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

NCT ID: NCT01980342

Last Updated: 2018-05-11

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 1 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-10-31
• Study Completion Date: 2018-04-04

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.

Conditions

Drug Interaction

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Efavirenz

Healthy, reproductive-age women using the etonogestrel contraceptive implant who will take a two-week course of efavirenz 400 mg orally each night.

Group Type: EXPERIMENTAL

Efavirenz

Intervention Type: DRUG

Healthy women who are using Nexplanon will be asked to take a 2-week course of reduced-dose efavirenz (400 mg daily).

Interventions

Efavirenz

Healthy women who are using Nexplanon will be asked to take a 2-week course of reduced-dose efavirenz (400 mg daily).

Intervention Type: DRUG

Other Intervention Names

Sustiva

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

American College of Obstetricians and Gynecologists

OTHER

Sponsor Role: collaborator

The Campbell Foundation

OTHER

Sponsor Role: collaborator

Johns Hopkins University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Johns Hopkins University Bayview Medical Center

Baltimore, Maryland, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

NA_00087585

Identifier Type: -

Identifier Source: org_study_id