Pharmacokinetic Study of 2 Doses of ATV/r OD + 2 NRTIs in Thai HIV-1 Infected Patients

The Pharmacokinetics of Atazanavir / Ritonavir 200/100 OD Versus 300/100 mg OD in Combination With 2 NRTIs in HIV Pre-treated Patients

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.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Atazanavir

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.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Thailand
  • Bangkok, Thailand, 10300
    • HIV-NAT, Thai Red Cross AIDS Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1; ATV/r 300/100 mg	Drug: Atazanavir; ATV/r 300/100mg OD vs ATV/r 200/100 mg OD
Active Comparator: 2; ATV/r 200/100 mg OD	Drug: Atazanavir; ATV/r 300/100mg OD vs ATV/r 200/100 mg OD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
the pharmacokinetics of atazanavir/ritonavir (ATV/RTV) 200/100 mg once daily in a sample of 22 patients experiencing virological success	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
The pharmacokinetic and pharmacodynamic between these patients and data from Thai cohort treated with ATV/RTV 300/100 mg OD	4 weeks
short term safety, tolerability and efficacy data in these PK participating patients	4 weeks

Collaborators and Investigators

• Sponsor: The HIV Netherlands Australia Thailand Research Collaboration
• Collaborators: Bristol-Myers Squibb
• Investigators: Principal Investigator: Kiat Ruxrungtham, MD, HIV-NAT Thai Red Cross AIDS Research Center

Publications and helpful links

General Publications

• 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.

Helpful Links

• The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT)

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Primary Completion (Actual): January 1, 2008
• Study Completion (Actual): January 1, 2008

Study Registration Dates

• First Submitted: December 13, 2006
• First Submitted That Met QC Criteria: December 14, 2006
• First Posted (Estimate): December 15, 2006

Study Record Updates

• Last Update Posted (Actual): July 17, 2020
• Last Update Submitted That Met QC Criteria: July 15, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: atazanavir/ritonavir; pharmacokinetic of ATV/r200/100 OD+2NRTIs
• 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 Protease Inhibitors; Viral Protease Inhibitors; Atazanavir Sulfate
• Other Study ID Numbers: HIV-NAT 073