Single Dose Safety, Tolerability And Pharmacokinetics Of Escalating Intravenous Doses Of Linezolid Followed By Evaluation Of The Effect Of Single Intravenous Doses Of Linezolid On QTc Interval In Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 49
- 试验地点
- 1
- 主要终点
- Cohort 1: Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs)
研究概览
简要总结
The FDA has asked Pfizer to assess the risk of linezolid on QT interval (obtained from ECG readings) which could predispose patients to ventricular arrhythmias. This study is conducted to satisfy this requirement.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 21 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 between the ages of 21 and 55 years.
- •Body mass Index (BMI) of 18 to 30 kg/m2; and a total body weight > 45 kg (99 lbs).
- •An informed consent document signed and dated.
排除标准
- •Evidence or history of clinically significant abnormality.
- •12-lead ECG demonstrating QTc >450 msec at Screening.
- •Receiving selective serotonin reuptake inhibitors (SSRIs) and/or sympathomimetic agents.
- •Abnormal liver function tests.
- •A positive urine drug screen, history of excessive alcohol and tobacco use.
研究组 & 干预措施
Cohort 1: Placebo
干预措施: Placebo (Drug)
Cohort 1: 900 mg linezolid
干预措施: Linezolid 900 mg (Drug)
Cohort 1: 1200 mg linezolid
干预措施: Linezolid 1200 mg (Drug)
Cohort 2: Placebo
干预措施: Placebo (Drug)
Cohort 2: 600 mg linezolid
干预措施: Linezolid 600 mg (Drug)
Cohort 2: 1200 mg linezolid
干预措施: Linezolid 1200 mg (Drug)
Cohort 2: 400 mg Moxifloxacin
干预措施: Moxifloxacin 400 mg (Drug)
结局指标
主要结局
Cohort 1: Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: From the time the subject had taken at least one dose of study treatment up to 5 weeks
All observed or volunteered AEs and SAEs regardless of treatment group or suspected causal relationship to the investigational product(s) were reported.
Cohort 2: Mean Time-Matched Difference in Time Corresponding to Beginning of Depolarization to Repolarization of the Ventricles, Corrected for Heart Rate Using Fridericia's Formula (QTcF Interval) Between Linezolid 600 mg and 1200 mg Compared to Placebo
时间窗: 0.5, 1, 2, 4, 8, 12, 24 hours post-dose
The time corresponding to the beginning of depolarization to repolarization of the ventricles (QT interval) was adjusted for ventricular rate (VR) using the QT and VR from each electrocardiogram by Fridericia's formula (QTcF = QT divided by cube root of VR in seconds). A measure of dispersion is not available.
次要结局
- Cohort 1: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC Inf) and Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUC Last)(predose, 30 minutes, and at 1 (end of infusion), 1.5, 2, 3, 4, 6, 8, 12, 24, and 46 hours after start of infusion)
- Cohort 1: Maximum Observed Plasma Concentration (Cmax)(predose, 30 minutes, and at 1 (end of infusion), 1.5, 2, 3, 4, 6, 8, 12, 24, and 46 hours after start of infusion)
- Cohort 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) and Plasma Decay Half-Life (t1/2)(predose, 30 minutes, and at 1 (end of infusion), 1.5, 2, 3, 4, 6, 8, 12, 24, and 46 hours after start of infusion)
- Cohort 1: Clearance of Linezolid (CL)(predose, 30 minutes, and at 1 (end of infusion), 1.5, 2, 3, 4, 6, 8, 12, 24, and 46 hours after start of infusion)
- Cohort 1: Steady-State Volume of Distribution (Vss)(predose, 30 minutes, and at 1 (end of infusion), 1.5, 2, 3, 4, 6, 8, 12, 24, and 46 hours after start of infusion)
- Cohort 2: Mean Time-Matched Difference in QTcF Intervals Between Moxifloxacin and Placebo(0.5, 1, 2, 4, 8, 12, 24 hours post-dose)
- Cohort 2: Mean Time-Matched Difference in Uncorrected QT Intervals Between Linezolid 600 mg and 1200 mg Compared to Placebo(0.5, 1, 2, 4, 8, 12, 24 hours post-dose)
- Cohort 2: AUC Inf and AUC Last(Predose, 30 minutes, 1, 2, 4, 8, 12 hours post-dose)
- Cohort 2: Cmax(Predose, 30 minutes, 1, 2, 4, 8, 12 hours post-dose)
- Cohort 2: Tmax and t1/2(Predose, 30 minutes, 1, 2, 4, 8, 12 hours post-dose)
- Cohort 2: CL(Predose, 30 minutes, 1, 2, 4, 8, 12 hours post-dose)
- Cohort 2: Vss(Predose, 30 minutes, 1, 2, 4, 8, 12 hours post-dose)
- Cohort 2: Number of Subjects With AEs and SAEs(From the time the subject had taken at least one dose of study treatment up to 5 weeks)