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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03075956
Other study ID # MIT-Es0001-C102
Secondary ID 2016-001808-32
Status Completed
Phase Phase 1
First received March 6, 2017
Last updated September 7, 2017
Start date January 31, 2017
Est. completion date August 2, 2017

Study information

Verified date February 2017
Source Estetra
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical 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 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.


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.


Recruitment information / eligibility

Status Completed
Enrollment 31
Est. completion date August 2, 2017
Est. primary completion date August 2, 2017
Accepts healthy volunteers Accepts Healthy Volunteers
Gender Female
Age group 18 Years to 55 Years
Eligibility Inclusion Criteria:

- 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).

Exclusion Criteria:

- Use of:

1. Any prescription drugs and/or herbal supplements acting on CYP3A4 functions, within 28 days prior to the first study dose administration until study completion.

2. 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.

- 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.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
5 mg E4 single-dose
A single oral dose of 5 mg E4 will be administered during Period 1 of the study.
15 mg E4 single-dose
A single oral dose of 15 mg E4 will be administered during Period 1 of the study.
45 mg E4 single-dose
A single oral dose of 45 mg E4 will be administered once orally during Period 1 of the study
15 mg E4 multiple-dose
15 mg E4 will be administered once daily orally for 14 consecutive days during Period 2 of the study

Locations

Country Name City State
Bulgaria COMAC Sofia

Sponsors (1)

Lead Sponsor Collaborator
Estetra

Country where clinical trial is conducted

Bulgaria, 

Outcome

Type Measure Description Time frame Safety issue
Primary Maximum concentration (Cmax) of estetrol in plasma after single dose regimen PK sampling on Day 1, 2, 3, 4, 5, 6, 7 and 8 From Day 1 (baseline) to Day 8 of the period 1 of the study
Primary 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 From Day 1 (baseline) to Day 8 of the period 1 of the study
Primary 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 From Day 1 (baseline) to Day 21 of the period 2 of the study
Primary AUC during a dosage interval (t) 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 From Day 1 (baseline) to Day 21 of the period 2 of the study
Primary 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 From up to Day 35 before randomization to End of Study (Day 36 [+4])
Secondary AUC0-24h of estetrol after single dose regimen PK sampling on Day 1, 2, 3, 4, 5, 6, 7 and 8 From Day 1 (baseline) to Day 8 of the period 1 of the study
Secondary 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 From Day 1 (baseline) to Day 8 of the period 1 of the study
Secondary 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 From Day 1 (baseline) to Day 8 of the period 1 of the study
Secondary 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 From Day 1 (baseline) to Day 8 of the period 1 of the study
Secondary 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 From Day 1 (baseline) to Day 21 of the period 2 of the study
Secondary 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 From Day 1 (baseline) to Day 21 of the period 2 of the study
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