Effectiveness of a New Tablet Formulation for Twice Daily Balsalazide Disodium in Males versus Females with Mildly to Moderately Active Ulcerative Colitis

Purpose: A new formulation of balsalazide disodium tablets (BDT) was developed to allow less frequent dosing for enhanced compliance in the treatment of ulcerative colitis (UC). This study reports on a subgroup analysis comparing the efficacy of BDT in males vs. females with active UC. Methods: Adult subjects with mildly to moderately active UC and a baseline Modified Mayo Disease Activity Index (MMDAI) score between 6 and 10, inclusive, with a subscale rating of ≥ 2 for rectal bleeding and mucosal appearance were randomized 2:1 to receive 3.3 g of BDT (dosed as three 1.1 g tablets twice daily) or PBO tablets for 8 weeks. The primary endpoint was the proportion of patients achieving clinical improvement (≥ 3 point improvement in MMDAI) and improvement in rectal bleeding (≥ 1 point improvement) at 8 weeks. Results: The intent-to-treat population (n=249, mean age: 44 years, 84% white, 49% male) had a median baseline MMDAI score of 8 and a median baseline rectal bleeding sub-score of 2. In males, the proportion of primary endpoint responders was greater in the BDT group (56.8%) than the PBO group (20.0%, p = 0.0001) (Figure). Similar results were obtained for pre-specified secondary endpoints of clinical remission (p = 0.004 vs. PBO) and mucosal healing (p = 0.0007 vs. PBO) (Figure). Although BDT produced a similar response in females, this effect is not statistically significant for the primary endpoint (BDT: 54.1% vs. PBO: 58.1%, p=0.67) or secondary endpoints at week 8 (Figure). However, when more stringent definitions of “clinical remission” (endoscopy score of 0 or 1 and rectal bleeding score of 0 at end of treatment) were applied, the effect of BDT was more consistent across gender groups. Adverse events and serious adverse events in the BDT group were similar to placebo, and not different between genders.Figure: Primary and Secondary Endpoints at 8 Weeks.Conclusion: For the treatment of mild-to-moderate active UC, BDT showed statistically significant efficacy in males, but not in females. The definition of clinical remission in the study may have contributed to the high PBO response in females. The potential influence of gender should be explored in studies of inflammatory bowel disease. Disclosure - Ellen J Scherl: received grants from, served as a consultant for, and is on the speakers' bureau for Salix Pharmaceuticals, Inc.; received grants from and served as a consultant for Abbott, Centocor, Janssen Research and Development, PDL BioPharma, Prometheus Laboratories, and UCB; received grants from Elan, Millennium Pharmaceuticals, and Osiris Therapeutics; and served as a consultant for AstraZeneca, Axcan Pharma, Berlex Inc., Cerimon Pharmaceuticals, Hospira Inc., NPS Pharmaceuticals, Inc., Optimer Pharmaceuticals, Questcor Pharmaceuticals, Shire, Sigma Tau Pharmaceuticals, Inc., Solvay Pharmaceuticals, Inc., and TAP Pharmaceuticals. Salam Zakko: has serves as principal investigator on a variety of Salix research protocols, is a recipient of unrestricted grants from Salix, lectures for Salix, and holds stock in Salix. 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.