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

Study Overview
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Brief Summary
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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

Official Title
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A Randomized, Parallel-group, Double-blind and Placebo-controlled, Multicenter Study to Assess the Efficacy and Safety of Vilaprisan in Subjects With Uterine Fibroids

Conditions
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Uterine Fibroids

Intervention / Treatment
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* Drug: Vilaprisan (BAY1002670)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vilaprisan (A1)<br>Vilaprisan in treatment period 1 for 12 weeks and in treatment period 2 for 12 weeks, separated by 1 bleeding episode. | Drug: Vilaprisan (BAY1002670)<br>* Orally, coated tablet 2 mg, once daily<br>|
| Experimental: Placebo+Vilaprisan (B1)<br>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)<br>* Orally, coated tablet 2 mg, once daily<br>Drug: Placebo<br>* Orally, coated tablet, once daily<br>|
| Experimental: Vilaprisan+Placebo (B2)<br>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)<br>* Orally, coated tablet 2 mg, once daily<br>Drug: Placebo<br>* Orally, coated tablet, once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Amenorrhea | 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. | The last 28 days of treatment period 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Heavy Menstrual Bleeding (HMB) Response | 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). | The last 28 days of treatment period 1 and treatment period 2 | 
| 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 and assessed by the AH method). | In treatment period 1 (12 weeks) and in treatment period 2 (12 weeks) | 
| 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 (assessed by the AH method). | In treatment period 1 (12 weeks) and in treatment period 2 (12 weeks) | 
| 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 UF-DBD (Uterine Fibroid Daily Bleeding Diary). | The last 28 days of treatment period 1 and treatment period 2 | 
| Number of Participants by Endometrial Biopsy Main Results (Majority Read, Main Diagnosis) | Number of participants with endometrial histology findings, e.g. benign endometrium, malignant neoplasm, hyperplasia without atypia, hyperplasia with atypia and endometrial polyps. | Up to 36 weeks | 
| 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. | In treatment period 1 (12 weeks) and in treatment period 2 (12 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heavy menstrual bleeding