Assess Safety and Efficacy of Vilaprisan in Subjects With Uterine Fibroids (ASTEROID 4)

• Sponsor: Bayer (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03400956
• Collaborator: (none)
• Enrollment: 103
• Locations: 87
• Arms: 3
• Actual Duration (Months): 41.2
• Patients Per Site: 1.2
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The primary objective of this study was to show superiority of vilaprisan in the treatment of heavy menstrual bleeding (HMB) in subjects with uterine fibroids compared to placebo

The secondary objectives of this study were to additionally evaluate the efficacy and safety of vilaprisan in subjects with uterine fibroids

Condition or Disease	Intervention/Treatment	Phase
Uterine Fibroids	Drug: Vilaprisan (BAY1002670); Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 103 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Parallel-group, Double-blind and Placebo-controlled, Multicenter Study to Assess the Efficacy and Safety of Vilaprisan in Subjects With Uterine Fibroids
• Actual Study Start Date: Jan 24, 2018
• Actual Primary Completion Date: Mar 23, 2019
• Actual Study Completion Date: Jun 30, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Vilaprisan (A1) Vilaprisan in treatment period 1 for 12 weeks and in treatment period 2 for 12 weeks, separated by 1 bleeding episode.	Drug: Vilaprisan (BAY1002670); Orally, coated tablet 2 mg, once daily
Experimental: Placebo+Vilaprisan (B1) Placebo in treatment period 1 for 12 weeks, and vilaprisan in treatment period 2 for 12 weeks, separated by 1 bleeding episode.	Drug: Vilaprisan (BAY1002670); Orally, coated tablet 2 mg, once daily; Drug: Placebo; Orally, coated tablet, once daily
Experimental: Vilaprisan+Placebo (B2) Vilaprisan in treatment period 1 for 12 weeks, and placebo in treatment period 2 for 12 weeks, separated by 1 bleeding episode.	Drug: Vilaprisan (BAY1002670); Orally, coated tablet 2 mg, once daily; Drug: Placebo; Orally, coated tablet, once daily

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Amenorrhea [The last 28 days of treatment period 1]

   Amenorrhea was defined as menstrual blood loss (MBL) < 2 mL during the last 28 days of treatment. The evaluation of MBL was based on the Alkaline hematin (AH) method.

Secondary Outcome Measures

1. Number of Participants With Heavy Menstrual Bleeding (HMB) Response [The last 28 days of treatment period 1 and treatment period 2]

   HMB was defined as MBL <80.00 mL during the last 28 days of treatment and >50% reduction compared to baseline (assessed by the AH method).

2. Time to Onset of Amenorrhea [In treatment period 1 (12 weeks) and in treatment period 2 (12 weeks)]

   Onset of amenorrhea was defined by the first day for which the MBL for all subsequent 28-day periods up to the end of a treatment period was <2 mL (amenorrhea defined similar to primary endpoint and assessed by the AH method).

3. Time to Onset of Controlled Bleeding [In treatment period 1 (12 weeks) and in treatment period 2 (12 weeks)]

   Onset of controlled bleeding was defined by the first day for which the MBL for all subsequent 28-day periods up to the end of a treatment period was <80.00 mL (assessed by the AH method).

4. Number of Participants With Absence of Bleeding (Spotting Allowed) [The last 28 days of treatment period 1 and treatment period 2]

   Absence of bleeding was defined as no scheduled or unscheduled bleeding (spotting allowed) during the last 28 days of a treatment period based on subjects' daily responses to the UF-DBD (Uterine Fibroid Daily Bleeding Diary).

5. Number of Participants by Endometrial Biopsy Main Results (Majority Read, Main Diagnosis) [Up to 36 weeks]

   Number of participants with endometrial histology findings, e.g. benign endometrium, malignant neoplasm, hyperplasia without atypia, hyperplasia with atypia and endometrial polyps.

6. Change From Baseline of Endometrial Thickness [In treatment period 1 (12 weeks) and in treatment period 2 (12 weeks)]

   Ultrasound examinations were performed. Endometrial thickness was measured in the medio-sagittal section as double-layer in millimeters. Summary statistics for change from baseline in endometrial thickness was provided in below table.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Women, 18 years or older in good general health

• Diagnosis of uterine fibroid(s) documented by ultrasound at screening with at least 1 fibroid with largest diameter more than 30 mm and less than 120 mm

• Heavy menstrual bleeding (HMB) in at least 2 bleeding periods during the screening period each with blood loss volume of >80.00 mL documented by the alkaline hematin (AH) method

• An endometrial biopsy performed during the screening period without significant histological disorder such as endometrial hyperplasia (including simple hyperplasia) or other significant endometrial pathology

• Use of an acceptable non-hormonal method of contraception (ie, either male condom, cap, diaphragm or sponge, each in combination with spermicide) starting at Visit 1 until the end of the study

Exclusion Criteria:

• Pregnancy or lactation (less than 3 months since delivery, abortion, or lactation before start of treatment)

• Hypersensitivity to any ingredient of the study drug

• Hemoglobin values ≤6 g/dL or any condition requiring immediate blood transfusion (subjects with hemoglobin values ≤10.9 g/dL will be recommended to use iron supplementation)

• Any diseases, conditions, or medications that can compromise the function of the body systems and could result in altered absorption, excessive accumulation, impaired metabolism, or altered excretion of the study drug

• Any diseases or conditions that might interfere with the conduct of the study or the interpretation of the results

• Abuse of alcohol, drugs or medicines (e.g. laxatives)

• Use of other treatments that might interfere with the conduct of the study or the interpretation of results

• Undiagnosed abnormal genital bleeding

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clearview Medical Research, LLC	Canyon Country	California	United States	91351
2	Diagnamics, Inc.	Encinitas	California	United States	92024
3	National Research Institute	Huntington Park	California	United States	90255
4	Grossmont Center for Clinical Research	La Mesa	California	United States	91942
5	West Coast OB/GYN Associates	La Mesa	California	United States	91942
6	National Research Institute	Panorama City	California	United States	91402
7	Artemis Institute for Clinical Research	San Diego	California	United States	92103
8	Medical Center for Clinical Research	San Diego	California	United States	92108
9	Women's Medical Research Group, LLC	Clearwater	Florida	United States	33759
10	Vital Pharma Research	Hialeah	Florida	United States	33016
11	Solutions Through Advanced Research, Inc.	Jacksonville	Florida	United States	32256
12	Health Awareness, Inc.	Jupiter	Florida	United States	33458
13	South Florida Clinical Research Institute	Margate	Florida	United States	33073
14	Savin Medical Group LLC	Miami Lakes	Florida	United States	33014
15	Suncoast Research Group, LLC	Miami	Florida	United States	33135
16	Advanced Pharma CR, LLC	Miami	Florida	United States	33147
17	Genoma Research Group, Inc.	Miami	Florida	United States	33165
18	Florida Research Center, Inc.	Miami	Florida	United States	33174
19	Miami Dade Medical Research Institute, LLC	Miami	Florida	United States	33176
20	Vista Health Research	Miami	Florida	United States	33176
21	Palmetto Professional Research	Miami	Florida	United States	33186
22	A Premier Medical Research of Florida, LLC	Orange City	Florida	United States	32763
23	Clinical Neurosciences Solutions, Inc. DBA CNS Healthcare	Orlando	Florida	United States	32801
24	Oviedo Medical Research, LLC	Oviedo	Florida	United States	32765
25	DMI Research	Pinellas Park	Florida	United States	33782
26	Physician Care Clinical Research	Sarasota	Florida	United States	34239
27	Journey Medical Research	Snellville	Georgia	United States	30078
28	Women's Healthcare Associates, PA	Idaho Falls	Idaho	United States	83404
29	New England Center for Clinical Research, Inc.	Fall River	Massachusetts	United States	02720
30	Altea Research Institute	Las Vegas	Nevada	United States	89102
31	Unified Women's Clinical Research	Greensboro	North Carolina	United States	27408
32	PMG Research of Wilmington	Wilmington	North Carolina	United States	28401
33	Unified Women's Clinical Research / Ocala, FL	Winston-Salem	North Carolina	United States	27103
34	Oregon Health and Science University	Portland	Oregon	United States	97239-3011
35	The Clinical Trial Center, LLC	Jenkintown	Pennsylvania	United States	19046
36	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
37	Vista Clinical Research	Columbia	South Carolina	United States	29201
38	Chattanooga Women for Women	Hixson	Tennessee	United States	37343
39	Women Partners in Health Obstetrics & Gynecology (OB/GYN)	Austin	Texas	United States	78705
40	Gadolin Research	Beaumont	Texas	United States	77702
41	Discovery Clinical Trials	Dallas	Texas	United States	75231
42	Advances in Health, Inc.	Houston	Texas	United States	77030
43	Discovery Clinical Trials	San Antonio	Texas	United States	78258
44	Center of Reproductive Medicine	Webster	Texas	United States	77598
45	Tidewater Physicians for Women	Norfolk	Virginia	United States	23502
46	Seattle Clinical Research Center	Seattle	Washington	United States	98105
47	GynPorCentrum s.r.o.	Krnov		Czechia	794 01
48	Gynekologie MUDr. Jaromir Karban s.r.o	Neratovice		Czechia	277 11
49	Privatni gynekologicko-porodnicka ordinace	Praha		Czechia	16000
50	GYNEVI s.r.o.	Rokycany		Czechia	337 01
51	Gynekologicka ambulance - Zabreh na Morave	Zabreh Na Morave		Czechia	78901
52	Funabashi Municipal Medical Center	Funabashi	Chiba	Japan	273-8588
53	Tsujinaka Hospital Kashiwanoha	Kashiwa	Chiba	Japan	277-0871
54	Matsudo City General Hospital	Matsudo	Chiba	Japan	270-2296
55	Hashimoto Clinic	Sapporo	Hokkaido	Japan	004-0052
56	Ena Odori Clinic	Sapporo	Hokkaido	Japan	060-0001
57	Tokeidai Memorial Clinic	Sapporo	Hokkaido	Japan	060-0031
58	Yoshio Clinic	Sapporo	Hokkaido	Japan	064-0808
59	Kosumo Clinic	Kako-gun	Hyogo	Japan	675-1115
60	Kobe City Medical Center General Hospital	Kobe	Hyogo	Japan	650-0047
61	Takamatsu Red Cross Hospital	Takamatsu	Kagawa	Japan	760-0017
62	Asahi-Clinic.	Takamatsu	Kagawa	Japan	760-0076
63	Kagawa Prefectural Central Hospital	Takamatsu	Kagawa	Japan	760-8557
64	Shonan Fujisawa Tokushukai Hospital	Fujisawa	Kanagawa	Japan	251-0041
65	Kyoto city Hospital	Nakagyo-ku	Kyoto	Japan	604-8845
66	Medical Topia Soka Hospital	Soka	Saitama	Japan	340-0028
67	Omi Medical Center	Kusatsu	Shiga	Japan	525-8585
68	Saiseikai Fukuoka General Hospital	Fukuoka		Japan	810-0001
69	Unoki Clinic	Kagoshima		Japan	892-0826
70	Tetsu-Nakamura Obstetrics and Gynecology Internal Medicine	Kagoshima		Japan	892-0845
71	Four Seasons Ladies' Clinic	Kumamoto		Japan	860-0846
72	Japanese Red Cross Kumamoto Hospital	Kumamoto		Japan	861-8520
73	Ijinkai Takeda General Hospital	Kyoto		Japan	601-1495
74	Japanese Red Cross Kyoto Daini Hospital	Kyoto		Japan	602-8026
75	Gokeikai Osaka Kaisei Hospital	Osaka		Japan	532-0003
76	Osaka City Hospital Organization Osaka City General Hospital	Osaka		Japan	534-0021
77	Medical Co. LEADING GIRLS Women's Clinic LUNA Shinsaibashi	Osaka		Japan	542-0086
78	Altai State Medical University	Barnaul		Russian Federation	656038
79	Maternity Hospital, 17	Saint-Petersburg		Russian Federation	192174
80	Close Joint Stock Company "Medical Company IDK"	Samara		Russian Federation	443067
81	Smolensk State Medical University	Smolensk		Russian Federation	214019
82	Med Estetic Center	St. Petersburg		Russian Federation	192177
83	"Granti-Med"	St. Petersburg		Russian Federation	198329
84	Scien. Res. Institute of Obsterics, Gyn. & Reproduction	St. Petersburg		Russian Federation	199034
85	Chernivtsi Regional Perinatal Center	Chernivtsi		Ukraine	58001
86	Vinnytsia City Clinical Maternity Hospital No 2	Vinnytsia		Ukraine	21001
87	Zaporizhzhia Regional Clinical Hospital	Zaporizhzhya		Ukraine	69103

