A Double-blind, Randomized, Placebo-controlled, Pharmacokinetic, Safety and Tolerability Study of CSL112 in Adult Subjects With Moderate Renal Impairment and in Healthy Adult Subjects With Normal Renal Function
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- CSL Behring
- 入组人数
- 32
- 试验地点
- 4
- 主要终点
- Plasma apoA-I and PC Tmax
研究概览
简要总结
This is a phase 1 multicenter, randomized, double-blind, placebo-controlled, ascending dose study to investigate the pharmacokinetics (PK), safety, and tolerability of CSL112 in adult subjects with moderate renal impairment and in healthy adult subjects with normal renal function.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men or women aged 18 to 85 years (inclusive) of age, with body weight 50 kg or more.
- •Subjects with renal impairment (RI) must have stable chronic moderate RI (estimated glomerular filtration rate [eGFR] ≥ 30 and < 60 mL/min/1.73 m2)
- •Healthy subjects must have normal renal function (eGFR ≥ 90 mL/min/1.73 m2)
排除标准
- •Evidence of a clinically significant medical condition, disorder or disease
- •Evidence of hepatobiliary disease
- •Any clinically relevant abnormal laboratory test result
- •Known history of allergies, hypersensitivity or deficiencies to CSL112 or any of its components
- •Other severe comorbid condition, concurrent medication, or other issue that renders the subject unsuitable for participation in the study, including: history of cancer, low platelet count, bleeding disorder or coagulopathy, significantly altered electrocardiogram waveform, unstable glycemia control in subjects with diabetes, acute renal failure, recent donation or loss of blood
- •Evidence or history of alcohol or substance abuse
研究组 & 干预措施
Low
A low dose of either CSL112 or placebo is to be administered as a single intravenous (IV) infusion. The placebo will be administered at the same frequency, volume and duration as the CSL112 infusion.
干预措施: Placebo (Other)
High
A high dose of either CSL112 or placebo is to be administered as a single intravenous (IV) infusion. The placebo will be administered at the same frequency, volume and duration as the CSL112 infusion.
干预措施: Placebo (Other)
High
A high dose of either CSL112 or placebo is to be administered as a single intravenous (IV) infusion. The placebo will be administered at the same frequency, volume and duration as the CSL112 infusion.
干预措施: CSL112 (Biological)
Low
A low dose of either CSL112 or placebo is to be administered as a single intravenous (IV) infusion. The placebo will be administered at the same frequency, volume and duration as the CSL112 infusion.
干预措施: CSL112 (Biological)
结局指标
主要结局
Plasma apoA-I and PC Tmax
时间窗: Before and at up to 10 time points (during up to 7 days) after infusion
Plasma apoA-I and PC Volume of distribution during terminal phase
时间窗: Before and at up to 10 time points (during up to 7 days) after infusion
Renal clearance of apoA-I
时间窗: Before and up to 48 hours after infusion
Renal clearance of apoA-I, calculated as Ae0-48/AUC0-48
Plasma apoA-I and PC AUC0-last and AUC 0-t
时间窗: Before and at up to 10 time points (during up to 7 days) after infusion
AUC from time point zero to the last quantifiable time point before the analyte first returns to baseline (AUC0-last) and/or a partial AUC from baseline to time point t (AUC0-t) with and without baseline correction
Plasma apolipoprotein A-I (apoA-I) and phosphatidylcholine (PC) area under the curve (AUC)
时间窗: Before and at up to 10 time points (during up to 7 days) after infusion
Baseline corrected plasma apoA-I and PC AUC0-infinity
Plasma apoA-I and PC Cmax
时间窗: Before and at up to 10 time points (during up to 7 days) after infusion
Plasma apoA-I and PC clearance
时间窗: Before and at up to 10 time points (during up to 7 days) after infusion
Plasma apoA-I and PC t1/2
时间窗: Before and at up to 10 time points (during up to 7 days) after infusion
Urinary excretion of apoA-I (Ae0-t)
时间窗: Before and up to 48 hours after infusion
Amount excreted (Ae) of apoA-I over a collection interval 0-t.
Urinary excretion of apoA-I (%fe0-t)
时间窗: Before and up to 48 hours after infusion
Percent fraction excreted (%fe) of apoA-I in urine over time interval 0-t, calculated as Ae0-t/Dose x 100.
次要结局
- Adverse drug reaction (ADR) or suspected ADR frequency (%)(Up to approximately 127 days)
- Urinary excretion of sucrose(Ae0-t)(Before and up to 48 hours after infusion)
- Clinically important change in drug-induced liver injury(From baseline (before infusion) up to Day 16.)
- Plasma sucrose AUC(Before and at up to 7 time points (during up to 2 days) after infusion)
- Plasma sucrose Clearance(Before and at up to 7 time points (during up to 2 days) after infusion)
- Plasma sucrose t1/2(Before and at up to 7 time points (during up to 2 days) after infusion)
- Adverse drug reaction (ADR) or suspected ADR frequency(Up to approximately 127 days)
- Urinary excretion of sucrose (%fe0-t)(Before and up to 48 hours after infusion)
- Clinically important change in renal status(From baseline (before infusion) up to Day 16.)
- Plasma sucrose Cmax(Before and at up to 7 time points (during up to 2 days) after infusion)
- Plasma sucrose Volume of distribution during terminal phase(Before and at up to 7 time points (during up to 2 days) after infusion)
- Urinary excretion of sucrose (clearance)(Before and up to 48 hours after infusion)
- Plasma sucrose AUC0-last and AUC 0-t(Before and at up to 7 time points (during up to 2 days) after infusion)
- Plasma sucrose Tmax(Before and at up to 7 time points (during up to 2 days) after infusion)
- Number of subjects with AEs(After the start of infusion up to approximately 127 days)
- Clinically significant changes in routine safety assessments(Up to approximately 97 days)