Budesonide Foam for Inducing Remission in Active Mild-to-moderate Ulcerative Proctitis or Ulcerative Proctosigmoiditis: Results of Two Randomized, Placebo-controlled Trials (2013)

Purpose: To evaluate the efficacy and safety of rectally administered budesonide foam (BF) in patients with active mild-to-moderate ulcerative proctitis (UP) or ulcerative proctosigmoiditis (UPS). Methods: Adult subjects with mild-to-moderately active UP or UPS were enrolled in one of two identically-designed, phase 3, multicenter, randomized, double-blind, placebo (PBO)-controlled studies (BUCF3001 and BUCF3002). Patients with a baseline Modified Mayo Disease Activity Index (MMDAI) score between 5 and 10, inclusive, with subscale ratings of ≥ 2 for both endoscopic appearance and rectal bleeding, were randomized 1:1 to receive BF (2 mg/25 mL BID for 2 weeks, followed by 2 mg/25 mL QD for 4 weeks) or PBO. The primary endpoint was the proportion of patients achieving remission at 6 weeks, defined as endoscopy score ≤1, rectal bleeding score of 0, and improvement or no change from baseline in stool frequency subscales of the MMDAI. Proportions of responders were compared between treatment groups using a logistic regression model. Safety assessments were conducted. Results: Demographic and baseline characteristics of randomized subjects were similar between the two trials (BUCF3001: n = 265, 57.4% females, mean MMDAI score: 7.9; BUCF3002: n = 281, 55.5% females, mean MMDAI score: 8.0) and between treatment groups within each trial. The proportion of subjects achieving remission was significantly greater for BF vs. PBO in both BUCF3001 (38.3% vs. 25.8%, p = 0.032) and BUCF3002 (44.0% vs. 22.4%, p < 0.0001) (Figure). For the pre-specified key secondary endpoints of endoscopy score ≤1 and rectal bleeding score of 0, BF was superior to PBO in both studies (Figure). Treatment-emergent adverse events (TEAEs), pooled across studies, were reported by 45.9% and 36.3% of BF and PBO subjects, respectively. Serious treatment emergent AEs were reported by five and three subjects in the pooled BF and PBO groups, respectively. There were no deaths.Figure: Primary and Key Secondary Endpoints at 6 Weeks.Conclusion: Data from two independently conducted trials support the efficacy and safety of rectally administered budesonide foam for achieving remission from mildly to moderately active ulcerative proctitis or ulcerative proctosigmoiditis. Disclosure - William J Sandborn - Consultant for Salix Brian Bosworth - Consultant/speaking: Salix, Shire, Abbott, Grant/research support: Salix, Pfizer, Janssen Salam Zakko - Principal investigator, Grant Support, Speaker Bureau, Stockholder: Salix Glenn Gordon: Principal investigator, Speaker Bureau: Salix Robert L. Rolleri: employee of and holds stock in Salix Pharmaceuticals, Inc. Jing Yu: employee of and holds stock in Salix Pharmaceuticals, Inc. Andrew C. Barrett: employee of and holds stock in Salix Pharmaceuticals, Inc. Enoch Bortey: employee of and holds stock in Salix Pharmaceuticals, Inc. Craig Paterson: employee of and holds stock in Salix Pharmaceuticals, Inc. William P. Forbes: officer and employee of and holds stock in Salix Pharmaceuticals, Inc.