E4/DRSP Ovarian Function Inhibition Study

A combined oral contraceptive (COC) containing 15 mg E4 and 3 mg DRSP administered for 24 days followed by 4 placebo tablets, is being evaluated for further development. This study will investigate the effect of this COC on ovarian function inhibition, levels of serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2) and progesterone during 3 treatment cycles in comparison with the reference COC 20 mcg EE/3 mg DRSP.


Eligibility Criteria:
Inclusion Criteria:

* Overtly healthy female subjects, as determined by medical history, physical examination including breast examination, gynecological examination (including cervical smear \[Pap smear\]), vital signs, ECG, echocardiogram, and laboratory tests.
* Negative pregnancy test at subject screening.
* Women who ovulate in the Pre-Treatment Cycle.
* Willing to use a non-hormonal method of contraception (e.g. condom) during the wash-out period, Pre-Treatment Cycle and Post-Treatment Cycle.
* BMI between 18.0 and 35.0 kg/m², inclusive, at time of Screening.
* Able to fulfill the requirements of the protocol and have indicated a willingness to participate in the study by providing written informed consent form (ICF).

Exclusion Criteria:

* Irregular menstrual cycle.
* Amenorrhea or abnormal uterine bleeding.
* Clinically relevant abnormal laboratory result at Screening.
* Clinically significant abnormalities of the uterus and/or ovaries detected by examination and/or ultrasound.
* Known hypersensitivity to any of the investigational or reference product ingredients.
* Intention to become pregnant during the course of the study.
* Pregnancy during accurate hormonal contraceptive use in the past.
* Dyslipoproteinemia requiring active treatment with antilipidemic agent.
* Diabetes mellitus with vascular involvement (nephropathy, retinopathy, neuropathy, other) or diabetes mellitus of more than 20-year duration.
* Any arterial hypertension.
* Any condition associated with an increased risk of venous thromboembolism and/or arterial thromboembolism.
* Complicated valvular heart disease.
* History of pregnancy-related cardiomyopathy or moderately or severely impaired cardiac function.
* Systemic lupus erythematosus.
* Presence or history of migraine with aura.
* Abnormal Papanicolaou (PAP) smear result.
* Presence of an undiagnosed breast mass.
* Current symptomatic gallbladder disease.
* History of COC-related cholestasis.
* Presence or history of severe hepatic disease.
* Presence or history of pancreatitis if associated with hypertriglyceridemia.
* Porphyria.
* Presence or history of hepatocellular adenoma or malignant liver tumors.
* Renal impairment.
* Hyperkaliemia or presence of conditions that predispose to hyperkaliemia.
* Presence or history of hormone-related malignancy.
* History of non-hormone-related malignancy within 5 years before Screening. Subjects with a non-melanoma skin cancer are allowed in the study.
* Use of drugs potentially triggering interactions with COCs.
* History of alcohol or drug abuse.
* Any prior procedure, disease or condition that could result in altered absorption, excessive accumulation, impaired metabolism, or altered excretion of the investigational product.
* Uncontrolled thyroid disorders.
* Have received an investigational drug within the last 2 cycles prior to start of Pre-Treatment Cycle. Subjects who participated in an oral contraceptive clinical study, using Food and Drug Administration (FDA)/European Union (EU) approved active ingredients, may start the Pre-Treatment Cycle one cycle after last medication intake of the preceding study.
* Sponsor, contract research organization (CRO) or PI's site personnel directly affiliated with this study.
* Is judged by the PI to be unsuitable for any reason.