Pharmacokinetic Study of Two HIV Protease Inhibitors in Patients

Study Overview
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Brief Summary
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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
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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.

Official Title
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The Pharmacokinetics of Lopinavir/Ritonavir in Combination With Atazanavir in HIV-Infected Subjects

Conditions
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HIV Infection

Intervention / Treatment
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* Drug: atazanavir
* Drug: lopinavir/ritonavir


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>Subjects on atazanavir/ritonavir will add lopinavir/ritonavir. | Drug: lopinavir/ritonavir<br>* Lopinavir/ritonavir 400 mg/100 mg twice daily on Days 6-16, then 800 mg/200 mg daily on Days 17-21.<br>* Other names: Kaletra 200 mg/50 mg tablets;|
| Experimental: Arm B<br>Subjects on lopinavir/ritonavir will add atazanavir. | Drug: atazanavir<br>* Atazanavir 300 mg daily on Days 6-12.<br>* Other names: Reyataz 300 mg capsules;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean pharmacokinetic parameters (Cmax, Cmin, AUC) for lopinavir, ritonavir, atazanavir |  | Day 6, Day 12 or 16, Day 20 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety (e.g., GI tolerance, lab abnormalities, ECG changes) |  | Day 6, Day 12 or Day 16, Day 20 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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antiretroviral therapy, protease inhibitors, drug interactions, HIV infection, acquired immunodeficiency syndrome, Treatment Experienced