Clinical trial NCT01980342: Pharmacokinetics and Pharmacodynamics of the Etonogestrel Contraceptive Implant When Co-administered With Efavirenz
Official title: Pharmacokinetics and Pharmacodynamics of the Etonogestrel Contraceptive Implant When Co-administered With Efavirenz
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Drug Interaction
Keywords: Long acting reversible contraception
HIV
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: American College of Obstetricians and Gynecologists
name: The Campbell Foundation
First posted: 2013-11-08
Enrollment: 1
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: This study evaluates whether there is an interaction between etonogestrel, the progestin hormone released by the contraceptive implant Nexplanon, and efavirenz, a common medication used to treat HIV. The endpoints measured in this study will help determine if such an interaction leads to decreased contraceptive efficacy of the contraceptive implant.

Detailed description: 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.

Eligibility 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.

Primary outcomes:
measure: Serum Concentration of Etonogestrel Before and After Two Weeks of Efavirenz
timeFrame: 6 weeks
Secondary outcomes:
measure: Serum Efavirenz Concentrations at the Start and End of the 2-week Dosing Period
timeFrame: 2 weeks
measure: Serum Hormone Markers of Ovulation
timeFrame: 6 weeks
measure: Transvaginal Ultrasound to Assess for Ovarian Follicular Development
timeFrame: 6 weeks
measure: Cervical Mucus Quality
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins University Bayview Medical Center
state: Maryland
Study officials:
References: