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

Purpose

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.

Condition	Intervention	Phase
HIV Infection	Drug: Efavirenz	Phase 3


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

Resource links provided by NLM:

MedlinePlus related topics: HIV/AIDS

Drug Information available for: Efavirenz

U.S. FDA Resources

Further study details as provided by Kirby Institute:

Primary Outcome Measures:

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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To compare the safety and tolerability of EFV 400 mg versus 600 mg given once daily. [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
To investigate the correlation between EFV concentration measurements from dried blood spots and concentration measured in matched plasma samples. [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]


Enrollment:	40
Study Start Date:	September 2011
Study Completion Date:	May 2013
Primary Completion Date:	May 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Reduced dose Efavirenz arm 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	Drug: Efavirenz 400 mg once daily; given as 2 x 200 mg + 1 x placebo
Active Comparator: Normal Efavirenz dose arm 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	Drug: Efavirenz 600 mg once daily; given as 3 x 200 mg once

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.

Eligibility


Ages Eligible for Study:	16 Years and older (Child, Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01271894

Locations


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

Sponsors and Collaborators

Kirby Institute

Chelsea and Westminster NHS Foundation Trust

Investigators


Principal Investigator:	Marta Boffito, Dr.	Chelsea & Westminster Hospital

More Information


Responsible Party:	Kirby Institute
ClinicalTrials.gov Identifier:	NCT01271894 History of Changes
Other Study ID Numbers:	NCHECR-ENCORE1-PK
Study First Received:	January 5, 2011
Last Updated:	May 10, 2013
Health Authority:	United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Kirby Institute:


HIV efavirenz pharmacokinetic

Additional relevant MeSH terms:


HIV Infections Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases Efavirenz Reverse Transcriptase Inhibitors Nucleic Acid Synthesis Inhibitors	Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-Retroviral Agents Antiviral Agents Anti-Infective 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

ClinicalTrials.gov processed this record on September 26, 2016