Comparative Trial in Hormone Withdrawal Associated Symptoms

Study Overview
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Brief Summary
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This clinical research study will examine whether an oral contraceptive pill taken with a monthly hormone-free interval of 4 days reduces hormone withdrawal associated symptoms compared to an oral contraceptive pill taken with a monthly hormone-free interval of 7 days after 4 cycles of treatment.

Official Title
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A Multi-centre, Randomized, Double-blind, Active Control, Parallel-group, 2-arm Study to Investigate the Effect of Ethinylestradiol / Drospirenone (0.02 mg/3 mg) Oral Contraception in a 24/4 Regimen Compared to Ethinylestradiol / Desogestrel (0.02 mg/0.15 mg) Oral Contraception in a 21/7 Regimen on Hormone Withdrawal Associated Symptoms in Otherwise Healthy Women After 4 Cycles of Treatment

Conditions
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Oral Contraceptive

Intervention / Treatment
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* Drug: EE20/DRSP (YAZ, BAY86-5300)
* Drug: Ethinylestradiol (EE) and desogestrel (DSG) (Mercilon)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects aged between 18 and 35 years (inclusive) Smokers with a maximum age of 30 years at time of informed consent Healthy female subjects requesting contraception and currently using a low-dose EE containing oral contraceptives (OC) in a 21-day regimen (for at least three months) and suffering from at least two of the hormone withdrawal associated symptoms headache, pelvic pain and bloating during all three months prior the planned baseline cycle and requiring further OC use To be valid for randomization, the total 7-day composite score of hormone-withdrawal symptoms during the baseline cycle must show an increase of at least 50% during Day 22 - 28 versus the 21-day composite score during Day 1 - 21 (21-day score divided by three [for normalization]) History of regular cyclic menstrual periods Exclusion Criteria: Presence or a history of venous or arterial thrombotic/thromboembolic events (e.g. deep venous thrombosis, pulmonary embolism, myocardial infarction) or of a cerebrovascular accident, or presence or history of prodrome of a thrombosis (e.g. transient ischemic attack, angina pectoris) and conditions that could increase the risk to suffer from any of the above mentioned disorders, e.g., a family history indicating a hereditary predisposition. Hereditary or acquired predisposition for venous or arterial thrombosis, such as APCresistance, antithrombin-III-deficiency, protein C deficiency, protein S deficiency, hyperhomocysteinemia and antiphospholipid-antibodies (anticardiolipin-antibodies, lupus anticoagulant). History of migraine with focal neurological symptoms. Diabetes mellitus with vascular involvement. Obesity (Body Mass Index >32.0 kg/m2) Moderate to severe hypertension (repeated measurements of systolic blood pressure >140 mmHg and/or diastolic blood pressure >90 mmHg). Pancreatitis or a history thereof if associated with severe hypertriglyceridemia. Presence or history of severe hepatic disease as long as liver function values have not returned to normal. Jaundice and / or pruritus related to cholestasis (Gilbert´s syndrome excepted), or history of cholestatic jaundice associated with pregnancy or previous combined OC use Severe renal insufficiency or acute renal failure. Presence or history of liver tumors (benign or malignant), or known or suspected sex-steroid influenced malignancies or premalignant disease (e.g. of the genital organs or the breasts).

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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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: EE20/DRSP (YAZ, BAY86-5300)<br>* 4 cycles of treatment / per cycle: 1 tablet (EE 0.02 mg / DRSP 3 mg) daily for 24 days followed by 1 placebo tablet daily for 4 days<br>|
| Active Comparator: Arm 2<br> | Drug: Ethinylestradiol (EE) and desogestrel (DSG) (Mercilon)<br>* 4 cycles of treatment / per cycle: 1 tablet (EE 0.02 mg / DSG 0.15 mg) daily for 21 days followed by 1 placebo tablet daily for 7 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline to cycle 4 in the sum of composite score during cycle days 22 - 28. The composite score comprises headache, pelvic pain and bloating (each measured by 7-point Likert scales). |  | Cycle days 22 - 28 of baseline cycle and cycle 4. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change from baseline to cycle 4 in the sum of individual scores during cycle days 22 - 28 (AUC of days 22 - 28 for each score), |  | Cycle days 22 - 28 of baseline cycle and cycle 4 | 
| change from baseline to cycle 4 in number of days, where individual hormone withdrawal symptoms are present on cycle days 22 - 28 (i.e. Likert Scale >= 1), |  | Cycle days 22 - 28 of baseline cycle and cycle 4 | 
| change from baseline to cycle 4 in maximum intensity of individual hormone withdrawal symptoms on cycle days 22 - 28, |  | Cycle days 22 - 28 of baseline cycle and cycle 4 | 
| rescue medication consumption |  | baseline cycle and cycle 4 | 
| bleeding pattern |  | reference period is 90 days. | 
| evaluation of questionnaires: Q-LES-Q (short version) |  | baseline cycle and cycle 4 | 
| Adverse Event collection |  | up to 10 days after end of cycle 4 | 
| heart rate |  | up to 10 days after end of cycle 4 | 
| blood pressure |  | up to 10 days after end of cycle 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hormone withdrawal associated symptoms