Clinical trial NCT00874523: Raltegravir and Atazanavir Dosing Strategy Study
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV Infection
Keywords: raltegravir
atazanavir
HIV infections
pharmacokinetics
antiretroviral agents
treatment experienced
Lead sponsor: Kirby Institute
Sponsor class: OTHER_GOV
First posted: 2009-04-02
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief 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.

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 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.

Primary outcomes:
measure: comparison of the mean steady-state atazanavir trough plasma concentrations for once (C24) and twice (C12) daily dosing strategies
timeFrame: 4 and 8 weeks
Secondary outcomes:
measure: comparison of mean steady-state raltegravir trough plasma concentrations for once (C24) and twice (C12) daily dosing
timeFrame: 4 and 8 weeks
measure: comparison of steady-state pharmacokinetic profiles of once and twice-daily atazanavir
timeFrame: 4 and 8 weeks
measure: comparison of the steady-state pharmacokinetic profiles of once and twice-daily raltegravir
timeFrame: 4 and 8 weeks
measure: change from baseline in fasting lipid and glycaemic parameters
timeFrame: weeks 4 and 8 and overall
measure: change from baseline in CD4+ T-lymphocyte count
timeFrame: weeks 4 and 8 and overall
measure: change from baseline in HIV-RNA
timeFrame: weeks 4 and 8 and overall
measure: all adverse events attributable to study treatment
timeFrame: week 8
measure: all serious, grade 3 or 4 clinical adverse events, and any adverse event leading to premature cessation of study treatment
timeFrame: week 8
Other outcomes:
Locations:
city: Sydney
country: Australia
facility: Holdsworth House Medical Practice
state: New South Wales
city: Sydney
country: Australia
facility: St Vincent's Hospital
state: New South Wales
Study officials:
affiliation: Kirby Institute
name: David A Cooper, MD DSc
role: PRINCIPAL_INVESTIGATOR
References: