Bacterial InfectionsPhase 1NCT00795145
A Study To Assess The Effect Of Linezolid On QTc Interval
A Phase 1 study testing Linezolid 900 mg, Linezolid 1200 mg and Linezolid 600 mg in people with Bacterial Infections, run by Pfizer at 1 site in Singapore.
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. Read more about this study
- Who is it for?
- Ages 21 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Bacterial Infections
- What is being tested?
- Linezolid 900 mg, Linezolid 1200 mg and Linezolid 600 mg
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 49 participants
- Where
- 1 siteSingapore
- Study dates
- Dec 2008to Mar 2009
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
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
- Being tested
- Placebo, Linezolid 900 mg, Linezolid 1200 mg, Linezolid 600 mg, Moxifloxacin 400 mg
- Keywords
- Linezolid, QTc interval, pharmacokinetics, therapeutic dose, supra-therapeutic dose
- Medical subject headings
- Bacterial Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Intravenous, Placebo control for blinding, Normal Saline, Single dose
Linezolid 900 mgDrug
Also called Zyvox
Intravenous, 900 mg linezolid, single dose
Linezolid 1200 mgDrug
Also called Zyvox
Intravenous, 1200 mg linezolid, single dose
PlaceboDrug
Intravenous, Placebo control for blinding, Normal Saline, Single dose
Linezolid 600 mgDrug
Also called Zyvox
Intravenous, 600 mg linezolid, single dose
Linezolid 1200 mgDrug
Also called Zyvox
Intravenous, 1200 mg linezolid, single dose
Moxifloxacin 400 mgDrug
Also called Avelox
Oral, 400 mg moxifloxacin, single dose
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1: Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
| Cohort 1: 900 mg linezolid | Experimental | Not described Receives: Drug: Linezolid 900 mg |
| Cohort 1: 1200 mg linezolid | Experimental | Not described Receives: Drug: Linezolid 1200 mg |
| Cohort 2: Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
| Cohort 2: 600 mg linezolid | Experimental | Not described Receives: Drug: Linezolid 600 mg |
| Cohort 2: 1200 mg linezolid | Experimental | Not described Receives: Drug: Linezolid 1200 mg |
| Cohort 2: 400 mg Moxifloxacin | Active comparator | Not described Receives: Drug: Moxifloxacin 400 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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)
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).
Measured: 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)
Measured: 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)
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Measured: 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)
Drug clearance = Dose / AUC inf
Measured: 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)
Vss = (mean residence time [The average total time molecules of a given dose spend in the body] extrapolated to infinity) multiplied by CL
Measured: 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 2: Mean Time-Matched Difference in QTcF Intervals Between Moxifloxacin and Placebo
A measure of dispersion is not available.
Measured: 0.5, 1, 2, 4, 8, 12, 24 hours post-dose
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.
Measured: 0.5, 1, 2, 4, 8, 12, 24 hours post-dose
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).
Measured: Predose, 30 minutes, 1, 2, 4, 8, 12 hours post-dose
Cohort 2: Cmax
Measured: Predose, 30 minutes, 1, 2, 4, 8, 12 hours post-dose
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.
Measured: Predose, 30 minutes, 1, 2, 4, 8, 12 hours post-dose
Cohort 2: CL
Drug clearance = Dose / AUC inf
Measured: Predose, 30 minutes, 1, 2, 4, 8, 12 hours post-dose
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
Measured: Predose, 30 minutes, 1, 2, 4, 8, 12 hours post-dose
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.
Measured: From the time the subject had taken at least one dose of study treatment up to 5 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Nov 2008 (estimated)
- Study startDec 2008
- Primary completionMar 2009
- Study completionMar 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Bacterial InfectionsStudies of the same condition, open and under way.
- More trials run by PfizerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Pfizer CT.gov Call Center, Study director, Pfizer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00795145
- Sponsor's protocol ID
- A5951151
- Status last verified
- May 2010
- First submitted
- 20 Nov 2008
- Last updated
- 22 Jun 2010
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00795145
- Acronym / sponsor ID
- A5951151
- Conditions
- Bacterial Infections
- Keywords
- Linezolid, QTc interval, pharmacokinetics, therapeutic dose, supra-therapeutic dose
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 49 participants (actual)
- Lead sponsor
- PfizerIndustry (pharma, biotech, devices)
- Study start
- Dec 2008
- Primary completion
- Mar 2009 (actual)
- Study completion
- Mar 2009 (actual)
- First posted
- 21 Nov 2008 (estimated)
- Results
- Posted 22 Jun 2010
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 21 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlaceboIntravenous, Placebo control for blinding, Normal Saline, Single dose | Drug | Cohort 1: Placebo |
| Linezolid 900 mgAlso: ZyvoxIntravenous, 900 mg linezolid, single dose | Drug | Cohort 1: 900 mg linezolid |
| Linezolid 1200 mgAlso: ZyvoxIntravenous, 1200 mg linezolid, single dose | Drug | Cohort 1: 1200 mg linezolid |
| PlaceboIntravenous, Placebo control for blinding, Normal Saline, Single dose | Drug | Cohort 2: Placebo |
| Linezolid 600 mgAlso: ZyvoxIntravenous, 600 mg linezolid, single dose | Drug | Cohort 2: 600 mg linezolid |
| Linezolid 1200 mgAlso: ZyvoxIntravenous, 1200 mg linezolid, single dose | Drug | Cohort 2: 1200 mg linezolid |
| Moxifloxacin 400 mgAlso: AveloxOral, 400 mg moxifloxacin, single dose | Drug | Cohort 2: 400 mg Moxifloxacin |
Primary outcome
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
All observed or volunteered AEs and SAEs regardless of treatment group or suspected causal relationship to the investigational product(s) were reported.
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
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.
13 secondary outcomes
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
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
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
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
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
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
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
Cohort 2: AUC Inf and AUC Last
Time frame: Predose, 30 minutes, 1, 2, 4, 8, 12 hours post-dose
Cohort 2: Cmax
Time frame: Predose, 30 minutes, 1, 2, 4, 8, 12 hours post-dose
Cohort 2: Tmax and t1/2
Time frame: Predose, 30 minutes, 1, 2, 4, 8, 12 hours post-dose
Cohort 2: CL
Time frame: Predose, 30 minutes, 1, 2, 4, 8, 12 hours post-dose
Cohort 2: Vss
Time frame: Predose, 30 minutes, 1, 2, 4, 8, 12 hours post-dose
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2010.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- To obtain contact information for a study center near you, click here.Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pfizer CT.gov Call Center study director
Pfizer
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Linezolid 900 mg, Linezolid 1200 mg and Linezolid 600 mg in people with Bacterial Infections, run by Pfizer at 1 site in Singapore.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Jun 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Jun 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jun 2010.