Cycle Control and Safety of E2-DRSP
Cycle Control and Safety of E2-DRSP
The study will be performed as a multi-center, randomized, double-blind, parallel-group trial
 in fertile women aged between 18 and 35 years inclusive. A total of 600 volunteers will be
 randomized into one of the six treatment groups. The study will be performed only in Germany.
 The investigational drug is an oral contraceptive. It contains the estrogen estradiol (E2)
 and the progestogen drospirenone (DRSP). As the contraceptive efficacy has not yet been
 proven for these new regimens, even a protection against unwanted pregnancies cannot be
 assured. The treatments will be applied daily for 7 cycles of 28 days each without pill-free
 interval, i.e., for 196 consecutive days. Treatment will be initiated after a screening
 period of approximately 1 to 2 weeks, the latter focused on confirmation of the baseline
 safety status. Tablet intake will start on the first day of the first menstrual/withdrawal
 bleeding after Visit 2, regardless of whether the volunteer is a first user (starter) or
 switching from another COC. In the following cycles, tablet intake is not to be triggered by
 any bleeding events. The primary objective of this study is to evaluate and compare the cycle
 control and bleeding patterns of six different treatment regimens with E2/DRSP during
 administration for 7 treatment cycles. Volunteers will be provided with a diary to document
 the intake of study medication, any bleeding events, and days without bleeding, pregnancy
 test results. Safety will be also assessed. During the whole study period, 4 visits are
 planned. At Screening and Final examination, a thorough physical examination and a
 gynecological examination (including breast palpation and cervical smear ) will be performed.
 Blood samples will be taken for safety laboratory parameters.Additional examinations can be
 performed any time, if this becomes necessary for medical reasons. At Visit 3 or in case of
 premature discontinuation of study the investigator will discuss options for follow-up
 contraception with the volunteer. The volunteer can start the intake of a post-treatment OC
 on the day after the last tablet intake of study medication, after a negative urine ß-HCG
 test (home pregnancy test) result.
Inclusion Criteria:

 -  Healthy female volunteers

 -  Age: 18 - 35 years (inclusive), smokers must not be older than 30 years at inclusion

 -  History of regular cyclic menstrual periods (with a cycle length between 25 and 35
 days)

 -  Willingness to use barrier methods of contraception (condoms with spermicide,
 diaphragms with spermicide, spermicidal vaginal suppositories) or abstinence during
 the trial

 Exclusion Criteria:

 -  Pregnancy, lactation (less than three menstrual cycles before Visit 1 following
 delivery, abortion, or lactation) - Obesity (BMI > 30.0 kg/m2)

 -  Abnormal, suspicious or unclear cervical smear (a cervical smear has to be taken at
 Visit 1 or a normal result has to be documented within the last 6 months before Visit
 1)

 -  Laboratory values outside inclusion range at Screening - Any disease that may worsen
 under hormonal treatment or might interfere with the conduct of the study or the
 interpretation of the results, as e.g.: - Cardiovascular -- 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, including
 prodromi (e.g., transient ischemic attack, angina pectoris) and conditions which could
 increase the risk to suffer from any of the above mentioned disorders, e.g., a family
 history indicating a hereditary predisposition. -- uncontrolled arterial hypertension
 (repeated measurements of systolic blood pressure > 140 mmHg and/or diastolic blood
 pressure > 90 mmHg)

 -  Liver -- presence or history of liver tumor (benign or malignant) -- 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 -- history of cholestatic
 jaundice associated with pregnancy or previous COC use

 -  Metabolic diseases -- uncontrolled diabetes mellitus with vascular involvement severe
 dyslipoproteinemia

 -  Other diseases: any known or suspected malignant or premalignant disease, uncontrolled
 thyroid disorder, chronic inflammatory bowel disease, severe renal insufficiency or
 acute renal failure, hemolytic uremic syndrome, sickle cell anemia, porphyria, history
 of hypertriglyceridemia-associated Pancreatitis, systemic lupus erythematodes,
 pemphigoid gestationis during a previous pregnancy, Sydenham chorea, herpes
 gestationis, otosclerosis-related hearing loss, history of migraine with focal
 neurologic symptoms, epilepsy, current or history of clinically significant
 depression, hereditary angioedema

 -  Additional sex steroids, other hormonal contraceptive methods (oral, transdermal)
 during treatment (blister in use at randomization should be finished); intra-uterine
 devices (IUD) with or without hormone release within 1 month prior to Visit 1,
 implants within 1 month prior Visit 1, depot progestins within 6 months prior to Visit
 1 - Surgical interventions scheduled in the study period