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

Phase 3

Completed

• Conditions: HIV Infection
• Interventions: Drug: Efavirenz

• Registration Number: NCT01271894
• Lead Sponsor: Kirby Institute

Brief Summary

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.

Detailed Description

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 Timeline

• Study First Submitted: 2011-01-05
• Study First Submitted QC: 2011-01-05
• Study First Posted: 2011-01-07
• Study Start: 2011-09
• Status Verified: 2012-11
• Primary Completion: 2013-05
• Study Completion: 2013-05
• Last Update Submitted: 2013-05-10
• Last Update Posted: 2013-05-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 40

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.

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Normal Efavirenz dose arm	Efavirenz	Patients randomized in the main study to receive EFV (600 mg once daily; 3 x 200 mg once daily) plus tenofovir/emtricitabine (300/200 mg) fixed-dose combination once daily
Reduced dose Efavirenz arm	Efavirenz	Participants randomized in main study to receive EFV (400 mg once daily; 2 x 200 mg + 1 x placebo once daily) plus tenofovir/emtricitabine (300/200 mg) fixed-dose combination once daily

Primary Outcome Measures

Name	Time	Method
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.	48 weeks

Secondary Outcome Measures

Name	Time	Method
To compare the safety and tolerability of EFV 400 mg versus 600 mg given once daily.	48 weeks
To investigate the correlation between EFV concentration measurements from dried blood spots and concentration measured in matched plasma samples.	48 weeks

Trial Locations

Locations (4)

Desmond Tutu HIV Foundation; 🇿🇦 Cape Town, South Africa

Chelsea and Westminister Hospital; 🇬🇧 London, United Kingdom

Thai Red Cross-AIDS Research Centre, HIV-NAT Research Collaboration; 🇹🇭 Bangkok, Thailand

Hospital J.M. Ramos Mejia; 🇦🇷 Buenos Aires, Argentina