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

Launched by ESTETRA · Mar 8, 2017

Keywords

ClinConnect Summary

This is an open-label, single-center, randomized, two-period, single and multiple oral dose study in 27 healthy female volunteers.

After a screening period, eligible subjects (n=27) will receive a single oral dose of 5, 15, or 45 mg E4 (Period 1). After at least 14-day washout, 18 subjects will continue the study (Period 2). They will receive 15 mg E4 once daily for 14 consecutive days.

Gender

FEMALE

Eligibility criteria

• 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.

Trial Officials