NCT04278729已完成1 期
A Prospective Multi-dose Study of Apixaban in Subjects With Nephrotic Syndrome
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- Steady-state Area Under the Plasma Concentration Versus Time Curve From Time Zero to 12 Hours of Apixaban
研究概览
简要总结
This phase I study is a single arm, multi-dose study that will evaluate steady-state apixaban pharmacokinetics (PK) and pharmacodynamics (PD) in subjects with Nephrotic Syndrome (NS) vs healthy control subjects. This study will enroll 20 subjects diagnosed with NS and 10 healthy control subjects. Comparing differences in steady-state apixaban PK/PD parameters between subjects with NS and healthy volunteers will be essential to identifying a safe and effective apixaban dose and dose administration schedule for future randomized controlled trials (RCTs).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 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
- •18-79 years of age
- •Confirmed diagnosis of NS, with at least one of the following (confirmed within 1 month prior to scheduled Day 1 Study Visit):
- •Nephrotic-range proteinuria, defined as >3.0 g/24 hours
- •UPC (ratio of protein to creatinine in random spot urine sample), defined as >3.0
- •Hypoalbuminemia, defined as <3.0 g/dL
- •Control Subjects
- •18-79 years of age
- •Normal albumin levels (>3.0 mg/dL)
- •No history of chronic kidney disease
排除标准
- •Age <18 or ≥80 years old
- •Serum Creatinine (SCr) ≥1.5 AND weight ≤60kg (these subjects would receive a reduced apixaban dose, per drug labeling)
- •Weight >120 kg OR body mass index (BMI) ≥40 kg/m^2
- •Estimated Glomerular Filtration Rate (eGFR) <15 mL/min or on dialysis
- •Signs and symptoms of increased risk of bleeding, including but not limited to: frequent nosebleeds, unexplained or worsening bruising, blood in urine or stool
- •Unwilling to avoid engaging in activities that may increase the risk of bleeding through body injury or bruising, during the study period (e.g., contact sports)
- •Baseline prolonged INR, defined as INR >1.4
- •If INR is elevated, but PT and aPTT are below the upper limit of normal (13.3 sec and 37.7 sec, respectively), then the subject may be cleared to receive the study drug at the discretion of one of the study physicians.
- •Platelets <100 x 109/L
- •History of stroke, or a history of gastrointestinal or intracranial bleeds
- •Use of any prescription medications, over-the-counter (OTC) medications, or herbal products that are strong inhibitors or inducers of CYP3A4 and/or P-gp within 14 days prior to Study Day 1 or anticipated need for such drugs during the study. Examples included:
- •Strong 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, non-steroidal anti-inflammatory drugs (NSAIDs), warfarin, rivaroxaban, dabigatran, edoxaban
- •Pregnancy or breastfeeding
- •Liver disease with impaired synthetic function (INR >1.4, total bilirubin >1.2)
- •Evidence of acute kidney disease by the KDIGO criteria (>1.5 x baseline SCr, or >0.3 mg/dL increase in SCr, over past 48 hours
- •Unwillingness to forgo drinking alcohol during the study period due to heightened bleeding risk.
研究组 & 干预措施
Nephrotic Syndrome Arm
Experimental
Patients diagnosed with Nephrotic syndrome will be in this arm.
干预措施: Apixaban 5 MG (Drug)
Healthy Arm
Experimental
Healthy volunteers will be in this arm.
干预措施: Apixaban 5 MG (Drug)
结局指标
主要结局
Steady-state Area Under the Plasma Concentration Versus Time Curve From Time Zero to 12 Hours of Apixaban
时间窗: Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose approximately on Day 8
Area Under the Curve (AUC (0-12)) is the area under the curve from time 0 to 12 hour after apixaban steady state concentration is reached.
次要结局
- Initial Dose Area Under the Plasma Concentration Versus Time Curve From Time Zero to 12 Hours of Apixaban(Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose)
- Initial dose Elimination of Half-Life of Apixaban(Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose)
- Initial dose Maximum Observed Plasma Concentration of Apixaban(Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose)
- Steady state Elimination of Half-Life of Apixaban(Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose approximately on Day 8)
- Steady-state Maximum Observed Plasma Concentration of Apixaban(Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose approximately on Day 8)
- Steady state Plasma Clearance as a Function of Bioavailability of Apixaban(Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose approximately on Day 8)
- Initial dose Plasma Clearance (CL) as a Function of Bioavailability (F) of Apixaban(Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose)
- Initial Thrombin Generation Assay (TGA)(Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose)
- Steady state Thrombin Generation Assay (TGA)(Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose approximately on Day 8)
- Initial dose Anti-Xa activity(Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose)
- Steady state Anti-Xa activity(Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose approximately on Day 8)
- Initial dose Activated Partial Thromboplastin Time (aPTT)(Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose)
- Steady state Activated Partial Thromboplastin Time (aPTT)(Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose approximately on Day 8)
- Initial dose International Normalised Ratio (INR)(Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose)
- Steady state International Normalised Ratio (INR)(Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose approximately on Day 8)
- Initial dose Prothrombin time (PT)(Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose)
- Steady state Prothrombin time (PT)(Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose approximately on Day 8)
- Total Adverse Events (AE)(From screening to Day 10 after initial study drug administration)
研究者
研究点 (1)
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