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A Study To Assess The Effect Of Linezolid On QTc Interval

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00795145
Recruitment Status : Completed
First Posted : November 21, 2008
Results First Posted : June 22, 2010
Last Update Posted : June 22, 2010
Sponsor:
Information provided by:
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Basic Science
Condition Bacterial Infections
Interventions Drug: Placebo
Drug: Linezolid 900 mg
Drug: Linezolid 1200 mg
Drug: Linezolid 600 mg
Drug: Moxifloxacin 400 mg
Enrollment 49
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Cohort 1: Sequence 1 Cohort 1: Sequence 2 Cohort 1: Sequence 3 Cohort 2: Sequence 1 Cohort 2: Sequence 2 Cohort 2: Sequence 3 Cohort 2: Sequence 4
Hide Arm/Group Description Subjects were randomly assigned to placebo first, then linezolid 900 milligrams (mg) followed by 1200 mg linezolid, after a washout period of 48 hours between doses in Sequence 1. Subjects were randomly assigned to linezolid 900 mg first, then placebo, followed by 1200 mg linezolid, after a washout period of 48 hours between doses in Sequence 2. Subjects were randomly assigned to linezolid 900 mg first, then 1200 mg linezolid, followed by placebo after a washout period of 48 hours between doses in Sequence 3. Subjects were randomly assigned to placebo, then moxifloxacin, followed by linezolid 600 mg and 1200 mg, after a washout period of 48 hours between doses in Sequence 1. Subjects were randomly assigned to linezolid 600 mg first, then linezolid 1200 mg followed by placebo and moxifloxacin, after a washout period of 48 hours between doses in Sequence 2. Subjects were randomly assigned to linezolid 1200 mg first, then moxifloxacin 400 mg followed by linezolid 600 mg and placebo after a washout period of 48 hours between doses in Sequence 3. Subjects were randomly assigned to moxifloxacin 400 mg first, then placebo followed by linezolid 1200 mg and 600 mg linezolid after a washout period of 48 hours between doses in Sequence 4.
Period Title: Cohort 1
Started 3 3 3 0 0 0 0
Completed 3 3 3 0 0 0 0
Not Completed 0 0 0 0 0 0 0
Period Title: Cohort 2
Started 0 0 0 10 10 10 10
Completed 0 0 0 10 10 10 10
Not Completed 0 0 0 0 0 0 0
Arm/Group Title Cohort 1: Placebo, Linezolid 900 mg and 1200 mg Cohort 2: Placebo, Linezolid 600 mg and 1200 mg, Moxifloxacin Total
Hide Arm/Group Description Subjects were randomly assigned to placebo followed by linezolid 900 mg then 1200 mg linezolid in Sequence 1; or, linezolid 900 mg then linezolid 1200 mg followed by placebo in Sequence 2; or, linezolid 900 mg then placebo followed by linezolid 1200 mg in Sequence 3. There was a washout period of 48 hours between doses. Subjects were randomly assigned to placebo first then moxifloxacin followed by linezolid 600 mg and 1200 mg linezolid last in Sequence 1; or linezolid 600 mg first then linezolid 1200 mg followed by placebo and moxifloxacin last in Sequence 2; or, linezolid 1200 mg first then moxifloxacin 400 mg followed by linezolid 600 mg and placebo last in Sequence 3; or, moxifloxacin 400 mg first then placebo followed by linezolid 1200 mg and 600 mg linezolid last in Sequence 4. There was a washout period of 48 hours between each dose. Total of all reporting groups
Overall Number of Baseline Participants 9 40 49
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 9 participants 40 participants 49 participants
<18 years 0 0 0
18 - 44 years 8 36 44
45 - 64 years 1 4 5
>=65 years 0 0 0
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 40 participants 49 participants
Female
4
  44.4%
20
  50.0%
24
  49.0%
Male
5
  55.6%
20
  50.0%
25
  51.0%
1.Primary Outcome
Title Cohort 1: Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set (SAS): All subjects who received at least 1 dose of study medication.
Arm/Group Title Cohort 1: Placebo Cohort 1: 900 mg Linezolid Cohort 1: 1200 mg Linezolid
Hide Arm/Group Description:
600 milliliters (mL) saline as a constant rate intravenous (IV) infusion of 60 minutes.
450 mL Zyvox plus 150 mL saline as a constant rate IV infusion of 60 minutes.
600 mL Zyvox as a constant rate IV infusion of 60 minutes.
Overall Number of Participants Analyzed 9 9 9
Measure Type: Number
Unit of Measure: participants
AEs 1 3 2
SAEs 0 0 0
2.Primary Outcome
Title 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
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetic (PK) parameter analysis population was defined as all subjects randomized and treated who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.
Arm/Group Title Cohort 2: 600 mg Linezolid Cohort 2: 1200 mg Linezolid Cohort 2: Placebo
Hide Arm/Group Description:
Zyvox IV Injection
Zyvox IV Injection
0.9% Saline
Overall Number of Participants Analyzed 40 40 40
Measure Type: Number
Unit of Measure: milliseconds (msec)
0.5 hour 421.31 422.34 419.84
1 hour 419.71 420.89 422.67
2 hours 414.27 412.30 419.80
4 hours 418.85 421.92 418.45
8 hours 409.75 412.25 411.13
12 hours 412.99 413.45 411.98
24 hours 414.83 417.27 415.47
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 2: 600 mg Linezolid, Cohort 2: Placebo
Comments Inferential analysis at 0.5 hour post-dose
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.47
Confidence Interval 90%
-0.7 to 3.64
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 2: 600 mg Linezolid, Cohort 2: Placebo
Comments Inferential analysis at 1 hour post-dose
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.96
Confidence Interval 90%
-5.13 to -0.79
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cohort 2: 600 mg Linezolid, Cohort 2: Placebo
Comments Inferential analysis at 2 hour post-dose
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -5.53
Confidence Interval 90%
-7.70 to -3.36
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Cohort 2: 600 mg Linezolid, Cohort 2: Placebo
Comments Inferential analysis at 4 hour post-dose
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.40
Confidence Interval 90%
-1.77 to 2.57
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Cohort 2: 600 mg Linezolid, Cohort 2: Placebo
Comments Inferential analysis at 8 hour post-dose
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.37
Confidence Interval 90%
-3.54 to 0.80
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Cohort 2: 600 mg Linezolid, Cohort 2: Placebo
Comments Inferential analysis at 12 hour post-dose
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.01
Confidence Interval 90%
-1.16 to 3.18
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Cohort 2: 600 mg Linezolid, Cohort 2: Placebo
Comments Inferential analysis at 24 hour post-dose
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.64
Confidence Interval 90%
-2.81 to 1.53
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Cohort 2: 1200 mg Linezolid, Cohort 2: Placebo
Comments Inferential analysis at 0.5 hour post-dose
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.49
Confidence Interval 90%
0.32 to 4.66
Estimation Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Cohort 2: 1200 mg Linezolid, Cohort 2: Placebo
Comments Inferential analysis at 1 hour post-dose
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.78
Confidence Interval 90%
-3.95 to 0.39
Estimation Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Cohort 2: 1200 mg Linezolid, Cohort 2: Placebo
Comments Inferential analysis at 2 hour post-dose
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -7.51
Confidence Interval 90%
-9.68 to -5.34
Estimation Comments [Not Specified]
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Cohort 2: 1200 mg Linezolid, Cohort 2: Placebo
Comments Inferential analysis at 4 hour post-dose
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 3.47
Confidence Interval 90%
1.30 to 5.64
Estimation Comments [Not Specified]
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Cohort 2: 1200 mg Linezolid, Cohort 2: Placebo
Comments Inferential analysis at 8 hour post-dose
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.13
Confidence Interval 90%
-1.04 to 3.30
Estimation Comments [Not Specified]
Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Cohort 2: 1200 mg Linezolid, Cohort 2: Placebo
Comments Inferential analysis at 12 hour post-dose
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.47
Confidence Interval 90%
-0.70 to 3.64
Estimation Comments [Not Specified]
Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Cohort 2: 1200 mg Linezolid, Cohort 2: Placebo
Comments Inferential analysis at 24 hour post-dose
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.80
Confidence Interval 90%
-0.37 to 3.97
Estimation Comments [Not Specified]
3.Secondary Outcome
Title 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)
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description
PK parameter analysis population
Arm/Group Title Cohort 1: 900 mg Linezolid Cohort 1: 1200 mg Linezolid
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 9 9
Mean (Standard Deviation)
Unit of Measure: microgram (ug)*hours (hr)/mL
AUC inf 223.49  (47.372) 346.89  (77.867)
AUC last 211.26  (48.542) 332.26  (71.313)
4.Secondary Outcome
Title Cohort 1: Maximum Observed Plasma Concentration (Cmax)
Hide Description [Not Specified]
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
Hide Outcome Measure Data
Hide Analysis Population Description
PK parameter analysis population
Arm/Group Title Cohort 1: 900 mg Linezolid Cohort 1: 1200 mg Linezolid
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 9 9
Mean (Standard Deviation)
Unit of Measure: ug/mL
22.3  (3.681) 29.37  (6.080)
5.Secondary Outcome
Title Cohort 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) and Plasma Decay Half-Life (t1/2)
Hide Description Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
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
Hide Outcome Measure Data
Hide Analysis Population Description
PK parameter analysis population
Arm/Group Title Cohort 1: 900 mg Linezolid Cohort 1: 1200 mg Linezolid
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 9 9
Median (Full Range)
Unit of Measure: hr
Tmax
1.0
(1.0 to 1.5)
1.0
(1.0 to 1.52)
t1/2
6.9
(5.0 to 10.3)
7.1
(5.1 to 11.9)
6.Secondary Outcome
Title Cohort 1: Clearance of Linezolid (CL)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
PK parameter analysis population
Arm/Group Title Cohort 1: 900 mg Linezolid Cohort 1: 1200 mg Linezolid
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 9 9
Mean (Standard Deviation)
Unit of Measure: mL/minute (min)/kilogram (kg)
1.0173  (0.14637) 0.8813  (0.16623)
7.Secondary Outcome
Title Cohort 1: Steady-State Volume of Distribution (Vss)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
PK parameter analysis population
Arm/Group Title Cohort 1: 900 mg Linezolid Cohort 1: 1200 mg Linezolid
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 9 9
Mean (Standard Deviation)
Unit of Measure: L/kg
0.6016  (0.06869) 0.5776  (0.04605)
8.Secondary Outcome
Title Cohort 2: Mean Time-Matched Difference in QTcF Intervals Between Moxifloxacin and Placebo
Hide Description A measure of dispersion is not available.
Time Frame 0.5, 1, 2, 4, 8, 12, 24 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
PK parameter analysis population
Arm/Group Title Cohort 2: Moxifloxacin Cohort 2: Placebo
Hide Arm/Group Description:
Oral administration, positive control, not blinded.
[Not Specified]
Overall Number of Participants Analyzed 40 40
Measure Type: Number
Unit of Measure: msec
0.5 hour 423.11 419.84
1 hour 429.50 422.67
2 hours 430.07 419.80
4 hours 428.29 418.45
8 hours 420.53 411.13
12 hours 419.02 411.98
24 hours 421.99 415.47
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 2: Moxifloxacin, Cohort 2: Placebo
Comments Inferential analysis at 0.5 hour post-dose
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 3.27
Confidence Interval 90%
1.10 to 5.44
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 2: Moxifloxacin, Cohort 2: Placebo
Comments Inferential analysis at 1 hour post-dose
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 6.83
Confidence Interval 90%
4.66 to 9.00
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cohort 2: Moxifloxacin, Cohort 2: Placebo
Comments Inferential analysis at 2 hour post-dose
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 10.27
Confidence Interval 90%
8.10 to 12.44
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Cohort 2: Moxifloxacin, Cohort 2: Placebo
Comments Inferential analysis at 4 hour post-dose
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 9.84
Confidence Interval 90%
7.67 to 12.01
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Cohort 2: Moxifloxacin, Cohort 2: Placebo
Comments Inferential analysis at 8 hour post-dose
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 9.40
Confidence Interval 90%
7.23 to 11.58
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Cohort 2: Moxifloxacin, Cohort 2: Placebo
Comments Inferential analysis at 12 hour post-dose
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 7.05
Confidence Interval 90%
4.87 to 9.22
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Cohort 2: Moxifloxacin, Cohort 2: Placebo
Comments Inferential analysis at 24 hour post-dose
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 6.52
Confidence Interval 90%
4.35 to 8.69
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Cohort 2: Mean Time-Matched Difference in Uncorrected QT Intervals Between Linezolid 600 mg and 1200 mg Compared to Placebo
Hide Description A measure of dispersion is not available.
Time Frame 0.5, 1, 2, 4, 8, 12, 24 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
PK parameter analysis population
Arm/Group Title Cohort 2: Placebo Cohort 2: 600 mg Linezolid Cohort 2: 1200 mg Linezolid
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 40 40 40
Measure Type: Number
Unit of Measure: msec
0.5 hour 424.08 422.60 420.60
1 hour 422.25 414.80 410.06
2 hours 421.15 415.40 406.76
4 hours 420.58 419.66 418.40
8 hours 405.30 399.66 406.40
12 hours 398.85 396.56 398.96
24 hours 416.38 415.80 419.06
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: 600 mg Linezolid
Comments Inferential analysis at 0.5 hour post-dose
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.49
Confidence Interval 90%
-5.54 to 2.57
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: 600 mg Linezolid
Comments Inferential analysis at 1 hour post-dose
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -7.45
Confidence Interval 90%
-11.51 to -3.40
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: 600 mg Linezolid
Comments Inferential analysis at 2 hour post-dose
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -5.75
Confidence Interval 90%
-9.81 to -1.70
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: 600 mg Linezolid
Comments Inferential analysis at 4 hour post-dose
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.92
Confidence Interval 90%
-4.97 to 3.13
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: 600 mg Linezolid
Comments Inferential analysis at 8 hour post-dose
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -5.64
Confidence Interval 90%
-9.69 to -1.58
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: 600 mg Linezolid
Comments Inferential analysis at 12 hour post-dose
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.29
Confidence Interval 90%
-6.34 to 1.77
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: 600 mg Linezolid
Comments Inferential analysis at 24 hour post-dose
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.59
Confidence Interval 90%
-4.64 to 3.47
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: 1200 mg Linezolid
Comments Inferential analysis at 0.5 hour post-dose
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.49
Confidence Interval 90%
-7.54 to 0.57
Estimation Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: 1200 mg Linezolid
Comments Inferential analysis at 1 hour post-dose
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -12.19
Confidence Interval 90%
-16.24 to -8.13
Estimation Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: 1200 mg Linezolid
Comments Inferential analysis at 2 hour post-dose
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -14.39
Confidence Interval 90%
-18.44 to -10.33
Estimation Comments [Not Specified]
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: 1200 mg Linezolid
Comments Inferential analysis at 4 hour post-dose
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.19
Confidence Interval 90%
-6.24 to 1.87
Estimation Comments [Not Specified]
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: 1200 mg Linezolid
Comments Inferential analysis at 8 hour post-dose
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.10
Confidence Interval 90%
-2.95 to 5.15
Estimation Comments [Not Specified]
Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: 1200 mg Linezolid
Comments Inferential analysis at 12 hour post-dose
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.11
Confidence Interval 90%
-3.94 to 4.17
Estimation Comments [Not Specified]
Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: 1200 mg Linezolid
Comments Inferential analysis at 24 hour post-dose
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.68
Confidence Interval 90%
-1.37 to 6.73
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Cohort 2: AUC Inf and AUC Last
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description
PK parameter analysis population
Arm/Group Title Cohort 2: 900 mg Linezolid Cohort 2: 1200 mg Linezolid
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 40 40
Mean (Standard Deviation)
Unit of Measure: ug *hr/mL
AUC Inf 141.75  (36.156) 328.75  (79.198)
AUC Last 129.52  (32.121) 299.40  (62.096)
11.Secondary Outcome
Title Cohort 2: Cmax
Hide Description [Not Specified]
Time Frame Predose, 30 minutes, 1, 2, 4, 8, 12 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
PK parameter analysis population
Arm/Group Title Cohort 2: 600 mg Linezolid Cohort 2: 1200 mg Linezolid
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 40 40
Mean (Standard Deviation)
Unit of Measure: ug/mL
15.06  (2.616) 30.76  (4.395)
12.Secondary Outcome
Title Cohort 2: Tmax and t1/2
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
PK parameter analysis population
Arm/Group Title Cohort 2: 600 mg Linezolid Cohort 2: 1200 mg Linezolid
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 40 40
Median (Full Range)
Unit of Measure: hr
Tmax
1.083
(1.0 to 2.0)
1.1
(1.0 to 2.0)
t1/2
6.095
(2.83 to 10.40)
6.796
(3.12 to 10.50)
13.Secondary Outcome
Title Cohort 2: CL
Hide Description Drug clearance = Dose / AUC inf
Time Frame Predose, 30 minutes, 1, 2, 4, 8, 12 hours post-dose
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Hide Analysis Population Description
PK parameter analysis population
Arm/Group Title Cohort 2: 600 mg Linezolid Cohort 2: 1200 mg Linezolid
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 40 40
Mean (Standard Deviation)
Unit of Measure: mL/min/kg
1.2825  (0.36529) 1.1000  (0.27875)
14.Secondary Outcome
Title Cohort 2: Vss
Hide Description 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
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Hide Analysis Population Description
PK parameter analysis population
Arm/Group Title Cohort 2: 600 mg Linezolid Cohort 2: 1200 mg Linezolid
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 40 40
Mean (Standard Deviation)
Unit of Measure: L/kg
0.6418  (0.08353) 0.6185  (0.06560)
15.Secondary Outcome
Title Cohort 2: Number of Subjects With AEs and SAEs
Hide Description 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
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SAS
Arm/Group Title Cohort 2: 600 mg Linezolid Cohort 2: 1200 mg Linezolid Cohort 2: Placebo Moxifloxacin 400 mg
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 40 40 40 40
Measure Type: Number
Unit of Measure: participants
AEs 3 7 4 10
SAEs 0 0 0 0
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Cohort 1: Placebo Cohort 1: 900 mg Linezolid Cohort 1: 1200 mg Linezolid Cohort 2: Placebo Cohort 2: 600 mg Linezolid Cohort 2: 1200 mg Linezolid Cohort 2: 400 mg Moxifloxacin
Hide Arm/Group Description [Not Specified] [Not Specified] [Not Specified] [Not Specified] [Not Specified] [Not Specified] [Not Specified]
All-Cause Mortality
Cohort 1: Placebo Cohort 1: 900 mg Linezolid Cohort 1: 1200 mg Linezolid Cohort 2: Placebo Cohort 2: 600 mg Linezolid Cohort 2: 1200 mg Linezolid Cohort 2: 400 mg Moxifloxacin
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/--   --/--   --/-- 
Hide Serious Adverse Events
Cohort 1: Placebo Cohort 1: 900 mg Linezolid Cohort 1: 1200 mg Linezolid Cohort 2: Placebo Cohort 2: 600 mg Linezolid Cohort 2: 1200 mg Linezolid Cohort 2: 400 mg Moxifloxacin
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/9 (0.00%)   0/9 (0.00%)   0/9 (0.00%)   0/40 (0.00%)   0/40 (0.00%)   0/40 (0.00%)   0/40 (0.00%) 
