Raltegravir and Atazanavir Dosing Strategy Study (SPARTA)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Kirby Institute
ClinicalTrials.gov Identifier:
NCT00874523
First received: March 31, 2009
Last updated: April 10, 2012
Last verified: April 2010
  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 3

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:


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 ]

Enrollment: 26
Study Start Date: July 2009
Study Completion Date: July 2011
Primary Completion Date: July 2011 (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
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: NCT00874523

Locations
Australia, New South Wales
Holdsworth House Medical Practice
Sydney, New South Wales, Australia, 2010
St Vincent's Hospital
Sydney, New South Wales, Australia, 2010
Sponsors and Collaborators
Kirby Institute
Investigators
Principal Investigator: David A Cooper, MD DSc Kirby Institute/UNSW
  More Information

No publications provided

Responsible Party: Kirby Institute
ClinicalTrials.gov Identifier: NCT00874523     History of Changes
Other Study ID Numbers: SPARTA
Study First Received: March 31, 2009
Last Updated: April 10, 2012
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 July 28, 2014