Table of Contents
Anti-Infective Advisory Committee March 24, 2000
Pharmacia & Upjohn is Seeking Approval of Linezolid for:
Linezolid - Presentation Agenda
Most Common Nosocomial Blood Culture Isolates (US Hospitals)
Increasing Incidence of Resistance in the US MRSE, MRSA, VRE, PRSP, GISA 1980-1999
Limitations of Current Antibiotics for Serious Gm+ Infections
New Antibacterials are Required to Treat Gm+ Bacterial Infections
Linezolid: First Antibacterial from a New Structural Class
Linezolid Profile
Linezolid : Unique Site of Action
Linezolid Profile (cont.)
Efficacy - Phase III Studies in Adults
In Vitro Susceptibility Database
Streptococci: Preclinical Summary
S. pneumoniae Sentry and Phase III Data
Staphylococci: Preclinical Summary
S. aureus Sentry and Phase III Data
Enterococci: Preclinical Summary
Enterococcus spp Sentry and Phase III Data
Laboratory Prediction of Resistance Mechanism
Characterization of Lab-derived Mutants
Linezolid Efficacious in Key Animal Models
Summary
Linezolid - Presentation Agenda
Steady-State Plasma Concentrations Linezolid PO 600 mg BID (Mean ? SD, N=16)
Linezolid Absolute Bioavailability After a Single IV or Oral 375 mg Dose (Mean ? SD, N = 12)
Clinical Pharmacology
Linezolid Metabolism
Linezolid Elimination
Clinical Pharmacology Summary
PPT Slide
Efficacy - Phase III Studies in Adults
Complicated SST (55)
Clinical Cure Complicated SST (55)
Pathogen Eradication Rates Complicated SST (55)
Uncomplicated SST (39A)
Clinical Cure Uncomplicated SST (39A)
Pathogen Eradication Rates Uncomplicated SST (39A)
Conclusions: SST
Efficacy - Phase III Studies in Adults
Patients Hospitalized with CAP (33)
Clinical Cure Patients Hospitalized with CAP (33)
Pathogen Eradication Rates Hospitalized CAP (33)
Outpatients with CAP (51)
Clinical Cure Outpatients with CAP (51)
Pathogen Eradication Rates Outpatient CAP (51)
Nosocomial Pneumonia (48A)
Clinical Cure Nosocomial Pneumonia (48A)
Pathogen Eradication Rates Nosocomial Pneumonia (48A)
Conclusions: Pneumonia
Efficacy - Phase III Studies in Adults
Methicillin-Resistant Staphylococcus (31)
Primary Source of Infection (31)
Clinical Cure - All Patients (31)
Clinical Cure - Complicated SST (31)
Clinical Cure - Nosocomial Pneumonia (31)
MRSA Pathogen Eradication (31)
VRE Study Design Considerations
VRE (54A, 54)
VRE - Primary Infection Source
Clinical Cure VRE (54A)
Clinical Cure - Interim Results VRE (54)
Clinical Cure (CE) by Diagnosis VRE (54A)
Clinical Cure (CE) by Diagnosis - Interim Results VRE (54)
Microbiologic Outcome (ME) in VRE (54A)
Compassionate Use (25)
Clinical Cure (CE) Compassionate Use (25)
Conclusions: VRE
Efficacy Conclusions
Resistance Surveillance
Resistance Development
PPT Slide
Early Development Issues
Drug Interactions with MAOIs
Phase I MAOI Studies
Linezolid - Phenylpropanolamine Systolic BP Effects
Phase II Analysis of Potential MAOI-Related Drug Interactions
Phase II MAOI Experience
Phase III Analysis of Potential MAOI-Related Drug Interactions
Phase III MAOI Experience
Blood Pressure Measurements in Phase III Patients with Concomitant MAOI Potentiators
MAOI Conclusions
Safety - Phase III Comparator-Controlled Studies
All AEs ? 2% (1 of 2) Phase III Comparator-Controlled Studies
All AEs ? 2% (2 of 2) Phase III Comparator-Controlled Studies
Drug-Related AEs ? 1% Phase III Comparator-Controlled Studies
Most Common Serious AEs Phase III Comparator-Controlled Studies
Laboratory Assessments
Percent of Patients with Chemistry Assays ? 2 Times Upper Limit of Normal
Cumulative Percentage Over Time - Patients With at Least One Substantially High ALT Value
ALT Values for Linezolid-Treated Patients with Substantially High Values
ALT Values for Comparator-Treated Patients with Substantially High Values
Percent of Patients with Hematology Assays < 75% of Lower Limit of Normal*
Cumulative Percentage Over Time - Patients With at Least One Substantially Low Platelet Count
Platelet Counts for Linezolid-Treated Patients with Substantially Low Values
Platelet Counts for Comparator-Treated Patients with Substantially Low Values
Platelet Conclusions
Safety Conclusions
Linezolid - Presentation Agenda
Linezolid Pediatric Drug Development
Linezolid - Pediatric Use Development Program
Linezolid - Pediatric Use Clinical Pharmacokinetics
Linezolid - Pediatric Use Phase II Study Design
Linezolid - Pediatric Use Most Common Drug-Related Adverse Events
Linezolid - Pediatric Use All Reported Serious Adverse Events
Linezolid - Pediatric Use Conclusions
Linezolid - Presentation Agenda
Linezolid Conclusions
Pharmacia & Upjohn is Seeking Approval of Linezolid for:
|