Genetics and HIV-1 Protease Inhibitors

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Colorado, Denver
ClinicalTrials.gov Identifier:
NCT01388543
First received: June 28, 2011
Last updated: December 11, 2012
Last verified: December 2012
  Purpose

This study evaluated the blood levels of atazanavir according to a genetic makeup for CYP3A5 (cytochrome P450 3A5, an enzyme that metabolizes atazanavir). The hypothesis was that people with a slow-metabolizing genotype would have higher blood levels of atazanavir compared to people with the normal metabolizing genotype.


Condition Intervention Phase
HIV
Drug: Atazanavir
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Official Title: Genetic-determinants of Protease Inhibitor Pharmacology

Resource links provided by NLM:


Further study details as provided by University of Colorado, Denver:

Primary Outcome Measures:
  • Drug levels and blood comparisons [ Time Frame: Day 7 ] [ Designated as safety issue: No ]
    Compare atazanavir oral clearance in genetically-determined CYP3A5 expressors versus CYP3A5 non-expressors

  • Drug levels and blood comparisons [ Time Frame: Day 14 ] [ Designated as safety issue: No ]
    Characterize the effect of ritonavir boosting on atazanavir oral clearance in genetically-determined CYP3A5 expressors versus CYP3A5 non-expressors


Enrollment: 31
Study Start Date: September 2006
Study Completion Date: June 2008
Primary Completion Date: June 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: CYP3A5 Expressors
A pre-screening genetic test determines CYP3A5 expressor status
Drug: Atazanavir
Atazanavir 400mg once daily for 7 days followed by atazanavir 300mg plus ritonavir 100mg for 7 days
Other Names:
  • Reyataz
  • Norvir
Active Comparator: CYP3A5 Non-expressors
A pre-screening genetic test determines CYP3A5 non-expressor status
Drug: Atazanavir
Atazanavir 400mg once daily for 7 days followed by atazanavir 300mg plus ritonavir 100mg for 7 days
Other Names:
  • Reyataz
  • Norvir

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Age 18 to 55 years
  • Negative HIV screening antibody test
  • CYP3A5 expressor status, race, and sex fit an enrollment opening.

Exclusion Criteria:

  • Pregnant or breast-feeding
  • Medical history of hepatitis B or C, autoimmune disease, active malignancy, kidney disease including nephrolithiasis
  • Organ dysfunction manifested by liver transaminases or serum creatinine >1.25 times the upper limit of normal, or any comprehensive metabolic test (except asymptomatic unconjugated hyperbilirubinemia), blood count, or lipid value > Grade I according to Division of AIDS (DAIDS) adverse drug event grading system (appendix).
  • Medical history of arrhythmias (including atrial fibrillation, atrioventricular block, and/or pacemaker)
  • Any QT interval abnormalities or other congenital arrhythmia syndromes on ECG or any ECG abnormality that in the opinion of the investigators would preclude entry into the study.
  • Medical history of any serious heart condition including congestive heart failure, myopathies, coronary artery disease, or unexplained syncope.
  • Medical history of bleeding disorders (i.e., hemophilia)
  • Hyperlipidemia
  • Any prescription, herbal, recreational, or over-the-counter medication contraindicated with ritonavir or atazanavir including, substrates/inhibitors/inducers of CYP3A/P-gp, cardio-active medication, or medications that alter the acid in the stomach. The study investigators will review each concurrent medication on a case-by-case basis.
  • Inability to refrain from grapefruit or grapefruit juice during the study.
  • Investigational drugs within the last 30 days.
  • Active alcohol / recreational drug abuse, or inability to give informed consent.
  • A body mass index below 18.5 or above 34.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01388543

Locations
United States, Colorado
University of Colorado Denver and Health Sciences Center
Aurora, Colorado, United States, 80045
Sponsors and Collaborators
University of Colorado, Denver
Investigators
Principal Investigator: Peter L. Anderson, PharmD University of Colorado Denver and Health Sciences Center
  More Information

Publications:
Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT01388543     History of Changes
Other Study ID Numbers: 06-0428, R03AI068438, BMSV-338
Study First Received: June 28, 2011
Last Updated: December 11, 2012
Health Authority: United States: Federal Government
United States: Institutional Review Board

Keywords provided by University of Colorado, Denver:
Pharmacokinetics
Clinical Pharmacology
Pharmacogenomics
HIV

Additional relevant MeSH terms:
Protease Inhibitors
Atazanavir
HIV Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 15, 2014