Trial Outcomes & Findings for A Study To Assess The Effect Of Linezolid On QTc Interval (NCT NCT00795145)
NCT ID: NCT00795145
Last Updated: 2010-06-22
Results Overview
All observed or volunteered AEs and SAEs regardless of treatment group or suspected causal relationship to the investigational product(s) were reported.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
49 participants
Primary outcome timeframe
From the time the subject had taken at least one dose of study treatment up to 5 weeks
Results posted on
2010-06-22
Participant Flow
Participant milestones
| Measure |
Cohort 1: Sequence 1
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.
|
Cohort 1: Sequence 2
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.
|
Cohort 1: Sequence 3
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.
|
Cohort 2: Sequence 1
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.
|
Cohort 2: Sequence 2
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.
|
Cohort 2: Sequence 3
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.
|
Cohort 2: Sequence 4
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.
|
|---|---|---|---|---|---|---|---|
|
Cohort 1
STARTED
|
3
|
3
|
3
|
0
|
0
|
0
|
0
|
|
Cohort 1
COMPLETED
|
3
|
3
|
3
|
0
|
0
|
0
|
0
|
|
Cohort 1
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Cohort 2
STARTED
|
0
|
0
|
0
|
10
|
10
|
10
|
10
|
|
Cohort 2
COMPLETED
|
0
|
0
|
0
|
10
|
10
|
10
|
10
|
|
Cohort 2
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Study To Assess The Effect Of Linezolid On QTc Interval
Baseline characteristics by cohort
| Measure |
Cohort 1: Placebo, Linezolid 900 mg and 1200 mg
n=9 Participants
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.
|
Cohort 2: Placebo, Linezolid 600 mg and 1200 mg, Moxifloxacin
n=40 Participants
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
n=49 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Customized
<18 years
|
0 participants
n=99 Participants
|
0 participants
n=107 Participants
|
0 participants
n=206 Participants
|
|
Age, Customized
18 - 44 years
|
8 participants
n=99 Participants
|
36 participants
n=107 Participants
|
44 participants
n=206 Participants
|
|
Age, Customized
45 - 64 years
|
1 participants
n=99 Participants
|
4 participants
n=107 Participants
|
5 participants
n=206 Participants
|
|
Age, Customized
>=65 years
|
0 participants
n=99 Participants
|
0 participants
n=107 Participants
|
0 participants
n=206 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=99 Participants
|
20 Participants
n=107 Participants
|
24 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=99 Participants
|
20 Participants
n=107 Participants
|
25 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: From the time the subject had taken at least one dose of study treatment up to 5 weeksPopulation: Safety Analysis Set (SAS): All subjects who received at least 1 dose of study medication.
All observed or volunteered AEs and SAEs regardless of treatment group or suspected causal relationship to the investigational product(s) were reported.
Outcome measures
| Measure |
Cohort 1: Placebo
n=9 Participants
600 milliliters (mL) saline as a constant rate intravenous (IV) infusion of 60 minutes.
|
Cohort 1: 900 mg Linezolid
n=9 Participants
450 mL Zyvox plus 150 mL saline as a constant rate IV infusion of 60 minutes.
|
Cohort 1: 1200 mg Linezolid
n=9 Participants
600 mL Zyvox as a constant rate IV infusion of 60 minutes.
|
Moxifloxacin 400 mg
|
|---|---|---|---|---|
|
Cohort 1: Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs)
AEs
|
1 participants
|
3 participants
|
2 participants
|
—
|
|
Cohort 1: Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs)
SAEs
|
0 participants
|
0 participants
|
0 participants
|
—
|
PRIMARY outcome
Timeframe: 0.5, 1, 2, 4, 8, 12, 24 hours post-dosePopulation: 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.
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.
Outcome measures
| Measure |
Cohort 1: Placebo
n=40 Participants
600 milliliters (mL) saline as a constant rate intravenous (IV) infusion of 60 minutes.
|
Cohort 1: 900 mg Linezolid
n=40 Participants
450 mL Zyvox plus 150 mL saline as a constant rate IV infusion of 60 minutes.
|
Cohort 1: 1200 mg Linezolid
n=40 Participants
600 mL Zyvox as a constant rate IV infusion of 60 minutes.
|
Moxifloxacin 400 mg
|
|---|---|---|---|---|
|
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
1 hour
|
419.71 milliseconds (msec)
|
420.89 milliseconds (msec)
|
422.67 milliseconds (msec)
|
—
|
|
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
2 hours
|
414.27 milliseconds (msec)
|
412.30 milliseconds (msec)
|
419.80 milliseconds (msec)
|
—
|
|
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
8 hours
|
409.75 milliseconds (msec)
|
412.25 milliseconds (msec)
|
411.13 milliseconds (msec)
|
—
|
|
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
24 hours
|
414.83 milliseconds (msec)
|
417.27 milliseconds (msec)
|
415.47 milliseconds (msec)
|
—
|
|
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 hour
|
421.31 milliseconds (msec)
|
422.34 milliseconds (msec)
|
419.84 milliseconds (msec)
|
—
|
|
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
4 hours
|
418.85 milliseconds (msec)
|
421.92 milliseconds (msec)
|
418.45 milliseconds (msec)
|
—
|
|
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
12 hours
|
412.99 milliseconds (msec)
|
413.45 milliseconds (msec)
|
411.98 milliseconds (msec)
|
—
|
SECONDARY outcome
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 infusionPopulation: PK parameter analysis population
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).
Outcome measures
| Measure |
Cohort 1: Placebo
n=9 Participants
600 milliliters (mL) saline as a constant rate intravenous (IV) infusion of 60 minutes.
|
Cohort 1: 900 mg Linezolid
n=9 Participants
450 mL Zyvox plus 150 mL saline as a constant rate IV infusion of 60 minutes.
|
Cohort 1: 1200 mg Linezolid
600 mL Zyvox as a constant rate IV infusion of 60 minutes.
|
Moxifloxacin 400 mg
|
|---|---|---|---|---|
|
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
|
223.49 microgram (ug)*hours (hr)/mL
Standard Deviation 47.372
|
346.89 microgram (ug)*hours (hr)/mL
Standard Deviation 77.867
|
—
|
—
|
|
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 last
|
211.26 microgram (ug)*hours (hr)/mL
Standard Deviation 48.542
|
332.26 microgram (ug)*hours (hr)/mL
Standard Deviation 71.313
|
—
|
—
|
SECONDARY outcome
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 infusionPopulation: PK parameter analysis population
Outcome measures
| Measure |
Cohort 1: Placebo
n=9 Participants
600 milliliters (mL) saline as a constant rate intravenous (IV) infusion of 60 minutes.
|
Cohort 1: 900 mg Linezolid
n=9 Participants
450 mL Zyvox plus 150 mL saline as a constant rate IV infusion of 60 minutes.
|
Cohort 1: 1200 mg Linezolid
600 mL Zyvox as a constant rate IV infusion of 60 minutes.
|
Moxifloxacin 400 mg
|
|---|---|---|---|---|
|
Cohort 1: Maximum Observed Plasma Concentration (Cmax)
|
22.3 ug/mL
Standard Deviation 3.681
|
29.37 ug/mL
Standard Deviation 6.080
|
—
|
—
|
SECONDARY outcome
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 infusionPopulation: PK parameter analysis population
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Outcome measures
| Measure |
Cohort 1: Placebo
n=9 Participants
600 milliliters (mL) saline as a constant rate intravenous (IV) infusion of 60 minutes.
|
Cohort 1: 900 mg Linezolid
n=9 Participants
450 mL Zyvox plus 150 mL saline as a constant rate IV infusion of 60 minutes.
|
Cohort 1: 1200 mg Linezolid
600 mL Zyvox as a constant rate IV infusion of 60 minutes.
|
Moxifloxacin 400 mg
|
|---|---|---|---|---|
|
Cohort 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) and Plasma Decay Half-Life (t1/2)
Tmax
|
1.0 hr
Interval 1.0 to 1.5
|
1.0 hr
Interval 1.0 to 1.52
|
—
|
—
|
|
Cohort 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) and Plasma Decay Half-Life (t1/2)
t1/2
|
6.9 hr
Interval 5.0 to 10.3
|
7.1 hr
Interval 5.1 to 11.9
|
—
|
—
|
SECONDARY outcome
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 infusionPopulation: PK parameter analysis population
Drug clearance = Dose / AUC inf
Outcome measures
| Measure |
Cohort 1: Placebo
n=9 Participants
600 milliliters (mL) saline as a constant rate intravenous (IV) infusion of 60 minutes.
