Comparative Study of BAY86-5300 With an Extended Flexible Regimen for Endometriosis

Study Overview
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Brief Summary
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This is a multi-center, randomized, double-blinded, placebo-controlled, parallel-group study (24-week treatment-comparison phase) with an open-label reference arm of active comparator (dienogest) followed by 28-week long-term treatment phase. The primary objective of this study is to confirm the superiority of BAY86-5300 when administered with an extended flexible regimen for the treatment of endometriosis-associated pelvic pain in comparison to placebo in Japanese endometriosis patients within 24 weeks. The secondary objective is to investigate the long-term safety of BAY86-5300 in patients treated with an extended flexible regimen for one year, and the bleeding pattern of BAY86-5300 when administered with an extended flexible regimen compared to dienogest.

Official Title
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A Multi-center, Randomized, Double-blinded, Placebo-controlled, and Open-label, Active-controlled, Parallel-group Comparative Study to Assess Efficacy and Safety of an Extended Flexible Regimen of BAY 86-5300 [0.02 mg Ethinylestradiol (β-CDC) and 3 mg Drospirenone] in the Patients With Endometriosis

Conditions
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Endometriosis

Intervention / Treatment
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* Drug: EE20/DRSP(BAY86-5300)
* Drug: Placebo
* Drug: Dienogest


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients diagnosed as having endometriosis by laparotomy or laparoscopy, or by identification of chocolate cyst of endometriosis, or patients with the clinical diagnosis of endometriosis, who fulfill the condition of pelvic tenderness or induration of Cul-de-sac or uterine immobility Patient with pelvic pain judged by the highest Visual Analogue Scale (VAS) value of 40 mm or higher which is determined during 2 menstrual cycles before randomization (baseline observation phase) Patients having the normal menstrual cycle (25 to 38 days) in the latest two menses before randomization (baseline observation phase) Patients who do not wish to become pregnant during the course of the study Exclusion Criteria: Patients who have organic diseases of which surgical treatment is prioritized by investigator Patients in whom any hormonal therapies, including combined oral contraceptives (COCs) and progestins, have failed for treatment of symptomatic endometriosis (moderate, severe pain) Patients for whom YAZ Combination Tablet is contraindicated (according to Japanese Labeling) Patients for whom dienogest is contraindicated (according to Japanese labeling of Dinagest Tab 1mg)

Ages Eligible for Study
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Minimum Age: 20 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br> | Drug: EE20/DRSP(BAY86-5300)<br>* One tablet [0.02 mg of ethinylestradiol (β-CDC) and 3 mg of drospirenone] / day<br>|
| Experimental: Arm 2<br> | Drug: Placebo<br>* One tablet (no active ingredient) / day and one tablet [0.02 mg of ethinylestradiol (β-CDC) and 3 mg of drospirenone] / day, for the first 24 weeks and the later 28 weeks, respectively<br>|
| Active Comparator: Arm 3<br> | Drug: Dienogest<br>* Dienogest 1mg twice a day (bid)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of pelvic pain from baseline period (8 weeks before start of treatment) to period of treatment (weeks 17-24) | The pelvic pain is measured as the severest pain marked by the participant on a Visual Analogue Scale (VAS) | Baseline period (8 weeks before start of treatment) and period of treatment (weeks 17-24) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pelvic pain during menstrual or withdrawal bleeding period (except for dyspareunia and defecation pain) | Pelvic pain is the worst pain on a 0-10 scale rated by the participant. | Weeks 17-24 of treatment period | 
| Pelvic pain during non-menstrual period and non-withdrawal bleeding period (except for dyspareunia and defecation pain) | Pelvic pain is the worst pain on a 0-10 scale rated by the participant. | Weeks 17-24 of treatment period | 
| Dyspareunia | In case having sexual intercourse, dyspareunia pain is the worst pain on a 0-10 scale rated by the participant in the last 24 hours. | Weeks 17-24 of treatment period | 
| Average of pain | The average of pain is the mean value of the Visual Analogue Scale (VAS) value during the time frame calculated for each patient based on daily record of Patient Diary. | Weeks 17-24 of treatment period | 
| Size of chocolate cyst | In case chocolate cyst is detected, size of chocolate cyst is a mean length (mm) of the longest axis and the short axis (crossing) of the largest chocolate cyst determined by transvaginal ultrasonography. | 24 weeks after taking the initial study medication | 
| Endometrial thickness | Endometrial thickness is the thickest value (mm) of endometrium determined by transvaginal ultrasonography. | 24 weeks after taking the initial study medication | 
| Number of days with spotting/bleeding | Number of days with spotting/bleeding is determined based on daily record of Patient Diary. | Up to 52 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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YAZ, Flexible regimen, Drospirenone, Ethinylestradiol Betadex, Endometriosis, Dienogest, Japanese Patients