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

NCT ID: NCT00096850

Last Updated: 2021-11-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

18 participants

Study Classification

INTERVENTIONAL

Study Completion Date

2007-12-31

Brief Summary

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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

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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.

Conditions

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HIV Infections Tuberculosis

Keywords

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HIV Seronegativity Antitubercular agents

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Atazanavir

Intervention Type 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.

Rifampin

Intervention Type DRUG

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

Ritonavir

Intervention Type 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.

Interventions

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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.

Intervention Type DRUG

Rifampin

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

Intervention Type 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.

Intervention Type DRUG

Other Intervention Names

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ATV RIF RTV

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

55 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections

NETWORK

Sponsor Role collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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David W. Haas, MD

Role: STUDY_CHAIR

Infectious Diseases, Vanderbilt University Medical Center

Locations

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Stanford CRS

Palo Alto, California, United States

Site Status

The Ohio State Univ. AIDS CRS

Columbus, Ohio, United States

Site Status

Vanderbilt Therapeutics CRS

Nashville, Tennessee, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 11996607 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16158886 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 16082056 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15287232 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 15353575 (View on PubMed)

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.

Reference Type RESULT
PMID: 17576825 (View on PubMed)

Other Identifiers

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10021

Identifier Type: REGISTRY

Identifier Source: secondary_id

ACTG A5213

Identifier Type: -

Identifier Source: secondary_id

A5213

Identifier Type: -

Identifier Source: org_study_id