Single-Dose Study to Evaluate the Pharmacokinetics, Pharmacodynamics, and Safety of Apixaban in Subjects on Hemodialysis
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 18
- 主要终点
- Geometric Mean of Maximum Observed Plasma Concentration (Cmax) of Metabolite BMS-730823
研究概览
简要总结
The purpose of this study is to assess the pharmacokinetics of a single oral dose of 5 mg Apixaban in subjects with normal renal function and subjects with end stage renal disease (ESRD) maintained with hemodialysis.
详细描述
Primary Purpose : To provide a clear understanding of the pharmacokinetics of Apixaban in subjects with ESRD and to determine the effect of hemodialysis on Apixaban pharmacokinetics .
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •The signed informed consent form.
- •Subjects with normal renal function classified based on calculated creatinine clearance (CLCr) determined by the cockcroft-gault calculation.
- •Eligible subjects with ESRD that is maintained with chronic and stable hemodialysis.
排除标准
- •Any history of abnormal bleeding or coagulation disorders including those in a first degree relative under 50 years of age.
- •History of significant head injury within the last two years.
- •Any gastrointestinal surgery that could impact the absorption of study drug.
- •Not expected to continue the hemodialysis treatment for the duration of the study.
- •INR, PT, or aPTT above the upper limit of normal, unless agreed upon between the investigator and BMS medical monitor.
- •History of allergy to Apixaban or Factor Xa inhibitors.
研究组 & 干预措施
Group B: Apixaban
干预措施: Apixaban (Drug)
Group A: Apixaban
干预措施: Apixaban (Drug)
结局指标
主要结局
Geometric Mean of Maximum Observed Plasma Concentration (Cmax) of Metabolite BMS-730823
时间窗: From 24 hours pre-dose to 72 hours post-dose
Maximum observed plasma concentration (Cmax) was measured by plasma concentration of BMS-730823 over time. The geometric means are reported in nanograms per milliliter (ng/mL).
Geometric Mean of Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinite Time (AUC(INF)) of Single 5mg Oral Dose of Apixaban
时间窗: From 24 hours pre-dose to 72 hours post-dose
The area under the concentration-time curve from time zero extrapolated to infinite time (AUC(INF)) was measured by plasma concentration of apixaban over time. The geometric means are reported in nanogram hours per milliliter (ng\*h/mL).
Geometric Mean of Area Under the Plasma Concentration-Time Curve From 2 to 6 Hours (AUC(2-6)) for Apixaban
时间窗: 2 to 6 hours post-dose
Area under the plasma concentration-time curve from 2 hours to 6 hours (AUC(2-6) for Apixaban was measured in participants with ESRD during dialysis in Period 1 only. Geometric Means were reported in nanogram hours per milliliter (ng\*hr/mL) and were determined from blood samples both entering and exiting the dialyzer.
Mean Hemodialysis Clearance (CLD) of BMS-730823
时间窗: 2 to 6 hours post-dose
Hemodialysis clearance (CLD) was calculated by dividing the cumulative amount of BMS-730823 excreted in dialysate by the respective cumulative plasma AUC over the same dialysate collection interval (AUC(2-6) entering). CLD measurements occurred only in period 1. Geometric means were reported in milliliters per minute (mL/min).
Percentage of BMS-730823 Extracted During Hemodialysis
时间窗: 2 to 6 hours post-dose
The percentage of BMS-730823 extracted during hemodialysis (extraction ratio) was calculated using the formula \[plasma AUC(2-6)exiting - AUC(2-6)entering\] / \[AUC(2-6) entering\] and converted to a percentage. The extraction ratio was measured in period 1 only, and was reported as a percentage.
Geometric Mean of Maximum Observed Plasma Concentration (Cmax) of Single 5mg Oral Dose of Apixaban
时间窗: 24 hours pre-dose to 72 hours post-dose
Maximum observed plasma concentration (Cmax) was measured by plasma concentration of apixaban over time. The geometric means are reported in nanograms per milliliter (ng/mL).
Median Time of Maximum Observed Plasma Concentration (Tmax) of a Single 5 mg Oral Dose of Apixaban
时间窗: From 24 hours pre-dose to 72 hours post-dose
Time of maximum observed plasma concentration (Tmax) for apixaban was derived from plasma concentrations versus time data. Medians were reported in hours.
Geometric Mean of Area Under the Plasma Concentration-Time Curve From 2 to 6 Hours (AUC(2-6)) for BMS-730823
时间窗: 2 to 6 hours post-dose
Area under the plasma concentration-time curve from 2 hours to 6 hours (AUC(2-6) for BMS-730823 was measured in participants with ESRD during dialysis in Period 1 only. Geometric Means were reported in nanogram hours per milliliter (ng\*hr/mL) and were determined from blood samples both entering and exiting the dialyzer.
Mean Renal Clearance (CLR) of BMS-730823
时间窗: 24 hours pre-dose to 72 hours post-dose
Renal clearance (CLR) was calculated by dividing the cumulative amount of BMS-730823 excreted in urine by the respective cumulative plasma AUC over the same urine collection interval. Geometric means were reported in milliliters per minute (mL/min).
Geometric Mean of Area Under the Concentration-time Curve From Time Zero to Time of the Last Quantifiable Concentration (AUC(0-T)) of Single 5mg Oral Dose of Apixaban
时间窗: 24 hours pre-dose to 72 hours post-dose
Area under the concentration-time curve from time zero to time of the last quantifiable concentration (AUC(0-T)) was measured by plasma concentration of apixaban over time. The geometric means are reported in nanogram hours per milliliter (ng\*h/mL).
Median Time of Maximum Observed Plasma Concentration (Tmax) of Metabolite BMS-730823
时间窗: From 24 hours pre-dose to 72 hours post-dose
Time of maximum observed plasma concentration (Tmax) for BMS-730823 was derived from plasma concentrations versus time data. Medians were reported in hours.
Mean Percent Dose of Apixaban Recovered in Urine (%UR)
时间窗: 24 hours pre-dose to 72 hours post-dose
The percent dose recovered in urine was calculated by dividing the cumulative amount of unchanged apixaban excreted in urine from the time of dose up to 72 hours post-dose by the apixaban dose administered.
Mean Percent Dose of Apixaban Recovered in Dialysate (%DR)
时间窗: 2 to 6 hours post-dose
Percent dose of Apixaban recovered in dialysate (%DR) was calculated by dividing the cumulative amount of apixaban excreted in each dialysate collection over 2-6 hours (DR(2-6)) by the apixaban dose. %DR was recorded only in period 1.
Geometric Mean of Area Under the Concentration-time Curve From Time Zero to Time of the Last Quantifiable Concentration (AUC(0-T)) of Metabolite BMS-730823
时间窗: From 24 hours pre-dose to 72 hours post-dose
Area under the concentration-time curve from time zero to time of the last quantifiable concentration (AUC(0-T)) was measured by plasma concentration of BMS-730823 over time. The geometric means are reported in nanogram hours per milliliter (ng\*h/mL).
Geometric Mean of Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinite Time (AUC(INF)) of BMS-730823
时间窗: 24 hours pre-dose to 72 hours post-dose
The area under the concentration-time curve from time zero extrapolated to infinite time (AUC(INF)) was measured by plasma concentration of BMS-730823 over time. The geometric means are reported in nanogram hours per milliliter (ng\*h/mL).
Mean Plasma Terminal Half-life (T-Half) of Single 5mg Oral Dose of Apixaban
时间窗: From 24 hours pre-dose to 72 hours post-dose
Plasma terminal half-life (T-Half) for apixaban was derived from plasma concentrations versus time data. Means were reported in hours.
Mean Plasma Terminal Half-life (T-Half) of BMS-730823
时间窗: 24 hours pre-dose to 72 hours post-dose
Mean plasma terminal half-life (T-Half) for BMS-730823 was derived from plasma concentrations versus time data.
Mean Renal Clearance (CLR) of Apixaban
时间窗: 24 hours pre-dose to 72 hours post-dose
Renal clearance (CLR) was calculated by dividing the cumulative amount of apixaban excreted in urine by the respective cumulative plasma AUC over the same urine collection interval. Geometric means were reported in milliliters per minute (mL/min).
Mean Hemodialysis Clearance (CLD) of Apixaban
时间窗: 2 to 6 hours post-dose
Hemodialysis clearance (CLD) was calculated by dividing the cumulative amount of apixaban excreted in dialysate by the respective cumulative plasma AUC over the same dialysate collection interval (AUC(2-6) entering). CLD measurements occurred only in period 1. Geometric means were reported in milliliters per minute (mL/min).
Percentage of Apixaban Extracted During Hemodialysis
时间窗: 2 to 6 hours post-dose
The percentage of apixaban extracted during hemodialysis (extraction ratio) was calculated using the formula \[plasma AUC(2-6) exiting - AUC(2-6) entering\] / \[AUC(2-6) entering\] and converted to a percentage. The extraction ratio was measured in period 1 only, and was reported as a percentage.
次要结局
- Mean Maximum Percent Change From Baseline International Normalized Ratio (INR) Following a Single 5 mg Oral Dose of Apixaban(From 24 hours pre-dose to 72 hours post-dose)
- Mean Maximum Percent Change From Baseline Activated Partial Thromboplastin Time (aPTT) Following a Single Oral Dose of 5 mg Apixaban(From 24 hours pre-dose to 72 hours post-dose)
- Mean Maximum Percent Change From Baseline Prothrombin Time (PT) Following a Single 5 mg Oral Dose of Apixaban(From 24 hours pre-dose to 72 hours post-dose)
- Mean Peak Anti-FXa Activity Following a Single Oral Dose of 5 mg Apixaban(From 24 hours pre-dose to 72 hours post-dose)