Evaluation of the Pharmacokinetics and Safety of ABT-493 and ABT-530 in Subjects With Normal and Impaired Renal Function
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
- 3
- 主要终点
- Number of subjects with adverse events
研究概览
简要总结
This is an open-label, single dose study designed to assess the pharmacokinetics and safety of ABT-493 and ABT-530 in subjects with either normal renal function or impaired renal function.
详细描述
Up to 48 subjects will be selected and enrolled according to the subject selection criteria: 8 subjects with mild renal impairment (Group 1), 8 subjects with moderate renal impairment (Group 2), 8 subjects with severe renal impairment (Group 3), 8 subjects with end stage renal disease that are not yet on dialysis (Group 4), 8 healthy subjects with normal renal function (Group 5), and 8 subjects with end stage renal disease on hemodialysis (Group 6).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •All Subjects
- •Females must have negative results for pregnancy tests performed:
- •At Screening on a urine specimen, and
- •On a serum sample obtained on Study Day -2 (prior to dosing).
- •Body Mass Index (BMI) is ≥ 18 to ≤ 38 kg/m2, inclusive.
- •Body Weight > 50 kg.
- •Subjects with Normal Renal Function
- •In addition to the main inclusion criteria above for all subjects, the following criteria must be met for subjects with normal renal function enrolled in Group 5:
- •Judged to be in general good health based upon the results of a medical history, physical examination, and 12-lead electrocardiogram (ECG).
- •At screening, estimated GFR (by MDRD equation) should be ≥ 90 mL/min/1.73 m
- •Subject with Renal Impairment
- •In addition to the main inclusion criteria for all subjects, the following criteria must be met for all subjects with renal impairment enrolled in Groups 1, 2, 3, 4 and 6:
- •Judged to be in stable condition and acceptable for study participation based upon the results of a medical history, physical examination, laboratory profile and ECG.
- •Presence of chronic renal impairment as indicated by medical history and a screening estimated GFR (by MDRD equation) < 90 mL/min/1.73 m
- •Subjects with ESRD undergoing hemodialysis should have been receiving dialysis for at least 1 month.
排除标准
- •History of significant sensitivity to any drug.
- •Pregnant or breastfeeding female.
- •Recent (6-month) history of drug or alcohol abuse.
- •Positive test result for hepatitis A virus immunoglobulin M (HAV-IgM), hepatitis B surface antigen (HBsAg) or hepatitis C virus antibody (HCV Ab) or HIV antibodies (HIV Ab). Negative HIV status will be confirmed at Screening and the results will be maintained confidentially by the study site.
- •Subjects on strict vegetarian diet.
研究组 & 干预措施
Group 3 - Severe Renal Impairment
Subjects with severe renal impairment. eGFR (by MDRD equation) range 15 - 29 mL/min/1.73 m2 as determined at Screening.
干预措施: ABT-530 (Drug)
Group 1 - Mild Renal Impairment
Subjects with mild renal impairment. eGFR (by MDRD equation) range 60 - 89 mL/min/1.73 m2 as determined at Screening.
干预措施: ABT-493 (Drug)
Group 1 - Mild Renal Impairment
Subjects with mild renal impairment. eGFR (by MDRD equation) range 60 - 89 mL/min/1.73 m2 as determined at Screening.
干预措施: ABT-530 (Drug)
Group 2 - Moderate Renal Impairment
Subjects with moderate renal impairment. eGFR (by MDRD equation) range 30 - 59 mL/min/1.73 m2 as determined at Screening.
干预措施: ABT-493 (Drug)
Group 2 - Moderate Renal Impairment
Subjects with moderate renal impairment. eGFR (by MDRD equation) range 30 - 59 mL/min/1.73 m2 as determined at Screening.
干预措施: ABT-530 (Drug)
Group 3 - Severe Renal Impairment
Subjects with severe renal impairment. eGFR (by MDRD equation) range 15 - 29 mL/min/1.73 m2 as determined at Screening.
干预措施: ABT-493 (Drug)
Group 4 - End Stage Renal Disease, Not Yet on Dialysis
Subjects with end stage renal disease, not yet on dialysis. eGFR (by MDRD equation) range < 15 mL/min/1.73 m2 as determined at Screening.
干预措施: ABT-493 (Drug)
Group 4 - End Stage Renal Disease, Not Yet on Dialysis
Subjects with end stage renal disease, not yet on dialysis. eGFR (by MDRD equation) range < 15 mL/min/1.73 m2 as determined at Screening.
干预措施: ABT-530 (Drug)
Group 5 - Normal Renal Function
Subjects with normal renal function. eGFR (by MDRD equation) range ≥ 90 mL/min/1.73 m2 as determined at Screening.