Sponsors and Collaborators

• Bayer

Investigators

• Study Director: Bayer Study Director, Bayer

Study Documents (Full-Text)

• Study Protocol - Feb 17, 2020
• Statistical Analysis Plan - May 20, 2020

More Information

Additional Information:

• Click here to find results for studies related to Bayer products
• Click here to find information about studies related to Bayer Healthcare products conducted in Europe

Publications

None provided.

• Responsible Party: Bayer
• ClinicalTrials.gov Identifier: NCT03400956
• Other Study ID Numbers: 15790; 2016-003561-26
• First Posted: Jan 17, 2018
• Last Update Posted: Jun 30, 2022
• Last Verified: Jun 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Bayer: Heavy menstrual bleeding
• Additional relevant MeSH terms: Leiomyoma; Myofibroma

Study Results

Participant Flow

Recruitment Details

The study was conducted at 87 study centers in USA, Japan, Czech Republic, Russia, and Ukraine between 24-Jan-2018 (first participant first visit) and 30-Jun-2021 (last participant last visit).

Pre-assignment Detail

Overall, 481 participants were screened, of them, 378 (78.6%) participants were not randomized to treatment. The majority of these (n=286) were screen failures. Of the 103 participants who were randomized, 91 participants received study treatment. Full analysis set (FAS) consisted of all randomized subjects, excluding randomized subjects who did not start treatment period 1 (never received study drug) due to the study being closed prematurely (7 [6.8%]), and included 96 (93.2%) subjects.

Arm/Group Title	Vilaprisan (A1)	Placebo+Vilaprisan (B1)	Vilaprisan+Placebo (B2)
Arm/Group Description	Vilaprisan in treatment period (TP) 1 for 12 weeks and in treatment period 2 for 12 weeks, separated by 1 bleeding episode.	Placebo in treatment period 1 for 12 weeks, and vilaprisan in treatment period 2 for 12 weeks, separated by 1 bleeding episode.	Vilaprisan in treatment period 1 for 12 weeks, and placebo in treatment period 2 for 12 weeks, separated by 1 bleeding episode.
Period Title: Treatment Period 1
STARTED	35	34	34
Treated	31	30	30
FAS	32	33	31
COMPLETED	31	26	25
NOT COMPLETED	4	8	9
Period Title: Treatment Period 1
STARTED	31	26	25
COMPLETED	9	10	9
NOT COMPLETED	22	16	16
Period Title: Treatment Period 1
STARTED	9	10	9
COMPLETED	5	7	5
NOT COMPLETED	4	3	4
Period Title: Treatment Period 1
STARTED	6	9	7
COMPLETED	6	9	5
NOT COMPLETED	0	0	2

