Pharmacokinetics of Apixaban in Nephrotic Syndrome
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 21
- 试验地点
- 1
- 主要终点
- Area under the concentration versus time curve after single dose (AUC) of apixaban
研究概览
简要总结
This study is to investigate the pharmacokinetics and pharmacodynamics of apixaban in nephrotic syndrome.
详细描述
Nephrotic syndrome (NS) is characterized by proteinuria and hypoalbuminemia, and patients with nephrotic syndrome are known to be hypercoaguable with increased incidence of venous thromboembolism necessitating anticoagulation. While classically warfarin has been used as an anticoagulant in NS, newer oral anticoagulants, such as apixaban, are increasingly used to treat venous thromboembolism (VTE) in the general population. It is unknown how hypoalbuminemia and proteinuria affect the pharmacokinetics and pharmacodynamics of apixaban.
This will be a parallel arm, single-dose pilot study of the pharmacokinetics of apixaban in adults with nephrotic syndrome. Goal enrollment of twenty subjects with non-diabetic nephropathy who have nephrotic-range proteinuria, defined as >3.5g/24 hours or UPC >3.5 and ten healthy control subjects without nephrotic syndrome. Each subject will be administered a single dose of apixaban 10 mg. Plasma drug concentration level and plasma anti-Xa activity levels will be measured at 0, 0.5, 1, 3, 4, 6, 8, 24 hours after drug administration in order to determine the maximum plasma concentration of apixaban, area under the curve, and half-life of apixaban in the setting of hypoalbuminemia and proteinuria due to nephrotic syndrome. Apixaban levels will be measured via liquid-chromatography spectrometry mass. Additionally, thrombin generation will be measured at 0, 3, 6, and 24 hours.
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 79 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Study subjects:
- •Between 18 and 79 years old
- •Confirmed diagnosis of Nephrotic Syndrome, with at least one of the following:
- •Nephrotic-range proteinuria, defined as >3.5 g/24 hours or UPC >3.5 (confirmed within 1 month prior to scheduled study visit)
- •Hypoalbuminemia, defined as <3 g/dL (confirmed within 1 month prior to scheduled study visit)
- •Control subjects:
- •Between 18 and 79 years old
- •Normal albumin levels (≥3.5 mg/dL)
- •No proteinuria (UPC <0.15)
- •Exclusion criteria:
- •Age <18 or ≥ 80 years old
- •SCr ≥ 1.5 AND weight ≤ 60kg (these subjects would receive a reduce dose of apixaban, per drug labeling)
- •On dialysis
- •Baseline prolonged PT/INR, PTT (as defined by greater than the upper limit of normal)
- •INR will be used as the primary lab value to evaluate bleeding risk (e.g. a patient presenting with an INR within normal limits, but prolonged PT or PTT, will not meet this exclusion criterion and will still be eligible for the study)
- •Reference Ranges
- •INR: >1.4
- •PT: >13.3 sec
- •aPTT: >37.7 sec
- •Platelets <100
- •History of GI bleed
- •History of intracranial bleed
- •History of stroke
- •Use of (but not limited to) the following medications within the past 14 days:
- •Inducers of CYP3A4 (e.g. rifampin, carbamazepine, phenytoin, St. John's wort, etc.)
- •Strong inhibitors of CYP3A4 (e.g. ketoconazole, ritonavir, clarithromycin, etc.)
- •Antiplatelet and/ or anticoagulant agents: heparin, aspirin* (see below), clopidogrel, prasugrel, NSAIDs, warfarin, rivaroxaban, dabigatran, edoxaban
- •Selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitors (SNRI)
- •Pregnancy/breastfeeding
- •Liver disease with impaired synthetic function (INR >1.4, total bilirubin >1.2)
- •Congestive heart failure
- •Special consideration for patients on aspirin: for patients on chronic low-dose aspirin therapy, we will allow a 7 day wash out period. This will only be allowed for patients who are taking aspirin as primary prophylaxis or for unclear indications. Patients who are on aspirin therapy for following indications will be excluded: primary prophylaxis of stroke due to atrial fibrillation, secondary prevention of stroke or myocardial infarction, history of coronary artery disease or peripheral vascular disease. For patients who meet the potential criteria for the 7-day wash out, their medical history will be reviewed by one of the clinician investigators to ensure that it is safe and appropriate to hold the agent.
- •Those subjects taking aspirin for the following reasons will be excluded:
- •Primary stroke prevention from atrial fibrillation
- •Secondary prevention due to prior stroke, heart attack or cardiac stent
- •Existing heart disease or peripheral vascular disease.
排除标准
- 未提供
研究组 & 干预措施
Nephrotic syndrome
Subjects with nephrotic syndrome will receive a single dose of apixaban 10 mg and will subsequently have blood drawn at 0, 0.5, 1, 3, 4, 6, 8, 24 hours after drug administration.
干预措施: apixaban (Drug)
Non-nephrotic syndrome
Subjects without nephrotic syndrome will receive a single dose of apixaban 10 mg and will subsequently have blood drawn at 0, 0.5, 1, 3, 4, 6, 8, 24 hours after drug administration.
干预措施: apixaban (Drug)
结局指标
主要结局
Area under the concentration versus time curve after single dose (AUC) of apixaban
时间窗: Predose; 0.5, 1, 3, 4, 6, and 8 hours (hr) postdose on Day 1; 24 hours postdose on Day 2
次要结局
- Apparent oral clearance (CL/F)(Predose; 0.5, 1, 3, 4, 6, and 8 hours postdose on Day 1; 24 hours postdose on Day 2)
- Mean terminal phase plasma half-life (t½)(Predose; 0.5, 1, 3, 4, 6, and 8 hours postdose on Day 1; 24 hours postdose on Day 2)
- Maximum observed drug concentration in plasma after single dose administration (Cmax)(Predose; 0.5, 1, 3, 4, 6, and 8 hours postdose on Day 1; 24 hours postdose on Day 2)
- Thrombin Generation Assay(Predose; 3 and 6 hours postdose on Day 1; 24 hours postdose on Day 2)
- Anti-Xa activity(Predose; 0.5, 1, 3, 4, 6, and 8 hours postdose on Day 1; 24 hours postdose on Day 2)