Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12609000179235
Ethics application status
Approved
Date submitted
13/03/2009
Date registered
17/04/2009
Date last updated
5/07/2012
Type of registration
Retrospectively registered

Titles & IDs
Public title
A randomised, open-label, cross-over study to examine the pharmacokinetics, and short-term safety and efficacy of two dosing strategies of raltegravir plus atazanavir in human immunodficiency virus (HIV)-infected patients
Scientific title
A randomised, open-label, cross-over study to examine the pharmacokinetics, and short-term safety and efficacy of two dosing strategies of raltegravir plus atazanavir in human immunodeficiency virus (HIV)-infected patients
Secondary ID [1] 280299 0
NCT00874523
Universal Trial Number (UTN)
Trial acronym
SPARTA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
chronic HIV infection 4474 0
Condition category
Condition code
Infection 4747 4747 0 0
Acquired immune deficiency syndrome (AIDS / HIV)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a randomised, open-label, cross-over 8 week study in virologically controlled HIV-infected adults currently receiving atazanavir–containing combination antiretroviral therapy. Participants will be randomised to receive either raltegravir 400 mg twice daily plus atazanavir 300 mg twice daily for 4 weeks followed by raltegravir 800 mg daily plus atazanavir 300 mg and ritonavir 100 mg daily for 4 weeks or. raltegravir 800 mg daily plus atazanavir 300 mg and ritonavir 100 mg daily for 4 weeks followed by raltegravir 400 mg twice daily plus atazanavir 300 mg twice daily for 4 weeks. The study has efficacy, safety and pharmacokinetic endpoints. All drugs will be administered orally. There will be no washout period between the crossover treatments.
Intervention code [1] 4217 0
Treatment: Drugs
Comparator / control treatment
A regimen comprising raltegravir 400 mg twice daily plus atazanavir 300 mg twice daily for 4 weeks will be compared to a regimen comprising raltegravir 800 mg daily plus atazanavir 300 mg and ritonavir 100 mg daily for 4 weeks. All drugs will be administered orally. Participants will commence one of the two regimens then change to the alternate regimen following 4 weeks of therapy.
Control group
Dose comparison

Outcomes
Primary outcome [1] 5613 0
comparison of the mean steady-state atazanavir trough plasma concentrations for once (C24) and twice (C12) daily dosing strategies. Drug concentrations in plasma will be quantitated using a validated high-performance liquid chromatography (HPLC) assay.
Timepoint [1] 5613 0
week 8
Secondary outcome [1] 9444 0
comparison of mean steady-state raltegravir trough plasma concentrations for once (C24) and twice (C12) daily dosing. Drug concentrations in plasma will be quantitated using a validated high-performance liquid chromatography (HPLC)assay.
Timepoint [1] 9444 0
week 8
Secondary outcome [2] 9445 0
comparison of the steady-state pharmacokinetic profiles (standard pharmacokinetic parameters [Cmax, Tmax, t1/2, CL/F, V/F, AUC] and concentration time plots) of once- and twice-daily atazanavir. Drug concentrations in plasma will be quantitated using a validated high-performance liquid chromatography (HPLC)assay.
Timepoint [2] 9445 0
week 8
Secondary outcome [3] 9446 0
comparison of the steady-state pharmacokinetic profiles (standard pharmacokinetic parameters [Cmax, Tmax, t1/2, CL/F, V/F, AUC] and concentration time plots) of once- and twice-daily raltegravir. Drug concentrations in plasma will be quantitated using a validated high-performance liquid chromatography (HPLC) assay.
Timepoint [3] 9446 0
week 8
Secondary outcome [4] 9447 0
change from baseline in fasting blood lipid and glycaemic parameters using automated laboratory analysis.
Timepoint [4] 9447 0
weeks 4 and 8 and time-weight change
Secondary outcome [5] 9448 0
change from baseline in CD4+ T-lymphocyte count in plasma using automated laboratory analysis.
Timepoint [5] 9448 0
weeks 4 and 8 and time-weighted change
Secondary outcome [6] 9449 0
change from baseline in plasma HIV-ribonucleic acid (RNA) using automated laboratory analysis.
Timepoint [6] 9449 0
weeks 4 and 8 and time-weight change
Secondary outcome [7] 9450 0
all serious, grade 3 or 4 clinical adverse events, and any adverse event leading to cessation of study treatment. Laboratory adverse events will be assessed on the basis of blood testing and automated laboratory analysis. Clinical adverse events will be assessed by standard physical examination (by medical practitioner).
Timepoint [7] 9450 0
week 8
Secondary outcome [8] 9451 0
all adverse events attributable to study treatment. Laboratory adverse events will be assessed on the basis of blood testing and automated laboratory analysis. Clinical adverse events will be assessed by standard physical examination (by medical practitioner).
Timepoint [8] 9451 0
week 8

Eligibility
Key inclusion criteria
aged 18 years or more with laboratory evidence of HIV-1 infection;
currently receiving 3 or more unchanged antiretroviral agents including atazanavir (with or without ritonavir boosting) for at least 24 weeks prior to study entry;
plasma HIV RNA less than 50 copies/mL for at least 24 weeks prior to study entry;
provide written, informed consent.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
prior clinical/virological failure on a protease inhibitor-containing regimen
no clinical history of primary HIV-1 protease mutations identified in local baseline genotypic analysis of HIV with interpretation using current International AIDS Society United States of America (IAS-USA) Drug Resistance Mutations in HIV-1;
women: pregnant, breastfeeding, or not willing to use adequate contraception (including barrier contraception) if of child-bearing potential;
laboratory abnormalities at screening:
o absolute neutrophil count (ANC) less than 750 x 106/L
o haemoglobin less than 8.5 g/dL
o platelet count less than 50 x 109/L
o asparate aminotransferase (AST), alanine aminotransferase (ALT) greater than 5 times the upper limit of normal (ULN)
o serum bilirubin greater than 5 times ULN;
chronic active hepatitis B virus (HBV) infection defined by presence of serum viral hepatitis B surface antigen (HBsAg) or hepatitis B deoxyribonucelic acid (HBV DNA)-positive;
any malabsorption syndrome likely to affect drug absorption (eg Crohn’s disease, chronic pancreatitis);
concurrent therapy with human growth hormone or other immunomodulatory agents;
concomitant medication contraindicated for use with either atazanavir or raltegravir therapy;
subjects who have discontinued any prohibited concomitant agent/s must have ceased this therapy at least 30 days prior to screening;
any inter-current illness requiring hospitalisation;
current excessive alcohol or illicit substance use;
unlikely to be able to remain in follow-up for the protocol-defined period.

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 randomisation by phone
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Sequence generation will use a randomisation table created by computer software. Randomisation will be stratified by current ritonavir therapy use.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 3 / Phase 4
Type of endpoint/s
Pharmacokinetics / pharmacodynamics
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/04/2009
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
24
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 4664 0
University
Name [1] 4664 0
National Centre in HIV Epidemiology/The University of New South Wales (NCHECR/UNSW)
Country [1] 4664 0
Australia
Primary sponsor type
University
Name
National Centre in HIV Epidemiology/The University of New South Wales
Address
Level 2,
376 Victoria Street
Darlinghurst NSW 2010
Country
Australia
Secondary sponsor category [1] 4210 0
None
Name [1] 4210 0
Address [1] 4210 0
Country [1] 4210 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 6700 0
St Vincent's Health Care Campus Human Research Ethics Committee
Ethics committee address [1] 6700 0
Ethics committee country [1] 6700 0
Australia
Date submitted for ethics approval [1] 6700 0
Approval date [1] 6700 0
17/12/2008
Ethics approval number [1] 6700 0
08/173; 08/SVH/168
Ethics committee name [2] 6701 0
The University of New South Wales
Ethics committee address [2] 6701 0
Ethics committee country [2] 6701 0
Australia
Date submitted for ethics approval [2] 6701 0
Approval date [2] 6701 0
20/01/2009
Ethics approval number [2] 6701 0
09009

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 29395 0
Address 29395 0
Country 29395 0
Phone 29395 0
Fax 29395 0
Email 29395 0
Contact person for public queries
Name 12642 0
Dianne Carey
Address 12642 0
National Centre in HIV Epidemiology and Clinical Research/The University of New South Wales
Level 2
376 Victoria Street
Darlinghurst NSW 2010
Country 12642 0
Australia
Phone 12642 0
+61 2 9385 0900
Fax 12642 0
Email 12642 0
[email protected]
Contact person for scientific queries
Name 3570 0
Dianne Carey
Address 3570 0
National Centre in HIV Epidemiology and Clinical Research/The University of New South Wales
Level 2
376 Victoria Street
Darlinghurst NSW 2010
Country 3570 0
Australia
Phone 3570 0
+61 2 9385 0900
Fax 3570 0
Email 3570 0
[email protected]

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.