Prevention of PregnancyPhase 2NCT03091595
E4/DRSP Ovarian Function Inhibition Study
A Phase 2 study testing 15 mg E4/3 mg DRSP and 20 mcg EE/3 mg DRSP in people with Prevention of Pregnancy, run by Estetra at 1 site in Netherlands.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 35 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Prevention of Pregnancy
- What is being tested?
- 15 mg E4/3 mg DRSP and 20 mcg EE/3 mg DRSP
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 82 participants
- Where
- 1 siteNetherlands
- Study dates
- 7 Feb 2017to 8 Jun 2018
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 35 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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).
Who cannot join
- 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.
Show all 34Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
- Conditions
- Prevention of Pregnancy
- Being tested
- 15 mg E4/3 mg DRSP, 20 mcg EE/3 mg DRSP
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
15 mg E4/3 mg DRSPDrug
Also called 15 mg estetrol combined with 3 mg drospirenone
15 mg E4/3 mg DRSP combined tablets will be administered orally once daily in a 24/4 day regimen for three consecutive cycles
20 mcg EE/3 mg DRSPDrug
Also called 20 mcg ethinylestradiol combined with 3 mg drospirenone (Yaz)
20 mcg EE/3 mg DRSP combined tablets will be administered orally once daily in a 24/4 day regimen for three consecutive cycles
| Study group | Role | What they receive |
|---|---|---|
| 15 mg E4/3 mg DRSP | Experimental | 15 mg E4 combined with 3 mg DRSP administered in a 24/4-day regimen. One tablet per day orally for 3 treatment cycles. Receives: Drug: 15 mg E4/3 mg DRSP |
| 20 mcg EE/3 mg DRSP | Active comparator | 20 mcg EE combined with 3 mg DRSP administered in a 24/4-day regimen. One tablet per day orally for 3 treatment cycles. Receives: Drug: 20 mcg EE/3 mg DRSP |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of subjects with ovarian inhibition at treatment Cycle 1
Ovarian inhibition will be assessed by rating the suppression of ovaries using the Hoogland score. This score is based on:
- the follicular size assessed by transvaginal ultrasound (TVUS)
- endogenous hormone levels: serum E2, and serum progesterone.
Measured: 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
Ovarian inhibition will be assessed by rating the suppression of ovaries using the Hoogland score. This score is based on:
- the follicular size assessed by TVUS
- endogenous hormone levels: serum E2, and serum progesterone.
Measured: 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 outcomes (16)
Serum level of luteinizing hormone (LH)
Blood samples will be taken at regular time points defined in the time frame.
Measured: 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)
Blood samples will be taken at regular time points defined in the time frame.
Measured: 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)
Blood samples will be taken at regular time points defined in the time frame.
Measured: 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)
Blood samples will be taken at regular time points defined in the time frame.
Measured: 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
Endometrial thickness will be measured using transvaginal ultrasound (TVUS). Maximum endometrial thickness was defined as the largest endometrial thickness during a cycle.
Measured: 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
Follicular size will be measured using TVUS.
Measured: Day 3 to Day 24 of Post-Treatment Cycle
Number of participants who experience at least one Treatment-Emergent Adverse Event (TEAE)
Measured: Day 1 to Follow-Up Visit (+ 30 days)
Number of participants who experience pregnancy during treatment
Measured: 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
Measured: Day 1 to End of Follow-Up Visit (+ 30 Days)
Number of participants who experience a clinically significant change in gynecological examination results
Measured: Day 1 to End of Follow-Up Visit (+ 30 Days)
Number of participants who experience a clinically significant change in clinical laboratory results
Measured: Day 1 to End of Follow-Up Visit (+ 30 Days)
Number of participants who experience a clinically significant change in electrocardiogram (ECG) results
Measured: 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
Measured: Day 1 to End of Cycle 3 (Day 28) (each treatment cycle = 28 days)
Change from Baseline in diastolic blood pressure
Measured: 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
Measured: 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
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2017
- Study start7 Feb 2017
- Primary completion8 Jun 2018
- Study completion8 Jun 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Prevention of PregnancyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 82 participants (actual)
Sponsor and investigators
- Lead sponsor
- Estetra
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Christine Klipping, Principal investigator, Dinox BV
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03091595
- Sponsor's protocol ID
- MIT-Es0001-C202
- Other IDs
- 2016-004267-40, 2016
- Status last verified
- Apr 2023
- First submitted
- 21 Mar 2017
- Last updated
- 3 May 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT03091595
- Acronym / sponsor ID
- MIT-Es0001-C202
- Conditions
- Prevention of Pregnancy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 82 participants (actual)
- Lead sponsor
- EstetraIndustry (pharma, biotech, devices)
- Study start
- 7 Feb 2017 (actual)
- Primary completion
- 8 Jun 2018 (actual)
- Study completion
- 8 Jun 2018 (actual)
- First posted
- 27 Mar 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 15 mg E4/3 mg DRSP | Experimental | Drug: 15 mg E4/3 mg DRSP15 mg E4 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 | Active comparator | Drug: 20 mcg EE/3 mg DRSP20 mcg EE combined with 3 mg DRSP administered in a 24/4-day regimen. One tablet per day orally for 3 treatment cycles. |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (34 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 15 mg E4/3 mg DRSPAlso: 15 mg estetrol combined with 3 mg drospirenone15 mg E4/3 mg DRSP combined tablets will be administered orally once daily in a 24/4 day regimen for three consecutive cycles | Drug | 15 mg E4/3 mg DRSP |
| 20 mcg EE/3 mg DRSPAlso: 20 mcg ethinylestradiol combined with 3 mg drospirenone (Yaz)20 mcg EE/3 mg DRSP combined tablets will be administered orally once daily in a 24/4 day regimen for three consecutive cycles | Drug | 20 mcg EE/3 mg DRSP |
Primary outcome
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: * the follicular size assessed by transvaginal ultrasound (TVUS) * endogenous hormone levels: serum E2, and serum progesterone.
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: * the follicular size assessed by TVUS * endogenous hormone levels: serum E2, and serum progesterone.
16 secondary outcomes
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)
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)
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)
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)
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)
Mean diameter of the largest follicle
Time frame: 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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 May 2023.
- Trial results were released to public view on the EudraCT (EudraCT Number: 2016-004267-40).Link provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for Prevention of Pregnancy
RecruitingPhase 4
Effectiveness of Two Aspirin Doses for Prevention of Hypertensive Disorders of Pregnancy: ASPIRIN TRIAL
Hypertensive Disorders of Pregnancy, Preeclampsia
Not yet recruitingPhase 3
To Assess the Efficacy and Safety of Pegcetacoplan for the Prevention of Recurrent C3G or Primary IC-MPGN in Kidney Transplant Recipients
C3 Glomerulopathy (C3G), Primary Immune-Complex Membranoproliferative
Not yet recruiting
Evaluating the Healthy Families PrEP Program for Women at Risk for HIV
HIV, Pregnancy
Not yet recruiting
Oral Sodium Bicarbonate for the Prevention of Labour Dystocia
Labour Dystocia
Not yet recruitingObservational study
Novel Antimicrobial Solution to Prevent Infections
Kidney Stone, Infection
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christine Klipping principal investigator
Dinox BV
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing 15 mg E4/3 mg DRSP and 20 mcg EE/3 mg DRSP in people with Prevention of Pregnancy, run by Estetra at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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).). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 May 2023.