Assess Safety and Efficacy of Vilaprisan in Subjects With Endometriosis

Study Overview
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Brief Summary
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The primary objective of this study was to assess the efficacy and safety of two doses of vilaprisan compared to placebo in women with symptomatic endometriosis. The secondary objective of this study was to evaluate the safety and tolerability of two different doses of vilaprisan in women with symptomatic endometriosis. With the implementation of protocol version 4.0 dated 11-Dec-2018, no new subjects were enrolled. The objectives above cannot be reached as only limited data is available from subjects recruited before the temporary pause.

Official Title
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A Randomized, Double-blind, Parallel-group, Multicenter Phase 2b Study to Assess the Efficacy and Safety of Two Different Doses of Vilaprisan (BAY1002670) Versus Placebo in Women With Symptomatic Endometriosis

Conditions
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Endometriosis

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed and dated informed consent Pre-menopausal women 18 years (inclusive) and above at the time of Visit 1 Women with endometriosis confirmed by laparoscopy or laparotomy OR diagnosed based on imaging Moderate to severe endometriosis-associated pelvic pain (EAPP) Adherence to screening period diary entries Willingness to use only standardized pain medication if needed Good general health (except for findings related to endometriosis) Normal or clinically insignificant cervical cytology not requiring further follow-up An endometrial biopsy performed at the screening phase without significant histological disorder Use of an acceptable non-hormonal method of contraception Willingness / ability to comply with electronic diary entry for the duration of study participation Exclusion Criteria: Pregnancy or lactation (less than 3 months since delivery, abortion, or lactation before Visit 1) Hypersensitivity to any ingredient of the study treatments Laboratory values outside the inclusion range before randomization, and considered clinically relevant 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 including elevated liver enzymes Any diseases or conditions that might interfere with the conduct of the study or the interpretation of the results Undiagnosed abnormal genital bleeding Abuse of alcohol, drugs, or medicines (e.g. laxatives) as evaluated by the investigator Use of other treatments that might interfere with the conduct of the study or the interpretation of the results Endometriosis-specific treatments for symptom relief except rescue pain medication according to protocol Simultaneous participation in another clinical trial with investigational medicinal product(s). Participation in another trial prior to study entry that might have an impact on the study objectives, at the discretion of the investigator Inability to cooperate with the study procedures for any reason Previous assignment to treatment (e.g. randomization) during this study (allowing previously randomized subjects to be re-included into the study may lead to bias) Hypersensitivity to any ingredient of standardized pain medication Wish for pregnancy during the study Regular use of pain medication due to other underlying diseases Non-responsiveness of EAPP to GnRH-a (Gonadotropin-releasing hormone agonists)

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 (BAY1002670) 2 mg<br>Premenopausal women 18 years and older with endometriosis with randomized ratio = 1:1:1 Vilaprisan: 2 mg | Drug: Vilaprisan (BAY1002670)<br>* Intake orally, once daily<br>|
| Experimental: Vilaprisan (BAY1002670) 4 mg<br>Premenopausal women 18 years and older with endometriosis with randomized ratio = 1:1:1 Vilaprisan: 4 mg | Drug: Vilaprisan (BAY1002670)<br>* Intake orally, once daily<br>|
| Placebo Comparator: Placebo group<br>Premenopausal women 18 years and older with endometriosis with randomized ratio = 1:1:1 | Drug: Matching Placebo<br>* Intake orally, once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Worst Pelvic Pain (Measured on a Numerical Rating Scale [NRS], Recorded in the Daily Endometriosis Symptom Diary [ESD]) | 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. | Screening period (up to a maximum of 75 days) + treatment period (up to a maximum of 168 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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. | 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 Endometriosis-associated Pelvic Pain (EAPP) | 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. | 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 Endometriosis-associated Pelvic Pain (EAPP) | 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. | Screening period (up to a maximum of 75 days) + treatment period (up to a maximum of 168 days) | 
| The Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 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. | Up to 6 months | 
| Number of Participants With Clinical Significant Abnormal Endometrial Histology Findings | Number of participants with endometrial histology findings, e.g. hyperplasia, malignant neoplasm or endometrial polyps | Up to 6 months | 
| Number of Participants With Clinical Significant Abnormal Ultrasound Examinations | 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. | Up to 6 months | 
| Number of Participants With Clinical Significant Abnormal Bone Mineral Density Measurements | A Dual-energy X-ray absorptiometry (DEXA) scan of the lumbar spine (lumbar anterior-posterior, L1-L4) and the hip/femoral neck were performed. | Up to 6 months | 
| Number of Participants With Clinical Significant Abnormal Laboratory Values | Clinical laboratory values including the values of hematology, general chemistry, urinalysis, coagulation, hormones, immunology and vitamins. | Up to 6 months |