Clinical trial NCT00420355: Pharmacokinetic Study of Two HIV Protease Inhibitors in Patients
Official title: The Pharmacokinetics of Lopinavir/Ritonavir in Combination With Atazanavir in HIV-Infected Subjects
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: HIV Infection
Keywords: antiretroviral therapy
protease inhibitors
drug interactions
HIV infection
acquired immunodeficiency syndrome
Treatment Experienced
Lead sponsor: University of Oklahoma
Sponsor class: OTHER
Collaborators: name: Abbott
First posted: 2007-01-11
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of this study is to determine the pharmacokinetics of lopinavir, ritonavir, and atazanavir when lopinavir/ritonavir and atazanavir are used in combination.

Detailed description: Thirty patients with HIV infection will be enrolled in this open-label, parallel arm pharmacokinetic study. Subjects receiving either lopinavir/ritonavir or atazanavir/ritonavir as part of their antiretroviral therapy will have a pharmacokinetic study performed over 12-20 days to examine whether coadministration of lopinavir and atazanavir alters the pharmacokinetics of either agent. The safety of these agents in combination will also be explored.

Eligibility criteria: Inclusion Criteria:

* HIV-seropositive
* Currently receiving atazanavir/ritonavir or lopinavir/ritonavir in combination with 2-3 nucleoside RT inhibitors or are antiretroviral treatment-naïve
* If female, is not of childbearing potential or is of childbearing potential and agrees to use a barrier method of contraception throughout the study

Exclusion Criteria:

* HIV-1 RNA \> 400 copies/mL if currently receiving antiretroviral therapy
* Concurrent use of CYP450 inhibitors or inducers
* Concurrent use of P-glycoprotein substrates, inhibitors, or inducers
* Concurrent use of medications known to interact with ritonavir or atazanavir
* Presence of a chronic health condition deemed by the investigators to potentially impair lopinavir, ritonavir, or atazanavir pharmacokinetics
* Presence of conduction abnormalities on electrocardiogram
* Women who are pregnant or breastfeeding
* Laboratory Abnormalities at baseline:

  * Aminotransferases \> 3x ULN
  * Serum bilirubin \> 5x ULN
  * Serum creatinine \> 1.5x ULN
  * Hemoglobin concentration \< 8.0 g/dL
  * Absolute neutrophil count \< 800 cells/μL
  * Platelet count \< 50,000 cells/μL

Primary outcomes:
measure: Mean pharmacokinetic parameters (Cmax, Cmin, AUC) for lopinavir, ritonavir, atazanavir
timeFrame: Day 6, Day 12 or 16, Day 20
Secondary outcomes:
measure: Safety (e.g., GI tolerance, lab abnormalities, ECG changes)
timeFrame: Day 6, Day 12 or Day 16, Day 20
Other outcomes:
Locations:
city: Oklahoma City
country: United States
facility: OUHSC General Clinical Research Center
state: Oklahoma
Study officials:
affiliation: University of Oklahoma
name: R. Chris Rathbun, Pharm.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rathbun CR, Liedtke MD, Blevins SM, Harrison D, Lockhart SM, Salvaggio M, Acosta EP. Electrocardiogram abnormalities with atazanavir and lopinavir/ritonavir. HIV Clin Trials. 2009 Sep-Oct;10(5):328-36. doi: 10.1310/hct1005-328.