干预措施: ABT-493 (Drug)
Group 5 - Normal Renal Function
Subjects with normal renal function. eGFR (by MDRD equation) range ≥ 90 mL/min/1.73 m2 as determined at Screening.
干预措施: ABT-530 (Drug)
Group 6 - End Stage Renal Disease, Requiring Dialysis.
Subjects with end stage renal disease, requiring dialysis. eGFR (by MDRD equation) < 15 mL/min/1.73 m2 as determined at Screening.
干预措施: ABT-493 (Drug)
Group 6 - End Stage Renal Disease, Requiring Dialysis.
Subjects with end stage renal disease, requiring dialysis. eGFR (by MDRD equation) < 15 mL/min/1.73 m2 as determined at Screening.
干预措施: ABT-530 (Drug)
结局指标
主要结局
Number of subjects with adverse events
时间窗: Up to 30 days
Total number of subjects with adverse events.
(SUB-STUDY 1) Area under the plasma concentration-time curve (AUC) from time 0 to infinity for the ABT-493 study drug.
时间窗: Prior to dosing (0-hour), 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 hours and 144 hours after dosing on Study Day 1.
The AUC from time 0 to infinity represents the total drug exposure over time.
Overall measurement of safety parameters
时间窗: SUB-STUDY 1 - Duration of 14 days SUB-STUDY 2 - Duration of 16 Days
Measurement of safety parameters include physical examinations, clinical laboratory tests, 12-lead ECGs (electrocardiograms) and vital signs.
Maximum plasma concentration (Cmax) of the ABT-493 study drug.
时间窗: (SUB-STUDY 1) Prior to dosing (0-hour), 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 hours and 144 hours after dosing on Study Day 1. (SUB-STUDY 2) Prior to dosing (0-hour), and at 1, 2, 3, 9, 12, 16, 24 hours after dosing on Study Day 1 of each Period.
The peak concentration that a drug achieves in a specified compartment after the drug has been administrated and before administration of a second dose.
Area under the plasma concentration-time curve (AUC) for the ABT-493 study drug.
时间窗: (SUB-STUDY 1) Prior to dosing (0-hour), 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 hours and 144 hours after dosing on Study Day 1. (SUB-STUDY 2) Prior to dosing (0-hour), and at 1, 2, 3, 9, 12, 16, 24 hours after dosing on Study Day 1 of each Period.
AUC reflects the actual body exposure to drug after administration of a dose of the drug.
(SUB-STUDY 1) Area under the plasma concentration-time curve (AUC) from time 0 to infinity for the ABT-530 study drug.
时间窗: Prior to dosing (0-hour), 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 hours and 144 hours after dosing on Study Day 1.
The AUC from time 0 to infinity represents the total drug exposure over time.
Maximum plasma concentration (Cmax) of the ABT-530 study drug.
时间窗: (SUB-STUDY 1) Prior to dosing (0-hour), 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 hours and 144 hours after dosing on Study Day 1. (SUB-STUDY 2) Prior to dosing (0-hour), 1, 2, 3, 9, 12, 16, 24 hours after dosing on Study Day 1 of each Period.
The peak concentration that a drug achieves in a specified compartment after the drug has been administrated and before administration of a second dose.
Area under the plasma concentration-time curve (AUC) for the ABT-530 study drug.
时间窗: (SUB-STUDY 1) Prior to dosing (0-hour), 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 hours and 144 hours after dosing on Study Day 1. (SUB-STUDY 2) Prior to dosing (0-hour), and at 1, 2, 3, 9, 12, 16, 24 hours after dosing on Study Day 1 of each Period.
AUC reflects the actual body exposure to drug after administration of a dose of the drug.
(SUB-STUDY 2) Area under the plasma concentration-time curve (AUC) during hemodialysis for the ABT-493 study drug.
时间窗: Prior to dosing (0-hour), and at 1, 2, 3, 9, 12, 16, 24 hours after dosing on Study Day 1 of each Period. Additional samples will be collected at 4, 5, and 6 hours after dosing on Study Day 1 of Period 2 only.
The AUC during hemodialysis represents the total drug exposure over time.
(SUB-STUDY 2) Area under the plasma concentration-time curve (AUC) during hemodialysis for the ABT-530 study drug.
时间窗: Prior to dosing (0-hour), and at 1, 2, 3, 9, 12, 16, 24 hours after dosing on Study Day 1 of each Period. Additional samples will be collected at 4, 5 and 6 hours after dosing on Study Day 1 of Period 2 only.
The AUC during hemodialysis represents the total drug exposure over time.
次要结局
未报告次要终点