Multicenter, open-label, randomized study to evaluate inhibition of ovulation during treatment with three transdermal patch formulations containing 0.55 mg ethinylestradiol (EE) and 2.10 mg gestodene (GSD) or 0.35 mg EE and 0.67 mg GSD or 0.275 mg EE and 1.05 mg GSD in healthy young female volunteers over a period of 3 treatment cycles - Inhibition of ovulation and pharmacokinetic study of 3 transdermal EE and GSD formulations

• Conditions: Prevention of Pregnancy; MedDRA version: 12.1Level: LLTClassification code 10060346Term: Transdermal contraception

• Registration Number: EUCTR2010-021255-81-NL
• Lead Sponsor: Bayer HealthCare AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-08-13
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 174

Inclusion Criteria

1.Healthy female subject
2.Age: 18 to 35 years (inclusive) at the first screening visit
3.Body mass index (BMI): = 18 kg/m²
4.Ability to understand and follow study-related instructions
5.Willingness to use non-hormonal methods of contraception during the entire study
6.Signed informed consent before any study specific tests or procedures are done
7.Confirmation of the subject’s health insurance coverage prior to the first screening examination

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1.Incompletely cured pre-existing diseases for which it can be assumed that the absorption, distribution, metabolism, elimination and effects of the study drugs will not be normal
2.Known or suspected malignant tumors (including after treatment)
3.Known or suspected benign tumors of the liver, pituitary and adrenal gland (including after treatment)
4.Known or suspected liver disorders, including disturbances of bilirubin metabolism (e.g. Dubin-Johnson and Rotor syndromes) and bile secretion/flow (cholestasis, also history of it)
5.Conditions/diseases known to occur or deteriorate with both pregnancy and COC use.
6.Presence or history of pancreatitis
7.Presence or history of venous or arterial thrombotic/thromboembolic events (e.g. deep vein thrombosis, pulmonary embolism, myocardial infarction) or of a cerebrovascular accident, including prodromi (e.g. transient ischaemic 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 hereditary predisposition
8.Diseases associated with adverse vascular events (e.g. diabetes mellitus, chronic inflammatory diseases like Crohn’s disease or colitis ulcerosa, severe disorders of lipid metabolism, sickle-cell anemia)
9.Severe renal insufficiency or acute renal failure
14.Skin diseases with suspected alteration of dermal resorption and/or increased risk for dermal intolerance (e.g. psoriasis, neurodermitis, urticaria)
16.Regular use of medicines other than contraceptives
17.Use of systemic or topical medicines or substances which oppose the study objectives or which might influence them within 4 weeks before the first study drug administration
18.Use of sex hormones (oral, transdermal, intravaginal) during the cycle preceding the pre-treatment cycle
19.Use of any long-acting injectable or implant hormonal therapy within 40 weeks prior to the first study drug administration
20.Use of an intra-uterine system (IUS) releasing hormones during the cycle preceding the pre-treatment cycle (non-hormonal intra-uterine devices are acceptable)
22.Smokers: at the age of 18 to 30 years inclusive (at first screening visit) with a daily consumption of > 10 cigarettes or at the age of 31 to 35 years inclusive (at first screening visit); former smokers who have stopped smoking at least 3 months prior to the first screening visit may be included
23.Donation of blood or plasmapheresis after signing the informed consent
24.Systolic blood pressure below 90 or above 140 mmHg (after at least 3 min in sitting position)
25.Diastolic blood pressure below 45 or above 90 mmHg (after at least 3 min in sitting position)
27.Clinically relevant findings in the physical examination (e.g. pronounced varicosis, thrombophlebitis, evidence of peripheral circulatory disturbances, skin abnormalities in the application area)
28.Clinically relevant findings in the gynecological examination including transvaginal ultrasound
29.Cervical cytological smear classified higher than II according to Papanicolaou (grading I - V)
30.Genital bleeding of unknown origin
31.Menstrual disorders suspicious of ovarian failure (e.g. oligomenorrhea, amenorrhea, hypomenorrhea)
32.Delivery, abortion or lactation less than 3 months before the first screening examination
33.Positive urine pregnancy test
34.Positive results for hepatitis B virus surface antigen (HBsAg), hepatitis C virus antibodies (anti-HCV), human immune deficiency virus antibodies (anti-HIV 1+2

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective of this study is to evaluate the inhibition of ovulation in treatment cycles 2 and 3 after dermal application of 3 different patch formulations containing ethinylestradiol (EE) / gestodene (GSD) for 3 treatment cycles;Secondary Objective: •Course of gonadotropins (FSH, LH) and ovarian steroids (E2, P)<br>•Endometrial thickness<br>•Pharmacokinetics of EE, GSD and SHBG <br>•Follicle size<br>;Primary end point(s): The primary pharmacodynamic variable will be the proportion of volunteers with ovulation in at least one of the treatment cycles 2 and 3.