|
Cohort 1: 900 mg Linezolid
n=9 Participants
450 mL Zyvox plus 150 mL saline as a constant rate IV infusion of 60 minutes.
|
Cohort 1: 1200 mg Linezolid
600 mL Zyvox as a constant rate IV infusion of 60 minutes.
|
Moxifloxacin 400 mg
|
|---|---|---|---|---|
|
Cohort 1: Clearance of Linezolid (CL)
|
1.0173 mL/minute (min)/kilogram (kg)
Standard Deviation 0.14637
|
0.8813 mL/minute (min)/kilogram (kg)
Standard Deviation 0.16623
|
—
|
—
|
SECONDARY outcome
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 infusionPopulation: PK parameter analysis population
Vss = (mean residence time \[The average total time molecules of a given dose spend in the body\] extrapolated to infinity) multiplied by CL
Outcome measures
| Measure |
Cohort 1: Placebo
n=9 Participants
600 milliliters (mL) saline as a constant rate intravenous (IV) infusion of 60 minutes.
|
Cohort 1: 900 mg Linezolid
n=9 Participants
450 mL Zyvox plus 150 mL saline as a constant rate IV infusion of 60 minutes.
|
Cohort 1: 1200 mg Linezolid
600 mL Zyvox as a constant rate IV infusion of 60 minutes.
|
Moxifloxacin 400 mg
|
|---|---|---|---|---|
|
Cohort 1: Steady-State Volume of Distribution (Vss)
|
0.6016 L/kg
Standard Deviation 0.06869
|
0.5776 L/kg
Standard Deviation 0.04605
|
—
|
—
|
SECONDARY outcome
Timeframe: 0.5, 1, 2, 4, 8, 12, 24 hours post-dosePopulation: PK parameter analysis population
A measure of dispersion is not available.
Outcome measures
| Measure |
Cohort 1: Placebo
n=40 Participants
600 milliliters (mL) saline as a constant rate intravenous (IV) infusion of 60 minutes.
|
Cohort 1: 900 mg Linezolid
n=40 Participants
450 mL Zyvox plus 150 mL saline as a constant rate IV infusion of 60 minutes.
|
Cohort 1: 1200 mg Linezolid
600 mL Zyvox as a constant rate IV infusion of 60 minutes.
|
Moxifloxacin 400 mg
|
|---|---|---|---|---|
|
Cohort 2: Mean Time-Matched Difference in QTcF Intervals Between Moxifloxacin and Placebo
1 hour
|
429.50 msec
|
422.67 msec
|
—
|
—
|
|
Cohort 2: Mean Time-Matched Difference in QTcF Intervals Between Moxifloxacin and Placebo
2 hours
|
430.07 msec
|
419.80 msec
|
—
|
—
|
|
Cohort 2: Mean Time-Matched Difference in QTcF Intervals Between Moxifloxacin and Placebo
4 hours
|
428.29 msec
|
418.45 msec
|
—
|
—
|
|
Cohort 2: Mean Time-Matched Difference in QTcF Intervals Between Moxifloxacin and Placebo
8 hours
|
420.53 msec
|
411.13 msec
|
—
|
—
|
|
Cohort 2: Mean Time-Matched Difference in QTcF Intervals Between Moxifloxacin and Placebo
12 hours
|
419.02 msec
|
411.98 msec
|
—
|
—
|
|
Cohort 2: Mean Time-Matched Difference in QTcF Intervals Between Moxifloxacin and Placebo
24 hours
|
421.99 msec
|
415.47 msec
|
—
|
—
|
|
Cohort 2: Mean Time-Matched Difference in QTcF Intervals Between Moxifloxacin and Placebo
0.5 hour
|
423.11 msec
|
419.84 msec
|
—
|
—
|
SECONDARY outcome
Timeframe: 0.5, 1, 2, 4, 8, 12, 24 hours post-dosePopulation: PK parameter analysis population
A measure of dispersion is not available.
