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PPT

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PPT

  1. 1. Zelnorm ® (tegaserod maleate) Advisory Committee Presentation Gastrointestinal Drugs July 14, 2004
  2. 2. Introduction John Cutt, PhD <ul><li>Objectives of the Presentation </li></ul><ul><li>Proposed indication </li></ul><ul><li>Review Zelnorm ® Phase III clinical trial information </li></ul><ul><li>Review postmarketing safety data </li></ul>
  3. 3. Introduction (continued) John Cutt, PhD <ul><li>Activity of tegaserod in GI tract </li></ul><ul><li>Clinical development program for chronic constipation </li></ul><ul><li>Zelnorm experience in clinical studies </li></ul><ul><li>Worldwide experience With Zelnorm </li></ul><ul><li>Conclusions </li></ul><ul><li>Agenda, speakers, and consultants </li></ul>
  4. 4. Unmet Need Charlene Prather, MD <ul><li>Division of Gastroenterology and Hepatology </li></ul><ul><li>St. Louis University School of Medicine </li></ul><ul><li>External Presenter </li></ul>
  5. 5. Efficacy and Safety in Chronic Constipation Eslie Dennis, MD Novartis Senior Medical Director, Gastroenterology <ul><li>Background </li></ul><ul><li>Tegaserod—Mechanism of action </li></ul><ul><li>Rationale for use of Zelnorm ® in the treatment of chronic constipation </li></ul><ul><li>Phase III chronic constipation studies </li></ul><ul><li>Pivotal Studies E2301, 2302 </li></ul><ul><li>Study Objectives </li></ul>
  6. 6. Efficacy and Safety in Chronic Constipation (continued) Eslie Dennis, MD, Senior Medical Director <ul><li>Studies E2301, E2301E, E2302 </li></ul><ul><li>Study design </li></ul><ul><li>Inclusion and exclusion criteria </li></ul><ul><li>Patient disposition </li></ul><ul><li>Demographic information and constipation symptoms prior to treatment </li></ul>
  7. 7. Efficacy and Safety in Chronic Constipation (continued) Eslie Dennis, MD, Senior Medical Director <ul><li>Results </li></ul><ul><li>Primary efficacy variable, responder = increase of > 1 CSBM, Wk 1-4 </li></ul><ul><li>Secondary efficacy variable, responder = increase of > 1 CSBM, Wk 1-12 </li></ul><ul><li>Weekly responder rate and complete spontaneous bowel movements </li></ul><ul><li>Further a priori secondary variables </li></ul><ul><ul><li>Satisfaction with bowel habits, stool form, straining </li></ul></ul>
  8. 8. Efficacy and Safety in Chronic Constipation (continued) Eslie Dennis, MD, Senior Medical Director <ul><li>Additional analyses </li></ul><ul><ul><li>Responder = ≥ 3 CSBM/wk during wk 1 – 4 </li></ul></ul><ul><ul><li>Responder = ≥ 3 CSBM/wk during wk 1 - 12 </li></ul></ul><ul><ul><li>Primary efficacy variable </li></ul></ul><ul><ul><ul><li>Responders by baseline bowel movements per wk </li></ul></ul></ul><ul><ul><ul><li>Responders by subgroup </li></ul></ul></ul><ul><ul><ul><li>Patients without IBS-like features </li></ul></ul></ul><ul><li>Efficacy in chronic constipation— summary </li></ul>
  9. 9. Efficacy and Safety in Chronic Constipation (continued) Eslie Dennis, MD, Senior Medical Director <ul><li>Safety in Chronic Constipation—12-wk safety profile </li></ul><ul><li>Exposure </li></ul><ul><li>Most frequent adverse events </li></ul><ul><li>Most frequent leading to discontinuation </li></ul><ul><li>Diarrhea </li></ul><ul><ul><li>Evaluation and management </li></ul></ul><ul><ul><li>No clinically significant consequences </li></ul></ul><ul><li>Serious adverse events </li></ul><ul><li>Laboratory evaluations </li></ul><ul><li>Summary of ECG abnormalities and QTc intervals </li></ul><ul><li>Abdominal and pelvic surgeries </li></ul>
  10. 10. Efficacy and Safety in Chronic Constipation (continued) Eslie Dennis, MD, Senior Medical Director <ul><li>Long-term safety profile (16 months) </li></ul><ul><li>Studies E2301, E2301E1 </li></ul><ul><li>Adverse events >5% </li></ul><ul><li>Conclusions </li></ul><ul><li>Proposed Indication </li></ul>
  11. 11. Safety Overview (continued) Bo Joelsson Head GI Clinical Research and Development <ul><li>Safety data — CC sNDA versus IBS-C NDA </li></ul><ul><li>Summary of patients treated in clinical trials and postmarketing </li></ul><ul><li>Serious adverse events in overall clinical experience </li></ul>
  12. 12. Safety Overview (continued) Bo Joelsson Head GI Clinical Research and Development <ul><li>Special Safety Topics </li></ul><ul><li>Experience in Clinical Trials and Postmarketing </li></ul><ul><li>Diarrhea </li></ul><ul><ul><li>Serious consequences </li></ul></ul><ul><li>Rectal bleeding </li></ul><ul><li>Ischemic colitis </li></ul><ul><li>Cholecystectomies </li></ul><ul><li>Biliary tract disorders </li></ul><ul><li>Ovarian disease </li></ul>
  13. 13. Safety Overview (continued) Bo Joelsson, Novartis, Head GI Clinical Research and Development <ul><li>Safety profile of Zelnorm  supports the use in patients with chronic constipation </li></ul><ul><li>Overall safety conclusions </li></ul>
  14. 14. Benefit/Risk Philip Schoenfeld, MD, MSEd, MSc (Epi) <ul><li>Assistant Professor of Medicine </li></ul><ul><li>University of Michigan School of Medicine </li></ul><ul><li>External presenter </li></ul>

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