A Study To Assess The Effect Of Linezolid On QTc Interval

NCT00795145 | Completed Phase 1 Results

• 1 other identifier: A5951151
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 1

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.

Conditions

Bacterial Infections

Keywords

Linezolid, QTc interval, pharmacokinetics, therapeutic dose, supra-therapeutic dose

Outcome Measures

Primary Outcomes (2)

• 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

• 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

Secondary Outcomes (13)

• 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

Study Arms (7)

Cohort 1: Placebo

PLACEBO COMPARATOR

Drug: Placebo

Cohort 1: 900 mg linezolid

EXPERIMENTAL

Drug: Linezolid 900 mg

Cohort 1: 1200 mg linezolid

EXPERIMENTAL

Drug: Linezolid 1200 mg

Cohort 2: Placebo

PLACEBO COMPARATOR

Drug: Placebo

Cohort 2: 600 mg linezolid

EXPERIMENTAL

Drug: Linezolid 600 mg

Cohort 2: 1200 mg linezolid

EXPERIMENTAL

Drug: Linezolid 1200 mg

Cohort 2: 400 mg Moxifloxacin

ACTIVE COMPARATOR

Drug: Moxifloxacin 400 mg

Interventions

Placebo DRUG

Intravenous, Placebo control for blinding, Normal Saline, Single dose

Cohort 1: Placebo

Linezolid 900 mg DRUG

Intravenous, 900 mg linezolid, single dose

Also known as: Zyvox

Cohort 1: 900 mg linezolid

Linezolid 1200 mg DRUG

Intravenous, 1200 mg linezolid, single dose

Also known as: Zyvox

Cohort 1: 1200 mg linezolid

Linezolid 600 mg DRUG

Intravenous, 600 mg linezolid, single dose

Also known as: Zyvox

Cohort 2: 600 mg linezolid

Moxifloxacin 400 mg DRUG

Oral, 400 mg moxifloxacin, single dose

Also known as: Avelox

Cohort 2: 400 mg Moxifloxacin

Eligibility Criteria

• Age: 21 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• Evidence or history of clinically significant abnormality.
• 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.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (1)

Pfizer Investigational Site

Singapore, 188770, Singapore

Location

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Bacterial Infections

Interventions

Linezolid; Moxifloxacin

Condition Hierarchy (Ancestors)

Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Acetamides; Amides; Organic Chemicals; Acetates; Acids, Acyclic; Carboxylic Acids; Oxazolidinones; Oxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.govCallCenter@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: November 20, 2008
• First Posted: November 21, 2008
• Study Start: December 1, 2008
• Primary Completion: March 1, 2009
• Study Completion: March 1, 2009
• Last Updated: June 22, 2010
• Results First Posted: June 22, 2010

Record last verified: 2010-05

Locations

SG (1)