Baseline Characteristics

Arm/Group Title	Vilaprisan (A1)	Placebo+Vilaprisan (B1)	Vilaprisan+Placebo (B2)	Total
Arm/Group Description	Vilaprisan in treatment period 1 for 12 weeks and in treatment period 2 for 12 weeks, separated by 1 bleeding episode.	Placebo in treatment period 1 for 12 weeks, and vilaprisan in treatment period 2 for 12 weeks, separated by 1 bleeding episode.	Vilaprisan in treatment period 1 for 12 weeks, and placebo in treatment period 2 for 12 weeks, separated by 1 bleeding episode.	Total of all reporting groups
Overall Participants	32	33	31	96
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	43.1 (5.5)	42.7 (6.0)	43.8 (4.3)	43.2 (5.3)
Sex: Female, Male (Count of Participants)
Female	32 100%	33 100%	31 100%	96 100%
Male	0 0%	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 6.3%	3 9.1%	5 16.1%	10 10.4%
Not Hispanic or Latino	30 93.8%	30 90.9%	26 83.9%	86 89.6%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	11 34.4%	11 33.3%	11 35.5%	33 34.4%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	6 18.8%	7 21.2%	8 25.8%	21 21.9%
White	13 40.6%	15 45.5%	10 32.3%	38 39.6%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	2 6.3%	0 0%	2 6.5%	4 4.2%
Endometrial thickness (Millimeters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Millimeters]	12.8 (4.5)	12.8 (2.9)	11.9 (3.9)	12.5 (3.9)

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Amenorrhea
Description	Amenorrhea was defined as menstrual blood loss (MBL) < 2 mL during the last 28 days of treatment. The evaluation of MBL was based on the Alkaline hematin (AH) method.
Time Frame	The last 28 days of treatment period 1

Outcome Measure Data

Analysis Population Description

FAS population with evaluable data.

Arm/Group Title	Vilaprisan (A1)	Placebo+Vilaprisan (B1)	Vilaprisan+Placebo (B2)
Arm/Group Description	Vilaprisan in treatment period 1 for 12 weeks and in treatment period 2 for 12 weeks, separated by 1 bleeding episode.	Placebo in treatment period 1 for 12 weeks, and vilaprisan in treatment period 2 for 12 weeks, separated by 1 bleeding episode.	Vilaprisan in treatment period 1 for 12 weeks, and placebo in treatment period 2 for 12 weeks, separated by 1 bleeding episode.
Measure Participants	32	33	31
Count of Participants [Participants]	29 90.6%	1 3%	25 80.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vilaprisan (A1), Placebo+Vilaprisan (B1), Vilaprisan+Placebo (B2)
	Comments	Vilaprisan (A1) and Vilaprisan+Placebo (B2) combined vs. Placebo+Vilaprisan (B1) in treatment period 1
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0.82
	Confidence Interval	(2-Sided) 95%; 0.72 to 0.93
	Parameter Dispersion	Type: Value:
	Estimation Comments	Number of subjects per treatment: 63 (Vilaprisan) / 33 (Placebo).

2. Secondary Outcome

Title	Number of Participants With Heavy Menstrual Bleeding (HMB) Response
Description	HMB was defined as MBL <80.00 mL during the last 28 days of treatment and >50% reduction compared to baseline (assessed by the AH method).
Time Frame	The last 28 days of treatment period 1 and treatment period 2

Outcome Measure Data

Analysis Population Description

FAS population with valuable data.

Arm/Group Title	Vilaprisan (A1)	Placebo+Vilaprisan (B1)	Vilaprisan+Placebo (B2)
Arm/Group Description	Vilaprisan in treatment period 1 for 12 weeks and in treatment period 2 for 12 weeks, separated by 1 bleeding episode.	Placebo in treatment period 1 for 12 weeks, and vilaprisan in treatment period 2 for 12 weeks, separated by 1 bleeding episode.	Vilaprisan in treatment period 1 for 12 weeks, and placebo in treatment period 2 for 12 weeks, separated by 1 bleeding episode.
Measure Participants	32	33	31
Treatment period 1	30 93.8%	7 21.2%	26 83.9%
Treatment period 2	6 18.8%	9 27.3%	1 3.2%

3. Secondary Outcome

Title	Time to Onset of Amenorrhea
Description	Onset of amenorrhea was defined by the first day for which the MBL for all subsequent 28-day periods up to the end of a treatment period was <2 mL (amenorrhea defined similar to primary endpoint and assessed by the AH method).
Time Frame	In treatment period 1 (12 weeks) and in treatment period 2 (12 weeks)

Outcome Measure Data

Analysis Population Description

FAS population with valuable data. In treatment period 2, participants who did not start the respective treatment period or had less than 28 days of treatment are included among censored observations.

