ContraceptionPhase 1NCT03075956
Safety, Tolerability and Pharmacokinetics of Estetrol (E4) After Single and Multiple Oral Doses in Healthy Female Volunteers
A Phase 1 study testing 5 mg E4 single-dose, 15 mg E4 single-dose and 45 mg E4 single-dose in people with Contraception and Menopause, run by Estetra at 1 site in Bulgaria.
Trial summary
Estetrol (E4) is being developed in two indications supporting women health care: first E4 is combined with a progestin, [drospirenone (DRSP)] and is used as a new combined oral contraceptive (COC) for the prevention of pregnancy and secondly, E4 is used alone as new hormone replacement therapy (HRT) for the treatment… Read more about this study
- Who is it for?
- Ages 18 to 55 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Contraception, Menopause
- What is being tested?
- 5 mg E4 single-dose, 15 mg E4 single-dose and 45 mg E4 single-dose
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 1 siteBulgaria
- Study dates
- 31 Jan 2017to 2 Aug 2017
- Phase
- Phase 1
- 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 55 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Postmenopausal or premenopausal overtly healthy female subject, as determined by medical history, physical examination including breast examination, gynecological examination [including cervical smear (Pap smear)], vital signs, ECG, and laboratory tests performed.
- Between the ages of 18 and 55 years inclusive at the time of signing the informed consent.
- Between the BMI of 18 and 35 kg/m2 inclusive and body weight ≥ 45kg.
- Negative serum pregnancy test results at screening and negative urine pregnancy test results at Day -1 of Period 1.
- Venous access sufficient to allow blood sampling as per the protocol.
- Reliable and willing to be available for the duration of the study and willing to comply with the study procedures.
- Have given written informed consent (IC) approved by the relevant EC governing the site.
- Negative test results for selected drugs of abuse and cotinine at the screening visit (does not include alcohol) and at check-in for Period 1 (includes alcohol).
Who cannot join
- Use of:
- Any prescription drugs and/or herbal supplements acting on CYP3A4 functions, within 28 days prior to the first study dose administration until study completion.
- Any over-the-counter medication or dietary supplements (vitamins included) within 14 days prior to the first study dose until study completion.
- Currently breastfeeding.
- Subjects who are not in euthyroid condition.
- Known hypersensitivity to any of the investigational product ingredients.
Show all 22Show fewer
- History of malignancy.
- History or presence of prolonged QT interval.
- Abnormal arterial tension.
- History or presence of disease of any major system organ class (e.g. cardiovascular, pulmonary, renal, hepatic, gastrointestinal, reproductive, endocrinological, neurological, psychiatric or orthopedic disease) as judged by the Investigator.
- History or presence of migraine with aura at any age or migraine without aura if > 35 years old.
- Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of drugs, or which may jeopardize the subject in case of participation in the study.
- History or presence of immunodeficiency diseases including a positive HIV test result, positive hepatitis B antigen or hepatitis C test result.
- Smokers.
- History of illicit drug or alcohol abuse within 12 months prior to first dose or evidence of such abuse.
- Donation or loss of
- ≥ 450 mL blood within 1 month prior to initial study drug administration.
- ≥ 250 mL blood within 2 weeks prior to initial study drug administration.
- Previous completion or withdrawal from this study.
- 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 Food and Drug Administration (FDA)/ European Union (EU) approved active ingredients, may be enrolled 2 months (60 days) after completing the preceding study.
- Sponsor, the 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Open-label, Single Center, Randomized, Two Period Study to Characterize the Safety, Tolerability and Pharmacokinetics (PK) of Estetrol (E4) After Single and Multiple Oral Doses in Healthy Female Volunteers
Estetrol (E4) is being developed in two indications supporting women health care: first E4 is combined with a progestin, [drospirenone (DRSP)] and is used as a new combined oral contraceptive (COC) for the prevention of pregnancy and secondly, E4 is used alone as new hormone replacement therapy (HRT) for the treatment of menopause related symptoms.
The current clinical trial is designed to collect more detailed information about the PK profile, safety and tolerability of different dosages of E4, given orally as a solid tablet.
Read the detailed description
This is an open-label, single-center, randomized, two-period, single and multiple oral dose study in 27 healthy female volunteers.
After a screening period, eligible subjects (n=27) will receive a single oral dose of 5, 15, or 45 mg E4 (Period 1). After at least 14-day washout, 18 subjects will continue the study (Period 2). They will receive 15 mg E4 once daily for 14 consecutive days.
