WOMEN&More: Efficacy, safety, and acceptability of mifepristone 50 mg once-weekly as a contraceptive

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Leiden University Medical Center

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

14 Apr 2025 → 29 May 2026

Decision date (initial)

2025-02-28

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Women on Waves · Karolinska Institutet · Children's Investment Fund Foundation

External identifiers

EU CT number

2022-502694-41-00

ClinicalTrials.gov

NCT06394999

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy

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

Secondary objectives 2

1. Exploration of pregnancy outcomes
2. Exploration of temporary increased liver functions

Conditions and MedDRA coding

Contraception

Study design 1 period

Regulatory references

Scientific advice from competent authorities

European Medicines Agency, Medicines Evaluation Board, Leids Universitair Medisch Centrum (LUMC)

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

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 17

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 placental rests after delivery
4. Undiagnosed post‐coital bleeding or unscheduled bleeding (spotting with COC, patch, vaginal ring, hormonal 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 C) or moderately 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 or non-inhaled corticosteroids or any drugs that may interact with mifepristone. These include hydantoins (e.g. phenytoin), barbiturates (e.g. phenobarbital), primidone, carbamazepine, rifampicin, oxcarbazepine, 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 principal 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Occurrence of pregnancy during treatment caused by user and method failure (Overall Pearl Index)

Secondary endpoints 4

1. 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
2. Acceptability assessment: User failure, Depression, Sexual functioning, Use of antidepressants, Weight changes, Bleeding profile, Side effects, Acceptability
3. 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
4. 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

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Leiden University Medical Center

Sponsor organisation

Leiden University Medical Center

Address

Albinusdreef 2

City

Leiden

Postcode

2333 ZA

Country

Netherlands

Scientific contact point

Organisation

Leiden University Medical Center

Contact name

Clinical Research Center, Dept. of Surgery

Public contact point

Organisation

Leiden University Medical Center

Contact name

Clinical Research Center, Dept. of Surgery

Locations

1 EU/EEA country · 14 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 19 files

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

Application history

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