The Effect of Efavirenz and Ritonavir-boosted Darunavir on the Pharmacokinetics of the HMG CoA Reductase Inhibitor Pitavastatin
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 34
- 试验地点
- 1
- 主要终点
- AUC
研究概览
简要总结
The main goal of this study is to determine how taking efavirenz affects the levels of pitavastatin in the bloodstream when both drugs are taken together and to see how darunavir with ritonavir affects the levels of pitavastatin in the bloodstream. Secondary goals are to see how taking pitavastatin affects the levels in the blood of efavirenz when both drugs are taken together and to see how taking pitavastatin affects the levels in the blood of darunavir.
详细描述
HIV infected persons are at risk for coronary heart disease due to chronic inflammation associated with the virus itself, the side effects of the antiretroviral (ARV) therapies which can cause elevated cholesterol, and the risk factors such as smoking, high blood pressure and family history of heart disease.
The most commonly prescribed ARVs for treatment of HIV are efavirenz and drugs in the protease inhibitor (PI) class such as darunavir with ritonavir. To treat elevated cholesterol in patients infected with HIV, guidelines recommend the use of statins (a class of lipid lowering drugs). PIs and efavirenz can increase the levels of some statins and reduce the levels of others in the bloodstream. Pitavastatin (Livalo) is a statin approved by the Food and Drug Administration (FDA) for the treatment of high cholesterol.
In order to be able to use pitavastatin safely in HIV-infected patients taking either darunavir with ritonavir or efavirenz, it is important to study how taking pitavastatin with darunavir and ritonavir or pitavastatin with efavirenz affect the levels of each of these drugs in the bloodstream.
Twenty-eight participants will be enrolled in one of two study arms: 14 in Arm A and 14 in Arm B.
Arm A:
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Absence of HIV-1 infection as documented by any licensed ELISA test kit within 21 days prior to study entry.
- •Male or female aged 18-60 years.
- •Able and willing to provide informed consent.
- •All men and women of reproductive potential must practice adequate birth control to prevent pregnancy from start of the study until completion of the study.
- •Women of childbearing potential must have a negative serum or urine pregnancy test within 14 days prior to study entry and day of entry.
- •Hemoglobin > 12.5 g/dL for men; > 11.5 g/dL for women;
- •Absolute neutrophil count >1,500 cells/mm3;
- •Platelet count > 100,000 platelets/mm3;
- •AST (SGOT)/ALT (SGPT) <1.5X ULN;
- •Creatinine <1.5 X ULN
- •Subject is within 20% (+/-) of ideal body weight and must weigh at least 50 kg
排除标准
- •Use of illicit drugs or alcohol which would interfere with the completion of this study.
- •Pregnancy or breast-feeding.
- •History of chronic illnesses such as hypertension, coronary artery disease, arthritis, diabetes, or any chronic gastrointestinal conditions which might interfere with drug absorption.
- •Any medical condition which, in the opinion of the investigator, would interfere with the subjects ability to participate in this protocol.
- •Use of prohibited protocol-specified drugs, prescription or over-the-counter within 14 days prior to study entry.
- •Participation in any investigational drug studies within 30 days prior to study entry.
研究组 & 干预措施
Arm B
Subjects assigned to Arm B will receive pitavastatin 2 mg daily and darunavir 800 mg with ritonavir 100 mg daily.
干预措施: Darunavir (Drug)
Arm A
Subjects assigned to Arm A will receive pitavastatin 2 mg at bedtime and efavirenz 600 mg at bedtime.
干预措施: Pitavastatin (Drug)
Arm A
Subjects assigned to Arm A will receive pitavastatin 2 mg at bedtime and efavirenz 600 mg at bedtime.
干预措施: Efavirenz (Drug)
Arm B
Subjects assigned to Arm B will receive pitavastatin 2 mg daily and darunavir 800 mg with ritonavir 100 mg daily.
干预措施: Pitavastatin (Drug)
Arm B
Subjects assigned to Arm B will receive pitavastatin 2 mg daily and darunavir 800 mg with ritonavir 100 mg daily.
干预措施: Ritonavir (Drug)
结局指标
主要结局
AUC
时间窗: 0 to 24 hours
24-hour area under the curve (AUC) for pitavastatin when coadministered with efavirenz and with darunavir/ritonavir and 24-hour AUC for efavirenz or darunavir when coadministered with pitavastatin
GMR of 24- Hour AUC of Pitavastatin When Coadministered With Efavirenz or With Darunavir/Ritonavir Over 24 Hour AUC of Pitavastatin
时间窗: 0 to 24 hours
Geometric Mean Ratio (GMR) of 24- Hour Area under the plasma drug concentration-time curve (AUC) of pitavastatin when coadministered with efavirenz or with darunavir/ritonavir over 24 Hour (AUC) of pitavastatin
次要结局
- GMR of Cmax of Pitavastatin When Coadministered With Efavirenz or With Darunavir/Ritonavir(Day 18)