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

A Multicenter, Open-label, Single-Arm Study to Evaluate the Contraceptive Efficacy and Safety of a Combined Oral Contraceptive Containing 15 mg Estetrol and 3 mg Drospirenone

Sponsors

Lead Sponsor: Estetra

Collaborator: PRA Health Sciences

Source Estetra
Brief 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.

Overall Status Completed
Start Date June 2016
Completion Date April 26, 2018
Primary Completion Date April 26, 2018
Phase Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
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 Up to 12 months (13 cycles with 1 cycle = 28 days)
Secondary Outcome
Measure Time Frame
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 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) 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) Up to 12 months (13 cycles with 1 cycle = 28 days)
Number of Subjects With Unscheduled Bleeding/Spotting Up to 11 months (12 cycles with 1 cycle = 28 days)
Number of Unscheduled Bleeding Days Per Cycle Up to 11 months (12 cycles with 1 cycle = 28 days)
Number of Unscheduled Spotting Days Per Cycle Up to 11 months (12 cycles with 1 cycle = 28 days)
Number of Subjects With Absence of Scheduled Bleeding and/or Spotting Up to 11 months (12 cycles with 1 cycle = 28 days)
Number of Scheduled Bleeding and/or Spotting Days Per Cycle Up to 11 months (12 cycles with 1 cycle = 28 days)
Number of Subjects With Abnormal Vital Signs From screening to end of treatment (12 months)
Number of Subjects With Abnormal Laboratory Assessment Results From screening to end of treatment (12 months)
Number of Subjects With Abnormal Physical Examination Results From screening to end of treatment (12 months)
Number of Subjects With Abnormal Gynecological Examination Results From screening to end of treatment (12 months)
Endometrial Biopsy Histology at Screening and End of Treatment Baseline and end of treatment (up to 13 cycles with 1 cycle = 28 days)
Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Results at Baseline and End of Treatment - Percentage Maximum (Sum of First 14 Items) Baseline and Cycle 13 (1 cycle = 28 days)
Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Results at Baseline and End of Treatment - Satisfaction With Medicine and Overall Life Satisfaction Over the Past Week Baseline and Cycle 13 (1 cycle = 28 days)
Change From Baseline to End of Treatment in the Score of the Menstrual Distress Questionnaire (MDQ) Baseline and Cycle 13 (1 cycle = 28 days)
Enrollment 1577
Condition
Intervention

Intervention Type: Drug

Intervention Name: 15 mg E4/3 mg DRSP

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.

Arm Group Label: 15 mg E4/3 mg DRSP

Other Name: 15 mg estetrol and 3 mg drospirenone

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.

Gender: Female

Minimum Age: 18 Years

Maximum Age: 50 Years

Healthy Volunteers: Accepts Healthy Volunteers

Overall Official
Last Name Role Affiliation
Estetra Study Director Estetra
Location
Facility: Hopital Saint-Pierre
Location Countries

Belgium

Verification Date

September 2019

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Number Of Arms 1
Arm Group

Label: 15 mg E4/3 mg DRSP

Type: Experimental

Description: 15 mg E4/3 mg DRSP tablet

Patient Data No
Study Design Info

Allocation: N/A

Intervention Model: Single Group Assignment

Primary Purpose: Prevention

Masking: None (Open Label)

Source: ClinicalTrials.gov