Efficacy, Safety, and Acceptability of Mifepristone 50 mg Once-weekly as a Contraceptive (WOMEN&More)

Prospective Phase III Multi-center Open-label Study of the Efficacy, Safety, and Acceptability of Mifepristone 50 mg Once-weekly as a Contraceptive

Participants in the study will use mifepristone 50 mg once-a-week for one year as a contraceptive. With this, we want to confirm that the chances of getting pregnant while using this contraceptive are very small. We also want to demonstrate that the use of mifepristone is safe, and it does not lead to any severe health problems. We expect fewer side effects compared to other frequently used contraceptives with hormones. Mifepristone does not contain these hormones. It is important to know how people experience that use of one tablet a week.

Study Overview

• Status: Active, not recruiting
• Conditions: Female Contraception
• Intervention / Treatment: Drug: Mifepristone 50 mg

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 Type: Interventional
• Enrollment (Actual): 615
• Phase: Phase 3

Contacts and Locations

Study Locations

• Netherlands
  • Alkmaar, Netherlands, 1815 JD
    • Noordwest Ziekenhuisgroep
  • Almelo, Netherlands, 7609 PP
    • Ziekenhuisgroep Twente
  • Almere Stad, Netherlands, 1315 RA
    • Flevoziekenhuis
  • Amsterdam, Netherlands, 1105 AZ
    • Amsterdam Universitair Medische Centra
  • Enschede, Netherlands, 7512 KZ
    • Medisch Spectrum Twente
  • Goes, Netherlands, 4462 RA
    • Admiraal de Ruyter Ziekenhuis
  • Groningen, Netherlands, 9728 NZ
    • Martini Ziekenhuis
  • Leeuwarden, Netherlands, 8934 AD
    • Medisch Centrum Leeuwarden
  • Leiden, Netherlands, 2333 ZA
    • Leiden University Medical Center
  • Maastricht, Netherlands, 6229 HX
    • Maastricht Universitair Medisch Centrum
  • Nijmegen, Netherlands, 6532 SZ
    • Canisius Wilhelmina Ziekenhuis
  • Rotterdam, Netherlands, 3045 PM
    • Franciscus Gasthuis
  • Utrecht, Netherlands, 3582 KE
    • Diakonessenhuis
  • Veldhoven, Netherlands, 5504 DB
    • Máxima Medisch Centrum

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: mifepristone 50 mg; mifepristone 50 mg once weekly	Drug: Mifepristone 50 mg; Once-weekly oral mifepristone 50 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Pearl Index	Nominator Number of pregnancies with conception during treatment period from the first day of pill intake to the last day of pill intake + 7 days Denominator The time period from the first day of pill intake to the last day of pill intake + 7 days. Cycles with documentation of no unprotected intercourse will be subtracted from this period, unless in the unlikely case that a pregnancy occurred in such a cycle.	0-12 months
Pearl Index by Method failure	Nominator Number of pregnancies with conception during cycles as defined in the denominator Denominator The number of cycles with perfect use times 1300. A cycle is defined as (at least) 28 days after the first day of mifepristone 50 mg intake. Cycles with documentation of no unprotected intercourse will be subtracted from this time period, unless in the unlikely case that a pregnancy occurred in such a cycle. Also, cycles with non-perfect use, i.e. without mifepristone 50 mg intake at least once every 7 days will be excluded. Diary charts and counting of remaining tablets will provide dosing information to determine (non-) perfect use.	0-12 months
Assess the contraceptive safety of once-weekly mifepristone 50 mg	Proportion of women 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	3, 6 and 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Depression	PHQ-9 questionnaire (mean value) and changes	baseline, 3, 6 and 12 months
Sexual functioning	Female Sexual Function Index (FSFI) (mean value) and changes	baseline, 3, 6 and 12 months
Use of antidepressants	Proportion of participants who use antidepressants or mood stabilizing drugs	baseline, 3, 6 and 12 months
Weight [kg]	Weight changes	baseline, 3, 6 and 12 months
Bleeding profile	Daily reported bleeding pattern and changes in bleeding pattern regarding amount of bleeding, pain, use of painkillers and effect on hemoglobin	0-365 days
Side effects	Proportion of participants with daily reported side-effects and changes	0-365 days
Acceptability	Proportion of participants who find the medication acceptable	3, 6 and 12 months
Liver function	Frequency of abnormal liver functions between 2 and 3 x ULN (ALT/AST) and time to become less than 2 x ULN	3, 6 and 12 months
Pregnancy outcomes	Number of abortions, miscarriages, ectopic pregnancies, preterm labor, growth restriction and congenital abnormalities	21 months

Collaborators and Investigators

• Sponsor: Leiden University Medical Center
• Collaborators: Karolinska Institutet; Children's Investment Fund Foundation; Women on Waves
• Investigators: Principal Investigator: Rebecca Gomperts, PhD, Leiden University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): May 2, 2025
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): January 1, 2028

Study Registration Dates

• First Submitted: April 29, 2024
• First Submitted That Met QC Criteria: April 29, 2024
• First Posted (Actual): May 1, 2024

Study Record Updates

• Last Update Posted (Actual): June 8, 2026
• Last Update Submitted That Met QC Criteria: June 4, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Oral; Weekly; Non-hormonal
• Additional Relevant MeSH Terms: Polycyclic Compounds; Steroids; Fused-Ring Compounds; Estrenes; Estranes; Mifepristone
• Other Study ID Numbers: 2022-502694-41-00

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No