A Study To Assess The Effect Of Linezolid On QTc Interval
- Conditions
- Bacterial Infections
- Interventions
- Registration Number
- NCT00795145
- Lead Sponsor
- Pfizer
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 49
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Cohort 1: Placebo Placebo - Cohort 1: 900 mg linezolid Linezolid 900 mg - Cohort 1: 1200 mg linezolid Linezolid 1200 mg - Cohort 2: Placebo Placebo - Cohort 2: 600 mg linezolid Linezolid 600 mg - Cohort 2: 1200 mg linezolid Linezolid 1200 mg - Cohort 2: 400 mg Moxifloxacin Moxifloxacin 400 mg -
- Primary Outcome Measures
Name Time Method Cohort 1: Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs) 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 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.
- Secondary Outcome Measures
Name Time Method 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 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).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 Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
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 Drug clearance = Dose / AUC inf
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 Vss = (mean residence time \[The average total time molecules of a given dose spend in the body\] extrapolated to infinity) multiplied by CL
Cohort 2: Mean Time-Matched Difference in QTcF Intervals Between Moxifloxacin and Placebo 0.5, 1, 2, 4, 8, 12, 24 hours post-dose A measure of dispersion is not available.
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 A measure of dispersion is not available.
Cohort 2: AUC Inf and AUC Last Predose, 30 minutes, 1, 2, 4, 8, 12 hours post-dose 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).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 Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. Tmax is the time to reach Cmax.
Cohort 2: CL Predose, 30 minutes, 1, 2, 4, 8, 12 hours post-dose Drug clearance = Dose / AUC inf
Cohort 2: Vss Predose, 30 minutes, 1, 2, 4, 8, 12 hours post-dose Vss = (mean residence time \[The average total time molecules of a given dose spend in the body\] extrapolated to infinity) multiplied by CL
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 All observed or volunteered AEs and SAEs regardless of treatment group or suspected causal relationship to the investigational product(s) were reported.
Trial Locations
- Locations (1)
Pfizer Investigational Site
🇸🇬Singapore, Singapore