- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03091595
E4/DRSP Ovarian Function Inhibition Study
April 29, 2023 updated by: Estetra
A Single-center, Randomized, Open-label, Two-arm Study to Evaluate the Ovarian Function Inhibition of a Monophasic Combined Oral Contraceptive (COC) Containing 15 mg Estetrol (E4) and 3 mg Drospirenone (DRSP) and a Monophasic COC Containing 20mcg Ethinylestradiol (EE)/3 mg DRSP (YAZ®), Administered Orally Once Daily in a 24/4 Day Regimen for Three Consecutive Cycles
A combined oral contraceptive (COC) containing 15 mg E4 and 3 mg DRSP administered for 24 days followed by 4 placebo tablets, is being evaluated for further development.
This study will investigate the effect of this COC on ovarian function inhibition, levels of serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2) and progesterone during 3 treatment cycles in comparison with the reference COC 20 mcg EE/3 mg DRSP.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
82
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
-
Groningen, Netherlands, 9713 CZ
- Dinox BV
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 35 years (Adult)
Accepts Healthy Volunteers
Yes
Description
Inclusion Criteria:
- Overtly healthy female subjects, as determined by medical history, physical examination including breast examination, gynecological examination (including cervical smear [Pap smear]), vital signs, ECG, echocardiogram, and laboratory tests.
- Negative pregnancy test at subject screening.
- Women who ovulate in the Pre-Treatment Cycle.
- Willing to use a non-hormonal method of contraception (e.g. condom) during the wash-out period, Pre-Treatment Cycle and Post-Treatment Cycle.
- BMI between 18.0 and 35.0 kg/m², inclusive, at time of Screening.
- Able to fulfill the requirements of the protocol and have indicated a willingness to participate in the study by providing written informed consent form (ICF).
Exclusion Criteria:
- Irregular menstrual cycle.
- Amenorrhea or abnormal uterine bleeding.
- Clinically relevant abnormal laboratory result at Screening.
- Clinically significant abnormalities of the uterus and/or ovaries detected by examination and/or ultrasound.
- Known hypersensitivity to any of the investigational or reference product ingredients.
- Intention to become pregnant during the course of the study.
- Pregnancy during accurate hormonal contraceptive use in the past.
- 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.
- Any arterial hypertension.
- Any condition associated with an increased risk of venous thromboembolism and/or arterial thromboembolism.
- Complicated valvular heart disease.
- History of pregnancy-related cardiomyopathy or moderately or severely impaired cardiac function.
- Systemic lupus erythematosus.
- Presence or history of migraine with aura.
- Abnormal Papanicolaou (PAP) smear result.
- 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.
- Any prior procedure, disease or condition that could result in altered absorption, excessive accumulation, impaired metabolism, or altered excretion of the investigational product.
- Uncontrolled thyroid disorders.
- Have received an investigational drug within the last 2 cycles prior to start of Pre-Treatment Cycle. Subjects who participated in an oral contraceptive clinical study, using Food and Drug Administration (FDA)/European Union (EU) approved active ingredients, may start the Pre-Treatment Cycle one cycle after last medication intake of the preceding study.
- Sponsor, contract research organization (CRO) or PI's site personnel directly affiliated with this study.
- Is judged by the PI to be unsuitable for any reason.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 15 mg E4/3 mg DRSP
15 mg E4 combined with 3 mg DRSP administered in a 24/4-day regimen.
One tablet per day orally for 3 treatment cycles.
|
15 mg E4/3 mg DRSP combined tablets will be administered orally once daily in a 24/4 day regimen for three consecutive cycles
Other Names:
|
Active Comparator: 20 mcg EE/3 mg DRSP
20 mcg EE combined with 3 mg DRSP administered in a 24/4-day regimen.
One tablet per day orally for 3 treatment cycles.
|
20 mcg EE/3 mg DRSP combined tablets will be administered orally once daily in a 24/4 day regimen for three consecutive cycles
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Proportion of subjects with ovarian inhibition at treatment Cycle 1
Time Frame: All assessments will be performed once every 3 days starting treatment Cycle 1 Day 3 (± 1 day) until Day 27 (± 1 day) (one treatment cycle = 28 days).
|
Ovarian inhibition will be assessed by rating the suppression of ovaries using the Hoogland score. This score is based on:
|
All assessments will be performed once every 3 days starting treatment Cycle 1 Day 3 (± 1 day) until Day 27 (± 1 day) (one treatment cycle = 28 days).
|
Proportion of subjects with ovarian inhibition at treatment Cycle 3
Time Frame: All assessments will be performed once every 3 days starting treatment Cycle 3 Day 3 (± 1 day) until Day 27 (± 1 day) (one treatment cycle = 28 days).
|
Ovarian inhibition will be assessed by rating the suppression of ovaries using the Hoogland score. This score is based on:
|
All assessments will be performed once every 3 days starting treatment Cycle 3 Day 3 (± 1 day) until Day 27 (± 1 day) (one treatment cycle = 28 days).
