ContraceptionPhase 1NCT03230539
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)
A Phase 1 study testing Ulipristal Acetate IUS delivering Cu and 5μg, Ulipristal Acetate IUS delivering Cu and 20μg and Ulipristal Acetate IUS delivering Cu and 40μg in people with Contraception, run by Population Council at 1 site in Dominican Republic.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 to 38 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Contraception
- What is being tested?
- Ulipristal Acetate IUS delivering Cu and 5μg, Ulipristal Acetate IUS delivering Cu and 20μg and Ulipristal Acetate IUS delivering Cu and 40μg
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteDominican Republic
- Study dates
- 1 May 2017to May 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 38 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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,
Show all 32Show fewer
- 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
- Abnormal, clinically significant, serum fasting clinical chemistry values
- Women with known abnormal thyroid status
- Women with known impaired hypothalamic-pituitary-adrenal reserve
- Average diastolic BP > 85 mm or systolic BP >135 mm Hg after 5-10 minutes rest
- Body mass index (BMI) > 30.0 (or ≤18) Kg/m2
- Women with uterine anomalies
- Use within the past 2 months of any implanted hormonal contraceptives including progestin-releasing intrauterine systems (IUS) or progestin-releasing subdermal implants. NOTE: Removal of implanted hormonal contraceptives must have been for personal reasons unrelated to the purpose of enrollment in this study.
- Current use of a non-hormone containing IUD. NOTE: Removal of an IUD must be for personal reasons unrelated to the purpose of enrollment in this study.
- Use of injectable contraceptives during the previous 3 months (e.g. Cyclofem) or 6 months (e.g. DMPA).
- Women who do not have at least two progesterone measurements ≥10nmol/L during the baseline cycle will be excluded from further participation in the study (See Section 13.4.1)
- Acute pelvic inflammatory disease or a history of pelvic inflammatory disease unless there has been a subsequent intrauterine pregnancy. Postpartum endometritis or infected abortion in the past 3 months.
- Genital bleeding of unknown etiology.
- Untreated acute cervicitis or vaginitis, including bacterial vaginosis or other lower genital tract infections until infection is controlled.
- Current behavior suggesting a high risk for pelvic inflammatory disease
- Mucopurulent cervicitis
- Wilson's disease
- Allergy to any component of the IUS
Trial locations and contacts
1 site in 1 country.
Dominican Republic1 site, 1 recruiting
- Recruiting
Profamilia
Santo Domingo
Vivian Brache, Lic., 809-681-8357, biomedica@codetel.net.do
Vivian Brache, Lic.
About this study
Official title: 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) on Ovulation, Endometrial Changes and Bleeding Patterns in Normally Cycling Women
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.
Read the detailed description
Intrauterine devices (IUD) such as the Copper IUD (Paragard) and the levonorgestrel (LNG) IUS (Mirena®) are considered highly safe and effective long acting reversible methods of contraception (LARC). Nevertheless discontinuations are high due to user complaints of heavy bleeding during the first few months after insertion of IUDs or irregular bleeding in the first year of use of an IUS. To prevent these bleeding problems and enhance the overall safety profile, a new IUS is being developed that will deliver copper to provide its well described contraceptive efficacy in combination with UPA, a progesterone receptor modulator (PRM) that may decrease the amount of bleeding associated with use of a Cu IUD.
Since results of human studies delivering antiovulatory doses of UPA orally or with vaginal rings have shown endometrial changes characterized as typical PAECs, the occurrence of these endometrial effects with lower doses of the PRM delivered in the endometrium via this investigational IUS requires evaluation with both histology assessments and measures of proliferation markers. We need to determine if small doses of UPA administered locally with a new Cu-IUS with UPA can result in reduced bleeding or amenorrhea, as observed in the monkey study, and whether or not endometrial modifications occur.
