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SSAT063- Pharmacokinetics of Efavirenz 400 mg Once Daily During Pregnancy in HIV-1 Infected Women

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02499874
Recruitment Status : Completed
First Posted : July 16, 2015
Last Update Posted : October 20, 2017
Mylan Inc.
Information provided by (Responsible Party):
St Stephens Aids Trust

Brief 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.

Condition or disease Intervention/treatment Phase
HIV Drug: Efavirenz Drug: tenofovir /emtricitabine Drug: tenofovir/lamivudine Drug: lamivudine/zidovudine Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 26 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pharmacokinetics of EFV 400mg Once Daily During Pregnancy in HIV+ Women
Study Start Date : August 2015
Actual Primary Completion Date : October 5, 2017
Actual Study Completion Date : October 5, 2017

Resource links provided by the National Library of Medicine

Drug Information available for: Efavirenz

Arm Intervention/treatment
Experimental: Single treatment arm
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
oral Efavirenz 400mg
Other Name: Sustiva

Drug: tenofovir /emtricitabine
tenofovir 245 mg/emtricitabine 200mg

Drug: tenofovir/lamivudine
tenofovir 245mg/lamivudine 300mg

Drug: lamivudine/zidovudine
lamivudine 300mg/zidovudine 600mg

Primary Outcome Measures :
  1. Pharmacokinetics (AUC and Ctrough) of Efavirenz 400mg during pregnancy and postpartum. [ Time Frame: 24 weeks ]
    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.

Secondary Outcome Measures :
  1. 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 [ Time Frame: 24 weeks ]
    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.

  2. 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 [ Time Frame: 24 weeks ]
    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.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Evidence of a personally signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study.
  2. HIV-1-infected pregnant female, stable on two nucleos/tide analogues (tenofovir/emtricitabine or tenofovir/lamivudine or zidovudine/lamivudine) and efavirenz 600mg once daily for more than 12 weeks and willing to take efavirenz 400 mg once daily at gestational age of 28 weeks +/- 3 weeks.
  3. Undetectable viral load (by local assay).
  4. CD4 count > 100 cells/mm3.
  5. Aged between 18 to 45 years, inclusive.

Exclusion Criteria:

  1. Viral load ≥ 50 copies/mL (or detectable by local assay).
  2. Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, ECG or clinical laboratory determinations.
  3. Positive blood screen for chronic hepatitis C (if available locally) or hepatitis B.
  4. Current or recent (within 3 months) gastrointestinal disease.
  5. Clinically relevant alcohol or drug use (positive urine drug screen) or history of alcohol or drug use considered by the Investigator to be sufficient to hinder compliance with treatment, follow-up procedures or evaluation of adverse events.
  6. Exposure to any investigational drug or placebo within 3 months prior to first dose of study drug.
  7. Use of any other drugs, including over-the-counter medications and herbal preparations, within two weeks prior to first dose of study drug, unless approved/prescribed by the Principal Investigator as known not to interact with study drugs.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02499874

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United Kingdom
St Stephen's Centre, Chelsea and Westminster Hospital
London, United Kingdom
Sponsors and Collaborators
St Stephens Aids Trust
Mylan Inc.
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Principal Investigator: Marta Boffito, MBBS,MD,PhD St. Stephen's AIDS Trust
Principal Investigator: Mohammed Lamorde, MBBS Infectious Diseases Institute (IDI)
Additional Information:
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Responsible Party: St Stephens Aids Trust Identifier: NCT02499874    
Other Study ID Numbers: SSAT063
First Posted: July 16, 2015    Key Record Dates
Last Update Posted: October 20, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
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Lamivudine, zidovudine drug combination
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Cytochrome P-450 CYP2C9 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Cytochrome P-450 CYP2C19 Inhibitors
Cytochrome P-450 CYP2B6 Inducers
Cytochrome P-450 Enzyme Inducers
Cytochrome P-450 CYP3A Inducers