SSAT063- Pharmacokinetics of Efavirenz 400 mg Once Daily During Pregnancy in HIV-1 Infected Women
Condition: HIV
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of the study is to measure the drug levels in your blood and to find out whether
      a reduced dose (400mg) of the anti-HIV medication Efavirenz is safe when taken during
      pregnancy.

      The study will recruit HIV infected women who take Efavirenz as part of their anti-hiv
      treatment and who are pregnant.

      Efavirenz has been shown to be safe in pregnancy and at the standard dose that everybody
      takes of 600mg once a day, it shows levels that are enough to treat HIV and give birth to a
      HIV negative baby.

      Efavirenz at a dose of 400mg once daily works against HIV too but this dose has not been
      given to HIV positive pregnant women.

      People with HIV may benefit from using a dose of efavirenz of 400mg instead of 600mg, as
      lower drug doses could have fewer side effects and be tolerated better.

      Dose reduction would also make the drug cheaper. This would allow more people to be treated
      and free up money for other important work in the fight against HIV such as education and
      prevention programs.

      However, it is not known whether 400mg of Efavirenz works as well as 600mg of Efavirenz
      during pregnancy and this is why the investigators are conducting this study, which aims to
      measure the amount of Efavirenz 400mg in HIV pregnant women's bodies when they are taking
      400mg of Efavirenz once a day.
    

Detailed description: 
      Protocol Number: SSAT 063

      EudraCT Number: 2014-002615-42

      Name of Investigational Product: Sustiva

      Name of active ingredients: Efavirenz

      Study title:Pharmacokinetics of Efavirenz 400mg once daily during pregnancy in HIV-1 infected
      women

      Name of Non Investigational Medicinal Product:

      Two nucleoside reverse transcriptase inhibitors (tenofovir/ emtricitabine or
      tenofovir/lamivudine or zidovudine/lamivudine)

      Phase of study: Phase I

      Objectives: The objectives of this study are:

        -  Primary

           -To investigate the pharmacokinetics of Efavirenz 400mg during pregnancy.

        -  Secondary

             -  To investigate the safety and tolerability of Efavirenz 400mg during pregnancy.

             -  To investigate the association between genetic polymorphisms in drug disposition
                genes and drug exposure.

      Study design: Two centre, approximately 18 weeks (excluding screening and follow up), open
      label, single treatment arm, pharmacokinetic study.

      Indication: HIV in pregnancy

      Methodology: Measurements of steady state pharmacokinetic profiles of efavirenz during the
      third trimester of pregnancy and 6 weeks postpartum in HIV-infected women on
      tenofovir/emtricitabine or tenofovir/lamivudine or zidovudine/lamivudine plus Efavirenz 400mg
      once daily.

      Planned sample size: The primary endpoint will be the comparison of efavirenz Ctrough during
      the third trimester of pregnancy versus postpartum. The efavirenz Ctrough from each patient
      will be compared between the two phases using geometric mean ratios (log10 transformed data).
      For this sequential design, a sample size of 25 patients would provide at least 80% power to
      detect a decrease in efavirenz Ctrough of 20% during the third trimester of pregnancy,
      compared to the postpartum phase.

      Up to 35 individuals may be screened to achieve 25 women completing all PK phases.

      Summary of eligibility criteria:

      Pregnant HIV-infected women with:

        -  Undetectable viral load

        -  CD4 count > 100 cells/mm3

        -  Stable on tenofovir/emtricitabine or tenofovir/lamivudine or zidovudine/lamivudine plus
           Efavirenz 600mg once daily for more than 12 weeks

      Number of study centres: Two (London, UK and Kampala, Uganda)

      Duration of treatment: Approximately 18 weeks: approximately four weeks prior to week 32 of
      pregnancy and up to 6 weeks postpartum (excluding screening and follow up visits)

      Dose and route of administration: All subjects will be administered oral efavirenz 400mg
      together with the rest of the oral antiretroviral combination (tenofovir 245mg/emtricitabine
      200mg or tenofovir 245mg/lamivudine 300mg or lamivudine 300mg/zidovudine 600mg) throughout
      the study period.

      Criteria for evaluation: Pharmacokinetic parameters of efavirenz will be evaluated during the
      third trimester (gestational age week 32 +/- 3 weeks) and 6 weeks (+/- 4 weeks) postpartum.

      Safety and tolerability of medications will also be assessed by questions, physical
      examination and laboratory parameters. These will be performed at regular intervals during
      the drug study.

      At delivery, if possible, a cord blood sample will be taken and at the same time a blood
      sample from the mother will be taken.

      Primary Endpoint:

      Pharmacokinetics of efavirenz 400mg during pregnancy.

      Secondary End point:

        1. Safety and tolerability of efavirenz 400mg during pregnancy.

        2. Association between genetic polymorphisms in drug disposition genes and drug exposure.
    

Intervention name(s): Efavirenz; tenofovir /emtricitabine; tenofovir/lamivudine; lamivudine/zidovudine
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): oral Efavirenz 400mg; tenofovir 245 mg/emtricitabine 200mg; tenofovir 245mg/lamivudine 300mg; lamivudine 300mg/zidovudine 600mg
Other intervention name(s): Sustiva
Intervention MeSH terms: Tenofovir; Lamivudine; Emtricitabine; Zidovudine; Efavirenz; Lamivudine, zidovudine drug combination
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment