1. Conclusions Sidney Cohen, MD Chairman, Department of Medicine Temple University School of Medicine Philadelphia, Pennsylvania Sidney Cohen, MD Chairman, Department of Medicine Temple University School of Medicine Philadelphia, Pennsylvania

2. CO 2 Irritable Bowel Syndrome (IBS)  Difficult to diagnose and treat  No measurable serologic or gastrointestinal motility marker of IBS  Diagnosis based on a compilation of symptoms  IBS treatment is empiric; no proven efficacious therapies for patients with abdominal pain, bloating, and constipation as their predominant symptoms  Difficult to diagnose and treat  No measurable serologic or gastrointestinal motility marker of IBS  Diagnosis based on a compilation of symptoms  IBS treatment is empiric; no proven efficacious therapies for patients with abdominal pain, bloating, and constipation as their predominant symptoms

3. CO 3 Tegaserod: Pharmacodynamic Effects  Tegaserod has a unique pharmacologic action that addresses the clinical components in IBS patients with abdominal pain, bloating, and constipation –Stimulates the peristaltic reflex, augmenting aboral propulsion –Diminishes visceral sensitivity, reducing pain  Tegaserod has a unique pharmacologic action that addresses the clinical components in IBS patients with abdominal pain, bloating, and constipation –Stimulates the peristaltic reflex, augmenting aboral propulsion –Diminishes visceral sensitivity, reducing pain

4. CO 4 Tegaserod Clinical Trials  Recruited a largely unrestricted population of patients with IBS who identified abdominal pain or discomfort and constipation as their predominant symptoms –Reflective of patients seen in common practice  Recruited a largely unrestricted population of patients with IBS who identified abdominal pain or discomfort and constipation as their predominant symptoms –Reflective of patients seen in common practice

5. CO 5 Tegaserod Clinical Effects: Symptoms of IBS Patients  Global relief of symptoms  Specific IBS symptoms –Abdominal discomfort and pain –Bloating –Constipation Stool frequency Stool consistency  Global relief of symptoms  Specific IBS symptoms –Abdominal discomfort and pain –Bloating –Constipation Stool frequency Stool consistency

6. CO 6 Effect on IBS Symptoms (B301) Placebo12 mg/d Pain score Bloating score *P <.05 versus placebo; † P <.01 versus placebo (change from baseline). * * * * * * * * † † † † † † † † † † † † † † * * * * † † † † * * * * † † † † † † † † † † * * * * * * † † † † † † † † † † † † † † † † † † † † † † † † † † † † † † † † † † † † † † Bowel movements Stool consistency

7. CO 7 Effect on IBS Symptoms (B351) Pain score Bloating score Bowel movements Stool consistency * * * * * * * * * * † † † † † † * * * * * * * * * * † † † † † † † † † † † † † † † † † † † † * * † † † † † † † † * * * * * * † † † † † † † † † † † † † † † † Placebo12 mg/d *P <.05 versus placebo; † P <.01 versus placebo (change from baseline). Significant: at least mild;  2 on a 6-point scale.

8. CO 8 Effect on IBS Symptoms (B307) Pain score Bloating score Bowel movements Stool consistency * * † † † † † † † † † † † † † † † † † † * * † † † † † † † † † † † † * * * * * * * * * * * * * * Placebo4-12 mg/d *P <.05 versus placebo; † P <.01 versus placebo (change from baseline). Significant: at least mild;  2 on a 6-point scale.

9. CO 9 Phase III Studies: Complete, Considerable, or Somewhat Relief B351 B301 B307 *P <.05 versus placebo. † P <.01 versus placebo. * * * * † † † * * * * * * † † * * † * † * *

10. CO 10 Phase III Studies Complete or Considerable Relief B351 B301 B307 *P <.05 versus placebo. † P <.01 versus placebo. * † * * * * † * * † † † † † † † †

11. CO 11 Summary  Tegaserod at a dose of 12 mg/d (6 mg BID) has been demonstrated to be effective in the treatment of abdominal pain, bloating, and constipation in IBS  Tegaserod is safe and well-tolerated –Diarrhea is the only drug-related side effect, which is self limiting and infrequently led to discontinuation  Tegaserod at a dose of 12 mg/d (6 mg BID) has been demonstrated to be effective in the treatment of abdominal pain, bloating, and constipation in IBS  Tegaserod is safe and well-tolerated –Diarrhea is the only drug-related side effect, which is self limiting and infrequently led to discontinuation

12. CO 12 Conclusion  Unique pharmacologic action that addresses the clinical components of constipation- predominant IBS –Enhances the peristaltic reflex and decreases visceral sensitivity  Positive and significant clinical effect in reducing abdominal pain, bloating, constipation and stool consistency, the hallmark symptoms of IBS  Effective in providing overall or global relief of the symptoms of IBS  Unique pharmacologic action that addresses the clinical components of constipation- predominant IBS –Enhances the peristaltic reflex and decreases visceral sensitivity  Positive and significant clinical effect in reducing abdominal pain, bloating, constipation and stool consistency, the hallmark symptoms of IBS  Effective in providing overall or global relief of the symptoms of IBS

13. CO 13 Bottom Line  In a clinical syndrome in which there has been no proven treatment, tegaserod is a strong first step in the management of constipation-predominant IBS