Raltegravir and Atazanavir Dosing Strategy Study - Full Text View

Sponsor:	Kirby Institute
Information provided by:	Kirby Institute
ClinicalTrials.gov Identifier:	NCT00874523

Purpose

To compare the steady-state pharmacokinetics and short-term efficacy and safety of two dosing strategies of raltegravir and atazanavir in virologically suppressed HIV-infected adults receiving atazanavir-containing combination antiretroviral therapy.

Condition	Intervention	Phase
HIV Infection	Drug: atazanavir plus raltegravir	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Pharmacokinetics/Dynamics Study Intervention Model: Crossover Assignment Masking: Open Label Primary Purpose: Treatment
Official 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 HIV-infected Patients

Resource links provided by NLM:

Genetics Home Reference related topics: complement factor I deficiency

MedlinePlus related topics: HIV/AIDS

Drug Information available for: BMS 232632 Atazanavir sulfate Raltegravir Raltegravir potassium

U.S. FDA Resources

Further study details as provided by Kirby Institute:

Primary Outcome Measures:

comparison of the mean steady-state atazanavir trough plasma concentrations for once (C24) and twice (C12) daily dosing strategies [ Time Frame: 4 and 8 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

comparison of mean steady-state raltegravir trough plasma concentrations for once (C24) and twice (C12) daily dosing [ Time Frame: 4 and 8 weeks ] [ Designated as safety issue: No ]
comparison of steady-state pharmacokinetic profiles of once and twice-daily atazanavir [ Time Frame: 4 and 8 weeks ] [ Designated as safety issue: No ]
comparison of the steady-state pharmacokinetic profiles of once and twice-daily raltegravir [ Time Frame: 4 and 8 weeks ] [ Designated as safety issue: No ]
change from baseline in fasting lipid and glycaemic parameters [ Time Frame: weeks 4 and 8 and overall ] [ Designated as safety issue: No ]
change from baseline in CD4+ T-lymphocyte count [ Time Frame: weeks 4 and 8 and overall ] [ Designated as safety issue: No ]
change from baseline in HIV-RNA [ Time Frame: weeks 4 and 8 and overall ] [ Designated as safety issue: No ]
all adverse events attributable to study treatment [ Time Frame: week 8 ] [ Designated as safety issue: Yes ]
all serious, grade 3 or 4 clinical adverse events, and any adverse event leading to premature cessation of study treatment [ Time Frame: week 8 ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	24
Study Start Date:	July 2009
Estimated Study Completion Date:	June 2010
Estimated Primary Completion Date:	June 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Arm A	Drug: atazanavir plus raltegravir atazanavir 300 mg + raltegravir 400 mg twice daily for 4 weeks then atazanavir 300 mg + ritonavir 100 mg + raltegravir 800 mg once daily for 4 weeks Other Names: Reyataz Isentress
Active Comparator: Arm B	Drug: atazanavir plus raltegravir atazanavir 300 mg + ritonavir 100 mg + raltegravir 800 mg once daily for 4 weeks then atazanavir 300 mg + raltegravir 400 mg twice daily for 4 weeks Other Names: Reyataz Isentress

Detailed Description:

Current HIV treatment guidelines recommend the construction of combination regimens comprising a minimum of three agents from at least two drug classes. There are problems with the current recommendations for although treatments are effective, their success is often limited by tolerability, adverse effects and the need to take many pills. Antiretroviral adherence remains vital and regimens should be simplified wherever possible to facilitate maximal adherence. The recent availability of the potent HIV integrase inhibitor, raltegravir, provides an opportunity to explore moves away from current regimen components. Evidence to support the use of novel regimens must be generated through adequately powered randomized clinical trials. However, before such trials can be undertaken, preliminary data to define the pharmacokinetics, safety and tolerability of these regimens are needed to minimize unnecessary risk for participants. This eight week study will investigate the steady-state pharmacokinetics, and short-term safety and efficacy of two dosing strategies (once and twice daily) of raltegravir plus atazanavir in treatment experienced HIV-infected adults.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

aged ≥ 18 years 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.

Exclusion Criteria :

prior clinical/virological failure on a PI-containing regimen
no clinical history of primary HIV-1 protease mutations identified in local baseline genotypic analysis of HIV with interpretation using current 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:
- absolute neutrophil count (ANC) < 750 cells/mL
- haemoglobin less than 8.5 g/dL
- platelet count less than 50 000 cells/mL
- AST, ALT > 5 times the upper limit of normal
- serum bilirubin > 5 times the upper limit of normal
chronic active hepatitis B infection defined by presence of serum viral hepatitis B surface antigen (HBsAg) or HBV DNA-positive
any malabsorption syndrome likely to affect drug absorption
concurrent therapy with human growth hormone or other immunomodulatory agents
concomitant medication contraindicated for use with either atazanavir or raltegravir therapy
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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00874523

Locations

Australia, New South Wales
St Vincent's Hospital
Sydney, New South Wales, Australia, 2010
Holdsworth House Medical Practice
Sydney, New South Wales, Australia, 2010

Sponsors and Collaborators

Kirby Institute

Investigators

Principal Investigator:

David A Cooper, MD DSc

NCHECR/UNSW

More Information

No publications provided

Responsible Party:	The National Centre in HIV Epidemiology and Clinical Research/The University of New South Wales, Sydney, Australia, NCHECR/UNSW
ClinicalTrials.gov Identifier:	NCT00874523 History of Changes
Other Study ID Numbers:	SPARTA
Study First Received:	March 31, 2009
Last Updated:	April 13, 2010
Health Authority:	Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by Kirby Institute:

raltegravir
atazanavir
HIV infections

pharmacokinetics
antiretroviral agents
treatment experienced

Additional relevant MeSH terms:

HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases

Anti-Retroviral Agents
Atazanavir
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents

ClinicalTrials.gov processed this record on February 08, 2012