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

November 16, 2004
May 17, 2012
Not Provided
Not Provided
  • 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 ]
  • Pharmacokinetic parameters of ATV when administered concurrently with RIF
  • safety and tolerability of ATV when coadministered with RIF
Complete list of historical versions of study NCT00096850 on ClinicalTrials.gov Archive Site
  • 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 ]
Not Provided
Not Provided
Not Provided
 
Safety, Tolerability, and Blood Levels of Ritonavir-Boosted Atazanavir and Rifampin When Taken Together in HIV Uninfected Adults
Safety, Tolerability, and Pharmacokinetic Interactions of Atazanavir and Rifampin in Healthy Volunteers

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.

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.

Interventional
Not Provided
Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • HIV Infections
  • Tuberculosis
  • 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
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.
Interventions:
  • Drug: Atazanavir
  • Drug: Rifampin
  • Drug: Ritonavir

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
18
December 2007
Not Provided

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
Both
18 Years to 55 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00096850
A5213, 10021, ACTG A5213
Not Provided
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Allergy and Infectious Diseases (NIAID)
AIDS Clinical Trials Group
Study Chair: David W. Haas, MD Infectious Diseases, Vanderbilt University Medical Center
National Institute of Allergy and Infectious Diseases (NIAID)
May 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP