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

NCT ID: NCT04792385

Last Updated: 2023-12-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 145 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-12-28
• Study Completion Date: 2023-11-24

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.

Detailed Description

This is a Phase 3, open-label, non-controlled study in healthy post-menarchal female participants who will be enrolled to receive once daily E4/DRSP 15/3 mg for six (6) 28-day cycles in a 24/4-day regimen (i.e. 24 days of active tablets followed by 4 days of placebo tablets [4-day hormone-free interval]). The study will include 6 visits:

At screening visit (Visit 1), informed consent will be signed by the participants and their parent(s) or legal representative(s) and the screening procedures will be performed. The site will also complete an Eligibility confirmation phone call to the participant after Visit 1. During the enrollment visit (Visit 2, between Days 12 and 19 of the pre-treatment cycle), eligibility criteria will be reviewed and the participant participation will be confirmed. Participants will be trained in the use of an electronic diary and will receive the study drug. A follow-up call will be performed after Visit 2, within 7 days following the first investigational product intake. Afterwards, the participants will attend 3 on-treatment visits at the clinical site [between Days 14 and 21 of the Cycle 1(Visit 3), Cycle 3 (Visit 4), and Cycle 6 (Visit 5)] and one visit after end of Cycle 6 (Visit 6).

For participants who consent to participate in a pharmacokinetics sub-study, blood samples for this sub-study will be taken at Visit 3 and Visit 5.

Adverse events will be followed throughout the study.

Conditions

Safety

Keywords

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

E4/DRSP 15/3 mg

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

Group Type: EXPERIMENTAL

E4/DRSP 15/3 mg combined tablet

Intervention Type: 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.

Interventions

E4/DRSP 15/3 mg combined tablet

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.

Intervention Type: DRUG

Other Intervention Names

15 mg estetrol monohydrate/3 mg drospirenone combined oral contraceptive

Eligibility Criteria

Inclusion Criteria

1. Post-menarchal female participant requesting combined oral contraceptive (COC) either for contraceptive or for therapeutic use.

2. Negative serum pregnancy test at screening and negative urine pregnancy test at enrollment.

3. 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.

4. Willing to use the investigational product for 6 consecutive cycles.

5. Good physical and mental health on the basis of medical, surgical and gynecological history, physical examination, clinical laboratory, and vital signs.

6. Body mass index (BMI) below or equal to the percentile 97 (P97) on the local pediatric BMI curves.

7. Able to fulfill the requirements of the protocol, undergo all study procedures including e-diary and questionnaires completion.

8. Having indicated the willingness to participate in the study by providing written assent.

9. Having parent(s) or legal representative(s) willing and able to provide written informed consent.

Exclusion Criteria

1. For participants who are not using hormonal contraception at screening, a menstrual cycle length shorter than 21 days or longer than 45 days.

2. Currently using an injectable or a dermally implantable hormonal method of contraception.

3. Known hypersensitivity to any of the investigational product ingredients.

4. Currently pregnant or breastfeeding or with the intention to become pregnant during the course of the study.

5. Less than 6 weeks since last delivery/2nd trimester abortion and before spontaneous menstruation has occurred following a delivery or 2nd trimester abortion.

6. Any condition representing a contraindication / precaution to the use of COCs, including but not limited to:

1. dyslipoproteinaemia,

2. diabetes mellitus with vascular involvement (nephropathy, retinopathy, neuropathy, other),

3. arterial hypertension (controlled and uncontrolled)

4. personal or first-degree family history of deep vein thrombosis or pulmonary embolism,

5. current or planned prolonged immobilization,

6. known inherited or acquired hypercoagulopathies or thrombogenic mutations (e.g. Factor V Leiden mutation),

7. current treatment with anticoagulants,

8. presence or history of arterial thromboembolism,

9. complicated valvular heart disease,

10. systemic lupus erythematosus,

11. presence or history of migraine with aura,

12. symptomatic gallbladder disease,

13. porphyria.

7. Within the past 6 months, undiagnosed (unexplained) abnormal vaginal bleeding, or any abnormal bleeding that could possibly recur during the study.

8. Presence or history of recurrent pelvic inflammatory disease.

9. Any clinically relevant lower genital tract infection (including gonorrhea and chlamydia infections) until successfully treated, in the opinion of the Investigator.

10. Presence or history of hepatic disease as long as liver function values have not returned to normal.

11. Renal impairment

12. Hyperkalemia or presence of conditions that predispose to hyperkalemia such as renal impairment, hepatic impairment, adrenal insufficiency and daily, long-term treatment for chronic conditions or diseases with medications that may increase serum potassium concentration (e.g. angiotensin-converting-enzyme (ACE) inhibitors, angiotensin-II receptor antagonists, potassium-sparing diuretics, potassium supplementation, heparin, aldosterone antagonist and non-steroidal anti-inflammatory drugs).

13. History of organ transplantation within 5 years before screening or chronic disease potentially necessitating organ transplantation during the anticipated course of the study.

14. Presence or history of sex hormone-related malignancy.

15. History of non-hormone-related malignancy within 5 years before screening.

16. Current regular use or regular use within 1 month prior to Visit 2 of drugs potentially triggering interactions with COCs including but not limited to:

1. Cytochrome P450 3A4 (CYP 3A4) inducers: barbiturates, primidone, bosentan, felbamate, griseofulvin, oxcarbazepine, topiramate, carbamazepine, phenytoin, rifampicin, St John's wort (Hypericum perforatum L).

2. CYP 3A4 inhibitors: azole antifungals excluding topical fluconazole, phenylbutazone, modafinil, cimetidine, verapamil, macrolides excluding azithromycin, diltiazem and grapefruit juice.

3. Human immunodeficiency virus (HIV)/Hepatitis C virus (HCV) protease inhibitors and non-nucleoside reverse transcriptase inhibitors.

17. History of alcohol or drug abuse (including laxatives) within 12 months prior to screening.

18. Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of drugs.

19. Uncontrolled thyroid disorders.

20. Participation in another investigational drug clinical study within 1 month (30 days) or have received an investigational drug within the last month (30 days) prior to screening.

21. Sponsor, Contract Research Organization (CRO) or Investigator's site personnel directly affiliated with this study.

22. The participant is judged by the Investigator to be unsuitable for any reason.

23. [Estonia-specific: Subjects who are at a gynecologist visit for the first time in their life may not sign the informed consent during this first visit.]

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Estetra

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Estetra

Role: STUDY_DIRECTOR

Estetra

Locations

KVL Medical Office/KVL Arstikabinet

Pärnu, , Estonia

East-Tallinn Central Hospital

Tallinn, , Estonia

Sexual Health Clinic, Tallinn

Tallinn, , Estonia

Sexual Health Clinic, Tartu

Tartu, , Estonia

VL-Medi Oy

Helsinki, , Finland

Lääkärikeskus Mehiläinen

Kuopio, , Finland

Lääkärikeskus Gyneko

Oulu, , Finland

Estetra Study Site

Batumi, , Georgia

Estetra Study Site

Tbilisi, , Georgia

Estetra Study Site

Tbilisi, , Georgia

Estetra Study Site

Tbilisi, , Georgia

A. Krumpane practice

Daugavpils, , Latvia

Childrens Clinical University Hospital

Riga, , Latvia

Estetra Study Site

Bialystok, , Poland

Estetra Study Site

Katowice, , Poland

Estetra Study Site

Lublin, , Poland

Estetra Study Site

Ostrowiec Świętokrzyski, , Poland

Estetra Study Site

Poznan, , Poland

Estetra Study Site

Raszyn, , Poland

Estetra Study Site

Wroclaw, , Poland

Akardo Medsite at Sturebadet Health Care

Stockholm, , Sweden

Karolinska University, Department of Gynecology and Reproductive Medicine

Stockholm, , Sweden

Karolinska University, WHO Center

Stockholm, , Sweden

Countries

Estonia; Finland; Georgia; Latvia; Poland; Sweden

Other Identifiers

2019-003002-27

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MIT-Es001-C303

Identifier Type: -

Identifier Source: org_study_id