A Study To Assess The Effect Of Linezolid On QTc Interval

This study has been completed.

Sponsor:

Information provided by:

Pfizer

ClinicalTrials.gov Identifier:

NCT00795145

First received: November 20, 2008

Last updated: May 17, 2010

Last verified: May 2010

History of Changes

Results First Received: March 2, 2010

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Pharmacokinetics/Dynamics Study; Intervention Model: Crossover Assignment; Masking: Double Blind (Subject, 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

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups

	Description
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.

Participant Flow for 2 periods

Period 1: Cohort 1

	Cohort 1: Sequence 1	Cohort 1: Sequence 2	Cohort 1: Sequence 3
STARTED	3	3	3
COMPLETED	3	3	3
NOT COMPLETED	0	0	0

Period 2: Cohort 2

	Cohort 2: Sequence 1	Cohort 2: Sequence 2	Cohort 2: Sequence 3	Cohort 2: Sequence 4
STARTED	10	10	10	10
COMPLETED	10	10	10	10
NOT COMPLETED	0	0	0	0

Baseline Characteristics

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Reporting Groups

	Description
Cohort 1: Placebo, Linezolid 900 mg and 1200 mg	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	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	Total of all reporting groups

Baseline Measures

	Cohort 1: Placebo, Linezolid 900 mg and 1200 mg	Cohort 2: Placebo, Linezolid 600 mg and 1200 mg, Moxifloxacin	Total
Number of Participants [units: participants]	9	40	49
Age, Customized [units: participants]
<18 years	0	0	0
18 - 44 years	8	36	44
45 - 64 years	1	4	5
>=65 years	0	0	0
Gender [units: participants]
Female	4	20	24
Male	5	20	25

Outcome Measures

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1. Primary:

Cohort 1: Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: From the time the subject had taken at least one dose of study treatment up to 5 weeks ]

Show Outcome Measure 1

2. 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 [ Time Frame: 0.5, 1, 2, 4, 8, 12, 24 hours post-dose ]

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3. 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) [ 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 ]

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4. Secondary:

Cohort 1: Maximum Observed Plasma Concentration (Cmax) [ 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 ]

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5. Secondary:

Cohort 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) and Plasma Decay Half-Life (t1/2) [ 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 ]

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6. Secondary:

Cohort 1: Clearance of Linezolid (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 ]

Show Outcome Measure 6

7. Secondary:

Cohort 1: Steady-State Volume of Distribution (Vss) [ 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 ]

Show Outcome Measure 7

8. Secondary:

Cohort 2: Mean Time-Matched Difference in QTcF Intervals Between Moxifloxacin and Placebo [ Time Frame: 0.5, 1, 2, 4, 8, 12, 24 hours post-dose ]

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9. Secondary:

Cohort 2: Mean Time-Matched Difference in Uncorrected QT Intervals Between Linezolid 600 mg and 1200 mg Compared to Placebo [ Time Frame: 0.5, 1, 2, 4, 8, 12, 24 hours post-dose ]

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10. Secondary:

Cohort 2: AUC Inf and AUC Last [ Time Frame: Predose, 30 minutes, 1, 2, 4, 8, 12 hours post-dose ]

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11. Secondary:

Cohort 2: Cmax [ Time Frame: Predose, 30 minutes, 1, 2, 4, 8, 12 hours post-dose ]

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12. Secondary:

Cohort 2: Tmax and t1/2 [ Time Frame: Predose, 30 minutes, 1, 2, 4, 8, 12 hours post-dose ]

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13. Secondary:

Cohort 2: CL [ Time Frame: Predose, 30 minutes, 1, 2, 4, 8, 12 hours post-dose ]

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14. Secondary:

Cohort 2: Vss [ Time Frame: Predose, 30 minutes, 1, 2, 4, 8, 12 hours post-dose ]

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15. Secondary:

Cohort 2: Number of Subjects With AEs and SAEs [ Time Frame: From the time the subject had taken at least one dose of study treatment up to 5 weeks ]

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Serious Adverse Events

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Other Adverse Events

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More Information

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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.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: 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.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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Results Point of Contact:

Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
phone: 1-800-718-1021
e-mail: ClinicalTrials.govCallCenter@pfizer.com

No publications provided

Responsible Party:	Director, Clinical Trial Disclosure Group, Pfizer, Inc.
ClinicalTrials.gov Identifier:	NCT00795145 History of Changes
Other Study ID Numbers:	A5951151
Study First Received:	November 20, 2008
Results First Received:	March 2, 2010
Last Updated:	May 17, 2010
Health Authority:	United States: Food and Drug Administration

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