Cycle Control Assessment of a Combined Oral Contraceptive Containing Estetrol and a Progestin P1 or P2

Study Overview
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Brief Summary
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This is an open-label, multi-centre, comparative study in young, healthy, female volunteers of reproductive age. Primary objective: - To investigate the effect of 2 dosages of estetrol combined with P1 or P2, on vaginal bleeding patterns (cycle control), in comparison with a combined oral contraceptive containing estradiol valerate and dienogest Secondary objectives: To investigate ovulation inhibition To investigate the effect on SHBG To assess pregnancy rate To evaluate subject satisfaction, dysmenorrhoea, acne, and body weight To investigate return of menstruation after treatment To evaluate general safety and acceptability

Official Title
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A Randomised Open-label Multi-centre Comparative Study to Evaluate Cycle Control of 2 Dosages of Estetrol Combined With Either P1 or P2, Compared to a Combined Oral Contraceptive Containing E2V and DNG

Conditions
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Contraception

Intervention / Treatment
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* Drug: estetrol, P 1 and placebo tablets
* Drug: estetrol, P2 and placebo tablets
* Drug: Estradiol valerate, dienogest and placebo tablets


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women willing to use a Combined Oral Contraceptive for 6 subsequent cycles Good physical and mental health Regular menstrual cycle (24-35 days) prior to screening Body mass index between (≥) 18 and (≤) 30 kg/m2 Exclusion Criteria: Previous use of any hormonal contraceptive method during the last 3 months prior to randomisation (only applicable for women who are not using a hormonal contraceptive method at the time of screening) Previous use of progestogen-only contraceptive methods during the last 3 months or during the last 6 months for depot progestogen preparations or an injectable hormonal method of contraception Use of phytoestrogens No spontaneous menstruation has occurred following a delivery or abortion Breastfeeding or within 2 months after stopping breastfeeding prior to the start of study medication and no spontaneous return of menstruation Status post-partum or post-abortion within a period of 2 months before screening Pregnancy during accurate hormonal contraceptive use in the past Intention to become pregnant during the study An abnormal cervical smear within one year before study start Untreated Chlamydia infection Known or suspected breast cancer or a history of breast cancer A history of (within 12 months) alcohol or drug abuse Any clinically relevant abnormality Contraindications for the contraceptive steroids used in the clinical trial Use of antihypertensive drugs or use of medications interacting with the contraceptive steroids used in the clinical trial Administration of any other investigational drug within 2 months prior to screening

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: estetrol dose 1 / P1<br> | Drug: estetrol, P 1 and placebo tablets<br>* 6 treatment cycles each consisting of 28 days of oral administration as follows: Days 1-24: one estetrol tablet and one P1 tablet per day Days 25-28: two placebo tablets per day<br>|
| Experimental: estetrol dose 1 / P2<br> | Drug: estetrol, P2 and placebo tablets<br>* 6 treatment cycles each consisting of 28 days of oral administration as follows: Days 1-24: one estetrol tablet and one P2 tablet per day Days 25-28: two placebo tablets per day<br>|
| Active Comparator: estradiol valerate/dienogest pill<br> | Drug: Estradiol valerate, dienogest and placebo tablets<br>* 6 treatment cycles each consisting of 28 days of oral administration as follows: Days 1-26: one tablet of Estradiol valerate/dienogest per day Days 26-28: one placebo tablet per day<br>|
| Experimental: estetrol dose 2 / P1<br> | Drug: estetrol, P 1 and placebo tablets<br>* 6 treatment cycles each consisting of 28 days of oral administration as follows: Days 1-24: one estetrol tablet and one P1 tablet per day Days 25-28: two placebo tablets per day<br>|
| Experimental: estetrol dose 2 / P2<br> | Drug: estetrol, P2 and placebo tablets<br>* 6 treatment cycles each consisting of 28 days of oral administration as follows: Days 1-24: one estetrol tablet and one P2 tablet per day Days 25-28: two placebo tablets per day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recording of vaginal bleeding events (diary) as a measure of Cycle control |  | 6 cycles of 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurement of pregnandiol glucuronide in urine as a measure of Ovulation inhibition |  | 6 cycles of 28 days | 
| Patient Reported Outcome questionnaire as a measure of Subject satisfaction |  | 6 cycles of 28 days | 
| Contacts patient-investigator to document Return of menstruation | (only in case the patient does not start up a new hormonal contraceptive method or in case of pregnancy wish) | for up to 1 year follow-up | 
| Recording of adverse events, physical examination and laboratory parameters as a measure of Safety and Tolerability |  | up to 8 months | 
| Measurement of SHBG in blood samples to assess the effect of treatment on SHBG |  | 6 cycles of 28 days | 
| Reporting of in-treatment pregnancies as a measure of pregnancy rate |  | 6 cycles of 28 days |