A Randomized, Subject and Investigator-blinded, Placebo Controlled, Single and Multiple Ascending Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of KAE609 Administered Intravenously in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 57
- 试验地点
- 1
- 主要终点
- Number of Participants With On-Treatments Adverse Events, Serious Adverse Events, and Deaths
研究概览
简要总结
This was a randomized, subject and investigator-blinded, placebo-controlled, single and multiple ascending intravenous (iv) dose study in healthy subjects to assess the safety and tolerability of KAE609 given in the vein.
详细描述
The study consisted of 2 parts: single-ascending dose (SAD) part and multiple ascending dose (MAD) part.
In Part A (Single-ascending dose (SAD) part), it was planned to recruit 6 active, 2 placebo subjects in each cohort:
- Cohort A1: 10.5 mg/placebo
- Cohort A2: 30 mg/placebo
- Cohort A3: 75 mg/placebo
- Cohort A4: 120 mg/placebo
- Cohort A5: 210 mg/placebo
In Part B (Multiple-ascending dose (MAD) part), Subjects were assigned to one of the following treatment arms in a ratio of 2:1 (6 active, 3 placebo):
- Cohort B1: 60 mg/placebo, every 24 hours (q24h) × 5 days
- Cohort B2: 120 mg/placebo, every 24 hours (q24h) × 5 days
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Other
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy male and female subjects 18 to 55 years of age inclusive, and in good health as determined by past medical history, physical examination, vital signs, electrocardiogram, and laboratory tests.
- •Subjects must weigh at least 50 kg to participate in the study, and must have a body mass index (BMI) within the range of 18.0 - 30.0 kg/m
排除标准
- •Use of other investigational drugs within 5 half-lives of Screening, or within 30 days of dosing, whichever is longer; or longer if required by local regulations.
- •Significant illness which has not resolved within two (2) weeks prior to initial dosing.
- •Pregnant or nursing (lactating) women.
- •Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant.
- •Sexually active males unwilling to use a condom during intercourse while taking investigational drug and for at least 2 weeks after last dose of investigational drug.
研究组 & 干预措施
Cohort A1: 10.5 mg/placebo
Single iv bolus dose of KAE609 or placebo administered at the clinical site by the study personnel.
干预措施: KAE609 (Drug)
Cohort A1: 10.5 mg/placebo
Single iv bolus dose of KAE609 or placebo administered at the clinical site by the study personnel.
干预措施: Placebo (Drug)
Cohort A2: 30 mg/placebo
Single iv bolus dose of KAE609 or placebo administered at the clinical site by the study personnel.
干预措施: KAE609 (Drug)
Cohort A2: 30 mg/placebo
Single iv bolus dose of KAE609 or placebo administered at the clinical site by the study personnel.
干预措施: Placebo (Drug)
Cohort A3: 75 mg/placebo
Single iv infusion dose of KAE609 or placebo administered at the clinical site by the study personnel.
干预措施: KAE609 (Drug)
Cohort A3: 75 mg/placebo
Single iv infusion dose of KAE609 or placebo administered at the clinical site by the study personnel.
干预措施: Placebo (Drug)
Cohort A4: 120 mg/placebo
Single iv infusion dose of KAE609 or placebo administered at the clinical site by the study personnel.
干预措施: KAE609 (Drug)
Cohort A4: 120 mg/placebo
Single iv infusion dose of KAE609 or placebo administered at the clinical site by the study personnel.
干预措施: Placebo (Drug)
Cohort A5: 210 mg/placebo
Single iv infusion dose of KAE609 or placebo administered at the clinical site by the study personnel.
干预措施: KAE609 (Drug)
Cohort A5: 210 mg/placebo
Single iv infusion dose of KAE609 or placebo administered at the clinical site by the study personnel.
干预措施: Placebo (Drug)
Cohort B1: 60 mg/placebo, every 24 hours (q24h) × 5 days
Multiple iv bolus doses of KAE609 or placebo administered at the clinical site by the study personnel.
干预措施: KAE609 (Drug)
Cohort B1: 60 mg/placebo, every 24 hours (q24h) × 5 days
Multiple iv bolus doses of KAE609 or placebo administered at the clinical site by the study personnel.
干预措施: Placebo (Drug)
Cohort B2: 120 mg/placebo, every 24 hours (q24h) × 5 days
Multiple iv infusion doses of KAE609 or placebo administered at the clinical site by the study personnel.
干预措施: KAE609 (Drug)
Cohort B2: 120 mg/placebo, every 24 hours (q24h) × 5 days
Multiple iv infusion doses of KAE609 or placebo administered at the clinical site by the study personnel.
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Participants With On-Treatments Adverse Events, Serious Adverse Events, and Deaths
时间窗: From study treatment start date till 30 days safety follow-up, assessed for up to 4 months
The distribution of adverse events was done via the analysis of frequencies for Adverse Event (AEs), Serious Adverse Event (SAEs) and Deaths, through the monitoring of relevant clinical and laboratory safety parameters.
次要结局
- Part A - Pharmacokinetic of KAE609: Maximum Observed Plasma Concentration (Cmax)(Day 1 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr))
- Part A - Pharmacokinetic of KAE609: Time to Reach the Maximum Concentration After Drug Administration (Tmax)(Day 1 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr))
- Part A - Pharmacokinetic of KAE609: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast)(Day 1 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr))
- Part A - Pharmacokinetic of KAE609: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf)(Day 1 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr))
- Part A - Pharmacokinetic of KAE609: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC0-24hrs)(Day 1 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr))
- Part A - Pharmacokinetic of KAE609: Terminal Elimination Half-life (T1/2)(Day 1 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr))
- Part A - Pharmacokinetic of KAE609: Clearance From Plasma (CL) Following Drug Administration(Day 1 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr))
- Part A - Pharmacokinetic of KAE609: Apparent Volume of Distribution During Terminal Phase (Vz)(Day 1 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr))
- Part B - Pharmacokinetic of KAE609: Maximum Observed Plasma Concentration (Cmax)(Days 1 and 5 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr))
- Part B - Pharmacokinetic of KAE609: Time to Reach the Maximum Concentration After Drug Administration (Tmax)(Days 1 and 5 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr))
- Part B - Pharmacokinetic of KAE609: Terminal Elimination Half-life (T1/2)(Days 1 and 5 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr))
- Part B - Pharmacokinetic of KAE609: Clearance From Plasma (CL) Following Drug Administration(Day 5 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr))
- Part B - Pharmacokinetic of KAE609: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast)(Day 5 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr))
- Part B - Pharmacokinetic of KAE609: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC0-24hrs)(Days 1 and 5 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr))
- Part B - Pharmacokinetic of KAE609: Apparent Volume of Distribution During Terminal Phase (Vz)(Day 5 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr))