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

October 28, 2021 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

18

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Palo Alto, California, United States, 94305-5107
        • Stanford CRS
    • Ohio
      • Columbus, Ohio, United States, 43210
        • The Ohio State Univ. AIDS CRS
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Vanderbilt Therapeutics CRS

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Pharmacokinetic parameters of ritonavir (RTV)-boosted ATV when administered concurrently with RIF
Time Frame: Throughout study
Throughout study
Safety and tolerability of RTV-boosted ATV when coadministered with RIF
Time Frame: Throughout study
Throughout study

Secondary Outcome Measures

Outcome Measure
Time Frame
Pharmacokinetics of RIF
Time Frame: Throughout study
Throughout study
Copy number of cellular drug transporter RNA in peripheral blood mononuclear cells (PBMCs)
Time Frame: Throughout study
Throughout study
UDP-glucuronosyltransferase (UGT)-1A1 genotype
Time Frame: At study entry
At study entry
Serum bilirubin concentration
Time Frame: Throughout study
Throughout study
urine thromboxane and prostacyclin concentrations
Time Frame: At study entry and first PK visit
At study entry and first PK visit

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborators

AIDS Clinical Trials Group

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Completion (Actual)

December 1, 2007

Study Registration Dates

First Submitted

November 16, 2004

First Submitted That Met QC Criteria

November 16, 2004

First Posted (Estimate)

November 17, 2004

Study Record Updates

Last Update Posted (Actual)

November 1, 2021

Last Update Submitted That Met QC Criteria

October 28, 2021

Last Verified

October 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • A5213
  • 10021 (Other Identifier: CTEP)
  • ACTG A5213

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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