Clinical trial NCT02817841: E4 FREEDOM (Female Response Concerning Efficacy and Safety of Estetrol/Drospirenone as Oral Contraceptive in a Multicentric Study) - United States/Canada Study
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Contraception
Keywords: Estetrol
Drospirenone
Prevention of pregnancy
Oral contraception
Lead sponsor: Estetra
Sponsor class: INDUSTRY
Collaborators: name: PRA Health Sciences
First posted: 2016-06-29
Enrollment: 2148
Sex: FEMALE
Minimum age (years): 16
Maximum age (years): 50
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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 16 to 50 years.


Eligibility criteria: Inclusion Criteria:

* Heterosexually active female at risk for pregnancy and requesting contraception.
* Negative serum pregnancy test at subject screening.
* 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.
* 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 combined oral contraceptive (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.
* History of alcohol or drug abuse (including laxatives) within 12 months prior to screening.
* Use of drugs potentially triggering interactions with COCs.
* 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/European (EU) approved active ingredients, may be enrolled 2 months (60 days) after completing the preceding study.
* Sponsor, 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.

Primary outcomes:
measure: The Number of On-treatment Pregnancies (With + 7-day Window) Per 100 Woman-years of Exposure (Pearl Index) in Subjects Aged 16 to 35 Years, Inclusive, at the Time of Screening
timeFrame: Up to 12 months (13 cycles with 1 cycle = 28 days)
Secondary outcomes:
measure: The Number of On-treatment Pregnancies (With +7-day Window) as Assessed by the Method Failure Pearl Index in Subjects Aged 16 to 35 Years, Inclusive, at the Time of Screening
timeFrame: Up to 12 months (13 cycles with 1 cycle = 28 days)
measure: The Number of On-treatment Pregnancies (With + 7-day Window) Per 100 Woman-years of Exposure (Pearl Index) in the Overall Study Population (16-50 Years)
timeFrame: Up to 12 months (13 cycles with 1 cycle = 28 days)
measure: The Number of On-treatment Pregnancies as Assessed by the Method Failure Pearl Index in the Overall Study Population (16-50 Years)
timeFrame: Up to 12 months (13 cycles with 1 cycle = 28 days)
measure: Rate of Pregnancy (Life-table Analysis) in Participants Aged 16 to 35 Years
timeFrame: Up to 12 months (13 cycles with 1 cycle = 28 days)
measure: Rate of Pregnancy (Life-table Analysis) in Participants Aged 16 to 50 Years
timeFrame: Up to 12 months (13 cycles with 1 cycle = 28 days)
measure: Number of Subjects With Unscheduled Bleeding/Spotting Episodes
timeFrame: Up to 11 months (12 cycles with 1 cycle = 28 days)
measure: Number of Unscheduled Bleeding Days Per Cycle
timeFrame: Up to 11 months (12 cycles with 1 cycle = 28 days)
measure: Number of Unscheduled Spotting Days Per Cycle
timeFrame: Up to 11 months (12 cycles with 1 cycle = 28 days)
measure: Number of Subjects With Absence of Scheduled Bleeding and/or Spotting
timeFrame: Up to 11 months (12 cycles with 1 cycle = 28 days)
measure: Number of Scheduled Bleeding and/or Spotting Days Per Cycle
timeFrame: Up to 11 months (12 cycles with 1 cycle = 28 days)
measure: Number of Subjects With Bleeding and/or Spotting Episodes by Reference Period
timeFrame: Up to 12 months (13 cycles with 1 cycle = 28 days)
measure: Mean Number of Bleeding and Spotting Days by Reference Period
timeFrame: up to 12 months (13 cycles)
measure: Number of Subjects With Treatment-emergent Adverse Events as a Measure of Safety and Tolerability.
timeFrame: Up to 12 months (13 cycles with 1 cycle = 28 days)
measure: Number of Participants With Clinically Significant out-of Range Hematology Results
timeFrame: Up to 12 months (13 cycles with 1 cycle = 28 days)
measure: Number of Participants With Clinically Significant out-of Range Serum Chemistry and Lipid Profile Results
timeFrame: Up to 12 months (13 cycles with 1 cycle = 28 days)
measure: Number of Subjects With Clinically Abnormal Vital Signs
timeFrame: Up to 12 months (13 cycles with 1 cycle = 28 days)
measure: Number of Participants With Clinically Abnormal Physical Examination Results
timeFrame: Baseline and end of treatment (Cycle 13 with 1 cycle = 28 days)
measure: Number of Participants With Clinically Abnormal Gynecological Examination Results
timeFrame: Baseline and end of treatment (Cycle 13 with 1 cycle = 28 days)
measure: 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)
timeFrame: Baseline and end of treatment (Cycle 13 with 1 cycle = 28 days)
measure: 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 and Contentment Over the Past Week
timeFrame: Baseline and end of treatment (Cycle 13 with 1 cycle = 28 days)
measure: Change From Baseline to End of Treatment in the Score of the Menstrual Distress Questionnaire (MDQ)
timeFrame: Baseline and end of treatment (Cycle 13 with 1 cycle = 28 days)
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Thomas Jefferson University Obstetrics and Gynecology
state: Pennsylvania
city: Quebec
country: Canada
facility: Clinique de Santé des Femmes
Study officials:
affiliation: Estetra
name: Estetra
role: STUDY_DIRECTOR
References: