Raltegravir and Atazanavir Dosing Strategy Study

HIV Infection Clinical Trial

— SPARTA  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00874523
• Other study ID #: SPARTA
• Status: Completed
• Phase: Phase 3
• First received: March 31, 2009
• Last updated: April 10, 2012
• Start date: July 2009
• Est. completion date: July 2011

Study information

• Verified date: April 2010
• Source: Kirby Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: July 2011
• Est. primary completion date: July 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infection
• HIV Infections

Intervention

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
• 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

Locations

Country	Name	City	State
Australia	Holdsworth House Medical Practice	Sydney	New South Wales
Australia	St Vincent's Hospital	Sydney	New South Wales

Sponsors (1)

Lead Sponsor	Collaborator
Kirby Institute

Country where clinical trial is conducted

Australia, 

Outcome

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