A Study To Assess The Effect Of Linezolid On QTc Interval

Bacterial Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00795145
• Other study ID #: A5951151
• Status: Completed
• Phase: Phase 1
• First received: November 20, 2008
• Last updated: May 17, 2010
• Start date: December 2008
• Est. completion date: March 2009

Study information

• Verified date: May 2010
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: March 2009
• Est. primary completion date: March 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 21 Years to 55 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Bacterial Infections

Intervention

Drug:
• Placebo
Intravenous, Placebo control for blinding, Normal Saline, Single dose
• Linezolid 900 mg
Intravenous, 900 mg linezolid, single dose
• Linezolid 1200 mg
Intravenous, 1200 mg linezolid, single dose
• Placebo
Intravenous, Placebo control for blinding, Normal Saline, Single dose
• Linezolid 600 mg
Intravenous, 600 mg linezolid, single dose
• Linezolid 1200 mg
Intravenous, 1200 mg linezolid, single dose
• Moxifloxacin 400 mg
Oral, 400 mg moxifloxacin, single dose

Locations

Country	Name	City	State
Singapore	Pfizer Investigational Site	Singapore

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

Singapore, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	From the time the subject had taken at least one dose of study treatment up to 5 weeks	Yes
Primary	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.	0.5, 1, 2, 4, 8, 12, 24 hours post-dose	No
Secondary	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).	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	No
Secondary	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	No
Secondary	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.	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	No
Secondary	Cohort 1: Clearance of Linezolid (CL)	Drug clearance = Dose / AUC inf	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	No
Secondary	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	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	No
Secondary	Cohort 2: Mean Time-Matched Difference in QTcF Intervals Between Moxifloxacin and Placebo	A measure of dispersion is not available.	0.5, 1, 2, 4, 8, 12, 24 hours post-dose	No
Secondary	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.	0.5, 1, 2, 4, 8, 12, 24 hours post-dose	No
Secondary	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).	Predose, 30 minutes, 1, 2, 4, 8, 12 hours post-dose	No
Secondary	Cohort 2: Cmax		Predose, 30 minutes, 1, 2, 4, 8, 12 hours post-dose	No
Secondary	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.	Predose, 30 minutes, 1, 2, 4, 8, 12 hours post-dose	No
Secondary	Cohort 2: CL	Drug clearance = Dose / AUC inf	Predose, 30 minutes, 1, 2, 4, 8, 12 hours post-dose	No
Secondary	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	Predose, 30 minutes, 1, 2, 4, 8, 12 hours post-dose	No
Secondary	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.	From the time the subject had taken at least one dose of study treatment up to 5 weeks	Yes

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