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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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:
Atazanavir
HIV Protease Inhibitors
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 September 30, 2014