Clinical trial NCT00795145: A Study To Assess The Effect Of Linezolid On QTc Interval
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Bacterial Infections
Keywords: Linezolid, QTc interval, pharmacokinetics, therapeutic dose, supra-therapeutic dose
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2008-11-21
Enrollment: 49
Sex: ALL
Minimum age (years): 21
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Cohort 1: Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: From the time the subject had taken at least one dose of study treatment up to 5 weeks
measure: 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
timeFrame: 0.5, 1, 2, 4, 8, 12, 24 hours post-dose
Secondary outcomes:
measure: 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)
timeFrame: 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
measure: Cohort 1: Maximum Observed Plasma Concentration (Cmax)
timeFrame: 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
measure: Cohort 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) and Plasma Decay Half-Life (t1/2)
timeFrame: 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
measure: Cohort 1: Clearance of Linezolid (CL)
timeFrame: 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
measure: Cohort 1: Steady-State Volume of Distribution (Vss)
timeFrame: 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
measure: Cohort 2: Mean Time-Matched Difference in QTcF Intervals Between Moxifloxacin and Placebo
timeFrame: 0.5, 1, 2, 4, 8, 12, 24 hours post-dose
measure: Cohort 2: Mean Time-Matched Difference in Uncorrected QT Intervals Between Linezolid 600 mg and 1200 mg Compared to Placebo
timeFrame: 0.5, 1, 2, 4, 8, 12, 24 hours post-dose
measure: Cohort 2: AUC Inf and AUC Last
timeFrame: Predose, 30 minutes, 1, 2, 4, 8, 12 hours post-dose
measure: Cohort 2: Cmax
timeFrame: Predose, 30 minutes, 1, 2, 4, 8, 12 hours post-dose
measure: Cohort 2: Tmax and t1/2
timeFrame: Predose, 30 minutes, 1, 2, 4, 8, 12 hours post-dose
measure: Cohort 2: CL
timeFrame: Predose, 30 minutes, 1, 2, 4, 8, 12 hours post-dose
measure: Cohort 2: Vss
timeFrame: Predose, 30 minutes, 1, 2, 4, 8, 12 hours post-dose
measure: Cohort 2: Number of Subjects With AEs and SAEs
timeFrame: From the time the subject had taken at least one dose of study treatment up to 5 weeks
Other outcomes:
Locations:
city: Singapore
country: Singapore
facility: Pfizer Investigational Site
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: