Table of Contents
Pleconaril for Treatment of the Common Cold FDA Antiviral Drugs Advisory Committee Meeting March 19, 2002
Agenda
Pleconaril
Indication
Impact of the Common Cold
Current Management of Viral Respiratory Illness
Human Picornaviruses
Incidence of Colds
Natural History of Picornavirus Colds in Adults
Picornavirus Colds Pathogenesis
Current Management of Colds
Current Management of Colds
Impact of Common Colds: Summary
Preclinical Profile and Clinical Pharmacology
Pleconaril Mechanism of Action
Distribution of Susceptibility to Pleconaril
Human Pharmacokinetic Profile
Human Pharmacokinetic Profile
Human Metabolism
Effects of Pleconaril on CYP 450
Oral Theophylline CYP 1A2 Probe Study
IV Midazolam CYP 3A Probe Study
Oral Contraceptive Interaction Study
Preclinical Safety
Clinical Efficacy and Safety
Clinical Development of Pleconaril for the Common Cold
Insights Gained from Phase II Studies
Pivotal Phase III Clinical Trials
Entry Criteria
Study Design
Patient Self-Assessments (Days 1-18)
Virological Assessments
Study Analysis Populations
PPT Slide
PPT Slide
Primary Efficacy Endpoint
Primary Efficacy Endpoint: ITT-I
PPT Slide
Consistency of Treatment Benefit: ITT-I
Primary Endpoint: ITT and RT-PCR Negative
Antiviral Effect: Virus Culture
Secondary Clinical Endpoints
Resolution of Individual Symptoms: ITT-I
Summary of Secondary Endpoints: ITT-I
Patients with Bothersome Symptoms by Day (Post Hoc)
Total Symptom Severity (Post Hoc)
Subgroup Analyses
Subgroup Analyses
Efficacy by Smoking Status: ITT-I (Pooled)
Antiviral Effect by Smoking Status
Total Symptom Severity by Smoking Status (Post Hoc)
Clinical Virology
Distribution of Baseline Susceptibility
Primary Endpoint: Baseline Susceptibility
Post-Baseline Viruses with Reduced Susceptibility
Clinical Outcome
Post-Baseline Viruses with Reduced Susceptibility
Overall Efficacy Conclusions
Clinical Safety
Exposure to Pleconaril
Adverse Events (=5%)
Severe Adverse Events (=0.5%)
Discontinuations Due to Adverse Events (=0.3%)
Clinical Laboratory Safety
Six-Week Prophylaxis Study
Menstrual Disorders: Six-Week Study
Menstrual Disorders: Summary
Pregnancy: Six Week Study
Pregnancy: 5-7 Day Treatment Studies
Safety Conclusions: 5 Day Treatment
Planned Clinical Studies
Drug Interaction Studies
Treatment Studies
Benefit-Risk Summary
Benefits of Pleconaril
Risks: Drug Interactions
Guidance for Physicians
Benefit-Risk Conclusions
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