Safety, Tolerability, and Blood Levels of Ritonavir-Boosted Atazanavir and Rifampin When Taken Together in HIV Uninfected Adults
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Purpose
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 | Intervention |
|---|---|
|
HIV Infections Tuberculosis |
Drug: Atazanavir Drug: Rifampin Drug: Ritonavir |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Safety, Tolerability, and Pharmacokinetic Interactions of Atazanavir and Rifampin in Healthy Volunteers |
- 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 ]
- 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 ]
| Enrollment: | 18 |
| Study Completion Date: | December 2007 |
| Arms | Assigned Interventions |
|---|---|
|
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 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
|
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.
Eligibility| Ages Eligible for Study: | 18 Years to 55 Years |
| Genders Eligible for Study: | Both |
| 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| United States, California | |
| Stanford CRS | |
| Palo Alto, California, United States, 94305-5107 | |
| United States, Ohio | |
| The Ohio State Univ. AIDS CRS | |
| Columbus, Ohio, United States, 43210 | |
| United States, Tennessee | |
| Vanderbilt Therapeutics CRS | |
| Nashville, Tennessee, United States, 37203 | |
| Study Chair: | David W. Haas, MD | Infectious Diseases, Vanderbilt University Medical Center |
More Information
Additional Information:
Publications:
| Responsible Party: | National Institute of Allergy and Infectious Diseases (NIAID) |
| ClinicalTrials.gov Identifier: | NCT00096850 History of Changes |
| Other Study ID Numbers: | A5213, 10021, ACTG A5213 |
| Study First Received: | November 16, 2004 |
| Last Updated: | May 17, 2012 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
|
HIV Seronegativity Antitubercular agents |
Additional relevant MeSH terms:
|
HIV Infections Acquired Immunodeficiency Syndrome Tuberculosis Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases Slow Virus Diseases Mycobacterium Infections Actinomycetales Infections Gram-Positive Bacterial Infections |
Bacterial Infections Antitubercular Agents Rifampin Ritonavir Atazanavir Anti-Bacterial Agents Anti-Infective Agents Therapeutic Uses Pharmacologic Actions Antibiotics, Antitubercular Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Leprostatic Agents Nucleic Acid Synthesis Inhibitors HIV Protease Inhibitors |
ClinicalTrials.gov processed this record on March 03, 2013
