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

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ClinicalTrials.gov Identifier: NCT02722421
Recruitment Status : Active, not recruiting
First Posted : March 30, 2016
Last Update Posted : May 29, 2019
Sponsor:
Collaborators:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Infectious Diseases Institute, Uganda
University of Liverpool
Feinberg School of Medicine, Northwestern University
Information provided by (Responsible Party):
Kimberly Scarsi, PharmD, MS, BCPS-ID, University of Nebraska

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.

Condition or disease Intervention/treatment Phase
HIV Contraception Drug: Levonorgestrel Drug: Efavirenz Phase 2

Detailed Description:

The investigators research team recently demonstrated that combined use of efavirenz (EFV) based antiretroviral therapy (ART), the only preferred first-line ART regimen in low and middle income countries, with a levonorgestrel (LNG)-releasing implant for one year reduced LNG plasma concentrations by approximately 50% compared to women not on ART. Importantly, the investigators also observed three unintended pregnancies (15%) in the investigators study group of women on EFV-based ART plus the LNG implant, in contrast to the <1% expected failure rate of the implant for women without drug interactions.

This study will determine if increasing the dose of the LNG-releasing subdermal implant effectively overcomes the known pharmacokinetic interaction with EFV- based ART. LNG pharmacokinetic results from the participants enrolled in this dose escalation study (n=28) will be compared to HIV-infected Ugandan women on standard dose LNG without concomitant EFV-based ART.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 28 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pharmacokinetic Evaluation of Increased Dose Levonorgestrel Implant and Efavirenz-Based Antiretroviral Therapy In HIV-Infected Ugandan Women
Actual Study Start Date : April 6, 2017
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: Efavirenz group
HIV-infected women receiving efavirenz-based antiretroviral therapy plus increased dose levonorgestrel subdermal implants.
Drug: Levonorgestrel
Increased dose levonorgestrel implant plus efavirenz-based antiretroviral therapy.
Other Names:
  • Jadelle
  • SinoImplant

Drug: Efavirenz
Participants will receive efavirenz-based ART as part of standard of care
Other Names:
  • Sustiva
  • Stocrin
  • Atripla
  • EFV




Primary Outcome Measures :
  1. Levonorgestrel plasma concentrations [ Time Frame: 24-weeks after implant placement ]
    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.


Secondary Outcome Measures :
  1. Levonorgestrel plasma concentrations [ Time Frame: 48 weeks after implant placement ]
    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.

  2. Levonorgestrel plasma concentrations [ Time Frame: Years 2-3 after implant placement ]
    This arm will only be continued if safety measures are met at weeks 24 and 48.

  3. Number of adverse events reported by the participant or provider during the study period [ Time Frame: 48 weeks after implant placement ]
    Adverse events reported by participants


Other Outcome Measures:
  1. Difference in levonorgestrel concentrations between patients based on pharmacogenetic polymorphisms [ Time Frame: 48 weeks after implant placement ]
    Levonorgestrel PK described by pharmacogenetic polymorphisms

  2. Influence of patient weight (in kg) on levonorgestrel concentrations [ Time Frame: 48 weeks after implant placement ]
    Levonorgestrel PK described by weight

  3. Participant satisfaction with the contraceptive implant reported as a likert scale based on a patient questionnaire [ Time Frame: 48 weeks after implant placement ]
    Patient reported satisfaction with contraceptive method



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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Evidence of a personally signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study.
  2. Participants who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
  3. Women age 18 years to 45 years
  4. Diagnosed with HIV infection
  5. Desiring LNG subdermal implant as a contraceptive method
  6. Receiving EFV-based ART for a minimum of 3 months prior to screening
  7. Must agree to have concurrent highly effective non-hormonal contraception with a copper intrauterine device (IUD), if not previously medically sterilized.
  8. 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.

Exclusion Criteria:

  1. HIV RNA > 50 copies/mL at screening visit
  2. Serum hemoglobin < 10.0 g/dl
  3. Elevations in serum levels of alanine transaminase (ALT) above 5 times the upper limit of normal
  4. Elevations in serum creatinine above 2.5 times the upper limit of normal
  5. 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.
  6. Currently pregnant or postpartum <30 days at study entry
  7. 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)
  8. For the EFV group, participants determined to be ineligible for IUD placement by the World Health Organization (WHO) Medical Eligibility Criteria for Contraceptive Use
  9. If participation in the study puts the participant at unacceptable risk based on the judgment of the study staff

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02722421


Locations
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Uganda
Infectious Diseases Institute
Kampala, Uganda
Sponsors and Collaborators
University of Nebraska
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Infectious Diseases Institute, Uganda
University of Liverpool
Feinberg School of Medicine, Northwestern University
Investigators
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Principal Investigator: Kimberly Scarsi, PharmD University of Nebraska

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Responsible Party: Kimberly Scarsi, PharmD, MS, BCPS-ID, Principal Investigator, University of Nebraska
ClinicalTrials.gov Identifier: NCT02722421     History of Changes
Other Study ID Numbers: 234-16-FB
First Posted: March 30, 2016    Key Record Dates
Last Update Posted: May 29, 2019
Last Verified: May 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Kimberly Scarsi, PharmD, MS, BCPS-ID, University of Nebraska:
efavirenz
levonorgestrel
contraceptive implant

Additional relevant MeSH terms:
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Anti-Retroviral Agents
Efavirenz
Levonorgestrel
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Cytochrome P-450 CYP2C9 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Cytochrome P-450 CYP2C19 Inhibitors
Cytochrome P-450 CYP2B6 Inducers
Cytochrome P-450 Enzyme Inducers
Cytochrome P-450 CYP3A Inducers
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents
Physiological Effects of Drugs
Contraceptives, Oral, Synthetic
Contraceptives, Oral