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Cohort 1: Placebo Cohort 1: 900 mg Linezolid Cohort 1: 1200 mg Linezolid Cohort 2: Placebo Cohort 2: 600 mg Linezolid Cohort 2: 1200 mg Linezolid Cohort 2: 400 mg Moxifloxacin
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/9 (11.11%)   3/9 (33.33%)   2/9 (22.22%)   4/40 (10.00%)   3/40 (7.50%)   7/40 (17.50%)   10/40 (25.00%) 
Eye disorders               
Eye pruritus  1  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/40 (2.50%)  1/40 (2.50%)  0/40 (0.00%)  0/40 (0.00%) 
Gastrointestinal disorders               
Abdominal distension  1  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/40 (0.00%)  0/40 (0.00%)  1/40 (2.50%)  0/40 (0.00%) 
Diarrhoea  1  1/9 (11.11%)  0/9 (0.00%)  1/9 (11.11%)  1/40 (2.50%)  0/40 (0.00%)  0/40 (0.00%)  1/40 (2.50%) 
Flatulence  1  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/40 (0.00%)  0/40 (0.00%)  0/40 (0.00%)  2/40 (5.00%) 
Frequent bowel movements  1  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/40 (0.00%)  0/40 (0.00%)  0/40 (0.00%)  1/40 (2.50%) 
Nausea  1  0/9 (0.00%)  0/9 (0.00%)  1/9 (11.11%)  0/40 (0.00%)  0/40 (0.00%)  4/40 (10.00%)  1/40 (2.50%) 
Tongue discolouration  1  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/40 (0.00%)  1/40 (2.50%)  1/40 (2.50%)  0/40 (0.00%) 
Vomiting  1  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/40 (0.00%)  0/40 (0.00%)  1/40 (2.50%)  0/40 (0.00%) 
General disorders               
Hunger  1  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/40 (0.00%)  0/40 (0.00%)  0/40 (0.00%)  1/40 (2.50%) 
Infusion site swelling  1  0/9 (0.00%)  2/9 (22.22%)  0/9 (0.00%)  0/40 (0.00%)  0/40 (0.00%)  0/40 (0.00%)  0/40 (0.00%) 
Oedema peripheral  1  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/40 (0.00%)  0/40 (0.00%)  0/40 (0.00%)  1/40 (2.50%) 
Infections and infestations               
Upper respiratory tract infection  1  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/40 (0.00%)  1/40 (2.50%)  0/40 (0.00%)  0/40 (0.00%) 
Investigations               
Urine output decreased  1  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/40 (0.00%)  0/40 (0.00%)  0/40 (0.00%)  1/40 (2.50%) 
Nervous system disorders               
Headache  1  0/9 (0.00%)  0/9 (0.00%)  1/9 (11.11%)  2/40 (5.00%)  0/40 (0.00%)  2/40 (5.00%)  2/40 (5.00%) 
Hypoaesthesia  1  0/9 (0.00%)  1/9 (11.11%)  0/9 (0.00%)  0/40 (0.00%)  0/40 (0.00%)  0/40 (0.00%)  0/40 (0.00%) 
Somnolence  1  0/9 (0.00%)  1/9 (11.11%)  0/9 (0.00%)  0/40 (0.00%)  0/40 (0.00%)  0/40 (0.00%)  0/40 (0.00%) 
Reproductive system and breast disorders               
Dysmenorrhoea  1  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/40 (0.00%)  0/40 (0.00%)  2/40 (5.00%)  0/40 (0.00%) 
Skin and subcutaneous tissue disorders               
Rash  1  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/40 (0.00%)  0/40 (0.00%)  0/40 (0.00%)  1/40 (2.50%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (12.1)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Pfizer has the right to review disclosures, requesting a delay of < 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), < 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
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Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
Phone: 1-800-718-1021
EMail: ClinicalTrials.govCallCenter@pfizer.com
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Responsible Party: Director, Clinical Trial Disclosure Group, Pfizer, Inc.
ClinicalTrials.gov Identifier: NCT00795145    
Other Study ID Numbers: A5951151
First Submitted: November 20, 2008
First Posted: November 21, 2008
Results First Submitted: March 2, 2010
Results First Posted: June 22, 2010
Last Update Posted: June 22, 2010