- Conditions
- Contraception, Menopause
- Being tested
- 5 mg E4 single-dose, 15 mg E4 single-dose, 45 mg E4 single-dose, 15 mg E4 multiple-dose
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
5 mg E4 single-doseDrug
Also called 5 mg estetrol
A single oral dose of 5 mg E4 will be administered during Period 1 of the study.
15 mg E4 single-doseDrug
Also called 15 mg estetrol
A single oral dose of 15 mg E4 will be administered during Period 1 of the study.
45 mg E4 single-doseDrug
Also called 45 mg estetrol
A single oral dose of 45 mg E4 will be administered once orally during Period 1 of the study
15 mg E4 multiple-doseDrug
Also called 15 mg estetrol
15 mg E4 will be administered once daily orally for 14 consecutive days during Period 2 of the study
| Study group | Role | What they receive |
|---|---|---|
| 5 mg E4 single-dose | Experimental | Group A: a single 5 mg E4 dose will be administered under fasted conditions during period 1. Receives: Drug: 5 mg E4 single-dose |
| 15 mg E4 single-dose | Experimental | Group B: a single 15 mg E4 dose will be administered under fasted conditions during period 1. Receives: Drug: 15 mg E4 single-dose |
| 45 mg E4 single-dose | Experimental | Group C: a single 45 mg E4 dose will be administered under fasted conditions during Period 1. Receives: Drug: 45 mg E4 single-dose |
| 15 mg E4 multiple-dose | Experimental | 15 mg E4 dose will be administered once daily for 14 consecutive days during Period 2. Receives: Drug: 15 mg E4 multiple-dose |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum concentration (Cmax) of estetrol in plasma after single dose regimen
PK sampling on Day 1, 2, 3, 4, 5, 6, 7 and 8
Measured: From Day 1 (baseline) to Day 8 of the period 1 of the study
Area under the plasma concentration versus time curve from time 0 to 72 hours (AUC0-72h) of estetrol after single dose regimen
PK sampling on Day 1, 2, 3, 4, 5, 6, 7 and 8
Measured: From Day 1 (baseline) to Day 8 of the period 1 of the study
Cmax at steady state (Cmaxss) of estetrol after multiple dose regimen
PK sampling on Day 1, every 2 days from Day 2 to Day 12, on Day 14, 15, 16, 17, 18, 19, 20, and 21
Measured: From Day 1 (baseline) to Day 21 of the period 2 of the study
AUC during a dosage interval (τ) of estetrol after multiple dose regimen
PK sampling on Day 1, every 2 days from Day 2 to Day 12, on Day 14, 15, 16, 17, 18, 19, 20, and 21
Measured: From Day 1 (baseline) to Day 21 of the period 2 of the study
Number of subjects with adverse events as a measure of safety and tolerability
Safety will be assessed by the monitoring of adverse events (AEs), treatment emergent adverse events (TEAEs), physical examination, vital signs, electrocardiograms (ECGs), clinical laboratory test results and transvaginal ultrasound (TVUS) results
Measured: From up to Day 35 before randomization to End of Study (Day 36 [+4])
Secondary outcomes (6)
AUC0-24h of estetrol after single dose regimen
PK sampling on Day 1, 2, 3, 4, 5, 6, 7 and 8
Measured: From Day 1 (baseline) to Day 8 of the period 1 of the study
AUC from time 0 to infinity (AUC0-inf) of estetrol after single dose regimen
PK sampling on Day 1, 2, 3, 4, 5, 6, 7 and 8
Measured: From Day 1 (baseline) to Day 8 of the period 1 of the study
Time of the maximum measured plasma concentration (Tmax) of estetrol after single dose regimen
PK sampling on Day 1, 2, 3, 4, 5, 6, 7 and 8
Measured: From Day 1 (baseline) to Day 8 of the period 1 of the study
Apparent first-order terminal elimination half-life (T1/2) of estetrol after single dose regimen
PK sampling on Day 1, 2, 3, 4, 5, 6, 7 and 8
Measured: From Day 1 (baseline) to Day 8 of the period 1 of the study
Minimum measured plasma concentration of estetrol at steady state (Cminss) after multiple dose regimen
PK sampling on Day 1, every 2 days from Day 2 to Day 12, on Day 14, 15, 16, 17, 18, 19, 20, and 21
Measured: From Day 1 (baseline) to Day 21 of the period 2 of the study
Tmax of estetrol at steady state (Tmaxss) after multiple dose regimen
