HIVPhase 4NCT02082652
A Pharmacokinetic Evaluation of Etonogestrel (ENG) Implant and Antiretroviral Therapy
A Phase 4 study testing Etonogestrel in people with HIV and Contraception, run by University of Pittsburgh at 1 site in Uganda.
Trial summary
Antiretroviral therapy (medicines used to treat HIV) can interact with hormonal contraceptives which might decrease their effectiveness. The single-rod etonogestrel contraceptive implant is being more commonly used in low- and middle-income countries because if the ease of insertion and removal. 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?
- Etonogestrel
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteUganda
- Study dates
- Oct 2014to Mar 2016
- Phase
- Phase 4
- 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
- Display willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures
- Age between 18 and 45 years and female sex
- Diagnosis of HIV-1 infection
- Desiring ENG subdermal implant as a contraceptive method
- Participants not yet eligible for ART (based on the Ugandan Treatment Guidelines); or participants receiving NVP or EFV-based ART for a minimum of 1 month prior to screening
- Participants on EFV-based ART must have an alternative form on effective non-hormonal contraception, such as surgical sterilization or copper intrauterine device in place
Who cannot join
- For potential participants on ART: HIV-1 RNA > 400 copies/mL at screening visit
- Serum hemoglobin < 9.0 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 ENG, NVP (for women taking NVP-based ART), or EFV (for women taking EFV-based ART) within 30 days of study entry. Due to the dynamic nature of drug interactions related to antiretroviral therapy, 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. Participants must have a negative urine pregnancy test and report no unprotected sex since the last menstrual period or in the last two weeks.
- Concurrent use of other hormonal contraception (Note: use of other forms of hormonal contraception is permissible until time of study enrollment/insertion of ENG implant. Transition from other forms of hormonal contraception to ENG subdermal implant will be accommodated according to ENG product labeling.)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Pharmacokinetic Evaluation of Etonogestrel (ENG) Implant and Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI)-Based Antiretroviral Therapy in HIV-Infected Ugandan Women
Antiretroviral therapy (medicines used to treat HIV) can interact with hormonal contraceptives which might decrease their effectiveness. The single-rod etonogestrel contraceptive implant is being more commonly used in low- and middle-income countries because if the ease of insertion and removal. Efavirenz and nevirapine are first-line HIV medicines in Sub-Saharan Africa and this study will help determine an effective way to use these medicines with the etonogestrel implant. The investigators hypothesize that women receiving nevirapine- or efavirenz-based antiretroviral therapy will have lower etonogestrel levels in their blood after six months of insertion as compared to women not taking antiretroviral therapy.
Read the detailed description
Modern contraceptive use by HIV-infected women not only prevents pregnancy-related complications and economic disparity, but also prevents perinatal HIV transmission. Despite the clear benefits of highly effective modern contraceptives, there are significant unanswered questions about their safety in women infected with HIV, particularly women who are on anti-retroviral therapy (ART). Currently, non-nucleoside reverse transcriptase inhibitors (NNRTIs), such as nevirapine (NVP) and efavirenz (EFV), are the most widely prescribed HIV medications in sub-Saharan Africa and recently the WHO recommended the EFV-based ART be recommended as first-line therapy for HIV-1 infected adults, including women of reproductive age. Contraceptive implants are becoming increasingly available and popular in sub-Saharan Africa, and the etonogestrel (ENG) implant is a single rod, making insertion and removal easier than other contraceptive implants. The clinical data on concurrent use of NNRTIs and the ENG implant are limited to six case reports of contraceptive failures in the setting of EFV-based ART, highlighting the potential for a clinically significant drug-drug interaction. The investigators aim to perform a pharmacokinetic (PK) study evaluating the interaction between the ENG implant and NNRTI-based ART. The investigators propose a non-randomized, open-label, parallel, three-group, sparse-sampling PK study to compare ENG PK parameters between a control group (no ART) and two treatment groups (EFV- or NVP-based ART) in 60 HIV-1 infected women, 20 women in each group. The primary endpoint is the comparison of the mean ENG concentrations at month 6 between the control group and NNRTI treatment groups. The investigators hypothesize that women in the EFV-based and NVP-based ART group will have a significantly lower mean ENG concentration 6 months post-implant insertion, as compared to women in the control group. The investigators also aim to: 1) predict the disposition of ENG in women on NNRTI-based ART over the subsequent 2.5 years of intended use through PK modeling of ENG concentrations beyond 6 months of use in HIV-infected women, 2) estimate the long-term impact of chronic ENG exposure on EFV or NVP concentrations measured before and during 6 months of combined use, and 3) compare side-effect frequencies of the ENG subdermal implant in women not on ART and on concomitant NNRTI-based ART. The results will guide clinicians caring for HIV-infected women on whether using NNRTI-based therapy together with the ENG implant will jeopardize contraceptive efficacy due to a reduction in ENG exposure.
- Conditions
- HIV, Contraception
- Being tested
- Etonogestrel
- Keywords
- Etonogestrel, Efavirenz, Nevirapine, Pharmacokinetics
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EtonogestrelDrug
Also called Implanon, Nexplanon
Etonogestrel single-rod subdermal implant (68mg/rod) is placed upon enrollment (day 0) and remains in place until participant requests removal or for the duration of active drug (currently approved for 3 years of use).
| Study group | Role | What they receive |
|---|---|---|
| Control group (No ART) | Active comparator | Etonogestrel implant in participants not yet receiving ART (control group) Receives: Drug: Etonogestrel |
| Nevirapine-based ART group | Active comparator | Etonogestrel implant in participants receiving nevirapine (NVP)-based ART Receives: Drug: Etonogestrel |
| Efavirenz-based ART group | Active comparator | Etonogestrel implant in participants receiving efavirenz (EFV)-based ART Receives: Drug: Etonogestrel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Etonogestrel plasma concentrations
Measured: 6 months after the implant is placed
Secondary outcomes (1)
NNRTI plasma concentrations
Applies only to participants being treated with either efavirenz- or nevirapine-based antiretroviral therapy
Measured: Over 6 months (baseline, Month 1, 3, and 6)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2014 (estimated)
- Study startOct 2014
- Primary completionMar 2016
- Study completionMar 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for HIVStudies of the same condition, open and under way.
- More trials run by University of PittsburghThe 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 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pittsburgh
- Sponsor type
- University, hospital or other
- Collaborators
- Makerere University
- Responsible party
- Principal investigator, Catherine Chappell, University of Pittsburgh
- Investigators
- Catherine A Chappell, MD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02082652
- Sponsor's protocol ID
- PRO14010195
- Status last verified
- Sep 2017
- First submitted
- 6 Mar 2014
- Last updated
- 14 Sep 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Chappell CA, Lamorde M, Nakalema S, Chen BA, Mackline H, Riddler SA, Cohn SE, Darin KM, Achilles SL, Scarsi KK. Efavirenz decreases etonogestrel exposure: a pharmacokinetic evaluation of implantable contraception with antiretroviral therapy. AIDS. 2017 Sep 10;31(14):1965-1972. doi: 10.1097/QAD.0000000000001591.
PubMed 28692531Neary M, Chappell CA, Scarsi KK, Nakalema S, Matovu J, Achilles SL, Chen BA, Siccardi M, Owen A, Lamorde M. Effect of patient genetics on etonogestrel pharmacokinetics when combined with efavirenz or nevirapine ART. J Antimicrob Chemother. 2019 Oct 1;74(10):3003-3010. doi: 10.1093/jac/dkz298.
PubMed 31299074
Study at a glance
From the registry record, last updated by the sponsor on 14 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pharmacokinetic Evaluation of Etonogestrel (ENG) Implant and Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI)-Based Antiretroviral Therapy in HIV-Infected Ugandan Women
- ClinicalTrials.gov ID
- NCT02082652
- Acronym / sponsor ID
- PRO14010195
- Conditions
- HIV, Contraception
- Keywords
- Etonogestrel, Efavirenz, Nevirapine, Pharmacokinetics
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- University of PittsburghUniversity, hospital or other
- Collaborators
- Makerere University
- Study start
- Oct 2014
- Primary completion
- Mar 2016 (actual)
- Study completion
- Mar 2016 (actual)
- First posted
- 10 Mar 2014 (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.
Antiretroviral therapy (medicines used to treat HIV) can interact with hormonal contraceptives which might decrease their effectiveness. The single-rod etonogestrel contraceptive implant is being more commonly used in low- and middle-income countries because if the ease of insertion and removal. Efavirenz and nevirapine are first-line HIV medicines in Sub-Saharan Africa and this study will help determine an effective way to use these medicines with the etonogestrel implant. The investigators hypothesize that women receiving nevirapine- or efavirenz-based antiretroviral therapy will have lower etonogestrel levels in their blood after six months of insertion as compared to women not taking antiretroviral therapy.
