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SafetyPhase 3NCT04792385

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

A Phase 3 study testing E4/DRSP 15/3 mg combined tablet in people with Safety, run by Estetra at 23 sites in 6 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 12 to 17 years, women onlyHealthy volunteers can take part
Conditions the study is for
Safety
What is being tested?
E4/DRSP 15/3 mg combined tablet
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
145 participants
Where
23 sitesin 6 countries
Study dates
28 Dec 2020to 24 Nov 2023
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 to 17 years
  • Women only
  • Healthy volunteers accepted
  • Child

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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:
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  • 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,
  • systemic lupus erythematosus,
  • presence or history of migraine with aura,
  • symptomatic gallbladder disease,
  • porphyria.
  • Within the past 6 months, undiagnosed (unexplained) abnormal vaginal bleeding, or any abnormal bleeding that could possibly recur during the study.
  • Presence or history of recurrent pelvic inflammatory disease.
  • Any clinically relevant lower genital tract infection (including gonorrhea and chlamydia infections) until successfully treated, in the opinion of the Investigator.
  • Presence or history of hepatic disease as long as liver function values have not returned to normal.
  • Renal impairment
  • 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).
  • History of organ transplantation within 5 years before screening or chronic disease potentially necessitating organ transplantation during the anticipated course of the study.
  • Presence or history of sex hormone-related malignancy.
  • History of non-hormone-related malignancy within 5 years before screening.
  • 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:
  • Cytochrome P450 3A4 (CYP 3A4) inducers: barbiturates, primidone, bosentan, felbamate, griseofulvin, oxcarbazepine, topiramate, carbamazepine, phenytoin, rifampicin, St John's wort (Hypericum perforatum L).
  • CYP 3A4 inhibitors: azole antifungals excluding topical fluconazole, phenylbutazone, modafinil, cimetidine, verapamil, macrolides excluding azithromycin, diltiazem and grapefruit juice.
  • Human immunodeficiency virus (HIV)/Hepatitis C virus (HCV) protease inhibitors and non-nucleoside reverse transcriptase inhibitors.
  • History of alcohol or drug abuse (including laxatives) within 12 months prior to screening.
  • Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of drugs.
  • Uncontrolled thyroid disorders.
  • 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.
  • Sponsor, Contract Research Organization (CRO) or Investigator's site personnel directly affiliated with this study.
  • The participant is judged by the Investigator to be unsuitable for any reason.
  • [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.]

Trial locations and contacts

23 sites in 6 countries.

23 sites in 6 countries

Poland7 sites

  • Estetra Study Site

    Bialystok, 15-224

  • Estetra Study Site

    Katowice, 40-301

  • Estetra Study Site

    Lublin, 20-093

  • Estetra Study Site

    Ostrowiec Świętokrzyski, 27-400

  • Estetra Study Site

    Poznan, 60-535

  • Estetra Study Site

    Raszyn, 05-090

  • Estetra Study Site

    Wroclaw, 50-414

Other trials in Poland

Estonia4 sites

  • KVL Medical Office/KVL Arstikabinet

    Pärnu

  • East-Tallinn Central Hospital

    Tallinn

  • Sexual Health Clinic, Tallinn

    Tallinn

  • Sexual Health Clinic, Tartu

    Tartu

Other trials in Estonia

Georgia4 sites

  • Estetra Study Site

    Batumi, 6004

  • Estetra Study Site

    Tbilisi, 0112

  • Estetra Study Site

    Tbilisi, 0159

  • Estetra Study Site

    Tbilisi, 0160

Other trials in Georgia

Finland3 sites

  • VL-Medi Oy

    Helsinki

  • Lääkärikeskus Mehiläinen

    Kuopio

  • Lääkärikeskus Gyneko

    Oulu

Other trials in Finland

Sweden3 sites

  • Akardo Medsite at Sturebadet Health Care

    Stockholm

  • Karolinska University, Department of Gynecology and Reproductive Medicine

    Stockholm

  • Karolinska University, WHO Center

    Stockholm

Other trials in Sweden

Latvia2 sites

  • A. Krumpane practice

    Daugavpils

  • Childrens Clinical University Hospital

    Riga

Other trials in Latvia

About this study

Official title: A Multicenter, Open-label, Single-Arm Study to Evaluate the Safety, Compliance and Pharmacokinetics Associated With the Use of a Combined Oral Contraceptive Containing 15 mg Estetrol Monohydrate and 3 mg Drospirenone in Post-menarchal Female Adolescents for 6 Cycles

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.

Read the 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
Being tested
E4/DRSP 15/3 mg combined tablet
Keywords
Estetrol, Drospirenone, Combined oral contraceptive, Oral contraception, Cycle control, Pharmacokinetics

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • E4/DRSP 15/3 mg combined tabletDrug

    Also called 15 mg estetrol monohydrate/3 mg drospirenone combined oral contraceptive

    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.

Study groups in NCT04792385
Study groupRoleWhat they receive
E4/DRSP 15/3 mgExperimentalSingle treatment arm will receive E4/DRSP 15/3 mg
Receives: Drug: E4/DRSP 15/3 mg combined tablet

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

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

  2. 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.

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

  3. 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.

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

  4. Number of participants with abnormal vital sign results

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

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

  5. 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.

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

  6. Number of participants with abnormal clinical laboratory assessment results

    Laboratory assessment will include blood hematology and biochemistry.

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

Secondary outcomes (14)

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

    The percentage of compliance per cycle is calculated as the ratio of the total number pills taken during the cycle based on the daily response values entered by the participant in the e-diary and the number of pills expected to be taken during the cycle based on the total number of treatment days.

    [Estonia-specific: the percentage of overall compliance is calculated as the ratio of the total number of pills taken across all cycles based on the daily response values entered by the participant in the e-diary and the number of pills expected to be taken from the start date of cycle 1 until the day of the last dose.]

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

  2. Mean plasma estetrol (E4) concentration

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

  3. Mean plasma drospirenone (DRSP) concentration

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

  4. Number of participants with unscheduled bleeding and/or spotting episodes

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

  5. Number of participants with absence of bleeding/spotting episodes

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

  6. Mean number of unscheduled bleeding and spotting days per cycle

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

  7. Mean number of scheduled bleeding and spotting days per cycle

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

  8. Change in the Score of the Menstrual Distress Questionnaire (MDQ) from baseline to Cycles 1, 3 and 6

    The MDQ is a standard method for measuring cyclical perimenstrual symptoms. The participants will rate common symptoms and feelings associated with menstruation using the following scale: 0 (no experience of symptom), 1 (present, mild), 2 (present, moderate), 3 (present, strong),and 4 (present, severe) observed during pre-menstrual (4 days before menstruation), menstrual (most recent flow) and intermenstrual (remainder of the cycle) phases.

    Measured: At Baseline and at Cycles 1, 3 and 6 (each cycle is 28 days)

  9. Change in the Visual Analogue Scale (VAS) score of dysmenorrhea from baseline to Cycles 1, 3 and 6

    Each day participants will be asked to score their menstruation pain of the previous 24 hours using a scale from 0 to 10, with 0 = no hurt and 10 = hurts worst.

    Measured: At Baseline, Cycles 1, 3, and at the end of treatment (Cycle 6) (each cycle is 28 days)

  10. Change in the number of days with dysmenorrhea from baseline to Cycles 1, 3 and 6

    Measured: At Baseline, Cycles 1, 3, and at the end of treatment (Cycle 6) (each cycle is 28 days)

  11. Number of participants who will use rescue medication for dysmenorrheal pain from baseline to Cycles 1, 3 and 6

    Measured: At Baseline, Cycles 1, 3, and at the end of treatment (Cycle 6) (each cycle is 28 days)

  12. Change in Health Questionnaire for children and Young People (KIDSCREEN-27 questionnaire) from baseline to Cycles 1, 3 and 6

    KIDSCREEN-27 is a validated health-related quality of life questionnaire developed for children and adolescents. This questionnaire measures five Rasch scaled dimensions of well-being including: (1) Physical Well-being (5 items), (2) Psychological Well-being (7 items), (3) Autonomy and Parents (7 items), (4) Peers and Social Support (4 items), and (5) School Environment (4 items). Responses are indicated using a 5-point ordinal scale with responses ranging from 'never' to 'always', 'not at all' to 'extremely', or 'poor' to 'excellent'.

    Measured: At Baseline, Cycles 1, 3, and at the end of treatment (Cycle 6) (each cycle is 28 days)

  13. Change in sex-hormone binding globulin (SHBG) level from baseline to Cycle 6

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

  14. Change in Activated protein C resistance endogenous thrombin potential based (APCr [ETP based]) level from baseline to Cycle 6

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Mar 2021
  2. Study start28 Dec 2020
  3. Primary completion24 Nov 2023
  4. Study completion24 Nov 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Prevention
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
145 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04792385
Sponsor's protocol ID
MIT-Es001-C303
Other IDs
2019-003002-27, 2019
Status last verified
Dec 2023
First submitted
5 Mar 2021
Last updated
22 Dec 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing E4/DRSP 15/3 mg combined tablet in people with Safety, run by Estetra at 23 sites in 6 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 39 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 23 sites in Poland, Estonia, Georgia, Finland, Sweden and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of participants with treatment-emergent adverse events (time frame: From Cycle 1 to end of study (between Days 16 and 23 of Cycle 7) (each cycle is 28 days)). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04792385.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Dec 2023.

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