Clinical trial NCT06394999: Efficacy, Safety, and Acceptability of Mifepristone 50 Mg Once-weekly As a Contraceptive
Official title: Prospective Phase III Multi-center Open-label Study of the Efficacy, Safety, and Acceptability of Mifepristone 50 Mg Once-weekly As a Contraceptive
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Female Contraception
Keywords: Oral
Weekly
Non-hormonal
Lead sponsor: Leiden University Medical Center
Sponsor class: OTHER
Collaborators: name: Karolinska Institutet
name: Women on Waves
name: Children's Investment Fund Foundation
First posted: 2024-05-01
Enrollment: 1186
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility criteria: Inclusion Criteria:

1. Age 18-35.
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 on-line diary 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 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.
6. History of gastric bypass.
7. Previous or current liver illness, previous or current infection affecting the liver (such as Hepatitis) or moderately abnormal liver enzymes at screening (ALAT, ASAT or bilirubin \> 2 ULN).
8. Current or previous cancer.
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 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.
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, irregular cystic endometrium, endometrium \> 15 mm, or an obvious sign of hydrosalpinx.

Primary outcomes:
measure: Overall Pearl Index
timeFrame: 0-12 months
measure: Pearl Index by Method failure
timeFrame: 0-12 months
measure: Assess the contraceptive safety of once-weekly mifepristone 50 mg
timeFrame: 3, 6 and 12 months
Secondary outcomes:
measure: Depression
timeFrame: baseline, 3, 6 and 12 months
measure: Sexual functioning
timeFrame: baseline, 3, 6 and 12 months
measure: Use of antidepressants
timeFrame: baseline, 3, 6 and 12 months
measure: Weight [kg]
timeFrame: baseline, 3, 6 and 12 months
measure: Bleeding profile
timeFrame: 0-365 days
measure: Side effects
timeFrame: 0-365 days
measure: Acceptability
timeFrame: 3, 6 and 12 months
measure: Liver function
timeFrame: 3, 6 and 12 months
measure: Pregnancy outcomes
timeFrame: 21 months
Other outcomes:
Locations:
city: Alkmaar
country: Netherlands
facility: Noordwest Ziekenhuisgroep
city: Almelo
country: Netherlands
facility: Ziekenhuisgroep Twente
city: Almere
country: Netherlands
facility: Flevoziekenhuis
city: Amsterdam
country: Netherlands
facility: Amsterdam Universitair Medische Centra
city: Enschede
country: Netherlands
facility: Medisch Spectrum Twente
city: Goes
country: Netherlands
facility: Admiraal De Ruyter Ziekenhuis
city: Groningen
country: Netherlands
facility: Martini Ziekenhuis
city: Leeuwarden
country: Netherlands
facility: Medisch Centrum Leeuwarden
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Maastricht
country: Netherlands
facility: Maastricht Universitair Medisch Centrum
city: Nijmegen
country: Netherlands
facility: Canisius Wilhelmina Ziekenhuis
city: Rotterdam
country: Netherlands
facility: Franciscus Gasthuis
city: Utrecht
country: Netherlands
facility: Diakonessenhuis
city: Veldhoven
country: Netherlands
facility: Maxima Medisch Centrum
Study officials:
affiliation: Leiden University Medical Center
name: Rebecca Gomperts, PhD
role: PRINCIPAL_INVESTIGATOR
References: