferential statistical analysis was performed.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

8 participants

Primary outcome timeframe

Screening period (up to a maximum of 75 days) + treatment period (up to a maximum of 168 days)

Results posted on

2022-05-04

Participant Flow

Study was conducted at 7 study centers worldwide, between 04-Jul-2018 (first participant first visit) and 26-Nov-2020 (last participant last visit).

With the implementation of protocol version 4.0 dated 11-Dec-2018, no new participants were enrolled. The objectives of this study cannot be reached as only limited data is available from participants recruited before the treatment stopped. Overall, 48 participants were screened, of whom 8 participants were randomized and received the study treatment.

Participant milestones

Participant milestones
Measure	Vilaprisan (BAY1002670) 2 mg Premenopausal women 18 years and older with endometriosis received the treatment of Vilaprisan 2 mg.	Vilaprisan (BAY1002670) 4 mg Premenopausal women 18 years and older with endometriosis received the treatment of Vilaprisan 4 mg	Placebo Premenopausal women 18 years and older with endometriosis received placebo.
Overall Study STARTED	2	4	2
Overall Study Treated	2	4	2
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	2	4	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Vilaprisan (BAY1002670) 2 mg Premenopausal women 18 years and older with endometriosis received the treatment of Vilaprisan 2 mg.	Vilaprisan (BAY1002670) 4 mg Premenopausal women 18 years and older with endometriosis received the treatment of Vilaprisan 4 mg	Placebo Premenopausal women 18 years and older with endometriosis received placebo.
Overall Study Study terminated	2	4	2

Baseline Characteristics

Assess Safety and Efficacy of Vilaprisan in Subjects With Endometriosis

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: Screening period (up to a maximum of 75 days) + treatment period (up to a maximum of 168 days)

Outcome measures

Outcome measures
Measure	Vilaprisan (BAY1002670) 2 mg n=2 Participants Premenopausal women 18 years and older with endometriosis received the treatment of Vilaprisan 2 mg.	Vilaprisan (BAY1002670) 4 mg n=4 Participants Premenopausal women 18 years and older with endometriosis received the treatment of Vilaprisan 4 mg	Placebo n=2 Participants Premenopausal women 18 years and older with endometriosis received placebo.
Mean Worst Pelvic Pain (Measured on a Numerical Rating Scale [NRS], Recorded in the Daily Endometriosis Symptom Diary [ESD]) Screening period	6.0 Scores on a scale Interval 5.3 to 6.8	5.8 Scores on a scale Interval 4.0 to 7.1	5.6 Scores on a scale Interval 5.5 to 5.7
Mean Worst Pelvic Pain (Measured on a Numerical Rating Scale [NRS], Recorded in the Daily Endometriosis Symptom Diary [ESD]) Treatment period	3.0 Scores on a scale Interval 2.0 to 4.0	3.8 Scores on a scale Interval 1.9 to 5.6	5.0 Scores on a scale Interval 4.1 to 5.9

SECONDARY outcome

Timeframe: Screening period (up to a maximum of 75 days) + treatment period (up to a maximum of 168 days)

Pain intensity was assessed on 11-point (0-10) NRS by ESD item 1. In ESD item 1, participants were asked to rate the worst pain in the target area during the past 24 hours, where 0= no pain and 10= worst imaginable pain and responses were recorded in ESD. Mean 'worst pelvic pain' on bleeding/non-bleeding days was calculated as the sum of the participant's daily assessments of the ESD item 1 ("worst pain" during the last 24 hours) on bleedings/non-bleeding days during a study period divided by number of bleeding/non-bleeding days with pain assessment in that study period. This was summarized by study period. No inferential statistical analysis was performed.

Outcome measures

Outcome measures
Measure	Vilaprisan (BAY1002670) 2 mg n=2 Participants Premenopausal women 18 years and older with endometriosis received the treatment of Vilaprisan 2 mg.	Vilaprisan (BAY1002670) 4 mg n=4 Participants Premenopausal women 18 years and older with endometriosis received the treatment of Vilaprisan 4 mg	Placebo n=2 Participants Premenopausal women 18 years and older with endometriosis received placebo.
Mean Worst Pelvic Pain (Measured on a Numerical Rating Scale [NRS], Recorded in the Daily Endometriosis Symptom Diary [ESD]) on Days With/Without Vaginal Bleeding Treatment period: Worst Pain on days with vaginal bleeding	NA Scores on a scale No participant had pain on vaginal bleeding days in the treatment period.	5.4 Scores on a scale Interval 3.8 to 7.0	6.0 Scores on a scale Interval 5.1 to 6.9
Mean Worst Pelvic Pain (Measured on a Numerical Rating Scale [NRS], Recorded in the Daily Endometriosis Symptom Diary [ESD]) on Days With/Without Vaginal Bleeding Screening period: Worst Pain on days with vaginal bleeding	6.5 Scores on a scale Interval 4.6 to 8.4	6.9 Scores on a scale Interval 4.9 to 8.4	7.0 Scores on a scale Interval 6.9 to 7.0
Mean Worst Pelvic Pain (Measured on a Numerical Rating Scale [NRS], Recorded in the Daily Endometriosis Symptom Diary [ESD]) on Days With/Without Vaginal Bleeding Screening period: Worst Pain on days without vaginal bleeding	5.9 Scores on a scale Interval 5.5 to 6.3	5.5 Scores on a scale Interval 3.7 to 6.7	5.3 Scores on a scale Interval 5.1 to 5.6
Mean Worst Pelvic Pain (Measured on a Numerical Rating Scale [NRS], Recorded in the Daily Endometriosis Symptom Diary [ESD]) on Days With/Without Vaginal Bleeding Treatment period: Worst Pain on days without vaginal bleeding	3.0 Scores on a scale Interval 2.0 to 4.0	3.7 Scores on a scale Interval 1.8 to 5.6	4.7 Scores on a scale Interval 4.0 to 5.5

SECONDARY outcome

Timeframe: Screening period (up to a maximum of 75 days) + treatment period (up to a maximum of 168 days)

Mean number of tablets of rescue pain medication 1 (Ibuprofen 200 mg) taken daily for EAPP was calculated as the sum of the tablets taken for EAPP during a study period divided by the number of days in that study period. This was summarized by study period. No inferential statistical analysis was performed.

Outcome measures

Outcome measures
Measure	Vilaprisan (BAY1002670) 2 mg n=2 Participants Premenopausal women 18 years and older with endometriosis received the treatment of Vilaprisan 2 mg.	Vilaprisan (BAY1002670) 4 mg n=4 Participants Premenopausal women 18 years and older with endometriosis received the treatment of Vilaprisan 4 mg	Placebo n=2 Participants Premenopausal women 18 years and older with endometriosis received placebo.
Mean Number of Tablets of Rescue Pain Medication 1 (Ibuprofen 200 mg) Taken Daily for Endometriosis-associated Pelvic Pain (EAPP) Screening period	0.61 Tablets Interval 0.35 to 0.86	1.01 Tablets Interval 0.0 to 2.14	1.03 Tablets Interval 0.31 to 1.74
Mean Number of Tablets of Rescue Pain Medication 1 (Ibuprofen 200 mg) Taken Daily for Endometriosis-associated Pelvic Pain (EAPP) Treatment period	0.09 Tablets Interval 0.01 to 0.17	0.16 Tablets Interval 0.05 to 0.42	0.81 Tablets Interval 0.33 to 1.3

SECONDARY outcome

Timeframe: Screening period (up to a maximum of 75 days) + treatment period (up to a maximum of 168 days)

Mean number of tablets of rescue pain medication 2 (Tramadol 50 mg) taken daily for EAPP was calculated as the sum of the tablets taken for EAPP during a study period divided by the number of days in that study period. This was summarized by study period. No inferential statistical analysis was performed.

Outcome measures

Outcome measures
Measure	Vilaprisan (BAY1002670) 2 mg n=2 Participants Premenopausal women 18 years and older with endometriosis received the treatment of Vilaprisan 2 mg.	Vilaprisan (BAY1002670) 4 mg n=4 Participants Premenopausal women 18 years and older with endometriosis received the treatment of Vilaprisan 4 mg	Placebo n=2 Participants Premenopausal women 18 years and older with endometriosis received placebo.
Mean Number of Tablets of Rescue Pain Medication 2 (Tramadol 50 mg) Taken Daily for Endometriosis-associated Pelvic Pain (EAPP) Screening period	0 Tablets Interval 0.0 to 0.0	0 Tablets Interval 0.0 to 0.0	0.17 Tablets Interval 0.0 to 0.34
Mean Number of Tablets of Rescue Pain Medication 2 (Tramadol 50 mg) Taken Daily for Endometriosis-associated Pelvic Pain (EAPP) Treatment period	0.01 Tablets Interval 0.0 to 0.03	0.01 Tablets Interval 0.0 to 0.05	0.02 Tablets Interval 0.01 to 0.02

SECONDARY outcome

Timeframe: Up to 6 months

An adverse event (AE) is any untoward medical occurrence (i.e. any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a patient or clinical investigation subject after providing written informed consent for participation in the study. TEAE is defined as AE that is observed or reported after the first administration of study drug or if it starts before the first administration of study drug and the intensity/grade worsens on treatment) in this study.

Outcome measures

Outcome measures
Measure	Vilaprisan (BAY1002670) 2 mg n=2 Participants Premenopausal women 18 years and older with endometriosis received the treatment of Vilaprisan 2 mg.	Vilaprisan (BAY1002670) 4 mg n=4 Participants Premenopausal women 18 years and older with endometriosis received the treatment of Vilaprisan 4 mg	Placebo n=2 Participants Premenopausal women 18 years and older with endometriosis received placebo.
The Number of Participants With Treatment Emergent Adverse Events (TEAEs) Non-serious TEAEs	2 Participants	3 Participants	2 Participants
The Number of Participants With Treatment Emergent Adverse Events (TEAEs) SAEs	1 Participants	3 Participants	0 Participants
The Number of Participants With Treatment Emergent Adverse Events (TEAEs) Deaths	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 6 months

Number of participants with endometrial histology findings, e.g. hyperplasia, malignant neoplasm or endometrial polyps

Outcome measures

Outcome measures
Measure	Vilaprisan (BAY1002670) 2 mg n=2 Participants Premenopausal women 18 years and older with endometriosis received the treatment of Vilaprisan 2 mg.	Vilaprisan (BAY1002670) 4 mg n=4 Participants Premenopausal women 18 years and older with endometriosis received the treatment of Vilaprisan 4 mg	Placebo n=2 Participants Premenopausal women 18 years and older with endometriosis received placebo.
Number of Participants With Clinical Significant Abnormal Endometrial Histology Findings Endometrial hyperplasia	0 Participants	0 Participants	0 Participants
Number of Participants With Clinical Significant Abnormal Endometrial Histology Findings Malignant neoplasm	0 Participants	0 Participants	0 Participants
Number of Participants With Clinical Significant Abnormal Endometrial Histology Findings Endometrial polyps	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 6 months

Ultrasound examinations (evaluated for efficacy and safety) will be performed by a qualified expert in performing gynecologic ultrasound exams. If possible, the same examiner should conduct all examinations of a subject throughout the study and the same ultrasound machine (per site) should be used throughout the study. Preferably the safety evaluation should be performed by transvaginal ultrasound (TVU). However, if deemed appropriate, transabdominal or transrectal ultrasound examinations can be performed instead. The chosen method should be used consistently throughout the study.

Outcome measures

Outcome measures
Measure	Vilaprisan (BAY1002670) 2 mg n=2 Participants Premenopausal women 18 years and older with endometriosis received the treatment of Vilaprisan 2 mg.	Vilaprisan (BAY1002670) 4 mg n=4 Participants Premenopausal women 18 years and older with endometriosis received the treatment of Vilaprisan 4 mg	Placebo n=2 Participants Premenopausal women 18 years and older with endometriosis received placebo.
Number of Participants With Clinical Significant Abnormal Ultrasound Examinations	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 6 months

A Dual-energy X-ray absorptiometry (DEXA) scan of the lumbar spine (lumbar anterior-posterior, L1-L4) and the hip/femoral neck were performed.

Outcome measures

Outcome measures
Measure	Vilaprisan (BAY1002670) 2 mg n=2 Participants Premenopausal women 18 years and older with endometriosis received the treatment of Vilaprisan 2 mg.	Vilaprisan (BAY1002670) 4 mg n=4 Participants Premenopausal women 18 years and older with endometriosis received the treatment of Vilaprisan 4 mg	Placebo n=2 Participants Premenopausal women 18 years and older with endometriosis received placebo.
Number of Participants With Clinical Significant Abnormal Bone Mineral Density Measurements	1 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 6 months

Clinical laboratory values including the values of hematology, general chemistry, urinalysis, coagulation, hormones, immunology and vitamins.

Outcome measures

Outcome measures
Measure	Vilaprisan (BAY1002670) 2 mg n=2 Participants Premenopausal women 18 years and older with endometriosis received the treatment of Vilaprisan 2 mg.	Vilaprisan (BAY1002670) 4 mg n=4 Participants Premenopausal women 18 years and older with endometriosis received the treatment of Vilaprisan 4 mg	Placebo n=2 Participants Premenopausal women 18 years and older with endometriosis received placebo.
Number of Participants With Clinical Significant Abnormal Laboratory Values	0 Participants	3 Participants	0 Participants

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Vilaprisan (BAY1002670) 2 mg

Serious events: 1 serious events

Other events: 2 other events

Deaths: 0 deaths

Vilaprisan (BAY1002670) 4 mg

Serious events: 3 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=2 participants at risk Premenopausal women 18 years and older with endometriosis received placebo	Vilaprisan (BAY1002670) 2 mg n=2 participants at risk Premenopausal women 18 years and older with endometriosis received the treatment of Vilaprisan 2 mg.	Vilaprisan (BAY1002670) 4 mg n=4 participants at risk Premenopausal women 18 years and older with endometriosis received the treatment of Vilaprisan 4 mg
Eye disorders Retinal detachment	0.00% 0/2 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	50.0% 1/2 • Number of events 2 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	0.00% 0/4 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).
Infections and infestations Gastroenteritis	0.00% 0/2 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	0.00% 0/2 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	25.0% 1/4 • Number of events 1 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adrenal adenoma	0.00% 0/2 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	0.00% 0/2 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	25.0% 1/4 • Number of events 1 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).
Reproductive system and breast disorders Endometriosis	0.00% 0/2 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	0.00% 0/2 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	25.0% 1/4 • Number of events 1 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).
Surgical and medical procedures Endometriosis ablation	0.00% 0/2 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	50.0% 1/2 • Number of events 1 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	0.00% 0/4 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).

Other adverse events

Additional Information

Therapeutic Area Head

Bayer

Phone: (+)1-888-84 22937

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER

Measure	Vilaprisan (BAY1002670) 2 mg n=2 Participants Premenopausal women 18 years and older with endometriosis received the treatment of Vilaprisan 2 mg.	Vilaprisan (BAY1002670) 4 mg n=4 Participants Premenopausal women 18 years and older with endometriosis received the treatment of Vilaprisan 4 mg	Placebo n=2 Participants Premenopausal women 18 years and older with endometriosis received placebo.	Total n=8 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=5 Participants	4 Participants n=7 Participants	2 Participants n=5 Participants	8 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	4 Participants n=7 Participants	2 Participants n=5 Participants	8 Participants n=4 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	2 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	7 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) White	2 Participants n=5 Participants	4 Participants n=7 Participants	2 Participants n=5 Participants	8 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

Measure	Placebo n=2 participants at risk Premenopausal women 18 years and older with endometriosis received placebo	Vilaprisan (BAY1002670) 2 mg n=2 participants at risk Premenopausal women 18 years and older with endometriosis received the treatment of Vilaprisan 2 mg.	Vilaprisan (BAY1002670) 4 mg n=4 participants at risk Premenopausal women 18 years and older with endometriosis received the treatment of Vilaprisan 4 mg
Eye disorders Dry eye	0.00% 0/2 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	0.00% 0/2 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	25.0% 1/4 • Number of events 1 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).
Gastrointestinal disorders Diarrhoea	0.00% 0/2 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	0.00% 0/2 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	25.0% 1/4 • Number of events 1 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).
Gastrointestinal disorders Nausea	50.0% 1/2 • Number of events 1 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	0.00% 0/2 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	25.0% 1/4 • Number of events 1 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).
Gastrointestinal disorders Toothache	0.00% 0/2 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	0.00% 0/2 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	25.0% 1/4 • Number of events 3 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).
General disorders Pyrexia	50.0% 1/2 • Number of events 1 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	0.00% 0/2 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	0.00% 0/4 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).
Infections and infestations Bronchitis	50.0% 1/2 • Number of events 1 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	0.00% 0/2 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	0.00% 0/4 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).
Infections and infestations Fungal skin infection	0.00% 0/2 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	0.00% 0/2 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	25.0% 1/4 • Number of events 1 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).
Infections and infestations Gingivitis	0.00% 0/2 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	50.0% 1/2 • Number of events 1 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	0.00% 0/4 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).
Infections and infestations Influenza	0.00% 0/2 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	0.00% 0/2 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	25.0% 1/4 • Number of events 2 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).
Infections and infestations Nasopharyngitis	0.00% 0/2 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	50.0% 1/2 • Number of events 3 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	25.0% 1/4 • Number of events 1 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).
Infections and infestations Pyelitis	50.0% 1/2 • Number of events 1 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	0.00% 0/2 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	0.00% 0/4 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).
Infections and infestations Tonsillitis	50.0% 1/2 • Number of events 1 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	0.00% 0/2 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	0.00% 0/4 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).
Infections and infestations Urinary tract infection	0.00% 0/2 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	0.00% 0/2 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	25.0% 1/4 • Number of events 1 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).
Infections and infestations Vaginal infection	50.0% 1/2 • Number of events 2 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	0.00% 0/2 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	0.00% 0/4 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).
Infections and infestations Vulvovaginal mycotic infection	50.0% 1/2 • Number of events 1 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	0.00% 0/2 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	0.00% 0/4 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).
Injury, poisoning and procedural complications Procedural pain	0.00% 0/2 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	50.0% 1/2 • Number of events 1 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	25.0% 1/4 • Number of events 1 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).
Investigations Cortisol increased	0.00% 0/2 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	0.00% 0/2 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	25.0% 1/4 • Number of events 1 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).
Investigations Intraocular pressure increased	0.00% 0/2 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	50.0% 1/2 • Number of events 1 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	0.00% 0/4 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).
Investigations Weight increased	0.00% 0/2 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	0.00% 0/2 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	25.0% 1/4 • Number of events 1 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).
Investigations Bone density decreased	0.00% 0/2 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	50.0% 1/2 • Number of events 1 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	0.00% 0/4 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).
Metabolism and nutrition disorders Iron deficiency	0.00% 0/2 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	0.00% 0/2 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	50.0% 2/4 • Number of events 2 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/2 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	0.00% 0/2 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	25.0% 1/4 • Number of events 2 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/2 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	0.00% 0/2 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	25.0% 1/4 • Number of events 1 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).
Nervous system disorders Headache	100.0% 2/2 • Number of events 20 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	50.0% 1/2 • Number of events 6 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	50.0% 2/4 • Number of events 27 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).
Psychiatric disorders Anxiety	0.00% 0/2 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	0.00% 0/2 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	25.0% 1/4 • Number of events 1 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).
Psychiatric disorders Depressed mood	0.00% 0/2 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	0.00% 0/2 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	25.0% 1/4 • Number of events 1 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).
Psychiatric disorders Mood altered	0.00% 0/2 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	0.00% 0/2 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	25.0% 1/4 • Number of events 1 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).
Psychiatric disorders Adjustment disorder	0.00% 0/2 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	0.00% 0/2 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	25.0% 1/4 • Number of events 1 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).
Reproductive system and breast disorders Vaginal discharge	50.0% 1/2 • Number of events 1 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	0.00% 0/2 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	0.00% 0/4 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).
Reproductive system and breast disorders Vulvovaginal dryness	0.00% 0/2 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	0.00% 0/2 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	25.0% 1/4 • Number of events 1 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).
Reproductive system and breast disorders Adenomyosis	100.0% 2/2 • Number of events 2 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	50.0% 1/2 • Number of events 1 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	0.00% 0/4 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).
Skin and subcutaneous tissue disorders Acne	0.00% 0/2 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	0.00% 0/2 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	50.0% 2/4 • Number of events 2 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).
Skin and subcutaneous tissue disorders Hyperhidrosis	50.0% 1/2 • Number of events 1 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	0.00% 0/2 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	0.00% 0/4 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).
Vascular disorders Hot flush	0.00% 0/2 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	0.00% 0/2 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).	25.0% 1/4 • Number of events 2 • Adverse event data were collected from first study medication intake until last visit of the subject (516 days on average).