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

This study has been completed.
Sponsor:
Collaborator:
AIDS Clinical Trials Group
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00096850
First received: November 16, 2004
Last updated: May 17, 2012
Last verified: May 2012
  Purpose

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.


Condition Intervention
HIV Infections
Tuberculosis
Drug: Atazanavir
Drug: Rifampin
Drug: Ritonavir

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Safety, Tolerability, and Pharmacokinetic Interactions of Atazanavir and Rifampin in Healthy Volunteers

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Pharmacokinetic parameters of ritonavir (RTV)-boosted ATV when administered concurrently with RIF [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Safety and tolerability of RTV-boosted ATV when coadministered with RIF [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Pharmacokinetics of RIF [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Copy number of cellular drug transporter RNA in peripheral blood mononuclear cells (PBMCs) [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • UDP-glucuronosyltransferase (UGT)-1A1 genotype [ Time Frame: At study entry ] [ Designated as safety issue: No ]
  • Serum bilirubin concentration [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • urine thromboxane and prostacyclin concentrations [ Time Frame: At study entry and first PK visit ] [ Designated as safety issue: No ]

Enrollment: 18
Study Completion Date: December 2007
Arms Assigned Interventions
Experimental: 1
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
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.
Other Name: ATV
Drug: Rifampin
From Days 1 to 27, participants will receive a 600 mg tablet orally daily.
Other Name: RIF
Drug: Ritonavir
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.
Other Name: RTV

Detailed Description:

TB is common in resource-limited countries, and people infected with HIV are especially at risk for TB infection. The antituberculous drug RIF lowers plasma concentrations of PIs by increasing the activity of enzymes responsible for PI breakdown. RIF has been shown to reduce PI effectiveness, a particular concern for HIV infected patients who are also being treated for TB. RTV has been shown to delay the plasma clearance of ATV and increase the plasma half-life of ATV. This study will evaluate the safety, tolerability, and pharmacokinetic (PK) interactions of RTV-boosted ATV, taken concurrently with RIF in HIV uninfected people.

Medical and medication history, a complete physical exam, blood collection, and an electrocardiogram (ECG) will occur at screening. Participants will be enrolled in this study for 41 to 58 days; there will be 3 dosing periods. 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. Study visits will occur at entry; at Days 5, 8, 11, 14, 19, 23, and 27; and at an additional visit between Days 41 and 48. Blood and urine collection will occur at all visits. A targeted physical exam, an ECG, and blood collection for PK analysis will occur at Days 8, 19, and 27.

  Eligibility

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

Note: As of 11/27/06, enrollment into Version 1.0 of the study is now closed. Any new study participants will enroll under Version 2.0.

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00096850

Locations
United States, California
Stanford CRS
Palo Alto, California, United States, 94305-5107
United States, Ohio
The Ohio State Univ. AIDS CRS
Columbus, Ohio, United States, 43210
United States, Tennessee
Vanderbilt Therapeutics CRS
Nashville, Tennessee, United States, 37203
Sponsors and Collaborators
AIDS Clinical Trials Group
Investigators
Study Chair: David W. Haas, MD Infectious Diseases, Vanderbilt University Medical Center
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00096850     History of Changes
Other Study ID Numbers: A5213, 10021, ACTG A5213
Study First Received: November 16, 2004
Last Updated: May 17, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
HIV Seronegativity
Antitubercular agents

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Tuberculosis
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Antitubercular Agents
Rifampin
Ritonavir
Atazanavir
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antibiotics, Antitubercular
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Leprostatic Agents
Nucleic Acid Synthesis Inhibitors
HIV Protease Inhibitors

ClinicalTrials.gov processed this record on April 22, 2014