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A Pharmacokinetic Evaluation of Etonogestrel (ENG) Implant and Antiretroviral Therapy

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified March 2014 by University of Pittsburgh
Sponsor:
Collaborator:
Makerere University
Information provided by (Responsible Party):
University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT02082652
First received: March 6, 2014
Last updated: March 7, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
HIV
Contraception
Drug: Etonogestrel
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pharmacokinetic Evaluation of Etonogestrel (ENG) Implant and Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI)-Based Antiretroviral Therapy in HIV-Infected Ugandan Women

Resource links provided by NLM:


Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:
  • Etonogestrel plasma concentrations [ Time Frame: 6 months after the implant is placed ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • NNRTI plasma concentrations [ Time Frame: Over 6 months (baseline, Month 1, 3, and 6) ] [ Designated as safety issue: No ]
    Applies only to participants being treated with either efavirenz- or nevirapine-based antiretroviral therapy


Estimated Enrollment: 60
Study Start Date: July 2014
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Control group (No ART)
Etonogestrel implant in participants not yet receiving ART (control group)
Drug: Etonogestrel
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).
Other Names:
  • Implanon
  • Nexplanon
Active Comparator: Nevirapine-based ART group
Etonogestrel implant in participants receiving nevirapine (NVP)-based ART
Drug: Etonogestrel
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).
Other Names:
  • Implanon
  • Nexplanon
Active Comparator: Efavirenz-based ART group
Etonogestrel implant in participants receiving efavirenz (EFV)-based ART
Drug: Etonogestrel
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).
Other Names:
  • Implanon
  • Nexplanon

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.

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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.)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02082652

Contacts
Contact: Catherine A Chappell, MD 412-641-1403 chappellca@upmc.edu

Locations
Uganda
Infectious Disease Institute Not yet recruiting
Kampala, Uganda
Contact: Mohammed Lamorde       mlamorde@idi.co.ug   
Sponsors and Collaborators
University of Pittsburgh
Makerere University
Investigators
Principal Investigator: Catherine A Chappell, MD University of Pittsburgh
  More Information

No publications provided

Responsible Party: University of Pittsburgh
ClinicalTrials.gov Identifier: NCT02082652     History of Changes
Other Study ID Numbers: PRO14010195
Study First Received: March 6, 2014
Last Updated: March 7, 2014
Health Authority: United States: Institutional Review Board
Uganda: Ministry of Health
Uganda: National Council for Science and Technology
Uganda: National Drug Authority
Uganda: Research Ethics Committee

Keywords provided by University of Pittsburgh:
Etonogestrel
Efavirenz
Nevirapine
Pharmacokinetics

Additional relevant MeSH terms:
3-keto-desogestrel
Desogestrel
Nevirapine
Reverse Transcriptase Inhibitors
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Contraceptive Agents
Contraceptive Agents, Female
Contraceptives, Oral
Contraceptives, Oral, Synthetic
Enzyme Inhibitors
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Physiological Effects of Drugs
Progestins
Reproductive Control Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014