Efficacy, Safety, and Acceptability of Mifepristone 50 mg Once-weekly as a Contraceptive

Phase 3

Recruiting

• Conditions: Contraception

• Registration Number: 2022-502694-41-00
• Lead Sponsor: Leiden University Medical Center

Brief Summary

Efficacy, safety, and acceptability of mifepristone 50 mg once-weekly as a contraceptive

Detailed Description

Mifepristone 50 mg, a progesterone receptor modulator, is a proven safe emergency contraceptive and a promising new weekly contraceptive. As mifepristone does not contain estrogens or progestogens, we anticipate users will not experience the undesirable side effects and health risks of current hormonal contraceptives. Furthermore, pills are a highly desired formulation approach and a weekly regimen instead of daily administration will likely contribute to a high acceptability and adherence among users. Based on promising early stage clinical data, we expect the use of weekly mifepristone 50 mg as a contraceptive will be safe, effective, and acceptable.

Study Timeline

• Study First Submitted: 2024-04-29
• Study First Submitted QC: 2024-04-29
• Study First Posted: 2024-05-01
• Study Start: 2025-05-02
• Status Verified: 2025-09
• Last Update Submitted: 2025-09-15
• Last Update Posted: 2025-09-16
• Primary Completion: 2029-04
• Study Completion: 2030-04-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 1186

Inclusion Criteria

1. Age 18-35 at the moment of signing the informed consent.
2. In case of 30 years or older, prior HPV or pap-test.
3. Understand and speak Dutch or English.
4. Willing to use mifepristone as the only method of contraception for 12 months.
5. Able to take oral medication and willing to adhere to the study protocol.
6. Have unprotected vaginal heterosexual intercourse with a non-sterilized partner at least once a month.
7. BMI < 35 kg/m2.
8. Willing to fill in a daily diary on the smartphone or computer and five times an on-line questionnaire.
9. Able to participate in the scheduled visits and comply with the study protocol.
10. Provide informed consent about participating in study and provide permission to request medical data in the event of complications or pregnancy.
11. In case of not using hormonal contraceptives, menstrual cycle of 21-35 days.
12. In case of Depo-Provera (3 month injectable) at least 3 cycles of 21-35 days after stop.
13. In case of necessary progesterone treatment, be willing to use condoms temporarily.

Exclusion Criteria

1. Currently pregnant or breast-feeding.
2. Desire to become pregnant within the following 12 months.
3. Signs of current endometritis, incomplete abortion after miscarriage or induced abortion, or retained pla-cental rests after delivery.
4. Undiagnosed post-coital bleeding or unscheduled bleeding (spotting with COC, patch, vaginal ring, hormo-nal IUD, implant allowed).
5. Known subfertility or history of ectopic pregnancy, unless intra-uterine pregnancy afterwards, or grade 3-4 endometriosis proven by laparoscopy.
6. History of gastric reduction or gastric bypass or use of weight-loss medicines.
7. Previous or current liver illness, previous or current infection affecting the liver (such as Hepatitis) or mod-erately abnormal liver enzymes at screening (ALAT, ASAT or bilirubin > 2 ULN).
8. Current or previous cancer or DCIS.
9. Family history of endometrial cancer, except BRCA genome mutation.
10. Known allergy to mifepristone.
11. Using non-dermal corticosteroids or any drugs that may interact with mifepristone. These include hydan-toins (e.g. phenytoin), barbiturates (e.g. phenobarbital), primidone, carbamazepine, rifampicin, oxcarbaze-pine, topiramate, rifabutin, felbamate, ritonavir, nelfinavir, griseofulvin and products containing St. John's wort (Hypericum perforatum).
12. Treatment with another investigational drug or participating in another intervention study, unless the prin-cipal investigators agree.
13. Undiagnosed reason for severe anemia or increased creatinine.
14. Abnormal previous PAP smear > pap II without colposcopic evaluation or untreated HSIL.
15. Systolic blood pressure ≥ 180 mmHg and/or diastolic ≥ 110 mmHg (hypertension with medical treatment allowed).
16. Intracavitary abnormalities on vaginal ultrasound, including intracavitary polyps or myomas, endometrium > 15 mm, or an obvious sign of hydrosalpinx.
17. Previous participation in the WOMEN&More trial.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Occurrence of pregnancy during treatment caused by user and method failure (Overall Pearl Index)		Occurrence of pregnancy during treatment caused by user and method failure (Overall Pearl Index)

Secondary Outcome Measures

Name	Time	Method
Proportion of participants with endometrial thickness >15 mm, endometrium with irregular cystic appearance on US; with ALT, AST elevation three times above normal levels or bilirubin two times above normal levels; with adverse events / serious adverse events		Proportion of participants with endometrial thickness >15 mm, endometrium with irregular cystic appearance on US; with ALT, AST elevation three times above normal levels or bilirubin two times above normal levels; with adverse events / serious adverse events
Acceptability assessment: User failure, Depression, Sexual functioning, Use of antidepressants, Weight changes, Bleeding profile, Side effects, Acceptability		Acceptability assessment: User failure, Depression, Sexual functioning, Use of antidepressants, Weight changes, Bleeding profile, Side effects, Acceptability
Proportion of participants either opting for an abortion or opting for continuing the pregnancy. In case of continuation: outcomes of pregnancies such as miscarriages, ectopic pregnancies, preterm labor, growth restriction and congenital abnormalities will be registered		Proportion of participants either opting for an abortion or opting for continuing the pregnancy. In case of continuation: outcomes of pregnancies such as miscarriages, ectopic pregnancies, preterm labor, growth restriction and congenital abnormalities will be registered
Figures about liver functions below 3 x Upper Limit Normal (ULN) (ALT/AST) or below 2 x ULN (bilirubin) are unknown, as time to normalization		Figures about liver functions below 3 x Upper Limit Normal (ULN) (ALT/AST) or below 2 x ULN (bilirubin) are unknown, as time to normalization

Trial Locations

Locations (14)

Noordwest Ziekenhuisgroep; 🇳🇱 Alkmaar, Netherlands

Ziekenhuisgroep Twente; 🇳🇱 Almelo, Netherlands

Flevoziekenhuis; 🇳🇱 Almere Stad, Netherlands

Amsterdam Universitair Medische Centra; 🇳🇱 Amsterdam, Netherlands

Admiraal De Ruyter Ziekenhuis; 🇳🇱 Goes, Netherlands

Martini Ziekenhuis; 🇳🇱 Groningen, Netherlands

Medisch Centrum Leeuwarden; 🇳🇱 Leeuwarden, Netherlands

Leiden University Medical Center; 🇳🇱 Leiden, Netherlands

Maastricht Universitair Medisch Centrum; 🇳🇱 Maastricht, Netherlands

Franciscus Gasthuis; 🇳🇱 Rotterdam, Netherlands

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