E4 FREEDOM (Female Response Concerning Efficacy and Safety of Estetrol/Drospirenone as Oral Contraceptive in a Multicentric Study) - EU/Russia Study
Condition: Contraception
Intervention: 15 mg E4/3 mg DRSP
Intervention description: 15 mg estetrol and 3 mg drospirenone tablets administered once daily for 13 consecutive cycles following a 24/4-day regimen, i.e. one 15 mg E4/3 mg DRSP active tablet per day for 24 consecutive days followed by one placebo tablet per day for 4 consecutive days.
Intervention MeSH terms: Drospirenone
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 1577.0
Sex: Female
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Estetrol

Summary:

      The objectives of this study are to evaluate the contraceptive efficacy, vaginal bleeding
      pattern (cycle control), and the general safety and acceptability of the 15 mg estetrol
      (E4)/3 mg drospirenone (DRSP) combination in healthy women aged 18 to 50 years.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Heterosexually active female at risk for pregnancy and requesting contraception.

          -  Negative serum pregnancy test at subject enrollment.

          -  Willing to use the investigational product as the primary method of contraception for
             13 consecutive cycles.

          -  Good physical and mental health on the basis of medical, surgical and gynecological
             history, physical examination, gynecological examination, clinical laboratory, and
             vital signs.

          -  Body mass index (BMI) below or equal to (≤) 35.0 kg/m2.

          -  Able to fulfill the requirements of the protocol and have indicated a willingness to
             participate in the study by providing written informed consent (IC).

          -  Willing and able to complete the diaries and questionnaires.

        Exclusion Criteria:

          -  Known hypersensitivity to any of the investigational product ingredients.

          -  Smoking if ≥ 35 years old, at screening.

          -  Any condition associated with decrease fertility.

          -  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.

          -  Arterial hypertension.

          -  Any condition associated with an increased risk of venous thromboembolism and/or
             arterial thromboembolism.

          -  Any condition associated with abnormal uterine/vaginal bleeding.

          -  Abnormal Pap test based on current international recommendations.

          -  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 (including laxatives) within 12 months prior to
             screening.

          -  Any condition that could result in altered absorption, excessive accumulation,
             impaired metabolism, or altered excretion of the investigational product.

          -  Uncontrolled thyroid disorders.

          -  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
             FDA/EU approved active ingredients, may be enrolled 2 months (60 days) after
             completing the preceding study.

          -  Sponsor, CRO or Investigator's site personnel directly affiliated with this study.

          -  Is judged by the Investigator to be unsuitable for any reason.