Outcome measures
| Measure |
Cohort 1: Placebo
n=40 Participants
600 milliliters (mL) saline as a constant rate intravenous (IV) infusion of 60 minutes.
|
Cohort 1: 900 mg Linezolid
n=40 Participants
450 mL Zyvox plus 150 mL saline as a constant rate IV infusion of 60 minutes.
|
Cohort 1: 1200 mg Linezolid
n=40 Participants
600 mL Zyvox as a constant rate IV infusion of 60 minutes.
|
Moxifloxacin 400 mg
|
|---|---|---|---|---|
|
Cohort 2: Mean Time-Matched Difference in Uncorrected QT Intervals Between Linezolid 600 mg and 1200 mg Compared to Placebo
0.5 hour
|
424.08 msec
|
422.60 msec
|
420.60 msec
|
—
|
|
Cohort 2: Mean Time-Matched Difference in Uncorrected QT Intervals Between Linezolid 600 mg and 1200 mg Compared to Placebo
1 hour
|
422.25 msec
|
414.80 msec
|
410.06 msec
|
—
|
|
Cohort 2: Mean Time-Matched Difference in Uncorrected QT Intervals Between Linezolid 600 mg and 1200 mg Compared to Placebo
2 hours
|
421.15 msec
|
415.40 msec
|
406.76 msec
|
—
|
|
Cohort 2: Mean Time-Matched Difference in Uncorrected QT Intervals Between Linezolid 600 mg and 1200 mg Compared to Placebo
4 hours
|
420.58 msec
|
419.66 msec
|
418.40 msec
|
—
|
|
Cohort 2: Mean Time-Matched Difference in Uncorrected QT Intervals Between Linezolid 600 mg and 1200 mg Compared to Placebo
8 hours
|
405.30 msec
|
399.66 msec
|
406.40 msec
|
—
|
|
Cohort 2: Mean Time-Matched Difference in Uncorrected QT Intervals Between Linezolid 600 mg and 1200 mg Compared to Placebo
12 hours
|
398.85 msec
|
396.56 msec
|
398.96 msec
|
—
|
|
Cohort 2: Mean Time-Matched Difference in Uncorrected QT Intervals Between Linezolid 600 mg and 1200 mg Compared to Placebo
24 hours
|
416.38 msec
|
415.80 msec
|
419.06 msec
|
—
|
SECONDARY outcome
Timeframe: Predose, 30 minutes, 1, 2, 4, 8, 12 hours post-dosePopulation: PK parameter analysis population
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).
Outcome measures
| Measure |
Cohort 1: Placebo
n=40 Participants
600 milliliters (mL) saline as a constant rate intravenous (IV) infusion of 60 minutes.
|
Cohort 1: 900 mg Linezolid
n=40 Participants
450 mL Zyvox plus 150 mL saline as a constant rate IV infusion of 60 minutes.
|
Cohort 1: 1200 mg Linezolid
600 mL Zyvox as a constant rate IV infusion of 60 minutes.
|
Moxifloxacin 400 mg
|
|---|---|---|---|---|
|
Cohort 2: AUC Inf and AUC Last
AUC Inf
|
141.75 ug *hr/mL
Standard Deviation 36.156
|
328.75 ug *hr/mL
Standard Deviation 79.198
|
—
|
—
|
|
Cohort 2: AUC Inf and AUC Last
AUC Last
|
129.52 ug *hr/mL
Standard Deviation 32.121
|
299.40 ug *hr/mL
Standard Deviation 62.096
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, 30 minutes, 1, 2, 4, 8, 12 hours post-dosePopulation: PK parameter analysis population
Outcome measures
| Measure |
Cohort 1: Placebo
n=40 Participants
600 milliliters (mL) saline as a constant rate intravenous (IV) infusion of 60 minutes.
|
Cohort 1: 900 mg Linezolid
n=40 Participants
450 mL Zyvox plus 150 mL saline as a constant rate IV infusion of 60 minutes.
|
Cohort 1: 1200 mg Linezolid
600 mL Zyvox as a constant rate IV infusion of 60 minutes.
|
Moxifloxacin 400 mg
|
|---|---|---|---|---|
|
Cohort 2: Cmax
|
15.06 ug/mL
Standard Deviation 2.616
|
30.76 ug/mL
Standard Deviation 4.395
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, 30 minutes, 1, 2, 4, 8, 12 hours post-dosePopulation: PK parameter analysis population
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. Tmax is the time to reach Cmax.
