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

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00096850
• Collaborator: AIDS Clinical Trials Group (Other)
• Enrollment: 18
• Locations: 3
• Arm: 1
• Patients Per Site: 6

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections; Tuberculosis	Drug: Atazanavir; Drug: Rifampin; Drug: Ritonavir	N/A

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 18 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Safety, Tolerability, and Pharmacokinetic Interactions of Atazanavir and Rifampin in Healthy Volunteers
• Actual Study Completion Date: Dec 1, 2007

Arms and Interventions

Arm

Intervention/Treatment

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 Names: ATV ; Drug: Rifampin; From Days 1 to 27, participants will receive a 600 mg tablet orally daily.; Other Names: 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 Names: RTV

Outcome Measures

Primary Outcome Measures

1. Pharmacokinetic parameters of ritonavir (RTV)-boosted ATV when administered concurrently with RIF [Throughout study]

2. Safety and tolerability of RTV-boosted ATV when coadministered with RIF [Throughout study]

Secondary Outcome Measures

1. Pharmacokinetics of RIF [Throughout study]

2. Copy number of cellular drug transporter RNA in peripheral blood mononuclear cells (PBMCs) [Throughout study]

3. UDP-glucuronosyltransferase (UGT)-1A1 genotype [At study entry]

4. Serum bilirubin concentration [Throughout study]

5. urine thromboxane and prostacyclin concentrations [At study entry and first PK visit]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Locations

	Site	City	State	Country	Postal Code
1	Stanford CRS	Palo Alto	California	United States	94305-5107
2	The Ohio State Univ. AIDS CRS	Columbus	Ohio	United States	43210
3	Vanderbilt Therapeutics CRS	Nashville	Tennessee	United States	37203

Sponsors and Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID)
• AIDS Clinical Trials Group

Investigators

• Study Chair: David W. Haas, MD, Infectious Diseases, Vanderbilt University Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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. Review.
• 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. Review.
• Kashuba AD. Drug-drug interactions and the pharmacotherapy of HIV infection. Top HIV Med. 2005 Jun-Jul;13(2):64-9. Review.
• 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. Review. Erratum in: Am J Health Syst Pharm. 2004 Nov 1;61(21):2243.
• Orrick JJ, Steinhart CR. Atazanavir. Ann Pharmacother. 2004 Oct;38(10):1664-74. Epub 2004 Sep 7. Review.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT00096850
• Other Study ID Numbers: A5213; 10021; ACTG A5213
• First Posted: Nov 17, 2004
• Last Update Posted: Nov 1, 2021
• Last Verified: Oct 1, 2021

• Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID): HIV Seronegativity; Antitubercular agents
• Additional relevant MeSH terms: Tuberculosis; Ritonavir; Atazanavir Sulfate; Rifampin

Study Results

No Results Posted as of Nov 1, 2021