HIVPhase 2NCT02722421
Pharmacologic Strategies to Use the Levonorgestrel Implant in HIV-infected Women
A Phase 2 study testing Levonorgestrel and Efavirenz in people with HIV and Contraception, run by University of Nebraska at 1 site in Uganda.
Trial summary
The purpose of this study is to determine whether increasing the dose of the levonorgestrel subdermal contraceptive implant will overcome a detrimental drug-drug interaction with efavirenz based antiretroviral therapy. Read more about this study
- Who is it for?
- Ages 18 to 45 years, women only
- Conditions the study is for
- HIV, Contraception
- What is being tested?
- Levonorgestrel and Efavirenz
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 1 siteUganda
- Study dates
- 6 Apr 2017to 30 Mar 2020
- Phase
- Phase 2
- 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 18 to 45 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Evidence of a personally signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study.
- Participants who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
- Women age 18 years to 45 years
- Diagnosed with HIV infection
- Desiring LNG subdermal implant as a contraceptive method
- Receiving EFV-based ART for a minimum of 3 months prior to screening
- Must agree to have concurrent highly effective non-hormonal contraception with a copper intrauterine device (IUD), if not previously medically sterilized.
- Participants must have a negative urine pregnancy test at entry and report no unprotected sex since the last menstrual period or in the last two weeks.
Who cannot join
- HIV RNA > 50 copies/mL at screening visit
- Serum hemoglobin < 10.0 g/dl
- Elevations in serum levels of alanine transaminase (ALT) above 5 times the upper limit of normal
- Elevations in serum creatinine above 2.5 times the upper limit of normal
- Use of drugs known to be contraindicated with LNG or EFV within 30 days of study entry. Due to the dynamic nature of drug interactions related to ART, the study team will review all concomitant medications at screening based on the US Department of Health and Human Services drug interaction table.
- Currently pregnant or postpartum <30 days at study entry
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- Concurrent use of other hormonal contraception (Note: use of other forms of hormonal contraception is permissible until time of study enrollment/insertion of LNG implant. Transition from other forms of hormonal contraception to LNG subdermal implant will be accommodated according to LNG product labeling)
- For the EFV group, participants determined to be ineligible for IUD placement by the World Health Organization (WHO) Medical Eligibility Criteria for Contraceptive Use
- If participation in the study puts the participant at unacceptable risk based on the judgment of the study staff
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Pharmacokinetic Evaluation of Increased Dose Levonorgestrel Implant and Efavirenz-Based Antiretroviral Therapy In HIV-Infected Ugandan Women
The purpose of this study is to determine whether increasing the dose of the levonorgestrel subdermal contraceptive implant will overcome a detrimental drug-drug interaction with efavirenz based antiretroviral therapy.
Read the detailed description
The investigators research team recently demonstrated that combined use of efavirenz (EFV) based antiretroviral therapy (ART), the only preferred first-line ART regimen in low and middle income countries, with a levonorgestrel (LNG)-releasing implant for one year reduced LNG plasma concentrations by approximately 50% compared to women not on ART. Importantly, the investigators also observed three unintended pregnancies (15%) in the investigators study group of women on EFV-based ART plus the LNG implant, in contrast to the <1% expected failure rate of the implant for women without drug interactions.
This study will determine if increasing the dose of the LNG-releasing subdermal implant effectively overcomes the known pharmacokinetic interaction with EFV- based ART. LNG pharmacokinetic results from the participants enrolled in this dose escalation study (n=28) will be compared to HIV-infected Ugandan women on standard dose LNG without concomitant EFV-based ART.
- Conditions
- HIV, Contraception
- Being tested
- Levonorgestrel, Efavirenz
- Keywords
- efavirenz, levonorgestrel, contraceptive implant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LevonorgestrelDrug
Also called Jadelle, SinoImplant
Increased dose levonorgestrel implant plus efavirenz-based antiretroviral therapy.
EfavirenzDrug
Also called Sustiva, Stocrin, Atripla, EFV
Participants will receive efavirenz-based ART as part of standard of care
| Study group | Role | What they receive |
|---|---|---|
| Efavirenz group | Experimental | HIV-infected women receiving efavirenz-based antiretroviral therapy plus increased dose levonorgestrel subdermal implants. Receives: Drug: Levonorgestrel; Drug: Efavirenz |
What is being measured
The primary outcome is the main question the study is designed to answer.
Levonorgestrel plasma concentrations
We will compare levonorgestrel plasma concentrations between the participants who are receiving increased dose levonorgestrel implants plus efavirenz to historical control participants of HIV-infected Ugandan women not receiving efavirenz.
Measured: 24-weeks after implant placement
Secondary outcomes (3)
Levonorgestrel plasma concentrations
We will compare levonorgestrel plasma concentrations between the participants who are receiving increased dose levonorgestrel implants plus efavirenz to historical control participants of HIV-infected Ugandan women not receiving efavirenz.
Measured: 48 weeks after implant placement
Levonorgestrel plasma concentrations
This arm will only be continued if safety measures are met at weeks 24 and 48.
Measured: Years 2-3 after implant placement
Number of adverse events reported by the participant or provider during the study period
Adverse events reported by participants
Measured: 48 weeks after implant placement
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Mar 2016 (estimated)
- Study start6 Apr 2017
- Primary completion5 Dec 2019
- Study completion30 Mar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIVStudies of the same condition, open and under way.
- More trials run by University of NebraskaThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Nebraska
- Sponsor type
- University, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Infectious Diseases Institute, Uganda, University of Liverpool, Northwestern University
- Responsible party
- Sponsor
- Investigators
- Kimberly K Scarsi, PharmD, Principal investigator, University of Nebraska
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02722421
- Sponsor's protocol ID
- 0234-16-FB
- Other IDs
- 1R01HD085887-01A1
- Status last verified
- Oct 2024
- First submitted
- 2 Mar 2016
- Last updated
- 3 Oct 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pharmacokinetic Evaluation of Increased Dose Levonorgestrel Implant and Efavirenz-Based Antiretroviral Therapy In HIV-Infected Ugandan Women
- ClinicalTrials.gov ID
- NCT02722421
- Acronym / sponsor ID
- 0234-16-FB
- Conditions
- HIV, Contraception
- Keywords
- efavirenz, levonorgestrel, contraceptive implant
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- University of NebraskaUniversity, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Infectious Diseases Institute, Uganda, University of Liverpool, Northwestern University
- Study start
- 6 Apr 2017 (actual)
- Primary completion
- 5 Dec 2019 (actual)
- Study completion
- 30 Mar 2020 (actual)
- First posted
- 30 Mar 2016 (estimated)
- 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 purpose of this study is to determine whether increasing the dose of the levonorgestrel subdermal contraceptive implant will overcome a detrimental drug-drug interaction with efavirenz based antiretroviral therapy.
Detailed description
The investigators research team recently demonstrated that combined use of efavirenz (EFV) based antiretroviral therapy (ART), the only preferred first-line ART regimen in low and middle income countries, with a levonorgestrel (LNG)-releasing implant for one year reduced LNG plasma concentrations by approximately 50% compared to women not on ART. Importantly, the investigators also observed three unintended pregnancies (15%) in the investigators study group of women on EFV-based ART plus the LNG implant, in contrast to the <1% expected failure rate of the implant for women without drug interactions.
This study will determine if increasing the dose of the LNG-releasing subdermal implant effectively overcomes the known pharmacokinetic interaction with EFV- based ART. LNG pharmacokinetic results from the participants enrolled in this dose escalation study (n=28) will be compared to HIV-infected Ugandan women on standard dose LNG without concomitant EFV-based ART.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Efavirenz group | Experimental | Drug: Levonorgestrel, Drug: EfavirenzHIV-infected women receiving efavirenz-based antiretroviral therapy plus increased dose levonorgestrel subdermal implants. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Evidence of a personally signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study.
- Participants who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
- Women age 18 years to 45 years
- Diagnosed with HIV infection
- Desiring LNG subdermal implant as a contraceptive method
Key exclusion criteria (9 listed)
- HIV RNA > 50 copies/mL at screening visit
- Serum hemoglobin < 10.0 g/dl
- Elevations in serum levels of alanine transaminase (ALT) above 5 times the upper limit of normal
- Elevations in serum creatinine above 2.5 times the upper limit of normal
- Use of drugs known to be contraindicated with LNG or EFV within 30 days of study entry. Due to the dynamic nature of drug interactions related to ART, the study team will review all concomitant medications at screening based on the US Department of Health and Human Services drug interaction table.
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 |
|---|---|---|
| LevonorgestrelAlso: Jadelle, SinoImplantIncreased dose levonorgestrel implant plus efavirenz-based antiretroviral therapy. | Drug | Efavirenz group |
| EfavirenzAlso: Sustiva, Stocrin, Atripla, EFVParticipants will receive efavirenz-based ART as part of standard of care | Drug | Efavirenz group |
Primary outcome
Levonorgestrel plasma concentrations
Time frame: 24-weeks after implant placement
We will compare levonorgestrel plasma concentrations between the participants who are receiving increased dose levonorgestrel implants plus efavirenz to historical control participants of HIV-infected Ugandan women not receiving efavirenz.
3 secondary outcomes
Levonorgestrel plasma concentrations
Time frame: 48 weeks after implant placement
Levonorgestrel plasma concentrations
Time frame: Years 2-3 after implant placement
Number of adverse events reported by the participant or provider during the study period
Time frame: 48 weeks after implant placement
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Oct 2024.
- Individual participant dataSharing planned: No
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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.
Kimberly K Scarsi, PharmD principal investigator
University of Nebraska
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Levonorgestrel and Efavirenz in people with HIV and Contraception, run by University of Nebraska at 1 site in Uganda.
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 8 inclusion and 9 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: finished, as of the sponsor's last update on 3 Oct 2024. 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 Uganda. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Levonorgestrel plasma concentrations (time frame: 24-weeks after implant placement). 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 3 Oct 2024.