Clinical trial NCT00411957: Pharmacokinetic Study of 2 Doses of ATV/r OD + 2 NRTIs in Thai HIV-1 Infected Patients
Official title: The Pharmacokinetics of Atazanavir / Ritonavir 200/100 OD Versus 300/100 mg OD in Combination With 2 NRTIs in HIV Pre-treated Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: HIV Infections
Keywords: atazanavir/ritonavir
pharmacokinetic of ATV/r200/100 OD+2NRTIs
Lead sponsor: The HIV Netherlands Australia Thailand Research Collaboration
Sponsor class: OTHER
Collaborators: name: Bristol-Myers Squibb
First posted: 2006-12-15
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Several studies from HIV-NAT have demonstrated high nevirapine, indinavir, saquinavir and lopinavir/r levels when compared to Caucasian patients. Until now, the pharmacokinetics of atazanavir have not been explored in a Thai population. We postulate that ATV levels, as with other PIs, are higher in Thai people. Therefore, the level of ATV in ATV/RTV 300/100 OD may be higher than the acceptable range and could be associated with ATV related toxicity.

Detailed description: We are interested in once daily ATV/RTV 200/100 mg OD because of the convenience, reduction in ATV doses which may improve adherence while reducing toxicity and cost. There are limited prospective studies evaluating pharmacokinetic and long term efficacy and safety of atazanavir/ritonavir once daily dose in combination of NRTIs in HIV-1 pretreated patients. We believe that the PK parameters of ATV/RTV given at 200/100mg daily in Thai patients will be equivalent to the ATV/RTV 300/100mg once daily dosing in Caucasian patients when combined with 2NRTIs, and that the once daily regimen will have better safety, tolerability profile, and cost saving while maintaining good CD4 and VL outcome. If, the pharmacokinetic profile of ATV/RTV 200/100 mg OD + 2NRTIs is in acceptable range or comparable with standard dose of ATV/RTV 300/100 mg OD, long term efficacy will be explored later.

Eligibility criteria: Inclusion Criteria:

* Written informed consent
* Adults HIV patients currently using ATV/RTV 300/100 mg OD plus 2 NRTIs
* HIV RNA \< 50 copies/ml

Exclusion Criteria:

* Inability to understand the nature and extent of the study and the procedures required.
* ALT/ AST more than 5x upper limit
* Relevant history or current condition, illness that might interfere with drug absorption, distribution, metabolism or excretion.
* Use of concomitant medication that may interfere with the pharmacokinetics of atazanavir, and ritonavir
* History of sensitivity/idiosyncrasy to the drug or chemically related compounds which may be employed in the study.
* Active drug abuse or heavy alcoholic drinking
* History of sensitivity/idiosyncrasy to the drug or chemically related compounds which may be employed in the study.
* Active drug abuse or heavy alcoholic drinking

Primary outcomes:
measure: the pharmacokinetics of atazanavir/ritonavir (ATV/RTV) 200/100 mg once daily in a sample of 22 patients experiencing virological success
timeFrame: 1 year
Secondary outcomes:
measure: The pharmacokinetic and pharmacodynamic between these patients and data from Thai cohort treated with ATV/RTV 300/100 mg OD
timeFrame: 4 weeks
measure: short term safety, tolerability and efficacy data in these PK participating patients
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Bangkok
country: Thailand
facility: HIV-NAT, Thai Red Cross AIDS Research Center
Study officials:
affiliation: HIV-NAT Thai Red Cross AIDS Research Center
name: Kiat Ruxrungtham, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Avihingsanon A, van der Lugt J, Kerr SJ, Gorowara M, Chanmano S, Ohata P, Lange J, Cooper DA, Phanuphak P, Burger DM, Ruxrungtham K. A low dose of ritonavir-boosted atazanavir provides adequate pharmacokinetic parameters in HIV-1-infected Thai adults. Clin Pharmacol Ther. 2009 Apr;85(4):402-8. doi: 10.1038/clpt.2008.244. Epub 2008 Dec 31.