Pharmacokinetics and Pharmacodynamics of the Etonogestrel Contraceptive Implant When Co-administered With Efavirenz
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.
|Study Design:||Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
- 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.
- 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.
|Study Start Date:||July 2014|
|Estimated Primary Completion Date:||June 2015 (Final data collection date for primary outcome measure)|
Healthy, reproductive-age women using the etonogestrel contraceptive implant who will take a two-week course of efavirenz 600mg orally each night.
Other Name: Sustiva
Please refer to this study by its ClinicalTrials.gov identifier: NCT01980342
|Contact: Jennifer A Robinson, MD, MPHfirstname.lastname@example.org|
|United States, Maryland|
|Johns Hopkins University Bayview Medical Center||Recruiting|
|Baltimore, Maryland, United States, 21224|
|Contact: Katrina Thaler, MPH 410-550-3060 email@example.com|
|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|