The Intensive Pharmacokinetics Sub-study of Encore1 (ENCORE1-PK)

Kirby Institute40 enrolled

Overview

Safety and efficacy are key issues in antiretroviral therapy (ART) selection. Efavirenz (EFV) is an important component of combination ART in treatment naive individuals. Like many drugs, there are inter-individual differences in the efficacy and tolerability of EFV. The Encore1 study provides an opportunity to examine the pharmacokinetics (PK)(processes by which a drug is absorbed, distributed, metabolized, and eliminated by the body) of EFV in blood samples collected over a 24-hour dosing interval in participants receiving either standard 600 mg or reduced 400 mg dose EFV once daily.

This sub-study will investigate the relationships between dosage, EFV plasma concentrations, toxicity and virological efficacy. EFV concentrations in dried blood spots and matched plasma and will be evaluated to determine the utility of dried blood spot measurements in measuring EFV plasma concentrations. Measurements dried blood spots could potentially be a cheap and easy alternative to measurements in plasma. Dried blood spots can be easily collected from venous blood or fingerprick, do not need plasma separation and potentially need less stringent storage conditions during shipment.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

SCREENING

Masking

DOUBLE

Enrollment

Conditions

HIV Infection

Interventions

EfavirenzDRUG

600 mg once daily; given as 3 x 200 mg once

EfavirenzDRUG

400 mg once daily; given as 2 x 200 mg + 1 x placebo

Eligibility

Sex: ALLMin age: 16 Years

Medical Language ↔ Plain English

All participants enrolled into the main Encore1 study at participating sub-study sites will be eligible to participate. Participants must meet the following additional inclusion criteria prior to intensive pharmacokinetic assessment. Inclusion Criteria: * provide written sub-study consent at or before week 0 * taken randomized study drugs for at least 4 weeks but less than 8 weeks * taken EFV in the evening for at least 7 days * taken all EFV doses over the 3 preceding days.

Locations (4)

Hospital J.M. Ramos Mejia

Buenos Aires, Argentina

Desmond Tutu HIV Foundation

Cape Town, South Africa

Thai Red Cross-AIDS Research Centre, HIV-NAT Research Collaboration

Bangkok, Thailand

Chelsea and Westminister Hospital

London, United Kingdom

Outcomes

Primary Outcomes

To compare the pharmacokinetic parameters of EFV determined from blood collected over a 24-hour dosing interval in blinded samples from participants taking either 600 mg or 400 mg once daily in combination with Truvada.

Time frame: 48 weeks

Secondary Outcomes

To compare the safety and tolerability of EFV 400 mg versus 600 mg given once daily.

Time frame: 48 weeks

To investigate the correlation between EFV concentration measurements from dried blood spots and concentration measured in matched plasma samples.

Time frame: 48 weeks

Data from ClinicalTrials.gov

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