Uterine Fibroids
Conditions
Keywords
Heavy menstrual bleeding
Brief summary
The primary objective of this study was to show superiority in the treatment of HMB of vilaprisan 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.
Interventions
2 mg of Vilaprisan once daily up to 2 x 12 weeks
DRUGPlacebo
Matching placebo was administered to group B1 and B2.
Sponsors
Bayer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Blinding will be applied to Treatment Groups A1, B1, and B2; Treatment Group A2 will be open-label
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
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 ≥ 30 mm and \< 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 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 month since delivery, abortion, or lactation before start of Treatment) * Hypersensitivity to any ingredient of the study drug * Any condition requiring immediate blood transfusion * Laboratory values outside inclusion range before randomization and considered as clinically relevant. * 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 (eg, laxatives) * Use of other treatments that might interfere with the conduct of the study or the interpretation of the results * Undiagnosed abnormal genital bleeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 measured by the alkaline hematin (AH) method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| 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 based on AH-method. |
| Number of Participants With Heavy Menstrual Bleeding (HMB) Response | The last 28 days of treatment period 1 and treatment period 2 | HMB response was defined as MBL \<80 mL during the last 28 days of treatment and \>50% reduction from baseline based on AH-method. |
| Number of Participants With Endometrial Histology Findings by Endometrial Biopsy Main Results (Majority Read, Main Diagnosis) | Up to 2 weeks after end of treatment | Number of participants with endometrial histology findings, e.g. benign endometrium, Malignant Neoplasm, Hyperplasia WHO 2014, no atypia or Hyperplasia WHO 2014, atypia and Endometrial Polyps. |
| Change From Baseline of Endometrial Thickness | Treatment phase (up to 2 weeks after end of treatment) and follow-up phase (starts on the day after the end of the treatment until the last study visit [up to approximately 2 years]) | 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. |
| 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 Uterine Fibroid Daily Bleeding Diary (UF-DBD). |
Countries
Bulgaria, China, Czechia, Israel, Malaysia, New Zealand, Singapore, South Africa, United States
Participant flow
Recruitment details
The study was conducted at 104 study centers in 9 countries worldwide between 17-Jan-2018 (first participant first visit) and 06-Apr- 2022 (last participant last visit).
Pre-assignment details
Overall, 646 participants were screened. Of the 646 screened participants, 553 (85.6%) participants were not randomized to treatment. The majority of these (n=403) were screen failures. Of the 93 participants who were randomized, 79 participants received study treatment.
Participants by arm
| Arm | Count |
|---|---|
| Vilaprisan (A1) Vilaprisan (2 mg) in treatment period 1 for 12 weeks and in treatment period 2 for 12 weeks, separated by 1 bleeding episode. | 18 |
| Vilaprisan (A2) Vilaprisan (2 mg) in treatment period 1 for 12 weeks and in treatment period 2 for 12 weeks without a break. | 21 |
| Placebo+Vilaprisan (B1) Placebo in treatment period 1 for 12 weeks, and vilaprisan (2 mg) in treatment period 2 for 12 weeks, separated by 1 bleeding episode. | 17 |
| Vilaprisan+Placebo (B2) Vilaprisan (2 mg) in treatment period 1 for 12 weeks and placebo in treatment period 2 for 12 weeks, separated by 1 bleeding episode. | 23 |
| Total | 79 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Follow-up Period | Withdrawal by Subject | 1 | 0 | 0 | 0 |
| Post-treatment Period 1 | Adverse Event | 2 | 0 | 0 | 0 |
| Post-treatment Period 1 | Other | 2 | 0 | 4 | 5 |
| Post-treatment Period 1 | Protocol Violation | 1 | 0 | 0 | 0 |
| Post-treatment Period 1 | Study terminated by sponsor | 5 | 0 | 5 | 6 |
| Post-treatment Period 1 | Withdrawal by Subject | 1 | 0 | 2 | 2 |
| Treatment Period 1 | Adverse Event | 0 | 0 | 0 | 1 |
| Treatment Period 1 | Lost to Follow-up | 1 | 0 | 0 | 0 |
| Treatment Period 1 | Other | 2 | 1 | 2 | 2 |
| Treatment Period 1 | Protocol Violation | 0 | 1 | 1 | 0 |
| Treatment Period 1 | Study terminated by sponsor | 2 | 0 | 0 | 1 |
| Treatment Period 1 | Withdrawal by Subject | 0 | 0 | 3 | 1 |
| Treatment Period 2 | Other | 1 | 6 | 0 | 0 |
| Treatment Period 2 | Study terminated by sponsor | 0 | 1 | 0 | 0 |
| Treatment Period 2 | Withdrawal by Subject | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Vilaprisan (A1) | Vilaprisan (A2) | Placebo+Vilaprisan (B1) | Vilaprisan+Placebo (B2) | Total |
|---|---|---|---|---|---|
| Age, Continuous | 43.1 Years STANDARD_DEVIATION 4.4 | 43.1 Years STANDARD_DEVIATION 5.8 | 42.5 Years STANDARD_DEVIATION 5.3 | 43.8 Years STANDARD_DEVIATION 5.1 | 43.2 Years STANDARD_DEVIATION 5.1 |
| Endometrial thickness | 13.6 Millimeters STANDARD_DEVIATION 7.6 | 11.0 Millimeters STANDARD_DEVIATION 5.4 | 11.9 Millimeters STANDARD_DEVIATION 6.5 | 10.5 Millimeters STANDARD_DEVIATION 3.9 | 11.7 Millimeters STANDARD_DEVIATION 5.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 1 Participants | 1 Participants | 0 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants | 20 Participants | 16 Participants | 22 Participants | 71 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 8 Participants | 5 Participants | 7 Participants | 25 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 5 Participants | 7 Participants | 11 Participants | 29 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 7 Participants | 6 Participants | 5 Participants | 5 Participants | 23 Participants |
| Sex: Female, Male Female | 18 Participants | 21 Participants | 17 Participants | 23 Participants | 79 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 69 | 0 / 22 | 0 / 18 | 0 / 21 | 0 / 17 | 0 / 23 |
| other Total, other adverse events | 30 / 69 | 8 / 22 | 9 / 18 | 4 / 21 | 6 / 17 | 7 / 23 |
| serious Total, serious adverse events | 2 / 69 | 1 / 22 | 3 / 18 | 6 / 21 | 3 / 17 | 6 / 23 |
Outcome results
Primary
Number of Participants With Amenorrhea
Amenorrhea was defined as menstrual blood loss (MBL) \<2 mL during the last 28 days of treatment measured by the alkaline hematin (AH) method.
Time frame: The last 28 days of treatment period 1
Population: FAS was analysed. FAS consists of all randomized participants, excluding randomized participants who did not start treatment period 1 due to the study being temporarily on hold, including 84 participants. Participants were analyzed as randomized.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vilaprisan (A1) | Number of Participants With Amenorrhea | 16 Participants |
| Vilaprisan (A2) | Number of Participants With Amenorrhea | 20 Participants |
| Placebo+Vilaprisan (B1) | Number of Participants With Amenorrhea | 4 Participants |
| Vilaprisan+Placebo (B2) | Number of Participants With Amenorrhea | 15 Participants |
Comparison: Vilaprisan (A1) and Vilaprisan+Placebo (B2) combined vs. Placebo+Vilaprisan (B1) in treatment period 1p-value: <0.000195% CI: [0.33, 0.78]Cochran-Mantel-Haenszel
Secondary
Change From Baseline of Endometrial Thickness
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: Treatment phase (up to 2 weeks after end of treatment) and follow-up phase (starts on the day after the end of the treatment until the last study visit [up to approximately 2 years])
Population: Participants in SAF with endometrial thickness measured and analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vilaprisan (A1) | Change From Baseline of Endometrial Thickness | Treatment phase | -2.2 Millimeters | Standard Deviation 3 |
| Vilaprisan (A1) | Change From Baseline of Endometrial Thickness | Follow-up phase | -3.0 Millimeters | Standard Deviation 4.6 |
| Vilaprisan (A2) | Change From Baseline of Endometrial Thickness | Follow-up phase | -0.5 Millimeters | Standard Deviation 3.8 |
| Vilaprisan (A2) | Change From Baseline of Endometrial Thickness | Treatment phase | -1.3 Millimeters | Standard Deviation 4.3 |
| Placebo+Vilaprisan (B1) | Change From Baseline of Endometrial Thickness | Treatment phase | -1.8 Millimeters | Standard Deviation 4.9 |
| Placebo+Vilaprisan (B1) | Change From Baseline of Endometrial Thickness | Follow-up phase | -3.1 Millimeters | Standard Deviation 4 |
| Vilaprisan+Placebo (B2) | Change From Baseline of Endometrial Thickness | Treatment phase | -1.8 Millimeters | Standard Deviation 3.4 |
| Vilaprisan+Placebo (B2) | Change From Baseline of Endometrial Thickness | Follow-up phase | -1.8 Millimeters | Standard Deviation 3.7 |
Secondary
Number of Participants With Absence of Bleeding (Spotting Allowed)
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 Uterine Fibroid Daily Bleeding Diary (UF-DBD).
