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OP011 Budesonide MMX® 9 mg for Inducing Remission in Patients with Mild-to-Moderate Ulcerative Colitis Not Adequately Controlled with Oral 5-ASAs

D.T. Rubin*1, R.D. Cohen1, W.J. Sandborn2, G.R. Lichtenstein3, J. Axler4, R. Riddell5, C. Zhu6, A.C. Barrett6, E. Bortey6, W.P. Forbes7

1The University of Chicago, Medicine, Chicago, United States, 2University of California San Diego, UC San Diego Health System, San Diego, United States, 3University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States, 4Toronto Digestive Disease Associates Inc., Toronto, Canada, 5Mt. Sinai Hospital, Pathology and Molecular Medicine, Toronto, Canada, 6Salix Pharmaceuticals, Inc., Raleigh, United States, 7Salix Pharmaceuticals Inc., Raleigh, United States

Background

Budesonide MMX® (B-MMX) is a once-daily, extended release oral formulation designed to provide targeted delivery of budesonide throughout the colon. Here we present data from a prospectively designed, randomised, double-blind, placebo-controlled trial to evaluate the efficacy and safety of B-MMX in patients experiencing an active UC flare despite treatment with an oral 5-ASA.

Methods

Patients with mildly to moderately active UC (UCDAI ≥4 and ≤10) inadequately controlled with oral 5-ASAs were randomised 1:1 to add once-daily B-MMX 9 mg or placebo (PBO) for 8 weeks to their existing 5-ASA. Patients were required to be on a stable, therapeutic dose of an oral 5-ASA (e.g., mesalamine ≥2.4 g/day or equivalent dose of another 5-ASA) throughout the study. Patients who increased their 5-ASA dose or administered other UC therapies were considered non-responders. The primary efficacy endpoint was combined clinical and endoscopic remission at Week 8, as defined by a UCDAI score of ≤1, with subscores of 0 for rectal bleeding, stool frequency and mucosal appearance. Secondary and exploratory endpoints assessed clinical remission (rectal bleeding and stool frequency subscores = 0), endoscopic remission (mucosal appearance subscore = 0) and histological healing (histological activity grade = 0, as assessed via central reading). Patients with missing data were considered non-responders.

Results

Of 510 patients enrolled, 458 (230 B-MMX, 228 PBO) were included in the intent-to-treat population (46% female, mean age: 44.5), which excluded patients with normal baseline mucosal histology or infectious colitis. Combined clinical and endoscopic remission was achieved in a greater percentage of B-MMX-treated patients than PBO-treated patients (13% vs. 7.5%, p=0.0488). This treatment effect was driven primarily by the mucosal appearance subscore. On this measure, a greater percentage of B-MMX-treated patients than PBO-treated patients achieved a score of 0 (20% vs. 12.3%, p=0.0248), indicative of endoscopic remission. B-MMX also induced histological healing in a greater percentage of patients than placebo (27% vs. 17.5%, p=0.0155). Overall, 31.8% and 27.1% of patients treated with B-MMX or placebo reported an AE, and the majority were mild or moderate in severity. Study discontinuation due to AEs occurred in 4.7% and 3.5% of the B-MMX and placebo groups, respectively.

Conclusion

In patients experiencing an active flare of UC despite baseline oral 5-ASA therapy, adding B-MMX 9 mg was significantly more effective than placebo at inducing combined clinical and endoscopic remission as well as histological healing. B-MMX was generally well-tolerated when given in combination with an oral 5-ASA.

ClinicalTrials.gov identifier: NCT01532648