Outcome measures
| Measure |
Cohort 1: Placebo
n=40 Participants
600 milliliters (mL) saline as a constant rate intravenous (IV) infusion of 60 minutes.
|
Cohort 1: 900 mg Linezolid
n=40 Participants
450 mL Zyvox plus 150 mL saline as a constant rate IV infusion of 60 minutes.
|
Cohort 1: 1200 mg Linezolid
600 mL Zyvox as a constant rate IV infusion of 60 minutes.
|
Moxifloxacin 400 mg
|
|---|---|---|---|---|
|
Cohort 2: Tmax and t1/2
t1/2
|
6.095 hr
Interval 2.83 to 10.4
|
6.796 hr
Interval 3.12 to 10.5
|
—
|
—
|
|
Cohort 2: Tmax and t1/2
Tmax
|
1.083 hr
Interval 1.0 to 2.0
|
1.1 hr
Interval 1.0 to 2.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, 30 minutes, 1, 2, 4, 8, 12 hours post-dosePopulation: PK parameter analysis population
Drug clearance = Dose / AUC inf
Outcome measures
| Measure |
Cohort 1: Placebo
n=40 Participants
600 milliliters (mL) saline as a constant rate intravenous (IV) infusion of 60 minutes.
|
Cohort 1: 900 mg Linezolid
n=40 Participants
450 mL Zyvox plus 150 mL saline as a constant rate IV infusion of 60 minutes.
|
Cohort 1: 1200 mg Linezolid
600 mL Zyvox as a constant rate IV infusion of 60 minutes.
|
Moxifloxacin 400 mg
|
|---|---|---|---|---|
|
Cohort 2: CL
|
1.2825 mL/min/kg
Standard Deviation 0.36529
|
1.1000 mL/min/kg
Standard Deviation 0.27875
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, 30 minutes, 1, 2, 4, 8, 12 hours post-dosePopulation: PK parameter analysis population
Vss = (mean residence time \[The average total time molecules of a given dose spend in the body\] extrapolated to infinity) multiplied by CL
Outcome measures
| Measure |
Cohort 1: Placebo
n=40 Participants
600 milliliters (mL) saline as a constant rate intravenous (IV) infusion of 60 minutes.
|
Cohort 1: 900 mg Linezolid
n=40 Participants
450 mL Zyvox plus 150 mL saline as a constant rate IV infusion of 60 minutes.
|
Cohort 1: 1200 mg Linezolid
600 mL Zyvox as a constant rate IV infusion of 60 minutes.
|
Moxifloxacin 400 mg
|
|---|---|---|---|---|
|
Cohort 2: Vss
|
0.6418 L/kg
Standard Deviation 0.08353
|
0.6185 L/kg
Standard Deviation 0.06560
|
—
|
—
|
SECONDARY outcome
Timeframe: From the time the subject had taken at least one dose of study treatment up to 5 weeksPopulation: SAS
All observed or volunteered AEs and SAEs regardless of treatment group or suspected causal relationship to the investigational product(s) were reported.
Outcome measures
| Measure |
Cohort 1: Placebo
n=40 Participants
600 milliliters (mL) saline as a constant rate intravenous (IV) infusion of 60 minutes.
|
Cohort 1: 900 mg Linezolid
n=40 Participants
450 mL Zyvox plus 150 mL saline as a constant rate IV infusion of 60 minutes.
|
Cohort 1: 1200 mg Linezolid
n=40 Participants
600 mL Zyvox as a constant rate IV infusion of 60 minutes.