Time frame: The last 28 days of treatment period 1 and treatment period 2
Population: FAS population was analysed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Vilaprisan (A1) | Number of Participants With Absence of Bleeding (Spotting Allowed) | Treatment period 2 | 6 Participants |
| Vilaprisan (A1) | Number of Participants With Absence of Bleeding (Spotting Allowed) | Treatment period 1 | 16 Participants |
| Vilaprisan (A2) | Number of Participants With Absence of Bleeding (Spotting Allowed) | Treatment period 2 | 13 Participants |
| Vilaprisan (A2) | Number of Participants With Absence of Bleeding (Spotting Allowed) | Treatment period 1 | 20 Participants |
| Placebo+Vilaprisan (B1) | Number of Participants With Absence of Bleeding (Spotting Allowed) | Treatment period 1 | 4 Participants |
| Placebo+Vilaprisan (B1) | Number of Participants With Absence of Bleeding (Spotting Allowed) | Treatment period 2 | 6 Participants |
| Vilaprisan+Placebo (B2) | Number of Participants With Absence of Bleeding (Spotting Allowed) | Treatment period 1 | 15 Participants |
| Vilaprisan+Placebo (B2) | Number of Participants With Absence of Bleeding (Spotting Allowed) | Treatment period 2 | 0 Participants |
Secondary
Number of Participants With Endometrial Histology Findings by Endometrial Biopsy Main Results (Majority Read, Main Diagnosis)
Number of participants with endometrial histology findings, e.g. benign endometrium, Malignant Neoplasm, Hyperplasia WHO 2014, no atypia or Hyperplasia WHO 2014, atypia and Endometrial Polyps.
Time frame: Up to 2 weeks after end of treatment
Population: Participants in safety analysis set with adequate tissue were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Vilaprisan (A1) | Number of Participants With Endometrial Histology Findings by Endometrial Biopsy Main Results (Majority Read, Main Diagnosis) | Malignant Neoplasm | 0 Participants |
| Vilaprisan (A1) | Number of Participants With Endometrial Histology Findings by Endometrial Biopsy Main Results (Majority Read, Main Diagnosis) | Hyperplasia WHO 2014, no atypia | 0 Participants |
| Vilaprisan (A1) | Number of Participants With Endometrial Histology Findings by Endometrial Biopsy Main Results (Majority Read, Main Diagnosis) | Endometrial Polyps | 1 Participants |
| Vilaprisan (A1) | Number of Participants With Endometrial Histology Findings by Endometrial Biopsy Main Results (Majority Read, Main Diagnosis) | Hyperplasia WHO 2014, atypia | 1 Participants |
| Vilaprisan (A1) | Number of Participants With Endometrial Histology Findings by Endometrial Biopsy Main Results (Majority Read, Main Diagnosis) | Benign Endometrium | 17 Participants |
| Vilaprisan (A2) | Number of Participants With Endometrial Histology Findings by Endometrial Biopsy Main Results (Majority Read, Main Diagnosis) | Hyperplasia WHO 2014, atypia | 0 Participants |
| Vilaprisan (A2) | Number of Participants With Endometrial Histology Findings by Endometrial Biopsy Main Results (Majority Read, Main Diagnosis) | Malignant Neoplasm | 0 Participants |
| Vilaprisan (A2) | Number of Participants With Endometrial Histology Findings by Endometrial Biopsy Main Results (Majority Read, Main Diagnosis) | Endometrial Polyps | 1 Participants |
| Vilaprisan (A2) | Number of Participants With Endometrial Histology Findings by Endometrial Biopsy Main Results (Majority Read, Main Diagnosis) | Hyperplasia WHO 2014, no atypia | 0 Participants |
| Vilaprisan (A2) | Number of Participants With Endometrial Histology Findings by Endometrial Biopsy Main Results (Majority Read, Main Diagnosis) | Benign Endometrium | 20 Participants |
| Placebo+Vilaprisan (B1) | Number of Participants With Endometrial Histology Findings by Endometrial Biopsy Main Results (Majority Read, Main Diagnosis) | Hyperplasia WHO 2014, atypia | 0 Participants |
| Placebo+Vilaprisan (B1) | Number of Participants With Endometrial Histology Findings by Endometrial Biopsy Main Results (Majority Read, Main Diagnosis) | Benign Endometrium | 17 Participants |
| Placebo+Vilaprisan (B1) | Number of Participants With Endometrial Histology Findings by Endometrial Biopsy Main Results (Majority Read, Main Diagnosis) | Hyperplasia WHO 2014, no atypia | 0 Participants |
| Placebo+Vilaprisan (B1) | Number of Participants With Endometrial Histology Findings by Endometrial Biopsy Main Results (Majority Read, Main Diagnosis) | Malignant Neoplasm | 0 Participants |
| Placebo+Vilaprisan (B1) | Number of Participants With Endometrial Histology Findings by Endometrial Biopsy Main Results (Majority Read, Main Diagnosis) | Endometrial Polyps | 1 Participants |
| Vilaprisan+Placebo (B2) | Number of Participants With Endometrial Histology Findings by Endometrial Biopsy Main Results (Majority Read, Main Diagnosis) | Malignant Neoplasm | 0 Participants |
| Vilaprisan+Placebo (B2) | Number of Participants With Endometrial Histology Findings by Endometrial Biopsy Main Results (Majority Read, Main Diagnosis) | Hyperplasia WHO 2014, no atypia | 0 Participants |
| Vilaprisan+Placebo (B2) | Number of Participants With Endometrial Histology Findings by Endometrial Biopsy Main Results (Majority Read, Main Diagnosis) | Benign Endometrium | 22 Participants |
| Vilaprisan+Placebo (B2) | Number of Participants With Endometrial Histology Findings by Endometrial Biopsy Main Results (Majority Read, Main Diagnosis) | Hyperplasia WHO 2014, atypia | 0 Participants |
| Vilaprisan+Placebo (B2) | Number of Participants With Endometrial Histology Findings by Endometrial Biopsy Main Results (Majority Read, Main Diagnosis) | Endometrial Polyps | 0 Participants |
Secondary
Number of Participants With Heavy Menstrual Bleeding (HMB) Response
HMB response was defined as MBL \<80 mL during the last 28 days of treatment and \>50% reduction from baseline based on AH-method.
Time frame: The last 28 days of treatment period 1 and treatment period 2
Population: FAS population was analysed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Vilaprisan (A1) | Number of Participants With Heavy Menstrual Bleeding (HMB) Response | Treatment period 1 | 17 Participants |
| Vilaprisan (A1) | Number of Participants With Heavy Menstrual Bleeding (HMB) Response | Treatment period 2 | 6 Participants |
| Vilaprisan (A2) | Number of Participants With Heavy Menstrual Bleeding (HMB) Response | Treatment period 2 | 14 Participants |
| Vilaprisan (A2) | Number of Participants With Heavy Menstrual Bleeding (HMB) Response | Treatment period 1 | 20 Participants |
| Placebo+Vilaprisan (B1) | Number of Participants With Heavy Menstrual Bleeding (HMB) Response | Treatment period 2 | 6 Participants |
| Placebo+Vilaprisan (B1) | Number of Participants With Heavy Menstrual Bleeding (HMB) Response | Treatment period 1 | 8 Participants |
| Vilaprisan+Placebo (B2) | Number of Participants With Heavy Menstrual Bleeding (HMB) Response | Treatment period 1 | 17 Participants |
| Vilaprisan+Placebo (B2) | Number of Participants With Heavy Menstrual Bleeding (HMB) Response | Treatment period 2 | 1 Participants |
Secondary
Time to Onset of Amenorrhea
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).
Time frame: In treatment period 1 (12 weeks) and in treatment period 2 (12 weeks)
Population: FAS population was analysed. 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.~For treatment arm Vilaprisan (A2), the combined data of treatment period 1 and treatment period 2 were entered.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Vilaprisan (A1) | Time to Onset of Amenorrhea | Treatment Period 1 | 3 Days |
| Vilaprisan (A1) | Time to Onset of Amenorrhea | Treatment periods 1 and 2 combined | NA Days |
| Vilaprisan (A1) | Time to Onset of Amenorrhea | Treatment Period 2 | 21 Days |
| Vilaprisan (A2) | Time to Onset of Amenorrhea | Treatment Period 1 | NA Days |
| Vilaprisan (A2) | Time to Onset of Amenorrhea | Treatment periods 1 and 2 combined | 9 Days |
| Vilaprisan (A2) | Time to Onset of Amenorrhea | Treatment Period 2 | NA Days |
| Placebo+Vilaprisan (B1) | Time to Onset of Amenorrhea | Treatment Period 2 | 2 Days |
| Placebo+Vilaprisan (B1) | Time to Onset of Amenorrhea | Treatment Period 1 | NA Days |
| Placebo+Vilaprisan (B1) | Time to Onset of Amenorrhea | Treatment periods 1 and 2 combined | NA Days |
| Vilaprisan+Placebo (B2) | Time to Onset of Amenorrhea | Treatment Period 1 | 6 Days |
| Vilaprisan+Placebo (B2) | Time to Onset of Amenorrhea | Treatment periods 1 and 2 combined | NA Days |
| Vilaprisan+Placebo (B2) | Time to Onset of Amenorrhea | Treatment Period 2 | NA Days |
Secondary
Time to Onset of Controlled Bleeding
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 based on AH-method.
Time frame: In treatment period 1 (12 weeks) and in treatment period 2 (12 weeks)
Population: FAS population was analysed. 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.~For treatment arm Vilaprisan (A2), the combined data of treatment period 1 and treatment period 2 were entered.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Vilaprisan (A1) | Time to Onset of Controlled Bleeding | Treatment period 1 | 1 Days |
| Vilaprisan (A1) | Time to Onset of Controlled Bleeding | Treatment periods 1 and 2 combined | NA Days |
| Vilaprisan (A1) | Time to Onset of Controlled Bleeding | Treatment period 2 | 1 Days |
| Vilaprisan (A2) | Time to Onset of Controlled Bleeding | Treatment period 1 | NA Days |
| Vilaprisan (A2) | Time to Onset of Controlled Bleeding | Treatment periods 1 and 2 combined | 1 Days |
| Vilaprisan (A2) | Time to Onset of Controlled Bleeding | Treatment period 2 | NA Days |
| Placebo+Vilaprisan (B1) | Time to Onset of Controlled Bleeding | Treatment period 1 | NA Days |
| Placebo+Vilaprisan (B1) | Time to Onset of Controlled Bleeding | Treatment period 2 | 1 Days |
| Placebo+Vilaprisan (B1) | Time to Onset of Controlled Bleeding | Treatment periods 1 and 2 combined | NA Days |
| Vilaprisan+Placebo (B2) | Time to Onset of Controlled Bleeding | Treatment period 1 | 1 Days |
| Vilaprisan+Placebo (B2) | Time to Onset of Controlled Bleeding | Treatment periods 1 and 2 combined | NA Days |
| Vilaprisan+Placebo (B2) | Time to Onset of Controlled Bleeding | Treatment period 2 | NA Days |