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Pharmacokinetic Study of Two HIV Protease Inhibitors in Patients

Primary Purpose

HIV Infection

Status
Terminated
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
atazanavir
lopinavir/ritonavir
Sponsored by
University of Oklahoma
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV Infection focused on measuring antiretroviral therapy, protease inhibitors, drug interactions, HIV infection, acquired immunodeficiency syndrome, Treatment Experienced

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept 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

Sites / Locations

  • OUHSC General Clinical Research Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Arm A

Arm B

Arm Description

Subjects on atazanavir/ritonavir will add lopinavir/ritonavir.

Subjects on lopinavir/ritonavir will add atazanavir.

Outcomes

Primary Outcome Measures

Mean pharmacokinetic parameters (Cmax, Cmin, AUC) for lopinavir, ritonavir, atazanavir

Secondary Outcome Measures

Safety (e.g., GI tolerance, lab abnormalities, ECG changes)

Full Information

First Posted
January 9, 2007
Last Updated
February 5, 2009
Sponsor
University of Oklahoma
Collaborators
Abbott
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1. Study Identification

Unique Protocol Identification Number
NCT00420355
Brief Title
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

2. Study Status

Record Verification Date
February 2009
Overall Recruitment Status
Terminated
Why Stopped
Unexpected adverse event
Study Start Date
April 2007 (undefined)
Primary Completion Date
October 2007 (Actual)
Study Completion Date
September 2008 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
University of Oklahoma
Collaborators
Abbott

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infection
Keywords
antiretroviral therapy, protease inhibitors, drug interactions, HIV infection, acquired immunodeficiency syndrome, Treatment Experienced

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
19 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm A
Arm Type
Experimental
Arm Description
Subjects on atazanavir/ritonavir will add lopinavir/ritonavir.
Arm Title
Arm B
Arm Type
Experimental
Arm Description
Subjects on lopinavir/ritonavir will add atazanavir.
Intervention Type
Drug
Intervention Name(s)
atazanavir
Other Intervention Name(s)
Reyataz 300 mg capsules
Intervention Description
Atazanavir 300 mg daily on Days 6-12.
Intervention Type
Drug
Intervention Name(s)
lopinavir/ritonavir
Other Intervention Name(s)
Kaletra 200 mg/50 mg tablets
Intervention Description
Lopinavir/ritonavir 400 mg/100 mg twice daily on Days 6-16, then 800 mg/200 mg daily on Days 17-21.
Primary Outcome Measure Information:
Title
Mean pharmacokinetic parameters (Cmax, Cmin, AUC) for lopinavir, ritonavir, atazanavir
Time Frame
Day 6, Day 12 or 16, Day 20
Secondary Outcome Measure Information:
Title
Safety (e.g., GI tolerance, lab abnormalities, ECG changes)
Time Frame
Day 6, Day 12 or Day 16, Day 20

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
R. Chris Rathbun, Pharm.D.
Organizational Affiliation
University of Oklahoma
Official's Role
Principal Investigator
Facility Information:
Facility Name
OUHSC General Clinical Research Center
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
19906626
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.
Results Reference
derived

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Pharmacokinetic Study of Two HIV Protease Inhibitors in Patients

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