Pharmacokinetics and Pharmacodynamics of the Etonogestrel Contraceptive Implant When Co-administered With Efavirenz
Condition: Drug Interaction
Intervention: Efavirenz
Intervention description: Healthy women who are using Nexplanon will be asked to take a 2-week course of reduced-dose efavirenz (400 mg daily).
Intervention MeSH terms: Efavirenz
Phase: Phase 4
Study type: Interventional
Primary purpose: Other
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: Female
Minimum age: 18 Years
Maximum age: 40 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Long acting reversible contraception; HIV

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.
    

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.