Arm/Group Title	Vilaprisan (A1)	Placebo+Vilaprisan (B1)	Vilaprisan+Placebo (B2)
Arm/Group Description	Vilaprisan in treatment period 1 for 12 weeks and in treatment period 2 for 12 weeks, separated by 1 bleeding episode.	Placebo in treatment period 1 for 12 weeks, and vilaprisan in treatment period 2 for 12 weeks, separated by 1 bleeding episode.	Vilaprisan in treatment period 1 for 12 weeks, and placebo in treatment period 2 for 12 weeks, separated by 1 bleeding episode.
Measure Participants	32	33	31
Treatment period 1	3	NA	3
Treatment period 2	3	4	NA

4. Secondary Outcome

Title	Time to Onset of Controlled Bleeding
Description	Onset of controlled bleeding was defined by the first day for which the MBL for all subsequent 28-day periods up to the end of a treatment period was <80.00 mL (assessed by the AH method).
Time Frame	In treatment period 1 (12 weeks) and in treatment period 2 (12 weeks)

Outcome Measure Data

Analysis Population Description

FAS population with valuable data. In treatment period 2, participants who did not start the respective treatment period or had less than 28 days of treatment are included among censored observations.

Arm/Group Title	Vilaprisan (A1)	Placebo+Vilaprisan (B1)	Vilaprisan+Placebo (B2)
Arm/Group Description	Vilaprisan in treatment period 1 for 12 weeks and in treatment period 2 for 12 weeks, separated by 1 bleeding episode.	Placebo in treatment period 1 for 12 weeks, and vilaprisan in treatment period 2 for 12 weeks, separated by 1 bleeding episode.	Vilaprisan in treatment period 1 for 12 weeks, and placebo in treatment period 2 for 12 weeks, separated by 1 bleeding episode.
Measure Participants	32	33	31
Treatment period 1	1	NA	1
Treatment period 2	1.5	1	NA

5. Secondary Outcome

Title	Number of Participants With Absence of Bleeding (Spotting Allowed)
Description	Absence of bleeding was defined as no scheduled or unscheduled bleeding (spotting allowed) during the last 28 days of a treatment period based on subjects' daily responses to the UF-DBD (Uterine Fibroid Daily Bleeding Diary).
Time Frame	The last 28 days of treatment period 1 and treatment period 2

Outcome Measure Data

Analysis Population Description

FAS population with valuable data.

Arm/Group Title	Vilaprisan (A1)	Placebo+Vilaprisan (B1)	Vilaprisan+Placebo (B2)
Arm/Group Description	Vilaprisan in treatment period 1 for 12 weeks and in treatment period 2 for 12 weeks, separated by 1 bleeding episode.	Placebo in treatment period 1 for 12 weeks, and vilaprisan in treatment period 2 for 12 weeks, separated by 1 bleeding episode.	Vilaprisan in treatment period 1 for 12 weeks, and placebo in treatment period 2 for 12 weeks, separated by 1 bleeding episode.
Measure Participants	32	33	31
Treatment period 1	29 90.6%	2 6.1%	25 80.6%
Treatment period 2	6 18.8%	8 24.2%	1 3.2%

6. Secondary Outcome

Title	Number of Participants by Endometrial Biopsy Main Results (Majority Read, Main Diagnosis)
Description	Number of participants with endometrial histology findings, e.g. benign endometrium, malignant neoplasm, hyperplasia without atypia, hyperplasia with atypia and endometrial polyps.
Time Frame	Up to 36 weeks

Outcome Measure Data

Analysis Population Description

Samples with sufficient tissue for analysis in SAF population was analyzed.

Arm/Group Title	Vilaprisan (A1)	Placebo+Vilaprisan (B1)	Vilaprisan+Placebo (B2)
Arm/Group Description	Vilaprisan in treatment period 1 for 12 weeks and in treatment period 2 for 12 weeks, separated by 1 bleeding episode.	Placebo in treatment period 1 for 12 weeks, and vilaprisan in treatment period 2 for 12 weeks, separated by 1 bleeding episode.	Vilaprisan in treatment period 1 for 12 weeks, and placebo in treatment period 2 for 12 weeks, separated by 1 bleeding episode.
Measure Participants	31	30	30
Adequate endometrial tissue	31 96.9%	30 90.9%	26 83.9%
Benign Endometrium	31 96.9%	30 90.9%	26 83.9%
Hyperplasia WHO 2014, no atypia	0 0%	0 0%	0 0%
Hyperplasia WHO 2014, atypia	0 0%	0 0%	0 0%
Malignant Neoplasm	0 0%	0 0%	0 0%
Endometrial Polyps	2 6.3%	0 0%	1 3.2%

7. Secondary Outcome

Title	Change From Baseline of Endometrial Thickness
Description	Ultrasound examinations were performed. Endometrial thickness was measured in the medio-sagittal section as double-layer in millimeters. Summary statistics for change from baseline in endometrial thickness was provided in below table.
Time Frame	In treatment period 1 (12 weeks) and in treatment period 2 (12 weeks)

Outcome Measure Data

Analysis Population Description

SAF was analyzed. Overall number of participants analyzed represents number of participants without missing data.

Arm/Group Title	Vilaprisan (A1)	Placebo+Vilaprisan (B1)	Vilaprisan+Placebo (B2)
Arm/Group Description	Vilaprisan in treatment period 1 for 12 weeks and in treatment period 2 for 12 weeks, separated by 1 bleeding episode.	Placebo in treatment period 1 for 12 weeks, and vilaprisan in treatment period 2 for 12 weeks, separated by 1 bleeding episode.	Vilaprisan in treatment period 1 for 12 weeks, and placebo in treatment period 2 for 12 weeks, separated by 1 bleeding episode.
Measure Participants	31	30	30
Treatment period 1	-2.5 (4.1)	-2.8 (2.6)	-3.1 (3.7)
Treatment period 2	-5.3 (7.6)	-3.5 (4.1)	-0.4 (4.1)

Adverse Events

Time Frame	For TEAEs: started from the first application of study medication up to 60 calendar days after end of treatment with study medication. For Post-treatment AEs: started from Day 61 after the end of treatment with study medication (All AEs identified during the safety follow-up are included in this portion).
Arm/Group Title	Vilaprisan (A1) - Treatment Emergent AEs		Placebo+Vilaprisan (B1) - Treatment Emergent AEs		Vilaprisan +Placebo (B2) - Treatment Emergent AEs		Vilaprisan (A1) - Post Treatment AEs		Placebo+Vilaprisan (B1) - Post Treatment AEs		Vilaprisan+Placebo (B2) - Post Treatment AEs
Arm/Group Description	Vilaprisan in treatment period 1 for 12 weeks and in treatment period 2 for 12 weeks, separated by 1 bleeding episode. TEAEs: defined as AEs that "started from the first application of study medication up to 60 calendar days after end of treatment with study medication".		Placebo in treatment period 1 for 12 weeks, and vilaprisan in treatment period 2 for 12 weeks, separated by 1 bleeding episode. TEAEs: defined as AEs that "started from the first application of study medication up to 60 calendar days after end of treatment with study medication".		Vilaprisan in treatment period 1 for 12 weeks, and placebo in treatment period 2 for 12 weeks, separated by 1 bleeding episode. TEAEs: defined as AEs that "started from the first application of study medication up to 60 calendar days after end of treatment with study medication".		Vilaprisan in treatment period 1 for 12 weeks and in treatment period 2 for 12 weeks, separated by 1 bleeding episode. Post-treatment AEs: defined as all AEs that started from Day 61 after the end of treatment with study medication. (All AEs identified during the safety follow-up are included in this portion).		Placebo in treatment period 1 for 12 weeks, and vilaprisan in treatment period 2 for 12 weeks, separated by 1 bleeding episode. Post-treatment AEs: defined as all AEs that started from Day 61 after the end of treatment with study medication. (All AEs identified during the safety follow-up are included in this portion).		Vilaprisan in treatment period 1 for 12 weeks, and placebo in treatment period 2 for 12 weeks, separated by 1 bleeding episode. Post-treatment AEs: defined as all AEs that started from Day 61 after the end of treatment with study medication. (All AEs identified during the safety follow-up are included in this portion).
All Cause Mortality
	Vilaprisan (A1) - Treatment Emergent AEs		Placebo+Vilaprisan (B1) - Treatment Emergent AEs		Vilaprisan +Placebo (B2) - Treatment Emergent AEs		Vilaprisan (A1) - Post Treatment AEs		Placebo+Vilaprisan (B1) - Post Treatment AEs		Vilaprisan+Placebo (B2) - Post Treatment AEs
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/31 (0%)		0/30 (0%)		0/30 (0%)		0/31 (0%)		0/30 (0%)		0/30 (0%)
Serious Adverse Events
	Vilaprisan (A1) - Treatment Emergent AEs		Placebo+Vilaprisan (B1) - Treatment Emergent AEs		Vilaprisan +Placebo (B2) - Treatment Emergent AEs		Vilaprisan (A1) - Post Treatment AEs		Placebo+Vilaprisan (B1) - Post Treatment AEs		Vilaprisan+Placebo (B2) - Post Treatment AEs
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/31 (3.2%)		4/30 (13.3%)		0/30 (0%)		7/31 (22.6%)		8/30 (26.7%)		3/30 (10%)
Blood and lymphatic system disorders
Anaemia	0/31 (0%)	0	1/30 (3.3%)	1	0/30 (0%)	0	0/31 (0%)	0	0/30 (0%)	0	0/30 (0%)	0
Endocrine disorders
Adrenal mass	0/31 (0%)	0	0/30 (0%)	0	0/30 (0%)	0	1/31 (3.2%)	1	0/30 (0%)	0	0/30 (0%)	0
Hepatobiliary disorders
Cholangitis	0/31 (0%)	0	0/30 (0%)	0	0/30 (0%)	0	1/31 (3.2%)	1	0/30 (0%)	0	0/30 (0%)	0
Investigations
Liver function test increased	0/31 (0%)	0	1/30 (3.3%)	1	0/30 (0%)	0	0/31 (0%)	0	0/30 (0%)	0	0/30 (0%)	0
Metabolism and nutrition disorders
Type 2 diabetes mellitus	0/31 (0%)	0	0/30 (0%)	0	0/30 (0%)	0	0/31 (0%)	0	1/30 (3.3%)	1	0/30 (0%)	0
Musculoskeletal and connective tissue disorders
Rheumatoid arthritis	0/31 (0%)	0	0/30 (0%)	0	0/30 (0%)	0	0/31 (0%)	0	1/30 (3.3%)	1	0/30 (0%)	0
Tendonitis	0/31 (0%)	0	1/30 (3.3%)	1	0/30 (0%)	0	0/31 (0%)	0	0/30 (0%)	0	0/30 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adrenal adenoma	0/31 (0%)	0	0/30 (0%)	0	0/30 (0%)	0	0/31 (0%)	0	1/30 (3.3%)	1	0/30 (0%)	0
Bile duct cancer	0/31 (0%)	0	0/30 (0%)	0	0/30 (0%)	0	1/31 (3.2%)	1	0/30 (0%)	0	0/30 (0%)	0
Breast cancer	0/31 (0%)	0	0/30 (0%)	0	0/30 (0%)	0	0/31 (0%)	0	0/30 (0%)	0	1/30 (3.3%)	1
Endometrial neoplasm	1/31 (3.2%)	1	0/30 (0%)	0	0/30 (0%)	0	1/31 (3.2%)	1	0/30 (0%)	0	0/30 (0%)	0
Uterine leiomyoma	0/31 (0%)	0	0/30 (0%)	0	0/30 (0%)	0	2/31 (6.5%)	2	0/30 (0%)	0	0/30 (0%)	0
Reproductive system and breast disorders
Heavy menstrual bleeding	0/31 (0%)	0	2/30 (6.7%)	2	0/30 (0%)	0	0/31 (0%)	0	0/30 (0%)	0	0/30 (0%)	0
Surgical and medical procedures
Hysterectomy	0/31 (0%)	0	0/30 (0%)	0	0/30 (0%)	0	1/31 (3.2%)	1	3/30 (10%)	3	1/30 (3.3%)	1
Myomectomy	0/31 (0%)	0	0/30 (0%)	0	0/30 (0%)	0	1/31 (3.2%)	1	2/30 (6.7%)	2	0/30 (0%)	0
Salpingectomy	0/31 (0%)	0	0/30 (0%)	0	0/30 (0%)	0	0/31 (0%)	0	1/30 (3.3%)	1	0/30 (0%)	0
Urinary cystectomy	0/31 (0%)	0	0/30 (0%)	0	0/30 (0%)	0	0/31 (0%)	0	1/30 (3.3%)	1	0/30 (0%)	0
Hysterosalpingo-oophorectomy	0/31 (0%)	0	0/30 (0%)	0	0/30 (0%)	0	1/31 (3.2%)	1	0/30 (0%)	0	0/30 (0%)	0
Hysterosalpingectomy	0/31 (0%)	0	0/30 (0%)	0	0/30 (0%)	0	0/31 (0%)	0	1/30 (3.3%)	1	1/30 (3.3%)	1
Uterine dilation and curettage	0/31 (0%)	0	0/30 (0%)	0	0/30 (0%)	0	0/31 (0%)	0	0/30 (0%)	0	1/30 (3.3%)	1
Endometriosis ablation	0/31 (0%)	0	0/30 (0%)	0	0/30 (0%)	0	0/31 (0%)	0	1/30 (3.3%)	1	0/30 (0%)	0
Uterine leiomyoma embolisation	0/31 (0%)	0	0/30 (0%)	0	0/30 (0%)	0	1/31 (3.2%)	1	0/30 (0%)	0	0/30 (0%)	0
Other (Not Including Serious) Adverse Events
	Vilaprisan (A1) - Treatment Emergent AEs		Placebo+Vilaprisan (B1) - Treatment Emergent AEs		Vilaprisan +Placebo (B2) - Treatment Emergent AEs		Vilaprisan (A1) - Post Treatment AEs		Placebo+Vilaprisan (B1) - Post Treatment AEs		Vilaprisan+Placebo (B2) - Post Treatment AEs
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/31 (58.1%)		19/30 (63.3%)		16/30 (53.3%)		10/31 (32.3%)		12/30 (40%)		12/30 (40%)
Blood and lymphatic system disorders
Anaemia	1/31 (3.2%)	1	2/30 (6.7%)	2	0/30 (0%)	0	2/31 (6.5%)	2	2/30 (6.7%)	3	1/30 (3.3%)	1
Iron deficiency anaemia	0/31 (0%)	0	1/30 (3.3%)	1	0/30 (0%)	0	0/31 (0%)	0	3/30 (10%)	3	2/30 (6.7%)	2
Ear and labyrinth disorders
Vertigo	2/31 (6.5%)	2	0/30 (0%)	0	0/30 (0%)	0	0/31 (0%)	0	0/30 (0%)	0	0/30 (0%)	0
Endocrine disorders
Hypothyroidism	0/31 (0%)	0	0/30 (0%)	0	0/30 (0%)	0	0/31 (0%)	0	2/30 (6.7%)	2	0/30 (0%)	0
Gastrointestinal disorders
Diarrhoea	2/31 (6.5%)	2	1/30 (3.3%)	1	0/30 (0%)	0	0/31 (0%)	0	0/30 (0%)	0	0/30 (0%)	0
Dyspepsia	0/31 (0%)	0	2/30 (6.7%)	2	2/30 (6.7%)	2	0/31 (0%)	0	0/30 (0%)	0	0/30 (0%)	0
Nausea	3/31 (9.7%)	3	1/30 (3.3%)	1	1/30 (3.3%)	1	0/31 (0%)	0	0/30 (0%)	0	1/30 (3.3%)	1
General disorders
Malaise	0/31 (0%)	0	2/30 (6.7%)	2	2/30 (6.7%)	2	0/31 (0%)	0	0/30 (0%)	0	0/30 (0%)	0
Infections and infestations
Bacterial vaginosis	2/31 (6.5%)	3	0/30 (0%)	0	0/30 (0%)	0	0/31 (0%)	0	1/30 (3.3%)	2	0/30 (0%)	0
Influenza	0/31 (0%)	0	1/30 (3.3%)	1	1/30 (3.3%)	1	0/31 (0%)	0	1/30 (3.3%)	1	2/30 (6.7%)	2
Nasopharyngitis	3/31 (9.7%)	3	3/30 (10%)	3	4/30 (13.3%)	4	5/31 (16.1%)	9	1/30 (3.3%)	1	5/30 (16.7%)	5
Vulvovaginal mycotic infection	2/31 (6.5%)	3	0/30 (0%)	0	1/30 (3.3%)	1	0/31 (0%)	0	0/30 (0%)	0	0/30 (0%)	0
Investigations
Blood pressure increased	0/31 (0%)	0	0/30 (0%)	0	0/30 (0%)	0	2/31 (6.5%)	2	0/30 (0%)	0	0/30 (0%)	0
Metabolism and nutrition disorders
Vitamin D deficiency	0/31 (0%)	0	0/30 (0%)	0	0/30 (0%)	0	2/31 (6.5%)	2	4/30 (13.3%)	4	3/30 (10%)	3
Musculoskeletal and connective tissue disorders
Back pain	2/31 (6.5%)	2	0/30 (0%)	0	1/30 (3.3%)	1	1/31 (3.2%)	1	1/30 (3.3%)	2	2/30 (6.7%)	3
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine leiomyoma	0/31 (0%)	0	0/30 (0%)	0	0/30 (0%)	0	2/31 (6.5%)	2	0/30 (0%)	0	0/30 (0%)	0
Nervous system disorders
Headache	4/31 (12.9%)	6	1/30 (3.3%)	1	4/30 (13.3%)	4	1/31 (3.2%)	1	0/30 (0%)	0	1/30 (3.3%)	1
Psychiatric disorders
Insomnia	1/31 (3.2%)	1	0/30 (0%)	0	0/30 (0%)	0	2/31 (6.5%)	2	1/30 (3.3%)	2	0/30 (0%)	0
Reproductive system and breast disorders
Intermenstrual bleeding	0/31 (0%)	0	0/30 (0%)	0	0/30 (0%)	0	0/31 (0%)	0	2/30 (6.7%)	2	1/30 (3.3%)	1
Ovarian cyst	1/31 (3.2%)	2	4/30 (13.3%)	5	0/30 (0%)	0	0/31 (0%)	0	2/30 (6.7%)	2	0/30 (0%)	0
Premenstrual syndrome	0/31 (0%)	0	3/30 (10%)	3	0/30 (0%)	0	0/31 (0%)	0	0/30 (0%)	0	1/30 (3.3%)	1
Uterine haemorrhage	0/31 (0%)	0	2/30 (6.7%)	3	0/30 (0%)	0	0/31 (0%)	0	0/30 (0%)	0	0/30 (0%)	0
Endometrial thickening	3/31 (9.7%)	3	0/30 (0%)	0	0/30 (0%)	0	0/31 (0%)	0	0/30 (0%)	0	1/30 (3.3%)	1
Genital haemorrhage	0/31 (0%)	0	2/30 (6.7%)	3	1/30 (3.3%)	1	0/31 (0%)	0	0/30 (0%)	0	0/30 (0%)	0
Skin and subcutaneous tissue disorders
Rash	0/31 (0%)	0	0/30 (0%)	0	3/30 (10%)	3	0/31 (0%)	0	0/30 (0%)	0	0/30 (0%)	0
Vascular disorders
Hypertension	0/31 (0%)	0	0/30 (0%)	0	0/30 (0%)	0	1/31 (3.2%)	1	2/30 (6.7%)	2	1/30 (3.3%)	1
Hot flush	4/31 (12.9%)	4	2/30 (6.7%)	2	1/30 (3.3%)	1	1/31 (3.2%)	1	0/30 (0%)	0	3/30 (10%)	3

Limitations/Caveats

The trial was terminated earlier than planned. It was sufficiently advanced to allow for meaningful analysis. In many subjects, follow up phase was longer than the planned one. Safety evaluations were not limited to the planned timepoints.

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.