Two double-blind placebo-controlled multicenter studies were conducted in North America in patients with mild to moderate active ulcerative proctitis. The primary measures of efficacy were the same in all trials (clinical disease activity index, sigmoidoscopic and histologic evaluations). The main difference between the studies was dosage regimen: 500 mg three times daily (1.5 g/d) in Study 1; and 500 mg twice daily (1.0 g/d) in Study 2. A total of 173 patients were studied (Study 1, N=79; Study 2, N=94). Eighty-nine (89) patients received mesalamine suppositories, and eighty-four (84) patients received placebo suppositories. Patients were evaluated clinically and sigmoidoscopically after three and six weeks of suppository treatment. In Study No. 1 patients were 17 to 73 years of age (mean = 39 yrs), 57% were female, and 97% were white. Patients had an average extent of proctitis (upper disease boundary) of 10.8 cm. Eighty-four percent (84%) of the study patients had multiple prior episodes of proctitis. In Study No. 2, patients were 21 to 72 years of age (mean = 39 yrs), 62% were female, and 96% were white. Patients had an average extent of proctitis (upper disease boundary) of 10.3 cm. Seventy-eight percent (78%) of the study patients had multiple prior episodes of proctitis.

Compared to placebo, mesalamine suppository treatment was statistically (p less than 0.01) superior to placebo in all trials with respect to improvement in stool frequency, rectal bleeding, mucosal appearance, disease severity, and overall disease activity after three and six weeks of treatment. Daily diary records indicated significant improvement in rectal bleeding in the first week of therapy while tenesmus and diarrhea improved significantly within two weeks. Investigators rated patients receiving mesalamine much improved compared to patients receiving placebo (p less than 0.001).

The effectiveness of mesalamine suppositories was statistically significant irrespective of sex, extent of proctitis, duration of current episode or duration of disease.

A multicenter, open-label, randomized, parallel group study in ninety-nine (99) patients diagnosed with mild to moderate ulcerative proctitis compared the clinical efficacy of the CANASA® 1000 mg suppository to that of the CANASA ® 500 mg suppository. The primary measures of efficacy included clinical disease activity index, sigmoidoscopic and histologic evaluations. Patients were randomized to one of two treatment groups, with a dosage regimen of one 500 mg mesalamine suppository BID, morning and HS, or one 1000 mg mesalamine suppository HS for 6 weeks. Patients were evaluated clinically and sigmoidoscopically after three and six weeks of suppository treatment. Of the eighty-one (81) patients in the Per Protocol population, forty-six (46) patients received mesalamine 500 mg suppositories BID, and thirty-five (35) patients received mesalamine 1000 mg suppositories HS.

The efficacy of the 1000 mg HS treatment was not statistically or clinically different after 6 weeks from the 500 mg BID treatment, and both were effective in the treatment of ulcerative proctitis. Both treatments resulted in a significant decrease between Baseline and 6 weeks in the Disease Activity Index (DAI), a composite index reflecting rectal bleeding, stool frequency, mucosal appearance at endoscopy, and a global assessment of disease. In the 500 mg BID group, the mean DAI value decreased from 6.6 to 1.6, and in the 1000 mg HS group, the mean DAI value decreased from 6.2 to 1.3 over 6 weeks of treatment, representing a decrease of greater than 75% in both groups. Seventy-eight percent (78%; 36/46) of patients in the 500 mg BID group and 86% (30/35) of the patients in the 1000 mg HS group achieved a substantial improvement in symptoms (defined as a DAI score of less than 3) after 6 weeks of treatment. These patients regained normal daily stools, lost their rectal bleeding, and lost signs of inflammation at endoscopic visualization. The time to onset of response to the study drug was within 3 weeks of initiation of therapy in each treatment group, but further improvement was observed between 3 and 6 weeks of treatment.