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

HIV Infection Clinical Trial

Official title:

The Intensive Pharmacokinetics Sub-study of Encore1: A Randomised, Double-blind, Placebo-controlled, Clinical Trial to Compare the Safety and Efficacy of Reduced Dose Efavirenz (EFV) With Standard Dose EFV Plus Two Nucleotide Reverse Transcriptase Inhibitors (N(t)RTI) in Antiretroviral-naïve HIV-infected Individuals Over 96 Weeks

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01271894
• Other study ID #: NCHECR-ENCORE1-PK
• Status: Completed
• Phase: Phase 3
• First received: January 5, 2011
• Last updated: May 10, 2013
• Start date: September 2011
• Est. completion date: May 2013

Study information

• Verified date: November 2012
• Source: Kirby Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: May 2013
• Est. primary completion date: May 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 16 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Screening

Related Conditions & MeSH terms

• HIV Infection

Intervention

Drug:
• Efavirenz
600 mg once daily; given as 3 x 200 mg once
• Efavirenz
400 mg once daily; given as 2 x 200 mg + 1 x placebo

Locations

Country	Name	City	State
Argentina	Hospital J.M. Ramos Mejia	Buenos Aires
South Africa	Desmond Tutu HIV Foundation	Cape Town
Thailand	Thai Red Cross-AIDS Research Centre, HIV-NAT Research Collaboration	Bangkok
United Kingdom	Chelsea and Westminister Hospital	London

Sponsors (2)

Lead Sponsor	Collaborator
Kirby Institute	Chelsea and Westminster NHS Foundation Trust

Countries where clinical trial is conducted

Argentina,  South Africa,  Thailand,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	To compare the safety and tolerability of EFV 400 mg versus 600 mg given once daily.		48 weeks	Yes
Secondary	To investigate the correlation between EFV concentration measurements from dried blood spots and concentration measured in matched plasma samples.		48 weeks	No