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Serum level of luteinizing hormone (LH)
Time Frame: On cycle Day 3, 6, 9, 12, 15, 18, 21, 24, 27 at treatment Cycle 1 and treatment Cycle 3 and on cycle Day 3 of the Treatment Cycle 2 (each treatment cycle = 28 days)
|
Blood samples will be taken at regular time points defined in the time frame.
|
On cycle Day 3, 6, 9, 12, 15, 18, 21, 24, 27 at treatment Cycle 1 and treatment Cycle 3 and on cycle Day 3 of the Treatment Cycle 2 (each treatment cycle = 28 days)
|
Serum level of follicle stimulating hormone (FSH)
Time Frame: On cycle Day 3, 6, 9, 12, 15, 18, 21, 24, 27 at treatment Cycle 1 and treatment Cycle 3 and on cycle Day 3 of the Treatment Cycle 2 (each treatment cycle = 28 days)
|
Blood samples will be taken at regular time points defined in the time frame.
|
On cycle Day 3, 6, 9, 12, 15, 18, 21, 24, 27 at treatment Cycle 1 and treatment Cycle 3 and on cycle Day 3 of the Treatment Cycle 2 (each treatment cycle = 28 days)
|
Serum level of estradiol (E2)
Time Frame: On cycle Day 3, 6, 9, 12, 15, 18, 21, 24, 27 at treatment Cycle 1 and treatment Cycle 3 and on cycle Day 3 of the Treatment Cycle 2 (each treatment cycle = 28 days)
|
Blood samples will be taken at regular time points defined in the time frame.
|
On cycle Day 3, 6, 9, 12, 15, 18, 21, 24, 27 at treatment Cycle 1 and treatment Cycle 3 and on cycle Day 3 of the Treatment Cycle 2 (each treatment cycle = 28 days)
|
Serum level of progesterone (P)
Time Frame: On cycle Day 3, 6, 9, 12, 15, 18, 21, 24, 27 at treatment Cycle 1 and treatment Cycle 3 and on cycle Day 3 of the Treatment Cycle 2 (each treatment cycle = 28 days)
|
Blood samples will be taken at regular time points defined in the time frame.
|
On cycle Day 3, 6, 9, 12, 15, 18, 21, 24, 27 at treatment Cycle 1 and treatment Cycle 3 and on cycle Day 3 of the Treatment Cycle 2 (each treatment cycle = 28 days)
|
Maximum endometrial thickness
Time Frame: From Baseline (study day 1), through 3 treatment cycles and up to Cycle Day 36 (±1) of the Post-Treatment Cycle (study day 120 (±1)) (each treatment cycle = 28 days)
|
Endometrial thickness will be measured using transvaginal ultrasound (TVUS).
Maximum endometrial thickness was defined as the largest endometrial thickness during a cycle.
|
From Baseline (study day 1), through 3 treatment cycles and up to Cycle Day 36 (±1) of the Post-Treatment Cycle (study day 120 (±1)) (each treatment cycle = 28 days)
|
Mean diameter of the largest follicle
Time Frame: Day 3 to Day 24 of Post-Treatment Cycle
|
Follicular size will be measured using TVUS.
|
Day 3 to Day 24 of Post-Treatment Cycle
|
Number of participants who experience at least one Treatment-Emergent Adverse Event (TEAE)
Time Frame: Day 1 to Follow-Up Visit (+ 30 days)
|
Day 1 to Follow-Up Visit (+ 30 days)
|
|
Number of participants who experience pregnancy during treatment
Time Frame: Cycle 1 Day 1 to Follow-Up Visit (+ 30 days) (each treatment cycle = 28 days)
|
Cycle 1 Day 1 to Follow-Up Visit (+ 30 days) (each treatment cycle = 28 days)
|
|
Number of participants who experience a clinically significant change in physical examination results
Time Frame: Day 1 to End of Follow-Up Visit (+ 30 Days)
|
Day 1 to End of Follow-Up Visit (+ 30 Days)
|
|
Number of participants who experience a clinically significant change in gynecological examination results
Time Frame: Day 1 to End of Follow-Up Visit (+ 30 Days)
|
Day 1 to End of Follow-Up Visit (+ 30 Days)
|
|
Number of participants who experience a clinically significant change in clinical laboratory results
Time Frame: Day 1 to End of Follow-Up Visit (+ 30 Days)
|
Day 1 to End of Follow-Up Visit (+ 30 Days)
|
|
Number of participants who experience a clinically significant change in electrocardiogram (ECG) results
Time Frame: Day 1 to End of Cycle 3 (Day 28) (each treatment cycle = 28 days)
|
Day 1 to End of Cycle 3 (Day 28) (each treatment cycle = 28 days)
|
|
Number of participants who experience a clinically significant change in echocardiogram results
Time Frame: Day 1 to End of Cycle 3 (Day 28) (each treatment cycle = 28 days)
|
Day 1 to End of Cycle 3 (Day 28) (each treatment cycle = 28 days)
|
|
Change from Baseline in diastolic blood pressure
Time Frame: From Baseline (study day 1), through 3 treatment cycles and up to Cycle Day 36 (±1) of the Post-Treatment Cycle (study day 120 (±1)) (each treatment cycle = 28 days)
|
From Baseline (study day 1), through 3 treatment cycles and up to Cycle Day 36 (±1) of the Post-Treatment Cycle (study day 120 (±1)) (each treatment cycle = 28 days)
|
|
Change from Baseline in systolic blood pressure
Time Frame: From Baseline (study day 1), through 3 treatment cycles and up to Cycle Day 36 (±1) of the Post-Treatment Cycle (study day 120 (±1)) (each treatment cycle = 28 days)
|
From Baseline (study day 1), through 3 treatment cycles and up to Cycle Day 36 (±1) of the Post-Treatment Cycle (study day 120 (±1)) (each treatment cycle = 28 days)
|
|
Change from Baseline in pulse rate
Time Frame: From Baseline (study day 1), through 3 treatment cycles and up to Cycle Day 36 (±1) of the Post-Treatment Cycle (study day 120 (±1)) (each treatment cycle = 28 days)
|
From Baseline (study day 1), through 3 treatment cycles and up to Cycle Day 36 (±1) of the Post-Treatment Cycle (study day 120 (±1)) (each treatment cycle = 28 days)
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
February 7, 2017
Primary Completion (Actual)
June 8, 2018
Study Completion (Actual)
June 8, 2018
Study Registration Dates
First Submitted
March 21, 2017
First Submitted That Met QC Criteria
March 21, 2017
First Posted (Actual)
March 27, 2017
Study Record Updates
Last Update Posted (Actual)
May 3, 2023
Last Update Submitted That Met QC Criteria
April 29, 2023
Last Verified
April 1, 2023
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Physiological Effects of Drugs
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Estrogens
- Natriuretic Agents
- Diuretics
- Hormone Antagonists
- Contraceptive Agents, Hormonal
- Contraceptive Agents
- Reproductive Control Agents
- Contraceptives, Oral
- Contraceptive Agents, Female
- Contraceptives, Oral, Hormonal
- Mineralocorticoid Receptor Antagonists
- Diuretics, Potassium Sparing
- Ethinyl Estradiol
- Drospirenone
Other Study ID Numbers
- MIT-Es0001-C202
- 2016-004267-40 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Prevention of Pregnancy
-
Warner ChilcottCompleted
-
Sebela Women's Health Inc.CompletedPrevention of PregnancyDominican Republic
-
Ocon Medical Ltd.WithdrawnReversible Prevention of PregnancyIsrael
-
Brown UniversityActive, not recruitingPrevention or Reduction of HIV Risk Behavior | Prevention or Reduction of Intimate Partner ViolenceSouth Africa
-
University Hospital, MontpellierAssociation Francaise pour la Recherche ThermaleCompletedPrevention of FallsFrance
-
Shanghai Cell Therapy Group Co.,LtdNot yet recruitingPostoperative Prevention of TumorChina
-
Federal State Budgetary Scientific Institution...CompletedPrevention of Diseases of the Musculoskeletal SystemRussian Federation
-
Federal State Budgetary Scientific Institution...CompletedPrevention of Diseases of the Musculoskeletal SystemRussian Federation
-
Federal State Budgetary Scientific Institution...CompletedPrevention of Diseases of the Musculoskeletal SystemRussian Federation
-
University of PennsylvaniaCompletedPrevention of Hair GrowthUnited States
Clinical Trials on 15 mg E4/3 mg DRSP
-
EstetraCompletedMenopause | ContraceptionBulgaria
-
EstetraCompleted
-
NEURALIS s.a.Active, not recruitingCovid19Belgium, Hungary, Russian Federation, Poland
-
EstetraPRA Health SciencesCompleted
-
EstetraPRA Health SciencesCompleted
-
EstetraCompletedContraception | Liver Metabolism | Hemostasis ParameterNetherlands
-
NEURALIS s.a.RecruitingPharmacokinetics | SafetyBulgaria
-
EstetraCompletedSafetyEstonia, Finland, Georgia, Latvia, Poland, Sweden
-
Donesta BioscienceCompleted