Back to resultsSafety, Tolerability, and Blood Levels of Ritonavir-Boosted Atazanavir and Rifampin When Taken Together in HIV Uninfected Adults
Primary Purpose
HIV Infections, Tuberculosis
Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Atazanavir
Rifampin
Ritonavir
Sponsored by
About this trial
This is an interventional treatment trial for HIV Infections focused on measuring HIV Seronegativity, Antitubercular agents
Eligibility 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
Sites / Locations
- Stanford CRS
- The Ohio State Univ. AIDS CRS
- Vanderbilt Therapeutics CRS
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
1
Arm Description
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.
Outcomes
Primary Outcome Measures
Pharmacokinetic parameters of ritonavir (RTV)-boosted ATV when administered concurrently with RIF
Safety and tolerability of RTV-boosted ATV when coadministered with RIF
Secondary Outcome Measures
Pharmacokinetics of RIF
Copy number of cellular drug transporter RNA in peripheral blood mononuclear cells (PBMCs)
UDP-glucuronosyltransferase (UGT)-1A1 genotype
Serum bilirubin concentration
urine thromboxane and prostacyclin concentrations
Full Information
NCT ID
NCT00096850
First Posted
November 16, 2004
Last Updated
October 28, 2021
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
AIDS Clinical Trials Group
1. Study Identification
Unique Protocol Identification Number
NCT00096850
Brief Title
Safety, Tolerability, and Blood Levels of Ritonavir-Boosted Atazanavir and Rifampin When Taken Together in HIV Uninfected Adults
Official Title
Safety, Tolerability, and Pharmacokinetic Interactions of Atazanavir and Rifampin in Healthy Volunteers
Study Type
Interventional
2. Study Status
Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
undefined (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
December 2007 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
AIDS Clinical Trials Group
4. Oversight
5. Study Description
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections, Tuberculosis
Keywords
HIV Seronegativity, Antitubercular agents
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
18 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Atazanavir
Other Intervention Name(s)
ATV
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Rifampin
Other Intervention Name(s)
RIF
Intervention Description
From Days 1 to 27, participants will receive a 600 mg tablet orally daily.
Intervention Type
Drug
Intervention Name(s)
Ritonavir
Other Intervention Name(s)
RTV
Intervention Description
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.
Primary Outcome Measure Information:
Title
Pharmacokinetic parameters of ritonavir (RTV)-boosted ATV when administered concurrently with RIF
Time Frame
Throughout study
Title
Safety and tolerability of RTV-boosted ATV when coadministered with RIF
Time Frame
Throughout study
Secondary Outcome Measure Information:
Title
Pharmacokinetics of RIF
Time Frame
Throughout study
Title
Copy number of cellular drug transporter RNA in peripheral blood mononuclear cells (PBMCs)
Time Frame
Throughout study
Title
UDP-glucuronosyltransferase (UGT)-1A1 genotype
Time Frame
At study entry
Title
Serum bilirubin concentration
Time Frame
Throughout study
Title
urine thromboxane and prostacyclin concentrations
Time Frame
At study entry and first PK visit
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David W. Haas, MD
Organizational Affiliation
Infectious Diseases, Vanderbilt University Medical Center
Official's Role
Study Chair
Facility Information:
Facility Name
Stanford CRS
City
Palo Alto
State/Province
California
ZIP/Postal Code
94305-5107
Country
United States
Facility Name
The Ohio State Univ. AIDS CRS
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Vanderbilt Therapeutics CRS
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
11996607
Citation
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.
Results Reference
background
PubMed Identifier
16158886
Citation
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.
Results Reference
background
PubMed Identifier
16082056
Citation
Kashuba AD. Drug-drug interactions and the pharmacotherapy of HIV infection. Top HIV Med. 2005 Jun-Jul;13(2):64-9.
Results Reference
background
PubMed Identifier
15287232
Citation
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. Erratum In: Am J Health Syst Pharm. 2004 Nov 1;61(21):2243.
Results Reference
background
PubMed Identifier
15353575
Citation
Orrick JJ, Steinhart CR. Atazanavir. Ann Pharmacother. 2004 Oct;38(10):1664-74. doi: 10.1345/aph.1D394. Epub 2004 Sep 7.
Results Reference
background
PubMed Identifier
17576825
Citation
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.
Results Reference
result
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Safety, Tolerability, and Blood Levels of Ritonavir-Boosted Atazanavir and Rifampin When Taken Together in HIV Uninfected Adults
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