Detailed description
Modern contraceptive use by HIV-infected women not only prevents pregnancy-related complications and economic disparity, but also prevents perinatal HIV transmission. Despite the clear benefits of highly effective modern contraceptives, there are significant unanswered questions about their safety in women infected with HIV, particularly women who are on anti-retroviral therapy (ART). Currently, non-nucleoside reverse transcriptase inhibitors (NNRTIs), such as nevirapine (NVP) and efavirenz (EFV), are the most widely prescribed HIV medications in sub-Saharan Africa and recently the WHO recommended the EFV-based ART be recommended as first-line therapy for HIV-1 infected adults, including women of reproductive age. Contraceptive implants are becoming increasingly available and popular in sub-Saharan Africa, and the etonogestrel (ENG) implant is a single rod, making insertion and removal easier than other contraceptive implants. The clinical data on concurrent use of NNRTIs and the ENG implant are limited to six case reports of contraceptive failures in the setting of EFV-based ART, highlighting the potential for a clinically significant drug-drug interaction. The investigators aim to perform a pharmacokinetic (PK) study evaluating the interaction between the ENG implant and NNRTI-based ART. The investigators propose a non-randomized, open-label, parallel, three-group, sparse-sampling PK study to compare ENG PK parameters between a control group (no ART) and two treatment groups (EFV- or NVP-based ART) in 60 HIV-1 infected women, 20 women in each group. The primary endpoint is the comparison of the mean ENG concentrations at month 6 between the control group and NNRTI treatment groups. The investigators hypothesize that women in the EFV-based and NVP-based ART group will have a significantly lower mean ENG concentration 6 months post-implant insertion, as compared to women in the control group. The investigators also aim to: 1) predict the disposition of ENG in women on NNRTI-based ART over the subsequent 2.5 years of intended use through PK modeling of ENG concentrations beyond 6 months of use in HIV-infected women, 2) estimate the long-term impact of chronic ENG exposure on EFV or NVP concentrations measured before and during 6 months of combined use, and 3) compare side-effect frequencies of the ENG subdermal implant in women not on ART and on concomitant NNRTI-based ART. The results will guide clinicians caring for HIV-infected women on whether using NNRTI-based therapy together with the ENG implant will jeopardize contraceptive efficacy due to a reduction in ENG exposure.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Control group (No ART) | Active comparator | Drug: EtonogestrelEtonogestrel implant in participants not yet receiving ART (control group) |
| Nevirapine-based ART group | Active comparator | Drug: EtonogestrelEtonogestrel implant in participants receiving nevirapine (NVP)-based ART |
| Efavirenz-based ART group | Active comparator | Drug: EtonogestrelEtonogestrel implant in participants receiving efavirenz (EFV)-based ART |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 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
- Display willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures
- Age between 18 and 45 years and female sex
- Diagnosis of HIV-1 infection
- Desiring ENG subdermal implant as a contraceptive method
Key exclusion criteria (7 listed)
- For potential participants on ART: HIV-1 RNA > 400 copies/mL at screening visit
- Serum hemoglobin < 9.0 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 ENG, NVP (for women taking NVP-based ART), or EFV (for women taking EFV-based ART) within 30 days of study entry. Due to the dynamic nature of drug interactions related to antiretroviral therapy, 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 |
|---|---|---|
| EtonogestrelAlso: Implanon, NexplanonEtonogestrel single-rod subdermal implant (68mg/rod) is placed upon enrollment (day 0) and remains in place until participant requests removal or for the duration of active drug (currently approved for 3 years of use). | Drug | Control group (No ART), Efavirenz-based ART group, Nevirapine-based ART group |
Primary outcome
Etonogestrel plasma concentrations
Time frame: 6 months after the implant is placed
1 secondary outcome
NNRTI plasma concentrations
Time frame: Over 6 months (baseline, Month 1, 3, and 6)
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 14 Sep 2017.
- Results publication: PubMed 28692531Chappell CA, Lamorde M, Nakalema S, Chen BA, Mackline H, Riddler SA, Cohn SE, Darin KM, Achilles SL, Scarsi KK. Efavirenz decreases etonogestrel exposure: a pharmacokinetic evaluation of implantable contraception with antiretroviral therapy. AIDS. 2017 Sep 10;31(14):1965-1972. doi: 10.1097/QAD.0000000000001591.
- Derived from this study: PubMed 31299074Neary M, Chappell CA, Scarsi KK, Nakalema S, Matovu J, Achilles SL, Chen BA, Siccardi M, Owen A, Lamorde M. Effect of patient genetics on etonogestrel pharmacokinetics when combined with efavirenz or nevirapine ART. J Antimicrob Chemother. 2019 Oct 1;74(10):3003-3010. doi: 10.1093/jac/dkz298.
- 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.
Catherine A Chappell, MD principal investigator
University of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Etonogestrel in people with HIV and Contraception, run by University of Pittsburgh 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 7 inclusion and 7 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 14 Sep 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 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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?
Etonogestrel plasma concentrations (time frame: 6 months after the implant is placed). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02082652, which also lists 2 linked publications.
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 14 Sep 2017.