Pharmacologic Strategies to Use the Levonorgestrel Implant in HIV-infected Women

NCT02722421 | Completed Phase 2 DMC

• 2 other identifiers: 0234-16-FB1R01HD085887-01A1
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

HIV; Contraception

Keywords

efavirenz; levonorgestrel; contraceptive implant

Outcome Measures

Primary Outcomes (1)

• 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.

  24-weeks after implant placement

Secondary Outcomes (3)

• Levonorgestrel plasma concentrations

  48 weeks after implant placement

• Levonorgestrel plasma concentrations

  Years 2-3 after implant placement

• Number of adverse events reported by the participant or provider during the study period

  48 weeks after implant placement

Other Outcomes (3)

• Difference in levonorgestrel concentrations between patients based on pharmacogenetic polymorphisms

  48 weeks after implant placement

• Influence of patient weight (in kg) on levonorgestrel concentrations

  48 weeks after implant placement

• Participant satisfaction with the contraceptive implant reported as a likert scale based on a patient questionnaire

  48 weeks after implant placement

Study Arms (1)

Efavirenz group

EXPERIMENTAL

HIV-infected women receiving efavirenz-based antiretroviral therapy plus increased dose levonorgestrel subdermal implants.

Drug: Levonorgestrel; Drug: Efavirenz

Interventions

Levonorgestrel DRUG

Increased dose levonorgestrel implant plus efavirenz-based antiretroviral therapy.

Also known as: Jadelle, SinoImplant

Efavirenz group

Efavirenz DRUG

Participants will receive efavirenz-based ART as part of standard of care

Also known as: Sustiva, Stocrin, Atripla, EFV

Efavirenz 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.
• 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.

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• University of Nebraska: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator
• Infectious Diseases Institute, Uganda: collaborator
• University of Liverpool: collaborator
• Northwestern University Feinberg School of Medicine: collaborator

Study Sites (1)

Infectious Diseases Institute

Kampala, Uganda

Location

MeSH Terms

Interventions

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

Intervention Hierarchy (Ancestors)

Norgestrel; Norpregnenes; Norpregnanes; Norsteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Tenofovir; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; 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

  University of Nebraska

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 2, 2016
• First Posted: March 30, 2016
• Study Start: April 6, 2017
• Primary Completion: December 5, 2019
• Study Completion: March 30, 2020
• Last Updated: October 3, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

UG (1)