Safety, Tolerability and Pharmacokinetics of Estetrol (E4) After Single and Multiple Oral Doses in Healthy Female Volunteers

Inclusion Criteria: * Postmenopausal or premenopausal overtly healthy female subject, as determined by medical history, physical examination including breast examination, gynecological examination \[including cervical smear (Pap smear)\], vital signs, ECG, and laboratory tests performed. * Between the ages of 18 and 55 years inclusive at the time of signing the informed consent. * Between the BMI of 18 and 35 kg/m2 inclusive and body weight ≥ 45kg. * Negative serum pregnancy test results at screening and negative urine pregnancy test results at Day -1 of Period 1. * Venous access sufficient to allow blood sampling as per the protocol. * Reliable and willing to be available for the duration of the study and willing to comply with the study procedures. * Have given written informed consent (IC) approved by the relevant EC governing the site. * Negative test results for selected drugs of abuse and cotinine at the screening visit (does not include alcohol) and at check-in for Period 1 (includes alcohol). Exclusion Criteria: * Use of: 1. Any prescription drugs and/or herbal supplements acting on CYP3A4 functions, within 28 days prior to the first study dose administration until study completion. 2. Any over-the-counter medication or dietary supplements (vitamins included) within 14 days prior to the first study dose until study completion. * Currently breastfeeding. * Subjects who are not in euthyroid condition. * Known hypersensitivity to any of the investigational product ingredients. * History of malignancy. * History or presence of prolonged QT interval. * Abnormal arterial tension. * History or presence of disease of any major system organ class (e.g. cardiovascular, pulmonary, renal, hepatic, gastrointestinal, reproductive, endocrinological, neurological, psychiatric or orthopedic disease) as judged by the Investigator. * History or presence of migraine with aura at any age or migraine without aura if \> 35 years old. * Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of drugs, or which may jeopardize the subject in case of participation in the study. * History or presence of immunodeficiency diseases including a positive HIV test result, positive hepatitis B antigen or hepatitis C test result. * Smokers. * History of illicit drug or alcohol abuse within 12 months prior to first dose or evidence of such abuse. * Donation or loss of * ≥ 450 mL blood within 1 month prior to initial study drug administration. * ≥ 250 mL blood within 2 weeks prior to initial study drug administration. * Previous completion or withdrawal from this study. * Participation in another investigational drug clinical study within 1 month (30 days) or have received an investigational drug within the last 3 months (90 days) prior to study entry. Subjects who participated in an oral contraceptive clinical study, using Food and Drug Administration (FDA)/ European Union (EU) approved active ingredients, may be enrolled 2 months (60 days) after completing the preceding study. * Sponsor, the Contract Research Organization (CRO) or Investigator's site personnel directly affiliated with this study. * Is judged by the Investigator to be unsuitable for any reason.