PK sampling on Day 1, every 2 days from Day 2 to Day 12, on Day 14, 15, 16, 17, 18, 19, 20, and 21
Measured: From Day 1 (baseline) to Day 21 of the period 2 of the study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Mar 2017
- Study start31 Jan 2017
- Primary completion2 Aug 2017
- Study completion2 Aug 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ContraceptionStudies 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 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Estetra
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Dobrin Sviranov, Prof, Principal investigator, Comac Medical
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03075956
- Sponsor's protocol ID
- MIT-Es0001-C102
- Other IDs
- 2016-001808-32, 2016
- Status last verified
- Feb 2017
- First submitted
- 6 Mar 2017
- Last updated
- 8 Sep 2017
- 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 8 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Single Center, Randomized, Two Period Study to Characterize the Safety, Tolerability and Pharmacokinetics (PK) of Estetrol (E4) After Single and Multiple Oral Doses in Healthy Female Volunteers
- ClinicalTrials.gov ID
- NCT03075956
- Acronym / sponsor ID
- MIT-Es0001-C102
- Conditions
- Contraception, Menopause
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- EstetraIndustry (pharma, biotech, devices)
- Study start
- 31 Jan 2017 (actual)
- Primary completion
- 2 Aug 2017 (actual)
- Study completion
- 2 Aug 2017 (actual)
- First posted
- 9 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.
Estetrol (E4) is being developed in two indications supporting women health care: first E4 is combined with a progestin, [drospirenone (DRSP)] and is used as a new combined oral contraceptive (COC) for the prevention of pregnancy and secondly, E4 is used alone as new hormone replacement therapy (HRT) for the treatment of menopause related symptoms.
The current clinical trial is designed to collect more detailed information about the PK profile, safety and tolerability of different dosages of E4, given orally as a solid tablet.
Detailed description
This is an open-label, single-center, randomized, two-period, single and multiple oral dose study in 27 healthy female volunteers.
After a screening period, eligible subjects (n=27) will receive a single oral dose of 5, 15, or 45 mg E4 (Period 1). After at least 14-day washout, 18 subjects will continue the study (Period 2). They will receive 15 mg E4 once daily for 14 consecutive days.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 5 mg E4 single-dose | Experimental | Drug: 5 mg E4 single-doseGroup A: a single 5 mg E4 dose will be administered under fasted conditions during period 1. |
| 15 mg E4 single-dose | Experimental | Drug: 15 mg E4 single-doseGroup B: a single 15 mg E4 dose will be administered under fasted conditions during period 1. |
| 45 mg E4 single-dose | Experimental | Drug: 45 mg E4 single-doseGroup C: a single 45 mg E4 dose will be administered under fasted conditions during Period 1. |
| 15 mg E4 multiple-dose | Experimental | Drug: 15 mg E4 multiple-dose15 mg E4 dose will be administered once daily for 14 consecutive days during Period 2. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Postmenopausal or premenopausal overtly healthy female subject, as determined by medical history, physical examination including breast examination, gynecological examination [including cervical smear (Pap smear)], vital signs, ECG, and laboratory tests performed.
- Between the ages of 18 and 55 years inclusive at the time of signing the informed consent.
- Between the BMI of 18 and 35 kg/m2 inclusive and body weight ≥ 45kg.
- Negative serum pregnancy test results at screening and negative urine pregnancy test results at Day -1 of Period 1.
- Venous access sufficient to allow blood sampling as per the protocol.
Key exclusion criteria (22 listed)
- Use of:
- Currently breastfeeding.
- Subjects who are not in euthyroid condition.
- Known hypersensitivity to any of the investigational product ingredients.
- History of malignancy.
