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

This study is not yet open for participant recruitment.
Verified November 2013 by Johns Hopkins University
American College of Obstetricians and Gynecologists
Information provided by (Responsible Party):
Michelle Fox, Johns Hopkins University Identifier:
First received: November 4, 2013
Last updated: NA
Last verified: November 2013
History: No changes posted

November 4, 2013
November 4, 2013
December 2013
December 2014   (final data collection date for primary outcome measure)
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.
Same as current
No Changes Posted
  • 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 therefor indicate a reduction in the implant's contraceptive effect.
Same as current
Not Provided
Not Provided
Pharmacokinetics and Pharmacodynamics of the Etonogestrel Contraceptive Implant When Co-administered With Efavirenz
Not Provided

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.

Not Provided
Phase 4
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Drug Interaction
Drug: Efavirenz
Other Name: Sustiva
Experimental: Efavirenz
Healthy, reproductive-age women using the etonogestrel contraceptive implant who will take a two-week course of efavirenz 600mg orally each night.
Intervention: Drug: Efavirenz
Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Not yet recruiting
Not Provided
December 2014   (final data collection date for primary outcome measure)

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 hCG (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.
18 Years to 40 Years
Contact: Jennifer A Robinson, MD, MPH 410-550-0336
United States
Michelle Fox, Johns Hopkins University
Johns Hopkins University
American College of Obstetricians and Gynecologists
Not Provided
Johns Hopkins University
November 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP