An Open-label, Single-dose Study of the Safety, Tolerability, and Pharmacokinetics of AMG 423 in Healthy Subjects and Subjects With Various Degrees of Renal Insufficiency and Effect of Hemodialysis on AMG 423 Pharmacokinetics
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 13
- 试验地点
- 1
- 主要终点
- AMG 423 Pharmacokinetic Parameters
研究概览
简要总结
A phase 1, open-label study in subjects with normal renal function and subjects with various degrees of renal insufficiency, including patients with end-stage renal disease (ESRD) requiring hemodialysis. The primary objective is to evaluate the single-dose PK of AMG 423 in subjects with various degrees of renal insufficiency, including patients with end-stage renal disease requiring hemodialysis.
详细描述
This study was conducted by Amgen as the IND holder, with Cytokinetics as a collaborator. Due to the termination of the collaboration agreement between Amgen and Cytokinetics in May 2021 and subsequent transfer of the omecamtiv mecarbil IND from Amgen to Cytokinetics, Cytokinetics is now listed as the sponsor.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Men or women ≥18 years of age
- •Laboratory test values (clinical chemistry and hematology)within normal limits, (other than test values out of the normal range for subjects with CKD [groups 1 and 3 through 5]), or clinically acceptable to the investigator and sponsor at screening and day -3
- •Free of any clinically significant disease or condition(s) (other than that consistent with CKD for subjects in groups 1 and 3 through 5) that require a physician's care and/or would interfere with the evaluations, procedures, or participation in the study per the investigator's discretion;
排除标准
- •Subjects whose second MDRD eGFR result during the screening period is not within 10% of the first eGFR result
- •Subjects who have received a functioning renal transplant within the past year
- •Subjects with ESRD who do not have a functioning hemodialysis access
- •Subjects with hemodynamic instability during hemodialysis
- •Subjects whose renal insufficiency is due to active autoimmune renal disease
- •Subjects with renal insufficiency or ESRD requiring hemodialysis and Troponin I > upper limit of normal (ULN) at screening or day -3
- •Subjects with history of heart disease or unstable angina within the last 3 months
- •Subjects with uncontrolled diabetes (Hb1Ac > 8%) and/or subjects who are able but unwilling to adhere to the required fasting intervals
研究组 & 干预措施
Group 1
End Stage Renal Diseas (ESRD) requiring hemodialysis
干预措施: AMG 423 (Drug)
Group 2
Normal renal function (eGFR >or = 80mL/min/1.73m^2)
干预措施: AMG 423 (Drug)
Group 3
Mild decrease in GFR (eGFR 60-79 mL/min/1.73m^2)
干预措施: AMG 423 (Drug)
Group 4
Moderate decrease in GFR (eGFR 30-59 mL/min/1.73m^2)
干预措施: AMG 423 (Drug)
Group 5
Severe decrease in GFR (eGFR 15-29 mL/min/1.73m^2)
干预措施: AMG 423 (Drug)
Group 6
Normal renal function (eGFR >or = 80mL/min/1.73m^2)
干预措施: AMG 423 (Drug)
结局指标
主要结局
AMG 423 Pharmacokinetic Parameters
时间窗: Twenty time points, up to eight days
Part A and Part B: Total AMG 423 pharmacokinetic parameters including area under the plasma concentration time curve (AUC) from time 0 to the time of the last quantifiable sample (AUC0-t) and maximum observed plasma concentration after dosing (Cmax).
次要结局
- Other Total AMG 423 PK Parameters(Twenty time points, up to eight days)
- AMG 423 Dialysis Clearance(Hours 4, 5, 6, 7 & 8 post-dose)
- AMG 423 Metabolites(Twenty time points, up to eight days)
- Safety(Up to 46 days, including a 28 day screening period)