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

NCT02499874 | Completed Phase 1 DMC

• 1 other identifier: SSAT063
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

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.

Conditions

HIV

Outcome Measures

Primary Outcomes (1)

• 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.

  24 weeks

Secondary Outcomes (2)

• 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

  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

  24 weeks

Study Arms (1)

Single treatment arm

EXPERIMENTAL

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

Interventions

Efavirenz DRUG

oral Efavirenz 400mg

Also known as: Sustiva

Single treatment arm

tenofovir /emtricitabine DRUG

tenofovir 245 mg/emtricitabine 200mg

Single treatment arm

tenofovir/lamivudine DRUG

tenofovir 245mg/lamivudine 300mg

Single treatment arm

lamivudine/zidovudine DRUG

lamivudine 300mg/zidovudine 600mg

Single treatment arm

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Evidence of a personally signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study.
• 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.
• Undetectable viral load (by local assay).
• CD4 count \> 100 cells/mm3.
• Aged between 18 to 45 years, inclusive.

You may not qualify if:

• Viral load ≥ 50 copies/mL (or detectable by local assay).
• Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, ECG or clinical laboratory determinations.
• Positive blood screen for chronic hepatitis C (if available locally) or hepatitis B.
• Current or recent (within 3 months) gastrointestinal disease.
• 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.
• Exposure to any investigational drug or placebo within 3 months prior to first dose of study drug.
• 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.

Sponsors & Collaborators

• St Stephens Aids Trust: lead
• Mylan Inc.: collaborator

Study Sites (1)

St Stephen's Centre, Chelsea and Westminster Hospital

London, United Kingdom

Location

Related Links

• UNAIDS is the leading advocate for worldwide action against HIV/AIDS. It promotes partnerships among and between other UN agencies, governments, corporations, media, sports and religious organizations, community-based groups
• BHIVA (the British HIV Association) is an organisation that represents healthcare professionals working in HIV in the UK. Its guidelines set out the medical and other care people living with HIV can expect to receive in the UK

MeSH Terms

Interventions

efavirenz; Tenofovir; Emtricitabine; Lamivudine; lamivudine, zidovudine drug combination

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Zalcitabine; Dideoxynucleosides

Study Officials

• Marta Boffito, MBBS,MD,PhD

  St. Stephen's AIDS Trust

  PRINCIPAL INVESTIGATOR

• Mohammed Lamorde, MBBS

  Infectious Diseases Institute (IDI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 7, 2015
• First Posted: July 16, 2015
• Study Start: August 1, 2015
• Primary Completion: October 5, 2017
• Study Completion: October 5, 2017
• Last Updated: October 20, 2017

Record last verified: 2017-10

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)