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

NCT02082652 | Completed Phase 4

• 1 other identifier: PRO14010195
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

HIV; Contraception

Keywords

Etonogestrel; Efavirenz; Nevirapine; Pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• Etonogestrel plasma concentrations

  6 months after the implant is placed

Secondary Outcomes (1)

• NNRTI plasma concentrations

  Over 6 months (baseline, Month 1, 3, and 6)

Study Arms (3)

Control group (No ART)

ACTIVE COMPARATOR

Etonogestrel implant in participants not yet receiving ART (control group)

Drug: Etonogestrel

Nevirapine-based ART group

ACTIVE COMPARATOR

Etonogestrel implant in participants receiving nevirapine (NVP)-based ART

Drug: Etonogestrel

Efavirenz-based ART group

ACTIVE COMPARATOR

Etonogestrel implant in participants receiving efavirenz (EFV)-based ART

Drug: Etonogestrel

Interventions

Etonogestrel DRUG

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).

Also known as: Implanon, Nexplanon

Control group (No ART); Efavirenz-based ART group; Nevirapine-based ART group

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.)

Sponsors & Collaborators

• University of Pittsburgh: lead
• Makerere University: collaborator

Study Sites (1)

Infectious Disease Institute

Kampala, Uganda

Location

Related Publications (2)

• 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.

  PMID: 28692531 RESULT

• Neary 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.

  PMID: 31299074 DERIVED

MeSH Terms

Interventions

etonogestrel

Study Officials

• Catherine A Chappell, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: March 6, 2014
• First Posted: March 10, 2014
• Study Start: October 1, 2014
• Primary Completion: March 1, 2016
• Study Completion: March 1, 2016
• Last Updated: September 14, 2017

Record last verified: 2017-09

Data Sharing

• IPD Sharing: Will not share

Locations

UG (1)