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. - Full Text View

Purpose

Clinical data suggests that the standard dose of the anti-HIV medication, efavirenz (EFV), could be reduced without compromising its effectiveness. Lower drug doses could have fewer side effects and would make EFV more affordable. The purpose of this study is to compare the safety and effectiveness, over 96 weeks, of standard (600mg) versus reduced dose (400mg) EFV in controlling HIV as part of initial combination antiretroviral therapy.

Condition	Intervention	Phase
HIV Infections	Drug: Efavirenz	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double (Participant, Investigator) Primary Purpose: Treatment
Official Title:	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:

The primary endpoint is the comparison between treatment groups of proportions of patients with HIV RNA <200 copies/mL 48 weeks after randomisation [ Time Frame: 1.5 years ]

Secondary Outcome Measures:

Virologic endpoints: proportion of patients with plasma HIV RNA <400 copies/mL and <50 copies/mL, and time to virological failure (HIV RNA ≥200 copies/ml) [ Time Frame: 2 years ]
Immunologic endpoints: mean change from baseline in CD4+ T cell count/µL [ Time Frame: 2 years ]
Clinical endpoints: rate of opportunistic disease or death, and rates of serious non-AIDS-defining illness and non-AIDS-related mortality [ Time Frame: 2 years ]
Metabolic endpoints: mean/median change from baseline in fasted lipids (TC, LDL-c, HDL-c and TG), mean/median change from baseline in fasted glucose, and rates of initiation or changes in existing lipid-lowering therapies [ Time Frame: 2 years ]
Adherence: median scores of self-reported adherence to randomised study medications [ Time Frame: 2 years ]
Mean/median change from baseline in selected serum biochemical parameters [ Time Frame: 2 years ]
Rates, types and severity of adverse events [ Time Frame: 2 years ]
Steady state EFV concentrations [ Time Frame: 1 year ]
Steady state EFV concentrations measured by plasma and dried blood spot samples


Enrollment:	630
Study Start Date:	August 2011
Study Completion Date:	August 2014
Primary Completion Date:	June 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: 600mg Efavirenz Eligible patients will be centrally randomised to receive tenofovir (TDF) (300mg qd)/emtricitabine (FTC) (200mg qd) + EFV (600mg qd; 3 x 200mg qd)	Drug: Efavirenz 3 x EFV 200mg tablets once daily Other Name: Matrix EFV 200mg (Efamat 200) tablets
Experimental: 400mg Efavirenz Eligible patients will be centrally randomised to receive TDF (300mg qd)/FTC (200mg qd) + EFV (400mg qd; 2 x 200mg + 1 x 200mg placebo qd).	Drug: Efavirenz 2 x EFV 200mg tablets plus 1x matched EFV placebo tablet once daily Other Names: Matrix EFV 200mg (Efamat 200) tablets Matrix EFV 200mg (Efamat 200) matched placebo tablets.

Detailed Description:

In this international, multicenter trial, 630 HIV infected patients who have not received any previous treatment for their HIV-infection will be enrolled. Participants will be randomized equally (1:1) to receive truvada (tenofovir and emtricitabine) with either the standard or reduced dose of EFV. Neither the study doctor nor the participant will know which treatment the participant is receiving. Physical examinations, laboratory analyses and questionnaires will be performed at the 11 study visits at screening, baseline (Week 0), Weeks 4, 12, 24, 36, 48, 60, 72, 84 and 96. The primary aim of this study is to compare between treatment groups the proportion of patients with undetectable HIV viral load (HIV RNA < 200 copies/mL) after 48 weeks. Information on immune function, drug adherence, resistance to antiretrovirals, quality of life, mental state and HIV-related conditions will also be collected. Blood samples will be collected for future testing. Interim analyses will be performed when the first 125 participants in each treatment group reach week 24 and when all participants reach week 24. These interim analyses will provide an early check that the reduced dose of EFV suppresses HIV infection as effectively as the standard dose of EFV. A follow-up analysis will be performed when all participants reach week 96.

Eligibility


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

Criteria

Inclusion Criteria:

HIV-1 positive by licensed diagnostic test
aged >16 years of age (or minimum age as determined by local regulations or as legal requirements dictate)
50 < CD4 <500 cells/µL
No prior AIDS-defining illness, using the CDC 1993 case definition (except pulmonary tuberculosis)
HIV RNA ≥1000 copies/mL
no prior exposure to ART (including short course ARVs for preventing MTCT)
calculated creatinine clearance (CLCr) more than or equal to 50 mL/min (Cockcroft-Gault formula)
provision of written informed consent.

Exclusion Criteria:

the following laboratory values:
- absolute neutrophil count (ANC) <500 cells/μL
- hemoglobin <7.0 g/dL
- platelet count <50,000 cells/μL
- AST and/or ALT >5 x ULN
pregnant women or nursing mothers
active opportunistic or malignant disease not under adequate control
use of immunomodulators within 30 days prior to screening
use of any prohibited medications
current alcohol or illicit substance use that might adversely affect study participation

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: NCT01011413

Locations


Australia, New South Wales
St Vincent's Hospital
Sydney, New South Wales, Australia, 2010

Sponsors and Collaborators

Kirby Institute

Investigators


Principal Investigator:	David Cooper, Professor	Kirby Institute

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

ENCORE1 Study Group, Carey D, Puls R, Amin J, Losso M, Phanupak P, Foulkes S, Mohapi L, Crabtree-Ramirez B, Jessen H, Kumar S, Winston A, Lee MP, Belloso W, Cooper DA, Emery S. Efficacy and safety of efavirenz 400 mg daily versus 600 mg daily: 96-week data from the randomised, double-blind, placebo-controlled, non-inferiority ENCORE1 study. Lancet Infect Dis. 2015 Jul;15(7):793-802. doi: 10.1016/S1473-3099(15)70060-5. Epub 2015 Apr 12. Erratum in: Lancet Infect Dis. 2015 Jul;15(7):761.

Winston A, Amin J, Clarke A, Else L, Amara A, Owen A, Barber T, Jessen H, Avihingsanon A, Chetchotisakd P, Khoo S, Cooper DA, Emery S, Puls R; ENCORE Cerebrospinal Fluid (CSF) Substudy Team; ENCORE Cerebrospinal Fluid CSF Substudy Team. Cerebrospinal fluid exposure of efavirenz and its major metabolites when dosed at 400 mg and 600 mg once daily: a randomized controlled trial. Clin Infect Dis. 2015 Apr 1;60(7):1026-32. doi: 10.1093/cid/ciu976. Epub 2014 Dec 11. Erratum in: Clin Infect Dis. 2015 Jul 1;61(1):143. Avinghsanon, Anchalee [corrected to Avihingsanon, Anchalee].

ENCORE1 Study Group. Efficacy of 400 mg efavirenz versus standard 600 mg dose in HIV-infected, antiretroviral-naive adults (ENCORE1): a randomised, double-blind, placebo-controlled, non-inferiority trial. Lancet. 2014 Apr 26;383(9927):1474-1482. doi: 10.1016/S0140-6736(13)62187-X. Epub 2014 Feb 10. Erratum in: Lancet. 2014 Apr 26;383(9927):1464.


Responsible Party:	Kirby Institute
ClinicalTrials.gov Identifier:	NCT01011413 History of Changes
Other Study ID Numbers:	NCHECR-ENCORE1
Study First Received:	November 9, 2009
Last Updated:	December 18, 2014

Keywords provided by Kirby Institute:


HIV ART Efavirenz Dose reduction

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 21, 2017

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. (encore1)