E4/DRSP Ovarian Function Inhibition Study

NCT03091595 | Completed Phase 2

• 2 other identifiers: MIT-Es0001-C2022016-004267-40
• Study Type: interventional
• Target: 82
• Locations: 1 country
• Sites: 1

Brief 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 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

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  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)

  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)

  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)

  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)

  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

  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)

Study Arms (2)

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.

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.

Drug: 20 mcg EE/3 mg DRSP

Interventions

15 mg E4/3 mg DRSP DRUG

15 mg E4/3 mg DRSP combined tablets will be administered orally once daily in a 24/4 day regimen for three consecutive cycles

Also known as: 15 mg estetrol combined with 3 mg drospirenone

15 mg E4/3 mg DRSP

20 mcg EE/3 mg DRSP DRUG

20 mcg EE/3 mg DRSP combined tablets will be administered orally once daily in a 24/4 day regimen for three consecutive cycles

Also known as: 20 mcg ethinylestradiol combined with 3 mg drospirenone (Yaz)

20 mcg EE/3 mg DRSP

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Estetra: lead

Study Sites (1)

Dinox BV

Groningen, 9713 CZ, Netherlands

Location

Related Links

• Trial results were released to public view on the EudraCT (EudraCT Number: 2016-004267-40).

MeSH Terms

Interventions

drospirenone; drospirenone and ethinyl estradiol combination

Study Officials

• Christine Klipping

  Dinox BV

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 21, 2017
• First Posted: March 27, 2017
• Study Start: February 7, 2017
• Primary Completion: June 8, 2018
• Study Completion: June 8, 2018
• Last Updated: May 3, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)