Safety, Tolerability, and Pharmacokinetic Interactions of Atazanavir and Rifampin in Healthy Volunteers
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 18
- 试验地点
- 3
- 主要终点
- Safety and tolerability of RTV-boosted ATV when coadministered with RIF
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Atazanavir (Drug)
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.
干预措施: Rifampin (Drug)
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.
干预措施: Ritonavir (Drug)
结局指标
主要结局
Safety and tolerability of RTV-boosted ATV when coadministered with RIF
时间窗: Throughout study
Pharmacokinetic parameters of ritonavir (RTV)-boosted ATV when administered concurrently with RIF
时间窗: Throughout study
次要结局
- Pharmacokinetics of RIF(Throughout study)
- Serum bilirubin concentration(Throughout study)
- urine thromboxane and prostacyclin concentrations(At study entry and first PK visit)
- Copy number of cellular drug transporter RNA in peripheral blood mononuclear cells (PBMCs)(Throughout study)
- UDP-glucuronosyltransferase (UGT)-1A1 genotype(At study entry)