Single-Dose Pharmacokinetics of BMS-790052 in Subjects With Hepatic Impairment Compared to Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 46
- 试验地点
- 2
- 主要终点
- Maximum Observed Plasma Concentration (Cmax) of BMS-790052
研究概览
简要总结
The purpose of this study is to assess the effects of hepatic impairment on the single dose pharmacokinetics of BMS-790052.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male and female subjects aged 18 to 70 years, with hepatic impairment conforming to Child-Pugh class A, B or C
- •Healthy subjects to the extent possible matched to the first four hepatically impaired subject in each Child-Pugh class with regard to age (approximately ± 10 years), body weight (approximately ± 20%) and gender
排除标准
- •History of esophageal and gastric variceal bleeding within past 6 months
- •Primarily cholestatic liver diseases
- •Active alcoholic hepatitis
- •Stable encephalopathy of >= Stage 2
- •Presence of severe ascites or edema
- •Presence of hepatopulmonary or hepatorenal syndrome
- •Positive for HCV, unless HCV RNA is undetectable
研究组 & 干预措施
BMS-790052 in Child-Pugh A
干预措施: BMS-790052 (Drug)
BMS-790052 in Child-Pugh B
干预措施: BMS-790052 (Drug)
BMS-790052 in Child-Pugh C
干预措施: BMS-790052 (Drug)
BMS-790052 in Healthy Subjects
干预措施: BMS-790052 (Drug)
结局指标
主要结局
Maximum Observed Plasma Concentration (Cmax) of BMS-790052
时间窗: Pre-dose (0), 0.5,1, 1.5, 2, 4, 8, 12, 24, 48, 72 hours post-dose (both healthy and hepatically impaired participants) and 96 hours post-dose (only for hepatically impaired participants)
Maximum observed plasma concentration following drug administration from the raw plasma concentration-time data. The plasma samples were analysed for BMS-790052 by using a validated liquid chromatography tandem mass spectrometric (LC-MS/MS) assay.
Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Last Measurable Concentration [AUC(0-T)] of BMS-790052
时间窗: Pre-dose (0), 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72 hours post-dose (both healthy and hepatically impaired participants) and 96 hours post-dose (only for hepatically impaired participants)
AUC(0-T) was calculated by the sum of linear trapezoids using non-compartmental analysis.
Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinite Time [AUC(INF)] of BMS-790052
时间窗: Pre-dose (0), 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72 hours post-dose (both healthy and hepatically impaired participants) and 96 hours post-dose (only for hepatically impaired participants)
AUC(INF) was estimated as AUC(0-T) + Ct/λ z, where λ z was the terminal elimination rate constant and Ct was the last observable concentration.
Time to Reach Maximum Observed Plasma Concentration (Tmax) of BMS-790052
时间窗: Pre-dose (0), 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72 hours post-dose (both healthy and hepatically impaired participants) and 96 hours post-dose (only for hepatically impaired participants)
Tmax was defined as the time required to reach maximum observed plasma concentration. Tmax was directly determined from the raw plasma concentration-time data.
Terminal Half-life (T-HALF) of BMS-790052
时间窗: Pre-dose (0), 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72 hours post-dose (both healthy and hepatically impaired participants) and 96 hours post-dose (only for hepatically impaired participants)
Terminal half-life was the time required for one half of the total amount of administered drug eliminated from the body.
Apparent Total Body Clearance (CLT/F) of BMS-790052
时间窗: Pre-dose (0), 0.5,1, 1.5, 2, 4, 8, 12, 24, 48, 72 hours post-dose (both healthy and hepatically impaired participants) and 96 hours post-dose (only for hepatically impaired participants)
Apparent total body clearance was calculated as dose/AUC(INF). AUC(INF) was estimated as AUC(0-T) + Ct/λ z, where λ z was the terminal elimination rate constant and Ct was the last observable concentration.
Apparent Clearance of Free BMS-790052 (CLu/F)
时间窗: Pre-dose (0), 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72 hours post-dose (both healthy and hepatically impaired participants) and 96 hours post-dose (only for hepatically impaired participants)
CLu/F was calculated by dividing the apparent total body clearance (CLT/F) by mean fraction of unbound drug (fu) for both (1 hour and 4 hour post dose) time points combined. Apparent total body clearance was calculated as dose/AUC(INF). AUC(INF) was estimated as AUC(0-T) + Ct/ λz, where λz was the terminal elimination rate constant and Ct was the last observable concentration.
The Apparent Volume of Distribution at Steady State (Vss/F)
时间窗: Pre-dose (0), 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72 hours post-dose (both healthy and hepatically impaired participants) and 96 hours post-dose (only for hepatically impaired participants)
Apparent volume of distribution was calculated by dividing the product of the dose and mean residence time (MRT) by AUC(INF). AUC(INF) was estimated as AUC(0-T) + Ct/λ z, where λ z was the terminal elimination rate constant and Ct was the last observable concentration.
次要结局
- Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), and Who Died(Day 1 to end of study for AEs and, Day 1 to up to 30 days after last dose for SAE.)