A Randomized, Double-blind, Placebo-controlled Phase I Study to Assess the Safety, Tolerability and Pharmacokinetics of SZEY-2108 Administreated as Single and Repeated Intravenous Doses in Chinese Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 64
- 试验地点
- 1
- 主要终点
- Safety of single and multiple ascending doses of SZEY-2108
研究概览
简要总结
This phase 1 study was designed to evaluate the safety and tolerability of SZEY-2108 in single and multiple intravenous infusions, the pharmacokinetic profile of SZEY-2108 after single and multiple intravenous infusions, and the effect of exposure to SZEY-2108 after a single intravenous infusion on QT/QTc interval. Metabolites in each biological matrix (blood, urine, feces) and excretion characteristics (feces) after SZEY-2108 were analyzed.
详细描述
This is a first-in-human, randomized, double-blind, placebo-controlled study consisting of 2 parts. Part 1: Single-dose intravenous infusion dose-escalation trial. A total of 44 ~ 52 healthy adult subjects will be enrolled in Part 1 and they will be administrated with SZEY-2108 or placebo by single intravenous infusion. Part 1 consists of 7 cohorts: 100mg，200mg，500mg, 1000mg, 2000mg，4000mg and the dose of last cohort to be determined. Four subjects will be randomized to SZEY-2108 or placebo at a ratio of 1:1 in the 100mg cohort and eight subjects at a ratio of 3:1 in other each cohort. Time for intravenous infusion is 2h±5 min and it may be extended to 3 h±5 min if intolerance occur in 2000mg and 4000mg cohort.
Subjects will be randomised to receive an intravenous infusion of SZEY-2108 or placebo on the morning of D1, then they will still be hospitalised for safety, tolerability, pharmacokinetic and C-QTc assessment, and finally will discharge the Phase I clinical study centre after completion of all assessments at D3. They are required to return to the study centre at D7 for a safety follow-up visit.
Part 2: Multi-dose intravenous infusion dose-escalation trial According to results of Part 1, administration dose and dosing interval may be adjusted in Part 2.
Thirty healthy adult subjects will be enrolled in Part 2 and they will receive multiple doses of SZEY-2108 or placebo by intravenous infusion. Part 2 consists of 3 cohorts: 1000mg at Q8h，2000mg at Q8h, and one dose level of 1000mg, 1500mg or 2000mg at Q6h. Ten subjects will be randomized to SZEY-2108 or placebo at a ratio of 4:1 in each cohort. Time for intravenous infusion is 2h±5 min and it may be extended to 3 h±5 min if intolerance occur in 2000mg cohort.
Subjects will be randomized to receive an intravenous infusion of SZEY-2108 or placebo at Q8h or Q6h on D1~D7 and on the morning of D8. They will still be hospitalised for safety, tolerability and pharmacokinetic assessment, and finally will discharge the Phase I clinical study centre after completion of all assessments at D9 or D10 (for faecal retention group). Subjects are required to return to the study centre at D15 for a safety follow-up visit.
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 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age between 18 and 45 years at the time of screening;
- •BMI between 19 and 28 kg/m2, and weight for males and females ≥ 50kg and 45kg, respectively;
- •No clinical relevant abnormalities
- •Sign informed consent
排除标准
- •Any clinical significant illness
- •Other medical or psychiatric may inappropriate for the study
- •Past history of allergic conditions or current comorbid allergies
- •Use of any prescription medications within 4 weeks prior to screening or use of any over-the-counter medications, herbs, supplements, and vitamins within 7 days prior to the use of the investigational drug;
- •History of cigarette, alcohol or drug abuse
- •Abnormal vital signs, such as blood pressure and pulse rate
- •Abnormal examination results, such as 12-ECG, eGFR, ALT, AST and TBL
- •Positive results of HBsAg, TPPA, HCV-Ab, or HIV-Ab
- •Blood loss or donation > 400ml within 3 months prior to screening
- •Pregant or breastfeeding females or subjects unwilling to contraception
研究组 & 干预措施
Single intravenous doses of SZEY-2108
Single escalating doses of SZEY-2108
干预措施: SZEY-2108 for injetion (Drug)
Single intravenous doses of placebo
Single intravenous doses of placebo to match SZEY-2108
干预措施: Placebo (Drug)
Multiple intravenous doses of SZEY-2108
Multiple intravenous doses of SZEY-2108 at Q8h or Q6h on D1~D7 and on the morning of D8.
干预措施: SZEY-2108 for injetion (Drug)
Multiple intravenous doses of placebo
Multiple intravenous doses of placebo at Q8h or Q6h on D1~D7 and on the morning of D8.
干预措施: Placebo (Drug)
结局指标
主要结局
Safety of single and multiple ascending doses of SZEY-2108
时间窗: Part 1: From the time of signed consent through the end of study date which occurs on Day 7±1;Part 2: From the time of signed consent through the end of study date which occurs on Day 15±1
Safety and tolerability as assessed through the determination and recording of the occurrence of AEs as well as by adverse changes in vital signs, ECG (e.g. QTc interval) parameters, and laboratory data.
次要结局
- Assessment of Pharmacokinetic Parameter (plasma): AUC(In Part 1：0 to 24 hours post-dose on Day 1 ；In Part 2：0 to 24 hours post-dose on Days 1~7 and on the morning of D8 (varied intervals per cohort))
- Assessment of Pharmacokinetic Parameter (plasma): Tmax(In Part 1：0 to 24 hours post-dose on Day 1 ；In Part 2：0 to 24 hours post-dose on Days 1~7 and on the morning of D8 (varied intervals per cohort))
- Assessment of Pharmacokinetic Parameter (plasma): t1/2(In Part 1：0 to 24 hours post-dose on Day 1 ；In Part 2：0 to 24 hours post-dose on Days 1~7 and on the morning of D8 (varied intervals per cohort))
- Assessment of Pharmacokinetic Parameter (plasma): CL(In Part 1：0 to 24 hours post-dose on Day 1 ；In Part 2：0 to 24 hours post-dose on Days 1~7 and on the morning of D8 (varied intervals per cohort))
- Assessment of Pharmacokinetic Parameter (urine): SZEY-2108(In Part 1：Day1: baseline ,0 to 4, 4 to 8, 8 to 12 and 12 to 24h ；In Part 2：Day1: baseline,0 to 2, 2 to 4, 4 to 8, 8 to 12 and 12 to 24h.)
- Assessment of Pharmacokinetic Parameter (plasma): Cmax measurement(In Part 1：0 to 24 hours post-dose on Day 1 ；In Part 2：0 to 24 hours post-dose on Days 1~7 and on the morning of D8 (varied intervals per cohort))
- Quantitative relationship between blood concentration and QTc interval of SZEY-2108.(In Part 1：Before dosing (Baseline) through 24 hours after the dose on Day 1 （The dose groups of 100mg and 200mg were excluded）)