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 |
|---|---|---|
| 5 mg E4 single-doseAlso: 5 mg estetrolA single oral dose of 5 mg E4 will be administered during Period 1 of the study. | Drug | 5 mg E4 single-dose |
| 15 mg E4 single-doseAlso: 15 mg estetrolA single oral dose of 15 mg E4 will be administered during Period 1 of the study. | Drug | 15 mg E4 single-dose |
| 45 mg E4 single-doseAlso: 45 mg estetrolA single oral dose of 45 mg E4 will be administered once orally during Period 1 of the study | Drug | 45 mg E4 single-dose |
| 15 mg E4 multiple-doseAlso: 15 mg estetrol15 mg E4 will be administered once daily orally for 14 consecutive days during Period 2 of the study | Drug | 15 mg E4 multiple-dose |
Primary outcome
Maximum concentration (Cmax) of estetrol in plasma after single dose regimen
Time frame: From Day 1 (baseline) to Day 8 of the period 1 of the study
PK sampling on Day 1, 2, 3, 4, 5, 6, 7 and 8
Area under the plasma concentration versus time curve from time 0 to 72 hours (AUC0-72h) of estetrol after single dose regimen
Time frame: From Day 1 (baseline) to Day 8 of the period 1 of the study
PK sampling on Day 1, 2, 3, 4, 5, 6, 7 and 8
Cmax at steady state (Cmaxss) of estetrol after multiple dose regimen
Time frame: From Day 1 (baseline) to Day 21 of the period 2 of the study
PK sampling on Day 1, every 2 days from Day 2 to Day 12, on Day 14, 15, 16, 17, 18, 19, 20, and 21
AUC during a dosage interval (τ) of estetrol after multiple dose regimen
Time frame: From Day 1 (baseline) to Day 21 of the period 2 of the study
PK sampling on Day 1, every 2 days from Day 2 to Day 12, on Day 14, 15, 16, 17, 18, 19, 20, and 21
Number of subjects with adverse events as a measure of safety and tolerability
Time frame: From up to Day 35 before randomization to End of Study (Day 36 [+4])
Safety will be assessed by the monitoring of adverse events (AEs), treatment emergent adverse events (TEAEs), physical examination, vital signs, electrocardiograms (ECGs), clinical laboratory test results and transvaginal ultrasound (TVUS) results
6 secondary outcomes
AUC0-24h of estetrol after single dose regimen
Time frame: From Day 1 (baseline) to Day 8 of the period 1 of the study
AUC from time 0 to infinity (AUC0-inf) of estetrol after single dose regimen
Time frame: From Day 1 (baseline) to Day 8 of the period 1 of the study
Time of the maximum measured plasma concentration (Tmax) of estetrol after single dose regimen
Time frame: From Day 1 (baseline) to Day 8 of the period 1 of the study
Apparent first-order terminal elimination half-life (T1/2) of estetrol after single dose regimen
Time frame: From Day 1 (baseline) to Day 8 of the period 1 of the study
Minimum measured plasma concentration of estetrol at steady state (Cminss) after multiple dose regimen
Time frame: From Day 1 (baseline) to Day 21 of the period 2 of the study
Tmax of estetrol at steady state (Tmaxss) after multiple dose regimen
Time frame: From Day 1 (baseline) to Day 21 of the period 2 of the study
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 8 Sep 2017.
- Individual participant dataSharing planned: No
Related trials for Contraception
Enrolling by invitation
Flo Digital Contraceptive Study
Contraception Use
Recruiting
Estimating the Impact of Sexuality Education and Mobile Health Services on Reproductive Health and Empowerment Among Adolescents in Sierra Leone for the Family Planning Impact Lab
Reproductive Health, Sexual Health
RecruitingPhase 4
Clinical and Biomarker Effects of Depot Medroxyprogesterone Acetate in Females With Sickle Cell Disease
Sickle Cell Disease (SCD), Vaso-Occlusive Pain Episode in Sickle Cell Disease
Not yet recruitingObservational study
FLOW: Influence of the Menstrual Cycle on Alcohol Use in Women
Alcohol Use, Alcohol Consumption
Not yet recruiting
Impact of Gender-Transformative Interventions on Contraceptive Use and Reproductive Autonomy in Somalia
Contraceptive Behavior, Social Norms
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.
Dobrin Sviranov, Prof principal investigator
Comac Medical
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing 5 mg E4 single-dose, 15 mg E4 single-dose and 45 mg E4 single-dose in people with Contraception and Menopause, run by Estetra at 1 site in Bulgaria.
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 8 inclusion and 22 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 8 Sep 2017. 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 Bulgaria. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Maximum concentration (Cmax) of estetrol in plasma after single dose regimen (time frame: From Day 1 (baseline) to Day 8 of the period 1 of the study). The study lists 5 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 8 Sep 2017.