Pleconaril for Treatment of the Common Cold FDA Antiviral Drugs Advisory Committee Meeting March 19, 2002

3/27/02


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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

Author: Mark Carpenter