|
Moxifloxacin 400 mg
n=40 Participants
|
|---|---|---|---|---|
|
Cohort 2: Number of Subjects With AEs and SAEs
AEs
|
3 participants
|
7 participants
|
4 participants
|
10 participants
|
|
Cohort 2: Number of Subjects With AEs and SAEs
SAEs
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
Adverse Events
Cohort 1: Placebo
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Cohort 1: 900 mg Linezolid
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Cohort 1: 1200 mg Linezolid
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Cohort 2: Placebo
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Cohort 2: 600 mg Linezolid
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Cohort 2: 1200 mg Linezolid
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Cohort 2: 400 mg Moxifloxacin
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Cohort 1: Placebo
n=9 participants at risk
|
Cohort 1: 900 mg Linezolid
n=9 participants at risk
|
Cohort 1: 1200 mg Linezolid
n=9 participants at risk
|
Cohort 2: Placebo
n=40 participants at risk
|
Cohort 2: 600 mg Linezolid
n=40 participants at risk
|
Cohort 2: 1200 mg Linezolid
n=40 participants at risk
|
Cohort 2: 400 mg Moxifloxacin
n=40 participants at risk
|
|---|---|---|---|---|---|---|---|
|
Eye disorders
Eye pruritus
|
0.00%
0/9
|
0.00%
0/9
|
0.00%
0/9
|
2.5%
1/40
|
2.5%
1/40
|
0.00%
0/40
|
0.00%
0/40
|
|
Gastrointestinal disorders
Abdominal distension
|
0.00%
0/9
|
0.00%
0/9
|
0.00%
0/9
|
0.00%
0/40
|
0.00%
0/40
|
2.5%
1/40
|
0.00%
0/40
|
|
Gastrointestinal disorders
Diarrhoea
|
11.1%
1/9
|
0.00%
0/9
|
11.1%
1/9
|
2.5%
1/40
|
0.00%
0/40
|
0.00%
0/40
|
2.5%
1/40
|
|
Gastrointestinal disorders
Flatulence
|
0.00%
0/9
|
0.00%
0/9
|
0.00%
0/9
|
0.00%
0/40
|
0.00%
0/40
|
0.00%
0/40
|
5.0%
2/40
|
|
Gastrointestinal disorders
Frequent bowel movements
|
0.00%
0/9
|
0.00%
0/9
|
0.00%
0/9
|
0.00%
0/40
|
0.00%
0/40
|
0.00%
0/40
|
2.5%
1/40
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/9
|
0.00%
0/9
|
11.1%
1/9
|
0.00%
0/40
|
0.00%
0/40
|
10.0%
4/40
|
2.5%
1/40
|
|
Gastrointestinal disorders
Tongue discolouration
|
0.00%
0/9
|
0.00%
0/9
|
0.00%
0/9
|
0.00%
0/40
|
2.5%
1/40
|
2.5%
1/40
|
0.00%
0/40
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/9
|
0.00%
0/9
|
0.00%
0/9
|
0.00%
0/40
|
0.00%
0/40
|
2.5%
1/40
|
0.00%
0/40
|
|
General disorders
Hunger
|
0.00%
0/9
|
0.00%
0/9
|
0.00%
0/9
|
0.00%
0/40
|
0.00%
0/40
|
0.00%
0/40
|
2.5%
1/40
|
|
General disorders
Infusion site swelling
|
0.00%
0/9
|
22.2%
2/9
|
0.00%
0/9
|
0.00%
0/40
|
0.00%
0/40
|
0.00%
0/40
|
0.00%
0/40
|
|
General disorders
Oedema peripheral
|
0.00%
0/9
|
0.00%
0/9
|
0.00%
0/9
|
0.00%
0/40
|
0.00%
0/40
|
0.00%
0/40
|
2.5%
1/40
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/9
|
0.00%
0/9
|
0.00%
0/9
|
0.00%
0/40
|
2.5%
1/40
|
0.00%
0/40
|
0.00%
0/40
|
|
Investigations
Urine output decreased
|
0.00%
0/9
|
0.00%
0/9
|
0.00%
0/9
|
0.00%
0/40
|
0.00%
0/40
|
0.00%
0/40
|
2.5%
1/40
|
|
Nervous system disorders
Headache
|
0.00%
0/9
|
0.00%
0/9
|
11.1%
1/9
|
5.0%
2/40
|
0.00%
0/40
|
5.0%
2/40
|
5.0%
2/40
|
|
Nervous system disorders
Hypoaesthesia
|
0.00%
0/9
|
11.1%
1/9
|
0.00%
0/9
|
0.00%
0/40
|
0.00%
0/40
|
0.00%
0/40
|
0.00%
0/40
|
|
Nervous system disorders
Somnolence
|
0.00%
0/9
|
11.1%
1/9
|
0.00%
0/9
|
0.00%
0/40
|
0.00%
0/40
|
0.00%
0/40
|
0.00%
0/40
|
|
Reproductive system and breast disorders
Dysmenorrhoea
|
0.00%
0/9
|
0.00%
0/9
|
0.00%
0/9
|
0.00%
0/40
|
0.00%
0/40
|
5.0%
2/40
|
0.00%
0/40
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/9
|
0.00%
0/9
|
0.00%
0/9
|
0.00%
0/40
|
0.00%
0/40
|
0.00%
0/40
|
2.5%
1/40
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER