Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12612000263897
Ethics application status
Approved
Date submitted
21/02/2012
Date registered
5/03/2012
Date last updated
8/06/2012
Type of registration
Retrospectively registered

Titles & IDs
Public 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 2N(t)RTI in antiretroviral-naive HIV-infected individuals over 96 weeks. Encore1 intensive pharmacokinetics sub-study
Scientific 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 2N(t)RTI in antiretroviral-naive HIV-infected individuals over 96 weeks. Encore1 intensive pharmacokinetics sub-study
Secondary ID [1] 280011 0
NCT01271894 (ClinicalTrials.gov)
Universal Trial Number (UTN)
U1111-1128-3627
Trial acronym
Encore1 intensive PK sub-study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
HIV infection 285898 0
Condition category
Condition code
Infection 286110 286110 0 0
Acquired immune deficiency syndrome (AIDS / HIV)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Efavirenz 600 mg orally once daily or efavirenz 400 mg orally once daily in combination with daily tenofovir/emtricabine (300/200 mg) fixed-drug combination for 96 weeks
http://clinicaltrials.gov/ct2/show/NCT01011413?term=Encore1&rank=2
Intervention code [1] 284316 0
Treatment: Drugs
Comparator / control treatment
600 mg (given as 3 x 200 mg tablets) plus tenofovir/emtricitabine (300/200 mg) fixed drug combination once daily for 96 weeks
Control group
Dose comparison

Outcomes
Primary outcome [1] 286567 0
To compare the pharmacokinetic parameters of EFV determined from blood collected over a 24-hour dosing interval in blinded samples from participants taking either EFV 600 mg or 400 mg once daily in combination with Truvada.
Timepoint [1] 286567 0
48 weeks
Secondary outcome [1] 296183 0
To compare the safety and tolerability of EFV 400 mg versus 600 mg given once daily by between-group comparison of adverse event and serious adverse event frequency, clinical assessment and results of DASS-21 and subject experience questionnaires.
Adverse events are those commonly observed with EFV therapy and included central nervous system events such as dizziness, vivid dreams, poor of concentration. Events will be assessed by clinical examination and use of questionnaires as above.
Timepoint [1] 296183 0
48 weeks
Secondary outcome [2] 296184 0
To compare pharmacokinetic parameters (AUC0-24, t1/2, Cmax, Tmax, Cmin, CL/F) between EFV 400 mg and 600 mg dosed once daily.
Timepoint [2] 296184 0
48 weeks

Eligibility
Key inclusion criteria
Main study participants at selected sites are eligible:
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.
Minimum age
16 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
nil

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomization by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomization by using a randomization table created by a computer software (i.e. computerised sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Pharmacokinetics / pharmacodynamics
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
20/12/2011
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
40
Accrual to date
Final
Recruitment outside Australia
Country [1] 4150 0
Argentina
State/province [1] 4150 0
Buenos Aires
Country [2] 4151 0
Thailand
State/province [2] 4151 0
Bangkok
Country [3] 4152 0
South Africa
State/province [3] 4152 0
Cape Town
Country [4] 4153 0
United Kingdom
State/province [4] 4153 0
London

Funding & Sponsors
Funding source category [1] 284748 0
Self funded/Unfunded
Name [1] 284748 0
Country [1] 284748 0
Primary sponsor type
University
Name
Kirby Institute/University of New South Wales
Address
UNSW
Sydney NSW 2052
Country
Australia
Secondary sponsor category [1] 283656 0
None
Name [1] 283656 0
Address [1] 283656 0
Country [1] 283656 0
Other collaborator category [1] 260559 0
Individual
Name [1] 260559 0
Dr Marta Boffito
Address [1] 260559 0
Chelsea & Westminster Hospital
Fulham Road
London SW7
Country [1] 260559 0
United Kingdom

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 286752 0
University of New South Wales Human Research Ethics Committee
Ethics committee address [1] 286752 0
UNSW
Sydney NSW 2052
Ethics committee country [1] 286752 0
Australia
Date submitted for ethics approval [1] 286752 0
Approval date [1] 286752 0
19/12/2011
Ethics approval number [1] 286752 0
HC11447

Summary
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, EFV demonstrates inter-individual differences in its efficacy and tolerability. 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 EFV 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.

http://clinicaltrials.gov/ct2/show/NCT01271894?term=Encore1&rank=3
Trial website
nil
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 33809 0
Address 33809 0
Country 33809 0
Phone 33809 0
Fax 33809 0
Email 33809 0
Contact person for public queries
Name 17056 0
Dr Dianne Carey
Address 17056 0
Kirby Institute
c/- CFI Building
cnr West and Boundary Sts
Darlinghurst NSW 2010
Country 17056 0
Australia
Phone 17056 0
+ 61 2 9385 0908
Fax 17056 0
+61 2 9385 0910
Email 17056 0
dcarey@kirby.unsw.edu.au
Contact person for scientific queries
Name 7984 0
Dr Rebekah Puls
Address 7984 0
Kirby Institute
c/- CFI Building
cnr West and Boundary Sts
Darlinghurst NSW 2010
Country 7984 0
Australia
Phone 7984 0
+ 61 2 9385 0900
Fax 7984 0
+ 61 2 9385 0910
Email 7984 0
rpuls@kirby.unsw.edu.au

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.