A Phase I Study to Assess the Pharmacokinetics of IK-1001 (Sodium Sulfide) in Subjects With Impaired Renal Function Following a Continuous 3-hour Intravenous Infusion
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Mallinckrodt
- 入组人数
- 28
- 试验地点
- 1
- 主要终点
- Thiosulfate in Plasma
研究概览
简要总结
This is a Phase 1 study to assess the pharmacokinetics (PK) of IK-1001 (sodium sulfide) in healthy volunteers as well as in subjects with varying degrees of impaired renal function. A total of 28 subjects will be enrolled into the study over a 6 month period. There will be 4 cohorts. The first cohort will consist of subjects with mild renal impairment, the fourth cohort will be subjects with intermediate renal impairment and the third cohort will be subjects with severe renal impairment and the second cohort will consist of normal healthy subjects. All subjects will receive the study drug for 3 hours as a single intravenous (IV) infusion and will be followed over a 7 day period.
详细描述
This is a Phase 1 pharmacokinetic study to assess the pharmacokinetics of IK-1001 in healthy volunteers as well as subjects with varying degrees of impaired renal function following a single intravenous infusion.
A total of 28 subjects will be enrolled into the study, including 6 normal subjects (Creatinine Clearance (CrCL) > 80 mL/min), 9 subjects with mild impairment (CrCL ≥ 50 to < 80 mL/min), 6 subjects with intermediate impairment (≥ 30 to < 50 mL/min) and 7 subjects with severe impairment (CrCL < 30 mL/min).
Mild, moderate and normal healthy subjects will receive IK-1001 as a single IV infusion for 3 hours at 1.5 mg/kg/hr. Blood, plasma, urine and exhaled air will be collected from each subject over 48 hours and at follow-up visit (Day 7), to evaluate pharmacokinetics of Hydrogen Sulfide (H2S) (exhaled air), IK-1001 (blood) and thiosulfate in plasma and urine. Severe subjects will receive IK-1001 as a single IV infusion for 3 hours at 1.0 mg/kg/hr.
For each dosing cohort, the study will consist of a screening visit (Days -28 to -1), a treatment visit (Day 0 (check-in) to Day 3), and a follow-up (exit) visit day 7 (+/- 2 days).
Study subjects will be enrolled to one of 4 cohorts and all will receive investigational product at the given dose level. The subjects will be considered to be enrolled in the study at randomization.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •For normal subjects arm (CrCL > 80 ml/min): Healthy male and female subjects age 18 to 70 years of age inclusive. Pregnant women are excluded and women of child-bearing potential must agree to the use of medically reliable contraceptive methods for the duration of the study and for 30 days after study.
- •For renally impaired arm: Male and female - pregnant women are excluded and women of child-bearing potential must agree to the use of medically reliable contraceptive methods for the duration of the study and for 30 days after study. Subjects with mild, moderate and severe renal function aged between 18 to 70 years old
- •Body mass index (BMI) within the range of 18 to 40 kg/m2
- •Electrocardiogram (ECG) recording without clinically relevant abnormalities
- •Having had no febrile or infectious disease for at least seven days prior to dosing of study drug
- •Able to communicate well with the study staff and to understand and comply with the requirements of the study, understand and sign the written informed consent
排除标准
- •High risk patients who may need an urgent dialysis during clinical conduct portion of the study (from Day -1 until last PK sampling on Day 7)
- •All smokers.
- •More than moderate alcohol consumption (>35 g ethanol regularly or > 2 drinks per day )
- •Any history of alcohol or drug abuse
- •Any active physical or psychiatric disease, acute or chronic
- •Any clinically relevant history of drug hypersensitivity, asthma, urticaria or other severe allergic diathesis
- •Pregnant or nursing women
- •Blood donation within 30 days
- •Participation in any clinical study within 30 days prior to the treatment phase of this study
- •Lab values outside of reference range and clinically relevant liver function tests (AST, ALT, gamma-GT)
- •Positive tests for HIV antibodies, Hepatitis B-virus surface antigen (HBsAg), Anti-Hepatitis C-virus antibodies (Anti-HCV)
研究组 & 干预措施
Sodium Sulfide - Mild Cohort
Mild renal impairment (RI) Cohort administered 1.5 mg/kg/hr infusion of Sodium sulfide intravenously for 3 hours.
干预措施: Sodium Sulfide (Drug)
Sodium Sulfide - Healthy Cohort
Healthy subjects received sodium sulfide intravenously at 1.5 mg/kg/hr for 3 hours
干预措施: Sodium Sulfide (Drug)
Sodium Sulfide - Moderate Cohort
Moderate RI cohort received sodium sulfide intravenously at 1.5 mg/kg/hr for 3 hours
干预措施: Sodium Sulfide (Drug)
Sodium Sulfide - Severe Cohort
Severe RI cohort received sodium sulfide intravenously at 1.0 mg/kg/hr for 3 hours
干预措施: Sodium Sulfide (Drug)
结局指标
主要结局
Thiosulfate in Plasma
时间窗: 8 hours after treatment
Total concentration of thiosulfate in plasma was measured through pharmacokinetic blood sampling.
Thiosulfate in Urine
时间窗: 48 hours after treatment
Total concentration of thiosulfate in urine was measure through pharmacokinetic urine collection
Sodium Sulfide in Blood
时间窗: 8 hours after treatment
Total concentration of sodium sulfide in blood was measured through pharmacokinetic blood sampling.
次要结局
未报告次要终点