- Conditions
- Contraception
- Being tested
- Ulipristal Acetate IUS delivering Cu and 5μg, Ulipristal Acetate IUS delivering Cu and 20μg, Ulipristal Acetate IUS delivering Cu and 40μg
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ulipristal Acetate IUS delivering Cu and 5μgDrug
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.
Ulipristal Acetate IUS delivering Cu and 20μgDrug
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.
Ulipristal Acetate IUS delivering Cu and 40μgDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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 Receives: 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 Receives: Drug: Ulipristal Acetate IUS delivering Cu and 40μg |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jul 2017
- Study start1 May 2017
- Primary completionJan 2018 (estimated)
- Study completionMay 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ContraceptionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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)
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Population Council
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ruth Merkatz, RN, Study director, Population Council
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03230539
- Sponsor's protocol ID
- 719
- Status last verified
- Aug 2017
- First submitted
- 13 Jul 2017
- Last updated
- 15 Aug 2017
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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) on Ovulation, Endometrial Changes and Bleeding Patterns in Normally Cycling Women
- ClinicalTrials.gov ID
- NCT03230539
- Acronym / sponsor ID
- 719
- Conditions
- Contraception
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Population CouncilUniversity, hospital or other
- Study start
- 1 May 2017 (actual)
- Primary completion
- Jan 2018 (estimated)
- Study completion
- May 2018 (estimated)
- First posted
- 26 Jul 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Intrauterine devices (IUD) such as the Copper IUD (Paragard) and the levonorgestrel (LNG) IUS (Mirena®) are considered highly safe and effective long acting reversible methods of contraception (LARC). Nevertheless discontinuations are high due to user complaints of heavy bleeding during the first few months after insertion of IUDs or irregular bleeding in the first year of use of an IUS. To prevent these bleeding problems and enhance the overall safety profile, a new IUS is being developed that will deliver copper to provide its well described contraceptive efficacy in combination with UPA, a progesterone receptor modulator (PRM) that may decrease the amount of bleeding associated with use of a Cu IUD.
Since results of human studies delivering antiovulatory doses of UPA orally or with vaginal rings have shown endometrial changes characterized as typical PAECs, the occurrence of these endometrial effects with lower doses of the PRM delivered in the endometrium via this investigational IUS requires evaluation with both histology assessments and measures of proliferation markers. We need to determine if small doses of UPA administered locally with a new Cu-IUS with UPA can result in reduced bleeding or amenorrhea, as observed in the monkey study, and whether or not endometrial modifications occur.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- 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)
| Arm | Type | Receives |
|---|---|---|
| UPA IUS 20 μg | Experimental | Drug: Ulipristal Acetate IUS delivering Cu and 20μgThis 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 | Experimental | Drug: Ulipristal Acetate IUS delivering Cu and 5μgThis 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 | Experimental | Drug: Ulipristal Acetate IUS delivering Cu and 40μgThis 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 |
Who may qualify
- Ages
- 21 to 38 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (32 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ulipristal Acetate IUS delivering Cu and 5μgThis 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 | UPA IUS 5 μg |
| Ulipristal Acetate IUS delivering Cu and 20μgThis 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 | UPA IUS 20 μg |
| Ulipristal Acetate IUS delivering Cu and 40μgThis 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 | UPA IUS 40 μg |
Primary outcome
The primary endpoint is the ability of the three doses of UPA as delivered by IUS to suppress bleeding.
Time frame: 12 weeks
Bleeding data obtained from diaries and CRFs.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Aug 2017.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ruth Merkatz, RN study director
Population Council
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ulipristal Acetate IUS delivering Cu and 5μg, Ulipristal Acetate IUS delivering Cu and 20μg and Ulipristal Acetate IUS delivering Cu and 40μg in people with Contraception, run by Population Council at 1 site in Dominican Republic.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 15 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Dominican Republic. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Ruth Merkatz, RN (212-327-8647, rmerkatz@popcouncil.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The primary endpoint is the ability of the three doses of UPA as delivered by IUS to suppress bleeding. (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Aug 2017.