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

Johns Hopkins University

Status and phase

Terminated

Phase 4

Conditions

Drug Interaction

Treatments

Drug: Efavirenz

Study type

Interventional

Funder types

Other

Identifiers

NCT01980342

NA_00087585

Details and patient eligibility

About

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.

Full 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.

Enrollment

1 patient

Sex

Female

Ages

18 to 40 years old

Volunteers

Accepts Healthy Volunteers

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.