Study of a 4-phasic Oral Contraceptive for the Treatment of Heavy Menstrual Bleeding

Study Overview
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Brief Summary
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To evaluate efficacy and safety of a combined oral contraceptive of estradiol valerate and dienogest in the treatment of heavy menstrual bleeding

Official Title
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A Multicenter, Double-blind, Randomized, Parallel-group, Placebo-controlled, 7 Cycle Duration (196 Days), Phase 3 Study to Investigate the Efficacy and Safety of Oral Estradiol Valerate / Dienogest Tablets for the Treatment of Heavy Menstrual Bleeding

Conditions
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Metrorrhagia

Intervention / Treatment
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* Drug: EV/DNG (Qlaira, Natazia, BAY86-5027)
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women 18 years or older in generally good health with a diagnosis of heavy menstrual bleeding without organic pathology, requesting contraception Willingness to use barrier contraception (e.g., condoms) from screening to study completion Willingness to use and collect sanitary protection (pads and tampons) provided by the sponsor and compatible with the alkaline hematin test throughout study completion Exclusion Criteria: Current diagnosis of organic uterine bleeding History of endometrial ablation, or dilatation and curettage within 2 months of Visit 1. Clinically significant pelvic findings (whether or not confirmed by transvaginal ultrasound [TVU]). Clinically significant abnormal results of breast examination (breast palpation). Positive pregnancy test at Visit 1 Less than three months since delivery, abortion, or lactation before to start Visit 1 Other contraceptive methods Any disease or condition that may worsen under hormonal treatment Smokers over the age of 35 Body mass index >32

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: Arm 1<br> | Drug: EV/DNG (Qlaira, Natazia, BAY86-5027)<br>* 2 days of 3 mg estradiol valerate (EV);5 days of 2 mg EV + 2 mg dienogest (DNG);17 days of 2 mg EV + 3 mg DNG;2 days of 1 mg EV;2 days of placebo. A blister card consists of 28 pills, taken orally once a day for 7 cycles of 28 days each.<br>|
| Placebo Comparator: Arm 2<br> | Drug: placebo<br>* Matching placebo to be taken orally daily for 7 cycles of 28 days each.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute change in Menstrual Blood Loss (MBL) at baseline and 90 days |  | 90 day baseline period and 90 days during treatment period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with successful treatment | Successful treatment is defined as no bleeding episode with MBL of 80 mL or more and a decrease to a value </=50% of MBL compared to 90 day run-in period | 90 days during treatment phase | 
| Percent change of MBL at baseline and 90 day period during treatment phase |  | Baseline and 90 days during treatment phase | 
| Absolute change of average MBL at baseline and up to cycle 7 (one cycle = 28 days) |  | Baseline and cycle 1, cycle 2, cycle 3, cycle 4, cycle 5, cycle 6, cycle 7 | 
| Proportion of subjects with improvement in the investigator's global assessment scale on Day 84 | Investigator's global assessment scale: 0 = not assessed; 1 = very much improved; 2 = much improved; 3 = improved; 4 = no change; 5 = worse; 6 = much worse; 7 = very much worse; Improvement is defined as the assessment score = 1, 2, or 3. | Treatment day 84 | 
| Proportion of subjects with improvement in the investigator's global assessment scale on Day 196 | Investigator's global assessment scale: 0 = not assessed; 1 = very much improved; 2 = much improved; 3 = improved; 4 = no change; 5 = worse; 6 = much worse; 7 = very much worse; Improvement is defined as the assessment score = 1, 2, or 3. | Treatment day 196 | 
| Proportion of subjects with improvement in the subject's global assessment scale on Day 84 | Subject's global assessment scale: 0 = not assessed; 1 = very much improved; 2 = much improved; 3 = improved; 4 = no change; 5 = worse; 6 = much worse; 7 = very much worse; Improvement is defined as the assessment score = 1, 2, or 3. | Treatment day 84 | 
| Proportion of subjects with improvement in the subject's global assessment scale on Day 196 | Subject's global assessment scale: 0 = not assessed; 1 = very much improved; 2 = much improved; 3 = improved; 4 = no change; 5 = worse; 6 = much worse; 7 = very much worse; Improvement is defined as the assessment score = 1, 2, or 3. | Treatment day 196 | 
| Number of participants with adverse events as a measure of safety and tolerability |  | Up to 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heavy Menstrual Bleeding, Efficacy, Safety, Oral contraceptive, Estradiol valerate, Dienogest