Pharmacokinetic Study of Two HIV Protease Inhibitors in Patients

University of Oklahoma (OU)

Status and phase: Terminated; Phase 4

Conditions: HIV Infection

Treatments: Drug: atazanavir; Drug: lopinavir/ritonavir

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00420355

12637

Details and patient eligibility

About

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

Full 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.

Enrollment: 19 patients

Sex: All

Ages: 18 to 60 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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19 participants in 2 patient groups

Arm A

Experimental group

Description:

Subjects on atazanavir/ritonavir will add lopinavir/ritonavir.

Treatment:

Drug: lopinavir/ritonavir

Arm B

Experimental group

Description:

Subjects on lopinavir/ritonavir will add atazanavir.

Treatment:

Drug: atazanavir