E4/DRSP Ovarian Function Inhibition Study

• Sponsor: Estetra (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03091595
• Collaborator: (none)
• Enrollment: 82
• Location: 1
• Arms: 2
• Actual Duration (Months): 16
• Patients Per Site Per Month: 5.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Prevention of Pregnancy	Drug: 15 mg E4/3 mg DRSP; Drug: 20 mcg EE/3 mg DRSP	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 82 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: A Single-center, Randomized, Open-label, Two-arm Study to Evaluate the Ovarian Function Inhibition of a Monophasic Combined Oral Contraceptive (COC) Containing 15 mg Estetrol (E4) and 3 mg Drospirenone (DRSP) and a Monophasic COC Containing 20mcg Ethinylestradiol (EE)/3 mg DRSP (YAZ®), Administered Orally Once Daily in a 24/4 Day Regimen for Three Consecutive Cycles
• Actual Study Start Date: Feb 7, 2017
• Actual Primary Completion Date: Jun 8, 2018
• Actual Study Completion Date: Jun 8, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 15 mg E4/3 mg DRSP 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; 15 mg E4/3 mg DRSP combined tablets will be administered orally once daily in a 24/4 day regimen for three consecutive cycles; Other Names: 15 mg estetrol combined with 3 mg drospirenone
Active Comparator: 20 mcg EE/3 mg DRSP 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; 20 mcg EE/3 mg DRSP combined tablets will be administered orally once daily in a 24/4 day regimen for three consecutive cycles; Other Names: 20 mcg ethinylestradiol combined with 3 mg drospirenone (Yaz)

Outcome Measures

Primary Outcome Measures

1. Proportion of subjects with ovarian inhibition at treatment Cycle 1 [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).]

   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.

2. Proportion of subjects with ovarian inhibition at treatment Cycle 3 [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).]

   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.

Secondary Outcome Measures

1. 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]

   Blood samples will be taken at regular time points defined in the time frame.

2. 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]

   Blood samples will be taken at regular time points defined in the time frame.

3. 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]

   Blood samples will be taken at regular time points defined in the time frame.

4. 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]

   Blood samples will be taken at regular time points defined in the time frame.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 35 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• 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).

Exclusion Criteria:

• 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.

• Abnormal Papanicolaou (PAP) smear result.

• Presence of an undiagnosed breast mass.

• Current symptomatic gallbladder disease.

• History of COC-related cholestasis.

• Presence or history of severe hepatic disease.

• Presence or history of pancreatitis if associated with hypertriglyceridemia.

• Porphyria.

• Presence or history of hepatocellular adenoma or malignant liver tumors.

• Renal impairment.

• Hyperkaliemia or presence of conditions that predispose to hyperkaliemia.

• Presence or history of hormone-related malignancy.

• History of non-hormone-related malignancy within 5 years before Screening. Subjects with a non-melanoma skin cancer are allowed in the study.

• Use of drugs potentially triggering interactions with COCs.

• History of alcohol or drug abuse.

• Any prior procedure, disease or condition that could result in altered absorption, excessive accumulation, impaired metabolism, or altered excretion of the investigational product.

• Uncontrolled thyroid disorders.

• Have received an investigational drug within the last 2 cycles prior to start of Pre-Treatment Cycle. Subjects who participated in an oral contraceptive clinical study, using Food and Drug Administration (FDA)/European Union (EU) approved active ingredients, may start the Pre-Treatment Cycle one cycle after last medication intake of the preceding study.

• Sponsor, contract research organization (CRO) or PI's site personnel directly affiliated with this study.

• Is judged by the PI to be unsuitable for any reason.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dinox BV	Groningen		Netherlands	9713 CZ

Sponsors and Collaborators

• Estetra

Investigators

• Principal Investigator: Christine Klipping, Dinox BV

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Estetra
• ClinicalTrials.gov Identifier: NCT03091595
• Other Study ID Numbers: MIT-Es0001-C202; 2016-004267-40
• First Posted: Mar 27, 2017
• Last Update Posted: Jul 26, 2018
• Last Verified: Mar 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Drospirenone; Ethinyl Estradiol

Study Results

No Results Posted as of Jul 26, 2018