Genetics and HIV-1 Protease Inhibitors

HIV Clinical Trial

Official title:

Genetic-determinants of Protease Inhibitor Pharmacology

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01388543
• Other study ID #: 06-0428
• Secondary ID: R03AI068438BMSV-
• Status: Completed
• Phase: Phase 4
• Start date: September 2006
• Est. completion date: June 2008

Study information

• Verified date: October 2019
• Source: University of Colorado, Denver
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: June 2008
• Est. primary completion date: June 2008
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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,

• Inability to give informed consent.

• A body mass index below 18.5 or above 34.

Related Conditions & MeSH terms

• HIV

Intervention

Drug:
• Atazanavir
Atazanavir 400mg once daily for 7 days followed by atazanavir 300mg plus ritonavir 100mg for 7 days

Locations

Country	Name	City	State
United States	University of Colorado Denver and Health Sciences Center	Aurora	Colorado

Sponsors (2)

Lead Sponsor	Collaborator
University of Colorado, Denver	National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

References & Publications (3)

Anderson PL, Aquilante CL, Gardner EM, Predhomme J, McDaneld P, Bushman LR, Zheng JH, Ray M, MaWhinney S. Atazanavir pharmacokinetics in genetically determined CYP3A5 expressors versus non-expressors. J Antimicrob Chemother. 2009 Nov;64(5):1071-9. doi: 10 — View Citation

Kile DA, MaWhinney S, Aquilante CL, Rower JE, Castillo-Mancilla JR, Anderson PL. A population pharmacokinetic-pharmacogenetic analysis of atazanavir. AIDS Res Hum Retroviruses. 2012 Oct;28(10):1227-34. Epub 2012 Apr 20. — View Citation

Wempe MF, Anderson PL. Atazanavir metabolism according to CYP3A5 status: an in vitro-in vivo assessment. Drug Metab Dispos. 2011 Mar;39(3):522-7. doi: 10.1124/dmd.110.036178. Epub 2010 Dec 9. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Day 7 Atazanavir Oral Clearance	Measure atazanavir oral clearance in genetically-determined CYP3A5 expressors versus CYP3A5 non-expressors	Day 7