A proof-of Concept, Randomized 3-month Study to Evaluate the Effects of Three Contraceptive Intrauterine Systems Delivering Copper and a Daily Dose of 5, 20 or 40 μg of Ulipristal Acetate (UPA)

NCT03230539 | Unknown Phase 1

• 1 other identifier: 719
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The UPA doses to be tested in this new IUS, 5, 20 or 40 μg per day, are not expected to suppress ovulation, however they should prevent endometrial growth resulting in endometrial atrophy, minimal bleeding, or even amenorrhea. It is anticipated that with low UPA doses, women will continue to ovulate and secrete progesterone (P) during the secretory phase of the menstrual cycle. As a result, PRM associated endometrial changes (PAECs) that have been described in previous UPA studies when ovulation was suppressed and associated with amenorrhea should not occur and endometria should retain normalcy. These expectations are based on our findings from a previous study in which the UPA doses tested were insufficient to block ovulation and participants maintained P secretion with normal endometria (protocol 349). Further evidence regarding the benefit of using low doses of UPA in a copper IUS stems from a small rhesus macaque proof of principle study that included an UPA-IUS delivering 40 or 60 μg/d of UPA, and fixed doses of E2 and cyclic P delivered via implants over 3 cycles.24 Indices of endometrial proliferation were significantly reduced in 3 out of 5 animals in that study; the endometria were atrophied with some glandular cysts, and typical PAECs were limited. Glands were generally small and tubular, however, in some animals they were large and dilated; resembling cysts with minimal evidence of proliferative activity.24 No bleeding was observed in the treated monkeys during progesterone withdrawal over the 3 cycles.

Conditions

Contraception

Outcome Measures

Primary Outcomes (1)

• The primary endpoint is the ability of the three doses of UPA as delivered by IUS to suppress bleeding.

  Bleeding data obtained from diaries and CRFs.

  12 weeks

Study Arms (3)

UPA IUS 20 μg

EXPERIMENTAL

This is a proof-of-concept study utilizing a randomized dose-finding, parallel design to assess the effects of an IUS delivering Cu and 5, 20, or 40 μg of UPA over 12 weeks.

Drug: Ulipristal Acetate IUS delivering Cu and 20μg

UPA IUS 5 μg

EXPERIMENTAL

This is a proof-of-concept study utilizing a randomized dose-finding, parallel design to assess the effects of an IUS delivering Cu and 5, 20, or 40 μg of UPA over 12 weeks

Drug: Ulipristal Acetate IUS delivering Cu and 5μg

UPA IUS 40 μg

EXPERIMENTAL

This is a proof-of-concept study utilizing a randomized dose-finding, parallel design to assess the effects of an IUS delivering Cu and 5, 20, or 40 μg of UPA over 12 weeks

Drug: Ulipristal Acetate IUS delivering Cu and 40μg

Interventions

Ulipristal Acetate IUS delivering Cu and 5μg DRUG

This is a proof-of-concept study utilizing a randomized dose-finding, parallel design to assess the effects of an IUS delivering Cu and 5, 20, or 40 μg of UPA over 12 weeks.

UPA IUS 5 μg

Ulipristal Acetate IUS delivering Cu and 20μg DRUG

This is a proof-of-concept study utilizing a randomized dose-finding, parallel design to assess the effects of an IUS delivering Cu and 5, 20, or 40 μg of UPA over 12 weeks.

UPA IUS 20 μg

Ulipristal Acetate IUS delivering Cu and 40μg DRUG

This is a proof-of-concept study utilizing a randomized dose-finding, parallel design to assess the effects of an IUS delivering Cu and 5, 20, or 40 μg of UPA over 12 weeks.

UPA IUS 40 μg

Eligibility Criteria

• Age: 21 Years - 38 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy women of reproductive age (21-38 years)
• Not at risk for pregnancy based on subject has undergone sterilization or subject is monogamous and her male partner has undergone sterilization
• Have regular menstrual cycles of 21-35 days duration
• Have an intact uterus and both ovaries
• Will be able to comply with the protocol
• Capable of giving informed consent

You may not qualify if:

• Women participating in another clinical trial within 30 days of initiation of this clinical trial
• Women not living in the catchment area of the clinic
• Known hypersensitivity to progestins or antiprogestins
• Known hypersensitivity to copper
• Any known chronic disease including HIV/AIDS
• All contraindications to IUD use,
• Desire to get pregnant during the study Breastfeeding
• Undiagnosed vaginal discharge or vaginal lesions or abnormalities
• Women with a current abnormal Pap. In accordance with the Bethesda system of classification: smear suggestive of high-grade pre-cancerous lesion(s), including HGSIL, are excluded;
• Women with LGSIL or ASCUS/high-risk HPV positive may participate if further evaluated with colposcopy and biopsy and no evidence of a lesion with a severity \> CIN I is present and/or endocervical curettage is negative.
• Women with a biopsy finding of CIN I should have follow up for this finding per standard of care; women are excluded it treatment is indicated.
• Known benign or malignant liver tumors; known active liver disease
• Cancer (past history of any carcinoma or sarcoma)
• Medically diagnosed severe depression currently or in the past
• Known or suspected alcoholism or drug abuse

Sponsors & Collaborators

• Population Council: lead

Study Sites (1)

Profamilia

Santo Domingo, Dominican Republic

RECRUITING

Study Officials

• Ruth Merkatz, RN

  Population Council

  STUDY DIRECTOR

Central Study Contacts

Ruth Merkatz, RN

CONTACT

212-327-8647; rmerkatz@popcouncil.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A proof-of concept, randomized 3-month study to evaluate the effects of three contraceptive intrauterine systems delivering Copper and a daily dose of 5, 20 or 40 μg of Ulipristal Acetate (UPA)

Study Record Dates

• First Submitted: July 13, 2017
• First Posted: July 26, 2017
• Study Start: May 1, 2017
• Primary Completion: January 1, 2018
• Study Completion: May 1, 2018
• Last Updated: August 15, 2017

Record last verified: 2017-08

Locations

DO (1)