Effect of Food on the Bioavailability of 30 mg Estetrol (E4) Tablet in Healthy Postmenopausal Female Volunteers

NCT03798197 | Completed Phase 1

• 2 other identifiers: MIT-Do001-C1012018-003761-34
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

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.

Conditions

Food-effect

Keywords

Estetrol; Menopausal hormone therapy

Outcome Measures

Primary Outcomes (3)

• Maximum concentration (Cmax) of Estetrol in plasma

  PK sampling

  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

• Area under the curve (AUC) from time zero to the last determinable concentration of Estetrol

  PK sampling

  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

• AUC0-inf of Estetrol

  PK sampling

  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 (4)

• Time of Cmax (Tmax)

  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

• Terminal phase rate constant (ke)

  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

• Terminal half-life (t1/2)

  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

• Number of subjects with adverse events as measure of safety and tolerability

  From Day 28 prior screening to end of study (Day 4 of Period 2)

Study Arms (2)

30 mg estetrol (E4) without food (fasted)

ACTIVE COMPARATOR

Treatment A (reference): One 30 mg E4 tablet administered orally following an overnight fast of at least 10 hours.

Drug: 30 mg estetrol (E4)

30 mg estetrol (E4) with food (fed)

EXPERIMENTAL

Treatment B (test): One 30 mg E4 tablet administered orally 30 min after the start of an FDA prescribed high-fat breakfast preceded by at least a 10 hours overnight fast.

Drug: 30 mg estetrol (E4)

Interventions

30 mg estetrol (E4) DRUG

All subjects received both Treatment A and Treatment B either at the first treatment period (Period 1) or at the second treatment period (Period 2). Approximately half of the subjects was randomized to receive either Treatment A followed by Treatment B (sequence AB), or Treatment B followed by Treatment A (sequence BA).

Also known as: 30 mg E4 tablet

30 mg estetrol (E4) with food (fed); 30 mg estetrol (E4) without food (fasted)

Eligibility Criteria

• Age: 40 Years - 65 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Donesta Bioscience: lead

Study Sites (1)

MC Comac Medical Ltd.

Sofia, Bulgaria

Location

MeSH Terms

Interventions

Estetrol

Intervention Hierarchy (Ancestors)

Estriol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Dobrin Svinarov, MD

  MC Comac Medical Ltd.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 7, 2019
• First Posted: January 9, 2019
• Study Start: January 30, 2019
• Primary Completion: April 6, 2019
• Study Completion: April 6, 2019
• Last Updated: May 7, 2019

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will not share

Locations

BU (1)