Bay1002670, Fibroids, Safety and Efficacy EU,US,Can, Jap

Study Overview
=================
Brief Summary
-----------------
The study is performed to assess the efficacy and safety of different doses of BAY1002670 in subjects with uterine fibroids. The dose-response relationship will be evaluated. Further, the study aims to establish a population pharmacokinetic/pharmacodynamic relationship for BAY1002670 in subjects with uterine fibroids. To assess the efficacy of BAY1002670 the interchangeability of menstrual pictogram and alkaline hematin method for the judgement of menstrual blood loss will be assessed.

Official Title
-----------------
A Randomized, Parallel-group, Double-blind, Placebo Controlled, Multi-center Study to Assess the Efficacy and Safety of Different Doses of BAY1002670 in Subjects With Uterine Fibroids Over 3 Months

Conditions
-----------------
Leiomyoma

Intervention / Treatment
-----------------
* Drug: BAY1002670
* Drug: BAY1002670
* Drug: BAY1002670
* Drug: BAY1002670
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Signed and dated informed consent Diagnosis of uterine fibroid(s) documented by transvaginal or abdominal ultrasound at screening with at least 1 fibroid with largest diameter 3.0 cm 18 to 50 years of age at the time of screening Heavy menstrual bleeding >80 mL documented by MP during the bleeding episode following the screening visit Normal or clinically insignificant cervical smear not requiring further follow-up An endometrial biopsy performed at the screening visit 1 (Visit 1), without significant histological disorder such as endometrial hyperplasia or other significant endometrial pathology Use of a non-hormonal barrier method of contraception starting at the bleeding episode following the screening visit 1 (Visit 1) until the end of the study Good general health (except for findings related to uterine fibroids) Exclusion Criteria: Pregnancy or lactation Uterine fibroid with largest diameter >10.0 cm Hypersensitivity to any ingredient of the study drug Laboratory values outside inclusion range before randomization and considered as clinically relevant Hemoglobin values <6 g/dL or any condition requiring immediate blood transfusion (subjects with hemoglobin values <10.9 g/dL will receive iron supplementation) Any diseases or conditions 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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VPR 4 mg<br> | Drug: BAY1002670<br>* Subjects received 4 milligram (mg) Vilaprisan (VPR) tablet once daily orally for 12 weeks (84 days) from the first week of the menstrual cycle following randomization.<br>|
| Experimental: VPR 2 mg<br> | Drug: BAY1002670<br>* Subjects received 2 mg VPR tablet once daily orally for 12 weeks (84 days) from the first week of the menstrual cycle following randomization.<br>|
| Experimental: VPR 1 mg<br> | Drug: BAY1002670<br>* Subjects received 1 mg VPR tablet once daily orally for 12 weeks (84 days) from the first week of the menstrual cycle following randomization.<br>|
| Experimental: VPR 0.5 mg<br> | Drug: BAY1002670<br>* Subjects received 0.5 mg VPR tablet once daily orally for 12 weeks (84 days) from the first week of the menstrual cycle following randomization.<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Subjects received matching placebo tablet once daily orally for 12 weeks (84 days) from the first week of the menstrual cycle following randomization.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects With Amenorrhea, Defined as no Scheduled or Unscheduled Bleeding/Spotting After the End of the Initial Bleeding Episode Until End of Treatment | Amenorrhea was defined as no scheduled or unscheduled bleeding/spotting after the end of the initial bleeding episode until end of treatment. Dose-response curve was estimated based on the primary endpoint. The 4 parameters characterizing the dose-response curve were reported in other pre-specified endpoints below. | After end of the initial bleeding episode until the end of treatment, up to 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Volume of Menstrual Blood Loss Per 28 Days From Baseline During Treatment by Reference Period (Assessed by Alkaline Hematin Method) | In the below table, N signifies subjects who were evaluable for the specific parameter at that timepoint for each arm, respectively. | From baseline to end of follow-up | 
| Time to Onset of Controlled Bleeding | Onset of controlled bleeding was defined by the first day, for which the MBL (assessed by MP, Version 2014) for all subsequent 28-day periods up to the end of the treatment period was less than 80 mL. Kaplan-Meier estimated time to onset of controlled bleeding (days) was reported. | During treatment period | 
| Change in Volume of Largest Fibroid Compared to Baseline Measured by MRI | Pelvic Magnetic resonance imagings (MRI), without contrast agents, were performed for volume measurements of the uterus and fibroids preferably using 1.5 Tesla scanners or higher. Images were sent to the imaging core laboratory for evaluation. Volume measurements of the uterus and fibroids were performed centrally by independent radiologist(s). | From baseline to end of follow-up period | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Uterine fibroids