Safety, Compliance and Pharmacokinetics of Estetrol Monohydrate/Drospirenone 15/3 mg in Post-menarchal Female Adolescents

NCT04792385 | Completed Phase 3

• 2 other identifiers: MIT-Es001-C3032019-003002-27
• Study Type: interventional
• Target: 145
• Locations: 6 countries
• Sites: 23

Brief Summary

To evaluate the safety, compliance, and pharmacokinetics profile of estetrol monohydrate (E4) 15 mg combined with drospirenone (DRSP) 3 mg in post-menarchal participants between the age of 12 and 17 years + 2 months.

Conditions

Safety

Keywords

Estetrol; Drospirenone; Combined oral contraceptive; Oral contraception; Cycle control; Pharmacokinetics

Outcome Measures

Primary Outcomes (6)

• Number of participants with treatment-emergent adverse events

  Treatment emergent adverse events (TEAEs) are those adverse events occurring from time point of first ingestion of the investigational product until last visit or any event already present that worsens in either intensity or frequency following exposure to the treatment.

  From Cycle 1 to end of study (between Days 16 and 23 of Cycle 7) (each cycle is 28 days)

• Number of participants with treatment-emergent adverse events related to the investigational product

  Treatment emergent adverse events (TEAEs) are those adverse events occurring from time point of first ingestion of the investigational product until last visit or any event already present that worsens in either intensity or frequency following exposure to the treatment. The causality of TEAEs (related or not related) is based on the following considerations: associative connections (time and/or place), pharmacological explanations, previous knowledge of the drug, presence of characteristic clinical or pathological phenomena, exclusion of other causes, and/or absence of alternative explanations.

  From Cycle 1 to end of study (between Days 16 and 23 of Cycle 7) (each cycle is 28 days)

• Number of participants with abnormal physical examination results

  The physical examination will include an evaluation of the following: body as a whole, skin, head, eyes, ears, nose, and throat, neck, cardiovascular, respiratory, musculoskeletal, neurologic, lymphatic/thyroid, abdomen.

  At Baseline and at the end of treatment (Cycle 6) (each cycle is 28 days)

• Number of participants with abnormal vital sign results

  Vital signs will include sitting systolic and diastolic blood pressures and heart rate.

  From Baseline to end of treatment (Cycle 6) (each cycle is 28 days)

• Number of participants with abnormal electrocardiogram (ECG) results

  The ECG interpretation scheme will include the analysis of the morphology, rhythm, conduction, ST segment, PR, QRS, QT and QTc (according to QTcFrid) intervals, T waves, U waves and the presence or absence of any pathological changes.

  At Baseline and at the end of treatment (Cycle 6) (each cycle is 28 days)

• Number of participants with abnormal clinical laboratory assessment results

  Laboratory assessment will include blood hematology and biochemistry.

  At Baseline and at the end of treatment (Cycle 6) (each cycle is 28 days)

Secondary Outcomes (14)

• Percentage of compliance by cycle [Estonia-specific: and overall compliance]

  At Cycles 1, 2, 3, 4, 5 ,6 (each cycle is 28 days)

• Mean plasma estetrol (E4) concentration

  At Cycle 1 and at the end of treatment (Cycle 6) (each cycle is 28 days)

• Mean plasma drospirenone (DRSP) concentration

  At Cycle 1 and at the end of treatment (Cycle 6) (each cycle is 28 days)

• Number of participants with unscheduled bleeding and/or spotting episodes

  At Cycles 1,2, 3, 4, 5, 6 (each cycle is 28 days)

• Number of participants with absence of bleeding/spotting episodes

  At Cycles 1,2, 3, 4, 5, 6 (each cycle is 28 days)

Study Arms (1)

E4/DRSP 15/3 mg

EXPERIMENTAL

Single treatment arm will receive E4/DRSP 15/3 mg

Drug: E4/DRSP 15/3 mg combined tablet

Interventions

E4/DRSP 15/3 mg combined tablet DRUG

One E4/DRSP 15/3 mg combined tablet once per day for 24 days followed by 4 days of placebo tablets; this 28-day cyclic regimen should be taken for 6 consecutive cycles.

Also known as: 15 mg estetrol monohydrate/3 mg drospirenone combined oral contraceptive

E4/DRSP 15/3 mg

Eligibility Criteria

• Age: 12 Years - 17 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Post-menarchal female participant requesting combined oral contraceptive (COC) either for contraceptive or for therapeutic use.
• Negative serum pregnancy test at screening and negative urine pregnancy test at enrollment.
• Aged 12 to 17 years and 2 months (inclusive) \[Estonia-specific: 15 to 17 years and 2 months (inclusive)\] at the time of signing the informed consent.
• Willing to use the investigational product for 6 consecutive cycles.
• Good physical and mental health on the basis of medical, surgical and gynecological history, physical examination, clinical laboratory, and vital signs.
• Body mass index (BMI) below or equal to the percentile 97 (P97) on the local pediatric BMI curves.
• Able to fulfill the requirements of the protocol, undergo all study procedures including e-diary and questionnaires completion.
• Having indicated the willingness to participate in the study by providing written assent.
• Having parent(s) or legal representative(s) willing and able to provide written informed consent.

You may not qualify if:

• For participants who are not using hormonal contraception at screening, a menstrual cycle length shorter than 21 days or longer than 45 days.
• Currently using an injectable or a dermally implantable hormonal method of contraception.
• Known hypersensitivity to any of the investigational product ingredients.
• Currently pregnant or breastfeeding or with the intention to become pregnant during the course of the study.
• Less than 6 weeks since last delivery/2nd trimester abortion and before spontaneous menstruation has occurred following a delivery or 2nd trimester abortion.
• Any condition representing a contraindication / precaution to the use of COCs, including but not limited to:
• dyslipoproteinaemia,
• diabetes mellitus with vascular involvement (nephropathy, retinopathy, neuropathy, other),
• arterial hypertension (controlled and uncontrolled)
• personal or first-degree family history of deep vein thrombosis or pulmonary embolism,
• current or planned prolonged immobilization,
• known inherited or acquired hypercoagulopathies or thrombogenic mutations (e.g. Factor V Leiden mutation),
• current treatment with anticoagulants,
• presence or history of arterial thromboembolism,
• complicated valvular heart disease,

Sponsors & Collaborators

• Estetra: lead

Study Sites (23)

KVL Medical Office/KVL Arstikabinet

Pärnu, Estonia

Location

East-Tallinn Central Hospital

Tallinn, Estonia

Location

Sexual Health Clinic, Tallinn

Tallinn, Estonia

Location

Sexual Health Clinic, Tartu

Tartu, Estonia

Location

VL-Medi Oy

Helsinki, Finland

Location

Lääkärikeskus Mehiläinen

Kuopio, Finland

Location

Lääkärikeskus Gyneko

Oulu, Finland

Location

Estetra Study Site

Batumi, 6004, Georgia

Location

Estetra Study Site

Tbilisi, 0112, Georgia

Location

Estetra Study Site

Tbilisi, 0159, Georgia

Location

Estetra Study Site

Tbilisi, 0160, Georgia

Location

A. Krumpane practice

Daugavpils, Latvia

Location

Childrens Clinical University Hospital

Riga, Latvia

Location

Estetra Study Site

Bialystok, 15-224, Poland

Location

Estetra Study Site

Katowice, 40-301, Poland

Location

Estetra Study Site

Lublin, 20-093, Poland

Location

Estetra Study Site

Ostrowiec Świętokrzyski, 27-400, Poland

Location

Estetra Study Site

Poznan, 60-535, Poland

Location

Estetra Study Site

Raszyn, 05-090, Poland

Location

Estetra Study Site

Wroclaw, 50-414, Poland

Location

Akardo Medsite at Sturebadet Health Care

Stockholm, Sweden

Location

Karolinska University, Department of Gynecology and Reproductive Medicine

Stockholm, Sweden

Location

Karolinska University, WHO Center

Stockholm, Sweden

Location

Study Officials

• Estetra

  Estetra

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 5, 2021
• First Posted: March 11, 2021
• Study Start: December 28, 2020
• Primary Completion: November 24, 2023
• Study Completion: November 24, 2023
• Last Updated: December 22, 2023

Record last verified: 2023-12

Locations

ES (4); FI (3); GE (4); SE (3); LA (2); PL (7)