E4 FREEDOM (Female Response Concerning Efficacy and Safety of Estetrol/Drospirenone as Oral Contraceptive in a Multicentric Study) - EU/Russia Study

Estetra1,577 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

PREVENTION

Masking

NONE

Enrollment

1,577

Conditions

Contraception

Interventions

15 mg E4/3 mg DRSPDRUG

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.

Eligibility

Sex: FEMALEMin age: 18 YearsMax age: 50 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (1)

Hopital Saint-Pierre

Brussels, Belgium

Outcomes

Primary Outcomes

The Number of On-treatment Pregnancies (With + 2-day Window) Per 100 Woman-years of Exposure (Pearl Index) in Subjects Aged 18 to 35 Years, Inclusive, at the Time of Screening

On-treatment pregnancies are defined as pregnancies with an estimated date of conception within the in-treatment period i.e. Day 1 to 2 days after the last intake of investigational product (whether active or inactive tablet). The Pearl Index, defined as the number of pregnancies per 100 women-years of treatment was calculated as: Pearl Index = (1300\*number of on-treatment pregnancies)/number of women 28-day equivalent cycles of treatment.Only at-risk cycles were included in the denominator of the Pearl Index calculation. At-risk-cycles were defined as cycles in which no other methods of birth control (including condoms) were used by the subject as confirmed in the subject diary and during which the subject confirmed that sexual intercourse had occurred.

Time frame: Up to 12 months (13 cycles with 1 cycle = 28 days)

Secondary Outcomes

The Number of On-treatment Pregnancies (With 2-day Window) as Assessed by the Method Failure Pearl Index in Subjects Aged 18 to 35 Years, Inclusive, at the Time of Screening

On-treatment pregnancies are defined as pregnancies with an estimated date of conception within the in-treatment period i.e. Day 1 to 2 days after the last intake of investigational product (whether active or inactive tablet). The Pearl Index, defined as the number of pregnancies per 100 women-years of treatment was calculated as: Pearl Index = (1300\*number of on-treatment pregnancies)/number of women 28-day equivalent cycles of treatment. The method failure Pearl Index includes only those pregnancies that were classified as method failure and not the pregnancies due to user failure, i.e. incorrect intake of the contraceptive method. Only at-risk cycles were included in the denominator of the Pearl Index calculation. At-risk-cycles were defined as cycles in which no other methods of birth control (including condoms) were used by the subject as confirmed in the subject diary and during which the subject confirmed that sexual intercourse had occurred.

Time frame: Up to 12 months (13 cycles with 1 cycle = 28 days)

The Number of On-treatment Pregnancies (With + 2-day Window) Per 100 Woman-years of Exposure (Pearl Index) in the Overall Study Population (18-50 Years)

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Time frame: Up to 12 months (13 cycles with 1 cycle = 28 days)

The Number of On-Treatment Pregnancies as Assessed by the Method Failure Pearl Index in the Overall Study Population (18-50 Years)

On-treatment pregnancies are defined as pregnancies with an estimated date of conception within the in-treatment period i.e. Day 1 to 2 days after the last intake of investigational product (whether active or inactive tablet). The Pearl Index, defined as the number of pregnancies per 100 women-years of treatment was calculated as: Pearl Index = (1300\*number of on-treatment pregnancies)/number of women 28-day equivalent cycles of treatment. The method failure Pearl Index includes only those pregnancies that were classified as method failure and not the pregnancies due to user failure, i.e. incorrect intake of the contraceptive method. Only at-risk cycles were included in the denominator of the Pearl Index calculation. At-risk-cycles were defined as cycles in which no other methods of birth control (including condoms) were used by the subject as confirmed in the subject diary and during which the subject confirmed that sexual intercourse had occurred.

Time frame: Up to 12 months (13 cycles with 1 cycle = 28 days)

Number of Subjects With Unscheduled Bleeding/Spotting

Unscheduled bleeding/spotting is defined as any bleeding/spotting that occurs while taking active hormones that does not meet the criteria for scheduled bleeding.