Raltegravir and Atazanavir Dosing Strategy Study (SPARTA)

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

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.

Study Overview

• Status: Completed
• Conditions: HIV Infection
• Intervention / Treatment: Drug: atazanavir plus raltegravir; Drug: atazanavir plus raltegravir

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.

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 3

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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: Isentress; Reyataz; 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: Isentress; Reyataz
Active Comparator: Arm B	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: Isentress; Reyataz; 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: Isentress; Reyataz

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
comparison of the mean steady-state atazanavir trough plasma concentrations for once (C24) and twice (C12) daily dosing strategies	4 and 8 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
comparison of mean steady-state raltegravir trough plasma concentrations for once (C24) and twice (C12) daily dosing	4 and 8 weeks
comparison of steady-state pharmacokinetic profiles of once and twice-daily atazanavir	4 and 8 weeks
comparison of the steady-state pharmacokinetic profiles of once and twice-daily raltegravir	4 and 8 weeks
change from baseline in fasting lipid and glycaemic parameters	weeks 4 and 8 and overall
change from baseline in CD4+ T-lymphocyte count	weeks 4 and 8 and overall
change from baseline in HIV-RNA	weeks 4 and 8 and overall
all adverse events attributable to study treatment	week 8
all serious, grade 3 or 4 clinical adverse events, and any adverse event leading to premature cessation of study treatment	week 8

Collaborators and Investigators

• Sponsor: Kirby Institute
• Investigators: Principal Investigator: David A Cooper, MD DSc, Kirby Institute, UNSW

Study record dates

Study Major Dates

• Study Start: July 1, 2009
• Primary Completion (Actual): July 1, 2011
• Study Completion (Actual): July 1, 2011

Study Registration Dates

• First Submitted: March 31, 2009
• First Submitted That Met QC Criteria: April 1, 2009
• First Posted (Estimate): April 2, 2009

Study Record Updates

• Last Update Posted (Estimate): April 12, 2012
• Last Update Submitted That Met QC Criteria: April 10, 2012
• Last Verified: April 1, 2010

More Information

Terms related to this study

• Keywords: HIV infections; pharmacokinetics; treatment experienced; raltegravir; atazanavir; antiretroviral agents
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; HIV Integrase Inhibitors; Integrase Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Raltegravir Potassium; Atazanavir Sulfate
• Other Study ID Numbers: SPARTA