A Pharmacokinetic Evaluation of Levonorgestrel Implant and Antiretroviral Therapy

NCT01789879 | Completed Phase 2

• 2 other identifiers: 0022-14-EP1R21HD074462-01
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The use of hormone contraception poses a significant challenge for the estimated 16 million HIV-infected women of childbearing age. This is due to known drug interactions with antiretroviral therapy (medicines used to treat HIV) that may jeopardize contraception effectiveness. By evaluating the impact of antiretroviral therapy on a levonorgestrel subdermal implant, the most widely available hormone implant in low and middle-income countries, this study will translate its findings into an evidence-based approach to co-manage these important medications. The investigators hypothesize that women receiving nevirapine or efavirenz-based antiretroviral therapy will have a significant decrease in the mean levonorgestrel plasma concentration measured six months after the implant's insertion as compared to those women who are not taking antiretroviral therapy. Although the implant's efficacy may be retained initially, the investigators propose that a decrease in levonorgestrel concentrations in women receiving antiretroviral therapy may jeopardize the implant's effectiveness near the end of its intended duration of use (5 years).

Conditions

HIV; Contraception

Keywords

Levonorgestrel; Efavirenz; Nevirapine; Pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• Levonorgestrel plasma concentrations

  Levonorgestrel plasma concentrations

  6 months and 1 year after implant

Secondary Outcomes (1)

• Non-nucleoside reverse transcriptase inhibitor (NNRTI) plasma concentrations

  Over 1 year (baseline, Months 1, 3, 6, 9, and 12)

Study Arms (3)

Control group (no current ART)

ACTIVE COMPARATOR

Levonorgestrel subdermal implant in subjects not yet receiving ART (control group)

Drug: Levonorgestrel

NVP-based ART group

ACTIVE COMPARATOR

Levonorgestrel subdermal implant in subjects receiving nevirapine-based ART

Drug: Levonorgestrel; Drug: Nevirapine

EFV-based ART group

ACTIVE COMPARATOR

Levonorgestrel subdermal implant in subjects receiving efavirenz-based ART

Drug: Levonorgestrel; Drug: Efavirenz

Interventions

Levonorgestrel DRUG

Levonorgestrel 2-rod subdermal implant (75mg/rod) placed on study day 0 after baseline evaluations and remains in place until the subject requests removal or for the duration of drug activity (currently approved for 5 years).

Also known as: Jadelle, SinoImplant

Control group (no current ART); EFV-based ART group; NVP-based ART group

Nevirapine DRUG

Nevirapine 200mg twice daily as part of a complete antiretroviral therapy regimen. Subjects will be on this therapy prior to entry in this study.

Also known as: Viramune, NVP

NVP-based ART group

Efavirenz DRUG

Efavirenz 600mg once daily as part of a complete antiretroviral therapy regimen. Subjects will be on this therapy prior to entry in this study.

Also known as: Sustiva, Atripla, Stocrin, EFV

EFV-based ART group

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Evidence of a personally signed and dated informed consent document indicating that the subject (or a legal representative) has been informed of all pertinent aspects of the study.
• Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
• Women age 18 years or older
• Diagnosed with HIV-1 infection
• Desiring LNG subdermal implant as a contraceptive method
• Subjects not yet eligible for ART (based on the Ugandan Treatment Guidelines); or subjects receiving nevirapine or efavirenz-based ART for a minimum of 1 month prior to screening

You may not qualify if:

• For patients currently 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 levonorgestrel, nevirapine (NVP group only), or efavirenz (EFV group only) 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 tables or the AIDS Clinical Trials Group Drug Interactions Database.
• Currently pregnant or postpartum \<30 days at study entry
• No concurrent use of other hormonal contraception is allowed during the study period

Sponsors & Collaborators

• University of Nebraska: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator
• Makerere University: collaborator
• University of Liverpool: collaborator

Study Sites (1)

Infectious Diseases Institute

Kampala, Uganda

Location

Related Publications (3)

• Scarsi KK*, Darin KM, Nakalema S, Back D, Byakika-Kibwika P, Else L, Dilly-Penchala S, Cohn S, Merry C, Lamorde M. Levonorgestrel implant + EFV-based ART: Unintended pregnancies and associated PK Data. Conference on Retroviruses and Opportunistic Infections. Seattle, WA. February 23-26, 2015. Abstract #85LB.

  RESULT

• Scarsi K, Lamorde M, Darin K, Penchala SD, Else L, Nakalema S, Byakika-Kibwika P, Khoo S, Cohn S, Merry C, Back D. Efavirenz- but not nevirapine-based antiretroviral therapy decreases exposure to the levonorgestrel released from a sub-dermal contraceptive implant. J Int AIDS Soc. 2014 Nov 2;17(4 Suppl 3):19484. doi: 10.7448/IAS.17.4.19484. eCollection 2014.

  PMID: 25393993 RESULT

• Scarsi KK, Darin KM, Nakalema S, Back DJ, Byakika-Kibwika P, Else LJ, Dilly Penchala S, Buzibye A, Cohn SE, Merry C, Lamorde M. Unintended Pregnancies Observed With Combined Use of the Levonorgestrel Contraceptive Implant and Efavirenz-based Antiretroviral Therapy: A Three-Arm Pharmacokinetic Evaluation Over 48 Weeks. Clin Infect Dis. 2016 Mar 15;62(6):675-682. doi: 10.1093/cid/civ1001. Epub 2015 Dec 8.

  PMID: 26646680 RESULT

MeSH Terms

Interventions

Levonorgestrel; Nevirapine; efavirenz; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

Intervention Hierarchy (Ancestors)

Norgestrel; Norpregnenes; Norpregnanes; Norsteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tenofovir; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Oxazines; Emtricitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Kimberly K Scarsi, PharmD, MSc

  University of Nebraska

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 7, 2013
• First Posted: February 12, 2013
• Study Start: March 4, 2014
• Primary Completion: September 1, 2014
• Study Completion: March 4, 2015
• Last Updated: September 1, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

UG (1)