Briefing Document
Drug Substance Date
Budesonide/Formoterol 4 February 2010
SYMBICORT (budesonide/formoterol) Inhalation Aerosol Briefing Document: Design and Feasibility Assessments for a Post-Marketing Safety Study
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Briefing Document Drug Substance Budesonide/Formoterol Date 4 February 2010
TABLE OF CONTENTS
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TITLE PAGE ...........................................................................................................1 TABLE OF CONTENTS.........................................................................................2 NAMING CONVENTIONS....................................................................................6 1. 1.1 2. 2.1 2.2 2.3 2.4 2.5 3. 3.1 3.2 3.2.1 3.2.2 3.2.2.1 3.2.2.2 3.3 4. 4.1 4.1.1 4.1.2 4.2 4.2.1 4.2.1.1 4.2.1.2 4.2.1.3 4.2.2 4.2.3 4.2.4 4.2.5 INTRODUCTION ...................................................................................................7 Regulatory Background ...........................................................................................7 GENERAL SAMPLE SIZE CONSIDERATIONS ...............................................11 Control Event Rate of 1 in 10,000 .........................................................................12 Control Event Rate of 1 in 1,000 ...........................................................................13 Control Event Rate of 1 in 100 ..............................................................................13 Estimation-based Approach to Trial Size ..............................................................14 Summary of General Sample Size Considerations ................................................15 ENDPOINTS OF INTEREST: EVENT RATES AND CLINICAL RELEVANCE........................................................................................................16 SYMBICORT Clinical Study Data........................................................................16 Serious Asthma-Related Event Endpoints .............................................................17 Asthma-Related Death and Asthma-Related Intubation........................................17 Composite Endpoints .............................................................................................18 FDA Asthma Composite Endpoint: Death, Intubation, and Hospitalization.........18 AstraZeneca-Expanded FDA Asthma Composite Endpoint: Death, Intubation, Hospitalization, and ED Visits (Systemic/Oral Corticosteroids) ........21 Summary of Endpoint Considerations ...................................................................23 POST-MARKETING SAFETY STUDY OPTIONS ............................................24 Randomized Clinical Trial .....................................................................................24 Other Clinical Considerations................................................................................24 Randomized Clinical Trial Outline ........................................................................24 Randomized Clinical Trial Study Design and Conduct Considerations ................27 Event Rates in Specific Subpopulations ................................................................27 African-American Patients.....................................................................................27 Pediatric and Adolescent Patients ..........................................................................27 Enriched Populations .............................................................................................28 Treatment Comparators .........................................................................................29 Additional Study Design Elements ........................................................................29 Treatment Duration ................................................................................................29 Regions ..................................................................................................................30 2

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