Safety, Tolerability, and Blood Levels of Ritonavir-Boosted Atazanavir and Rifampin When Taken Together in HIV Uninfected Adults

NCT00096850 | Completed

• 3 other identifiers: A521310021ACTG A5213
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 3

Brief Summary

Rifampin (RIF) is used for the treatment of tuberculosis (TB), an infectious disease that affects many people with HIV. RIF was shown to lower concentrations and decrease the effectiveness of some anti-HIV drugs, including the HIV protease inhibitor (PI) atazanavir (ATV) boosted with ritonavir (RTV). The purpose of this study is to determine the interactions between RTV-boosted ATV and evaluate the safety and tolerability of giving these drugs together in HIV uninfected adults.

Conditions

HIV Infections; Tuberculosis

Keywords

HIV Seronegativity; Antitubercular agents

Outcome Measures

Primary Outcomes (2)

• Pharmacokinetic parameters of ritonavir (RTV)-boosted ATV when administered concurrently with RIF

  Throughout study

• Safety and tolerability of RTV-boosted ATV when coadministered with RIF

  Throughout study

Secondary Outcomes (5)

• Pharmacokinetics of RIF

  Throughout study

• Copy number of cellular drug transporter RNA in peripheral blood mononuclear cells (PBMCs)

  Throughout study

• UDP-glucuronosyltransferase (UGT)-1A1 genotype

  At study entry

• Serum bilirubin concentration

  Throughout study

• urine thromboxane and prostacyclin concentrations

  At study entry and first PK visit

Study Arms (1)

1

EXPERIMENTAL

From Days 1 to 8, participants will receive 600 mg RIF every 24 hours. From Days 9 to 19, participants will receive 300 mg ATV and 100 mg RTV every 12 hours and 600 mg RIF every 24 hours. From Days 20 to 27, participants will receive 400 mg ATV and 100 mg RTV every 12 hours and 600 mg RIF every 24 hours.

Drug: Atazanavir; Drug: Rifampin; Drug: Ritonavir

Interventions

Atazanavir DRUG

From Days 9 to 19, participants will receive a 300 mg tablet orally daily. From Days 20 to 27, participants will receive a 400 mg tablet orally daily.

Also known as: ATV

1

Rifampin DRUG

From Days 1 to 27, participants will receive a 600 mg tablet orally daily.

Also known as: RIF

1

Ritonavir DRUG

From Days 9 to 19, participants will receive a 100 mg tablet orally daily. From Days 20 to 27, participants will receive a 100 mg tablet orally twice daily.

Also known as: RTV

1

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• HIV uninfected
• Normal creatinine clearance
• Willing to use acceptable means of contraception during the study and for at least 6 weeks after stopping study medications

You may not qualify if:

• Using or anticipating use of certain medications, including any medication metabolized by CYP3A
• Active drug use or dependence that, in the opinion of the investigator, may interfere with the study
• Cannot stop consuming alcoholic beverages, grapefruit, or grapefruit juice for the duration of the study
• Cannot stop consuming coffee or caffeine-containing products for 12 hours prior to Day 8, 19, and 27 PK studies
• Serious illness that, in the opinion of the investigator, may interfere with the study
• Hospitalization for any reason within 14 days prior to study entry
• History of hypersensitivity to study drugs or their formulations
• Active or previous history of cardiovascular, kidney, liver, blood, neurologic, gastrointestinal, psychiatric, endocrine, or immunologic disease. Patients with chronic illnesses such as hypertension, coronary heart disease, arthritis, diabetes, or chronic gastrointestinal conditions that may affect drug absorption are also excluded.
• ECG showing first-degree or greater heart block or a QT interval greater than 440 msec within 30 days of study entry
• Previous participation in this study
• Pregnancy or breastfeeding

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections: collaborator

Study Sites (3)

Stanford CRS

Palo Alto, California, 94305-5107, United States

Location

The Ohio State Univ. AIDS CRS

Columbus, Ohio, 43210, United States

Location

Vanderbilt Therapeutics CRS

Nashville, Tennessee, 37203, United States

Location

Related Publications (6)

• Finch CK, Chrisman CR, Baciewicz AM, Self TH. Rifampin and rifabutin drug interactions: an update. Arch Intern Med. 2002 May 13;162(9):985-92. doi: 10.1001/archinte.162.9.985.

  PMID: 11996607 BACKGROUND

• Fujiwara PI, Clevenbergh P, Dlodlo RA. Management of adults living with HIV/AIDS in low-income, high-burden settings, with special reference to persons with tuberculosis. Int J Tuberc Lung Dis. 2005 Sep;9(9):946-58.

  PMID: 16158886 BACKGROUND

• Kashuba AD. Drug-drug interactions and the pharmacotherapy of HIV infection. Top HIV Med. 2005 Jun-Jul;13(2):64-9.

  PMID: 16082056 BACKGROUND

• Musial BL, Chojnacki JK, Coleman CI. Atazanavir: a new protease inhibitor to treat HIV infection. Am J Health Syst Pharm. 2004 Jul 1;61(13):1365-74. doi: 10.1093/ajhp/61.13.1365.

  PMID: 15287232 BACKGROUND

• Orrick JJ, Steinhart CR. Atazanavir. Ann Pharmacother. 2004 Oct;38(10):1664-74. doi: 10.1345/aph.1D394. Epub 2004 Sep 7.

  PMID: 15353575 BACKGROUND

• Acosta EP, Kendall MA, Gerber JG, Alston-Smith B, Koletar SL, Zolopa AR, Agarwala S, Child M, Bertz R, Hosey L, Haas DW. Effect of concomitantly administered rifampin on the pharmacokinetics and safety of atazanavir administered twice daily. Antimicrob Agents Chemother. 2007 Sep;51(9):3104-10. doi: 10.1128/AAC.00341-07. Epub 2007 Jun 18.

  PMID: 17576825 RESULT

MeSH Terms

Conditions

HIV Infections; Tuberculosis

Interventions

Atazanavir Sulfate; Rifampin; Ritonavir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles

Study Officials

• David W. Haas, MD

  Infectious Diseases, Vanderbilt University Medical Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 16, 2004
• First Posted: November 17, 2004
• Study Completion: December 1, 2007
• Last Updated: November 1, 2021

Record last verified: 2021-10

Locations

US (3)