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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
TRIPLE
Enrollment
49
Intravenous, Placebo control for blinding, Normal Saline, Single dose
Intravenous, 900 mg linezolid, single dose
Intravenous, 1200 mg linezolid, single dose
Pfizer Investigational Site
Singapore, Singapore
Cohort 1: Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs)
All observed or volunteered AEs and SAEs regardless of treatment group or suspected causal relationship to the investigational product(s) were reported.
Time frame: From the time the subject had taken at least one dose of study treatment up to 5 weeks
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
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.
Time frame: 0.5, 1, 2, 4, 8, 12, 24 hours post-dose
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)
AUC inf = Area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time. AUC last = Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t).
Time frame: 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)
Time frame: 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)
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
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Intravenous, Placebo control for blinding, Normal Saline, Single dose
Intravenous, 600 mg linezolid, single dose
Intravenous, 1200 mg linezolid, single dose
Oral, 400 mg moxifloxacin, single dose
Time frame: 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)
Drug clearance = Dose / AUC inf
Time frame: 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)
Vss = (mean residence time \[The average total time molecules of a given dose spend in the body\] extrapolated to infinity) multiplied by CL
Time frame: 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
A measure of dispersion is not available.
Time frame: 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
A measure of dispersion is not available.
Time frame: 0.5, 1, 2, 4, 8, 12, 24 hours post-dose
Cohort 2: AUC Inf and AUC Last
AUC inf = Area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time. AUC last = Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t).
Time frame: Predose, 30 minutes, 1, 2, 4, 8, 12 hours post-dose
Cohort 2: Cmax
Time frame: Predose, 30 minutes, 1, 2, 4, 8, 12 hours post-dose
Cohort 2: Tmax and t1/2
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. Tmax is the time to reach Cmax.
Time frame: Predose, 30 minutes, 1, 2, 4, 8, 12 hours post-dose
Cohort 2: CL
Drug clearance = Dose / AUC inf
Time frame: Predose, 30 minutes, 1, 2, 4, 8, 12 hours post-dose
Cohort 2: Vss
Vss = (mean residence time \[The average total time molecules of a given dose spend in the body\] extrapolated to infinity) multiplied by CL
Time frame: Predose, 30 minutes, 1, 2, 4, 8, 12 hours post-dose
Cohort 2: Number of Subjects With AEs and SAEs
All observed or volunteered AEs and SAEs regardless of treatment group or suspected causal relationship to the investigational product(s) were reported.
Time frame: From the time the subject had taken at least one dose of study treatment up to 5 weeks