A study on the maintenance of ovulation inhibition after intentional application errors during 84 days of treatment with a contraceptive transdermal patch

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Mylan Pharmaceuticals Inc.

Participant type

Healthy volunteers

Age range

18-64 years

Gender

Female

Therapeutic area

Phenomena and Processes [G] - Reproductive and Urinary Physiological Phenomena [G08]

Trial duration

1 Dec 2025 → ongoing

Decision date (initial)

2025-11-17

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Mylan Pharmaceuticals, Inc

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Pharmacodynamic, Efficacy

To investigate if ovulation inhibition with MR-130A-01 is maintained despite intentional 24-hour and 48-hour application errors

Secondary objectives 10

1. To evaluate ovulation inhibition properties of MR-130A-01 in the study population
2. To evaluate ovarian activity, classified by the HSS during treatment with MR-130A-01 with scheduled application errors in comparison with regular application
3. To determine the luteal phase adequacy in case of HSS 5 or 6
4. To assess the effects of MR 130A-01 on the diameter of the largest FLS and endometrial thickness during treatment with scheduled application errors in comparison with regular application
5. To evaluate the effect of MR 130A-01 on pituitary and ovarian hormone concentrations during treatment with scheduled application errors in comparison with regular application
6. To describe the effect of scheduled application errors on systemic exposure during treatment with MR-130A-01
7. To check treatment compliance
8. To assess patch adhesion performance
9. To assess overall safety and tolerability of MR-130A-01 as well as local tolerability of the transdermal therapeutic system
10. To assess the bleeding pattern during treatment with MR-130A-01

Conditions and MedDRA coding

Investigation of maintenance of ovulation inhibition after intentional application errors for indication of contraception in healthy subjects

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. 1. Healthy, post-menarcheal and premenopausal women of age 18 to 35 years (inclusive).
2. 2. BMI ≥18.0 kg/m2 at screening examination.
3. 3. Participants must be in good physical and mental health as determined by vital signs, medical history, and physical and gynaecological examination, as assessed by the investigator.
4. 4. Written informed consent, after having been informed about benefits and potential risks of the clinical trial, as well as details of the insurance taken out to cover the participants participating in the clinical trial.
5. 5. Status at least 3 months after a delivery, abortion, and stopping lactation, if applicable, before screening.
6. 6. Has regular menstrual cycles that are between 21 and 35 days in duration as reported by the participant during anamnesis, with an intact uterus and ovaries. If the participant uses hormonal birth control at screening, historic data should be used to evaluate this criterion.
7. 7. Both ovaries must be visible on TVUS examination during screening.
8. 8. Ovulatory pre-treatment cycle, as confirmed by a progesterone concentration >10.0 nmol/L.
9. 9. Participants must consent to use reliable non-hormonal contraceptive methods (male condoms, diaphragm, or heterosexual abstinence) throughout the study, unless the participant has a history of female sterilization or sterilization of the sexual partner.

Exclusion criteria 33

1. 1. Known hypersensitivity or intolerance to any ingredient of the investigational product.
2. 10. History or presence of hypertension or hypertension with vascular disease or elevated blood pressure (BP) defined as systolic BP ≥140 mm Hg or diastolic BP ≥90 mm Hg, measured in sitting position after at least 5 minutes of rest (a single reading of blood pressure level is not sufficient to classify a woman as hypertensive).
3. 11. Pulse rate (PR) < 50 bpm or > 90 bpm
4. 12. Presence of deep vein thrombosis/pulmonary embolism.
5. 13. Has any comorbid condition that may require major surgery with prolonged immobilization during the study period.
6. 14. Presence of liver disease including severe (decompensated) cirrhosis, benign (e.g., hepatocellular adenoma) or malignant liver tumors.
7. 15. Chronic disease potentially necessitating organ transplantation during the anticipated course of the study.
8. 2. History or presence of dermal sensitivity to medicated patches or to topical applications including bandages, surgical tape.
9. 3. Pregnancy or a positive serum beta human chorionic gonadotropin (β-hCG) pregnancy test at screening.
10. 4. Clinically relevant abnormal findings from serum biochemistry and hematology and HBsAG/ Hepatitis C virus/ human immunodeficiency virus (HIV) serology as evaluated by the investigator
11. 5. ASAT (aspartate-aminotransferase) > 20 % upper limit of normal (ULN), ALAT (alanine-aminotransferase) > 10 % ULN, bilirubin > 20% ULN (except in case of existing Morbus Gilbert-Meulengracht deduced from anamnesis/medical history) and creatinine > 0.1 mg/dL ULN (limit of > 0.1 mg/dL corresponds to > 9 µmol/l ULN).
12. 6. Use of a non-hormonal intra-uterine device within the pre-treatment cycle or any hormonal contraception as follows: • Short-acting hormonal contraceptives such as oral, patch, ring or intrauterine systems within the menstrual cycle prior to the pre-treatment cycle. • Injectable (intramuscularly or subcutaneously) within 10 months (three-month treatment duration), 6 months (two-month treatment duration) or 3 months (one-month treatment duration) prior to the start of pre-treatment cycle or implants within the menstrual cycle prior to the pre-treatment cycle.
13. 7. Known or suspected malignancy or history thereof.
14. 8. Unexplained vaginal bleeding within the past 6 months suspicious for serious condition, or any abnormal bleeding which is expected to recur during the study (e.g. bleeding from cervical polyp, recurrent bleeding after sex).
15. 9. History or presence of ischemic heart disease, coronary artery disease, myocardial infarction, stroke, other cerebrovascular diseases including transient ischemic attacks (TIAs).
16. 16. Participants having any other known contraindication to progestin-only contraception as defined by category 3 or 4 conditions per World Health Organization Medical eligibility criteria for contraceptive use, 2015 or Centers for Disease Control and Prevention (CDC) US Medical Eligibility Criteria (US MEC) for Contraceptive Use, 2016
17. 17. History or presence of systemic lupus erythematosus with positive (or unknown) antiphospholipid antibodies.
18. 18. History (even with no evidence of current disease) or presence of or suspected carcinoma of breast.
19. 19. Participant has requirement to be on treatment with medications prohibited during the study (phenytoin, carbamazepine, barbiturates, primidone, topiramate, oxcarbazepine) or rifampin or rifabutin therapy, see Chapter 13.2.1 for additional information on prohibited medications).
20. 20. Presence or history of acute or chronic diseases especially of the skin, which could affect dermal absorption or metabolism, which may interfere with the bioavailability and/or the pharmacokinetics of the Investigational Medicinal Product (IMP) based on assessment of the investigator
21. 21. Skin abnormality (e.g., tattoo or scar) at all possible application sites (at least two different applications sites with normal skin situation are required)
22. 22. History or presence of clinically significant depression, as per investigator’s judgment
23. 23. Any condition that, in the opinion of the investigator may jeopardize the participant’s safety or trial conduct according to the protocol.
24. 24. Participation in another clinical trial at same time or within the preceding 30 days (calculated from the date of the last IMP intake).
25. 25. Recent history (within prior 12 months) of drug or alcohol abuse or at the Investigator’s discretion, history greater than 12 months prior and at risk for noncompliance.
26. 26. Abnormal cervical smear (Pap ≥ 3 acc. to Munich III nomenclature) at screening examination, or history of documented abnormal cervical smear (Pap ≥ 3) within one year of screening.
27. 27. Blood and plasma donation or other blood loss of more than 400 ml or plasmapheresis after signing the informed consent form (ICF).
28. 28. In case of preceding washout phase from hormonal contraception (see Chapter 13.2.1 of the Clinical Trial Protocol), no spontaneous menses within 46 days after stop of short-acting hormonal contraceptive.
29. 29. Close affiliation with the sponsor or the investigational site; e.g., a close relative of the investigator, dependent person (e.g., employee of or student at the investigational site), employee of the sponsor or affiliates.
30. 30. Participant is in custody or submitted to an institution by a court order of an authority or a court of law.
31. 31. Participants suspected or known not to follow instructions.
32. 32. Participants who are unable to understand the written and verbal instructions, in particular regarding the risks and inconveniences they will be exposed to during their participation in the clinical trial
33. 33. Criteria, which in the opinion of the investigator preclude participation for scientific reasons, for reasons of compliance, or for reasons of the participant’s safety.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Ovulation incidence in cycles with regular application, in cycles with 24h application errors & in cycles with 48h application errors. Ovulation is defined as Hoogland-Skouby score 5 or 6 in combination with positive Landgren criterion (i.e., rupture, or development into a luteinized unruptured follicle, of a follicle like structure > 13 mm, with concomitant estradiol [E2] concentrations >100 pmol/L & followed by a luteal phase with progesterone [P] concentrations > 16.0 nmol/L during ≥ 5 days

Secondary endpoints 10

1. • Ovulation incidence overall • Ovulation incidence per treatment cycle
2. HSS determined for each treatment cycle
3. Fulfilment of Landgren criterion in cycles with HSS 5 or 6
4. FLS diameter and endometrial thickness determined by Transvaginal Ultrasonography (TVUS)
5. Pituitary (luteinizing hormone [LH]) and ovarian (estradiol [E2], progesterone [P]) hormone concentrations in serum
6. Plasma concentration of NGMN and its metabolite norgestrel determined: immediately (5min) before and at the end of one scheduled patch-free window (once each per 24/48-hour application-error cycle), and immediately (5min) before application of a new patch (trough, once per regular-application cycle)
7. Plasma concentrations of NGMN and norgestrel
8. Assessment of adhesion score by the participants themselves and by the site personnel
9. Safety and tolerability: treatment-emergent Adverse Events (TEAE); safety clinical laboratory parameters; incidence of application site reactions (skin irritation scores assessed by the participants)
10. Bleeding pattern determined as incidences of bleeding and/or spotting episodes, number of observed days of bleeding and/or spotting, bleeding only and spotting only, incidences of complete absence of bleeding or spotting (excluding the first episode)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Mylan Pharmaceuticals Inc.

Sponsor organisation

Mylan Pharmaceuticals Inc.

Address

3711 Collins Ferry Road

City

Morgantown

Postcode

26505-2362

Country

United States

Scientific contact point

Organisation

Mylan Pharmaceuticals Inc.

Contact name

EUClinicalTrials@viatris

Public contact point

Organisation

Mylan Pharmaceuticals Inc.

Contact name

EUClinicalTrials@viatris

Third parties 6

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 22 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications