A Phase 1 interventional study of Efavirenz and tenofovir /emtricitabine in HIV, sponsored by St Stephens Aids Trust. Completed at 1 site in United Kingdom. Open to female participants aged 18 Years to 45 Years. Per ClinicalTrials.gov, last updated 2017-10-20.
Sponsored by St Stephens Aids Trust · Phase 1, Interventional, and Treatment
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.
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
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:
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:
Exclusion Criteria:
All subjects will be administered oral Efavirenz 400mg together with the rest of the oral antiretroviral combination (tenofovir 245 mg/emtricitabine 200mg or tenofovir 245mg/lamivudine 300mg or lamivudine 300mg/zidovudine 600mg) throughout the study period
Drug: Efavirenz · Drug: tenofovir /emtricitabine · Drug: tenofovir/lamivudine · Drug: lamivudine/zidovudine
oral Efavirenz 400mg
Also known as: Sustiva
tenofovir 245 mg/emtricitabine 200mg
tenofovir 245mg/lamivudine 300mg
lamivudine 300mg/zidovudine 600mg
Pharmacokinetics (AUC and Ctrough) of Efavirenz 400mg during pregnancy and postpartum.
The pharmacokinetic parameters calculated for efavirenz will be trough concentration (Ctrough), defined as the concentration at 24 hours after the observed drug dose, the maximum observed plasma concentration (Cmax), elimination half-life (t1/2), time point at Cmax (Tmax), and total drug exposure, expressed as the area under the plasma concentration-time curve from 0-24 hours after dosing (AUC0-24h). Efavirenz pharmacokinetic parameters measure during the third trimester of pregnancy and postpartum will be compared by calculating geometric mean ratios and 90% confidence intervals.
Time frame: 24 weeks
Safety and tolerability (based on physical examination, laboratory tests and the DIVISION OF AIDS (DAIDS) table for granding the severity of adult and and the pediatric adverse events of Efavirenz 400mg during pregnancy and 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.
Time frame: 24 weeks
Association between polymorphisms in drug disposition genes and exposure in order to understand whether polymorphism of certain genes encoding for efavirenz metabolic enzymes are behind differences in efavirenz pharmacokinetics between people
candidate gene approach will be utilised to examine loci of interest. This procedure will provide potentially important information on genetic influences on plasma drug concentrations and give insight into how to improve the management of HIV-infected patients by individualising therapy. These studies will not be powered for genetic associations but will enable us to build a data base of genotype-phenotype. Prospective genetic studies would need to be planned based on these preliminary data.
Time frame: 24 weeks
Plan to share: No
This study is completed, as verified in Oct 2017. You cannot join it, but the record below documents what was studied.
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St Stephens Aids Trust