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Pharmacokinetics and Pharmacodynamics of the Etonogestrel Contraceptive Implant When Co-administered With Efavirenz

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified July 2014 by Johns Hopkins University
Sponsor:
Collaborators:
American College of Obstetricians and Gynecologists
The Campbell Foundation
Information provided by (Responsible Party):
Jennifer Robinson, Johns Hopkins University
ClinicalTrials.gov Identifier:
NCT01980342
First received: November 4, 2013
Last updated: July 30, 2014
Last verified: July 2014
  Purpose

Women now make up nearly half of the world's HIV-infected population, and many of these women with HIV are of reproductive age. There is a growing need to provide effective contraception for those women who want or need to be protected against pregnancy. However, there is concern for decreased contraceptive efficacy in women on antiretroviral therapy who rely on hormonal contraception due to drug-drug interactions. Of particular concern is a possible interaction with etonogestrel, the active hormone in a long-acting reversible contraceptive implant. We propose a pilot study to evaluate the effect of efavirenz (EFV), a commonly used non-nucleoside reverse transcriptase inhibitor, on the pharmacokinetics of the etonogestrel implant. We will recruit 18 healthy women who have had the implant in place for 12 to 24 months. They will be asked to take a two-week course of efavirenz. During these two weeks and for four additional weeks, we will monitor semi-weekly etonogestrel concentrations, and serum, ultrasound, and cervical mucus markers of ovulation. We will also assess efavirenz concentration at baseline and at the end of the two-week treatment course. We will derive pharmacokinetic parameters and compare concentrations across time points. Results will help to inform the design of larger studies, and of similar studies with different antiretroviral medications. We hypothesize that taking efavirenz while using the etonogestrel contraceptive implant will not result in an increased incidence of ovulation.


Condition Intervention Phase
Drug Interaction
Drug: Efavirenz
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label

Resource links provided by NLM:


Further study details as provided by Johns Hopkins University:

Primary Outcome Measures:
  • Serum concentration of etonogestrel before and after two weeks of efavirenz [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    We will draw a baseline serum etonogestrel immediately prior to a participant starting the 2-week course of efavirenz. Serial blood samples will subsequently be drawn over the next 6 weeks to assess for changes in serum etonogestrel concentration. We will be looking to see if the serum etonogestrel concentration decreases below the level necessary for reliable ovulation suppression.


Secondary Outcome Measures:
  • Serum efavirenz concentrations at the start and end of the 2-week dosing period [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
    We will assess serum efavirenz concentrations at the beginning and end of the 2-week dosing period. By comparing these concentrations to historical controls, we will determine whether taking efavirenz while using the etonogestrel implant alters the serum concentration of efavirenz.

  • Serum hormone markers of ovulation [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    We will test serial blood samples for levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol, and progesterone to determine whether the etonogestrel implant is able to suppress ovulation during and after a course of efavirenz.

  • Transvaginal ultrasound to assess for ovarian follicular development [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    For the entire 6 week period of the study, participants will undergo twice-weekly transvaginal ultrasound to assess for the development of ovarian follicles. This direct assessment of follicular development will be combined with serum hormone concentrations to determine if efavirenz increases the incidence of ovulation in women using the etonogestrel implant for contraception.

  • Cervical mucus quality [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    Cervical mucus quality will be assessed twice weekly throughout the study period. The etonogestrel implant exerts a secondary contraceptive effect by causing cervical mucus to become thick and sticky, and therefore less permissive to the movement of sperm through the female genital tract. We will assess whether efavirenz causes a change in cervical mucus quality that would make sperm penetration more likely, and therefore indicate a reduction in the implant's contraceptive effect.


Estimated Enrollment: 18
Study Start Date: July 2014
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Efavirenz
Healthy, reproductive-age women using the etonogestrel contraceptive implant who will take a two-week course of efavirenz 600mg orally each night.
Drug: Efavirenz
Other Name: Sustiva

  Eligibility

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy women aged 18-40 years who have a Nexplanon®/Implanon® in place that is palpable on exam, had the device placed between 12 and 24 months prior to enrollment, and can provide documentation of when the implant was placed
  • Able to speak and read English
  • Documented HIV-negative status within 30 days of enrollment
  • BMI between 18.5 and 24.9 kg/m2
  • Willingness to take a two-week course of efavirenz
  • Willingness to comply with study visit schedule (as described below), including blood sampling, transvaginal ultrasounds, and cervical mucus assessment
  • Negative urine human chorionic gonadotropin pregnancy test at study entry
  • Normal laboratory values within 30 days of study entry, as specified below:

    • White blood cell count ≥ 4500 and ≤ 11000 cells/mm3
    • Platelet count ≥ 100,000 platelets/mm3
    • Hemoglobin ≥ 8.0 g/dL
    • International normalized ratio (INR) ≤ 1.8
    • Aspartate transaminase (SGOT) and alanine aminotransferase (SGPT) ≤ 3 times the upper limit of normal (ULN) (upper limit of normal)
    • Creatinine ≤ 1.5 x ULN
    • Serum amylase ≤ 1.5 x ULN
    • Total bilirubin ≤ 2.0 x ULN
  • Agree to use an additional reliable method of contraception while participating in the study. Acceptable methods include:

    • Abstinence
    • Condoms (male or female) with or without spermicide
    • Pre-existing sterilization of subject or her male partner
  • Willingness to abstain from alcohol consumption during the study period
  • Willingness to abstain from any grapefruit product or supplement for the duration of the study.

Exclusion Criteria:

  • Breastfeeding
  • Hypersensitivity to efavirenz
  • History of seizure disorder
  • Initiated, discontinued, or changed doses of drugs that are cytochrome P450 isoenzyme 3A4 (CYP3A4) inducers or inhibitors within 30 days of study entry.
  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: NCT01980342

Contacts
Contact: Jennifer A Robinson, MD, MPH 410-550-0336 jrobin87@jhmi.edu

Locations
United States, Maryland
Johns Hopkins University Bayview Medical Center Recruiting
Baltimore, Maryland, United States, 21224
Contact: Katrina Thaler, MPH    410-550-3060    kstouff3@jhmi.edu   
Principal Investigator: Jennifer A Robinson, MD, MPH         
Sub-Investigator: Anne E Burke, MD, MPH         
Sub-Investigator: Roxanne Jamshidi, MD, MPH         
Sub-Investigator: Natalie Whaley, MD         
Sub-Investigator: Charles Flexner, MD         
Sponsors and Collaborators
Johns Hopkins University
American College of Obstetricians and Gynecologists
The Campbell Foundation
  More Information

No publications provided

Responsible Party: Jennifer Robinson, Adjunct Faculty, Johns Hopkins University
ClinicalTrials.gov Identifier: NCT01980342     History of Changes
Other Study ID Numbers: NA_00087585
Study First Received: November 4, 2013
Last Updated: July 30, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Johns Hopkins University:
Long acting reversible contraception
HIV

Additional relevant MeSH terms:
Efavirenz
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 19, 2014