Clinical trial NCT03798197: Effect of Food on the Bioavailability of 30 mg Estetrol (E4) Tablet in Healthy Postmenopausal Female Volunteers
Official title: An Open-label, Single-center, Randomized, Two Period, Two Sequence Crossover Study to Characterize the Effect of Food on the Bioavailability of 30 mg Estetrol (E4) Tablet in Healthy Postmenopausal Female Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Food-effect
Keywords: Estetrol
Menopausal hormone therapy
Lead sponsor: Donesta Bioscience
Sponsor class: INDUSTRY
First posted: 2019-01-09
Enrollment: 28
Sex: FEMALE
Minimum age (years): 40
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: Assessment of the effect of a high fat meal on the quantity in blood of a female sex hormone called estetrol (E4).

The study also aims at determining how subject tolerate the study drug and how safe it is for them.


Eligibility criteria: Inclusion Criteria:

* Overtly healthy postmenopausal females as determined by medical history, physical examination including breast examination, gynecological examination, cervical smear (Pap smear) if subject has cervix, vital signs, and laboratory tests performed within 28 days before first study drug intake.
* Between the ages of 40 and 65 years inclusive at the time of signing the informed consent (IC).
* Between the Body Mass Index (BMI) of 18 and 30 kg/m2 inclusive and body weight ≥ 45 kg.
* For non-hysterectomized women: intact uterus with bi-layer endometrial thickness ≤ 5 mm on transvaginal ultrasound (TVUS).
* Non-smokers.
* Negative test results for selected drugs of abuse and cotinine.
* Venous access sufficient to allow blood sampling as per the protocol.
* Subject is able to understand and comply with the protocol requirements, instructions, and protocol-stated restrictions.
* Subject has provided signed and dated written IC before participation in the study.

Exclusion Criteria:

* For non-hysterectomized women: uterine disease or medical condition including:

  * Bi-layer endometrial thickness \>5mm as determined by TVUS;
  * Presence of fibroid(s) that obscure(s) evaluation of endometrium by TVUS;
  * History or presence of uterine cancer;
  * Presence of any significant uterine, ovarian or other adnexa related abnormality as determined by TVUS;
  * Presence of an endometrial polyp.
* Undiagnosed vaginal bleeding in the last 12 months.
* Any history of malignancy.
* History of venous or arterial thromboembolic disease
* Abnormal blood pressure.
* Use of :

  * Any prescription drugs within 28 days prior to the first study dose administration.
  * Any over-the-counter (OTC) medication or dietary supplements (vitamins included) within 14 days prior to the first study dose administration.
* Users of progestin implants or oestrogen alone injectable drug therapy are not allowed to participate unless treatment was stopped more than 3 months prior to screening.
* Users of oestrogen pellet or progestin injectable drug therapy are not allowed to participate unless treatment was stopped more than 6 months prior to screening.
* Subjects who are not in euthyroid condition.
* History of hypersensitivity or existing contraindication to E4 or intolerance to any component of the formulations or test meal.
* Presence or history of gallbladder disease, unless cholecystectomy has been performed.
* 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 human immunodeficiency virus (HIV) test result, positive hepatitis B surface antigen (HBsAg) or hepatitis C test result.
* History of illicit drug or alcohol abuse within 12 months prior to first study dose or evidence of such abuse as indicated by laboratory values within 28 days prior to first study dose.
* Consumption of foods or beverages containing the following products during the specified timeframes prior to study drug administration in Period 1: caffeine or xanthine - 48 hours; alcohol - 48 hours; grapefruit/seville orange/citrus fruit and/or star fruit - 7 days. Others Fruit juices: 72 hours prior to study drug administration.
* 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.
* Sponsor, Contract Research Organization (CRO) or Investigator's site personnel or their relatives directly affiliated with this study.
* History or presence of clinically relevant disease of any major system organ class (SOC) (e.g. cardiovascular, pulmonary, renal, hepatic, gastrointestinal, reproductive, endocrinological, neurological, psychiatric or orthopedic disease) as judged by the Investigator.
* 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.
* Is judged by the Investigator to be unsuitable for any reason.

Primary outcomes:
measure: Maximum concentration (Cmax) of Estetrol in plasma
timeFrame: Predose, 10, 20, 30, 45 min, 1, 1.25, 1.5, 1.75, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 hours post-dose
measure: Area under the curve (AUC) from time zero to the last determinable concentration of Estetrol
timeFrame: Predose, 10, 20, 30, 45 min, 1, 1.25, 1.5, 1.75, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 hours post-dose
measure: AUC0-inf of Estetrol
timeFrame: Predose, 10, 20, 30, 45 min, 1, 1.25, 1.5, 1.75, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 hours post-dose
Secondary outcomes:
measure: Time of Cmax (Tmax)
timeFrame: Predose, 10, 20, 30, 45 min, 1, 1.25, 1.5, 1.75, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 hours post-dose
measure: Terminal phase rate constant (ke)
timeFrame: Predose, 10, 20, 30, 45 min, 1, 1.25, 1.5, 1.75, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 hours post-dose
measure: Terminal half-life (t1/2)
timeFrame: Predose, 10, 20, 30, 45 min, 1, 1.25, 1.5, 1.75, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 hours post-dose
measure: Number of subjects with adverse events as measure of safety and tolerability
timeFrame: From Day 28 prior screening to end of study (Day 4 of Period 2)
Other outcomes:
Locations:
city: Sofia
country: Bulgaria
facility: MC Comac Medical Ltd.
Study officials:
affiliation: MC Comac Medical Ltd.
name: Dobrin Svinarov, MD
role: PRINCIPAL_INVESTIGATOR
References: