Title: Phase III efficacy and safety of RU-0211, a novel chloride channel activator, for the treatment of constipation
Abstract: and placebo (P, n=447) on constipation symptoms and stool frequency over 12 weeks in adults with CC.This was followed by a 4-week treatment free withdrawal period.Response was prospectively defined as minimum 7 days treatment and an increase of > = 1 CSBM/ week compared to baseline.The primary efficacy variable was the response during the first month of treatment.Secondary endpoints included response over 3 months and intensity of specific symptoms (bloating/distention, abdominal discomfort/pain, straining, stool consistency).Satisfaction with bowel habits and overall bothersomeness of symptoms were also assessed.Results: 90% of pts were women, with CC symptoms for an average of 19 years.Both T 2 mg b.i.d, and 6 mg b.i.d, were superior to P in increasing CSBM/week either after 4 weeks (Response rate 41.4%, 43.2% and 24.9% respectively, p<0.0001 vs P) and 12 weeks (40.3%, 44.8% and 26.9% respectively p<0.O001 vs P).Both doses decreased abdominal discomfort/pain, bloating/distention, straining and stool consistency (p< 0.05 for all symptoms vs P).Satisfaction with bowel habits was improved and overall bothersomeness of symptoms decreased (p< 0.05 for both doses vs P).The response was rapid and sustained over 12 weeks.During the withdrawal period, all parameters measured with T (2 or 6 mg b.i.d.) became indistinguishable from P within 2 weeks.T was well tolerated.The most frequem adverse events reported were headaches and nasopharyngitis, both occurring more commonly in pts receiving P than pts treated with T. Conclusions: Tegaserod (2 mg b.i.d. and 6 mg b.i.d.) is effective in the treatment of CC and its related symptoms.The effect is rapid and sustained over at least 3 months.Sponsored by Novartis Pharmaceutieal~ Corporation 372 Phase Ill Eflqcacy and Safety of RU..