WOMEN&More: 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.

Recruitment & Eligibility

Status: Ongoing, recruiting

Sex: Female

Target Recruitment: 1186

Inclusion Criteria

Age 18-35 at the moment of signing the informed consent

Provide informed consent about participating in study and provide permission to request medical data in the event of complications or pregnancy

In case of not using hormonal contraceptives, menstrual cycle of 21‐35 days

In case of Depo-Provera (3 month injectable) at least 3 cycles of 21‐35 days after stop

In case of necessary progesterone treatment, be willing to use condoms temporarily

In case of 30 years or older, prior HPV or pap‐test

Understand and speak Dutch or English

Willing to use mifepristone as the only method of contraception for 12 months

Able to take oral medication and willing to adhere to the study protocol

Have unprotected vaginal heterosexual intercourse with a non‐sterilized partner at least once a month

BMI < 35 kg/m2

Willing to fill in a daily diary in the study app and five times an on-line questionnaire

Able to participate in the scheduled visits and comply with the study protocol

Exclusion Criteria

Currently pregnant or breast-feeding

Known allergy to mifepristone

Using non‐dermal 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)

Treatment with another investigational drug or participating in another intervention study, unless the principal investigators agree

Undiagnosed reason for severe anemia or increased creatinine

Abnormal previous PAP smear > pap II without colposcopic evaluation or untreated HSIL

Systolic blood pressure ≥ 180 mmHg and/or diastolic ≥ 110 mmHg (hypertension with medical treatment allowed)

Intracavitary abnormalities on vaginal ultrasound, including intracavitary polyps or myomas, endometrium > 15 mm, or an obvious sign of hydrosalpinx

Previous participation in the WOMEN&More trial

Desire to become pregnant within the following 12 months

Signs of current endometritis, incomplete abortion after miscarriage or induced abortion, or retained placental rests after delivery

Undiagnosed post‐coital bleeding or unscheduled bleeding (spotting with COC, patch, vaginal ring, hormonal IUD, implant allowed)

Known subfertility or history of ectopic pregnancy, unless intra‐uterine pregnancy afterwards

History of gastric reduction or gastric bypass

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)

Current or previous cancer

Family history of endometrial cancer, except BRCA genome mutation

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): Academic Medical Center at the University of Amsterdam
🇳🇱
Amsterdam, Netherlands
Diakonessenhuis Stichting
🇳🇱
Utrecht, Netherlands
Admiraal De Ruyter Ziekenhuis B.V.
🇳🇱
Goes, Netherlands
Academisch Ziekenhuis Maastricht
🇳🇱
Maastricht, Netherlands
Medisch Centrum Leeuwarden B.V.
🇳🇱
Leeuwarden, Netherlands
Noordwest Ziekenhuisgroep Stichting
🇳🇱
Alkmaar, Netherlands
Sint Franciscus Vlietland Groep Stichting
🇳🇱
Rotterdam, Netherlands
Stichting Martini Ziekenhuis
🇳🇱
Groningen, Netherlands
Flevoziekenhuis Stichting
🇳🇱
Almere, Netherlands
Ziekenhuisgroep Twente Stichting
🇳🇱
Almelo, Netherlands
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Academic Medical Center at the University of Amsterdam
🇳🇱Amsterdam, Netherlands
Judith Huirne
Site contact
+31205669111
j.huirne@amsterdamumc.nl