Two placebo-controlled studies (Studies 1 and 2) have demonstrated the efficacy of mesalamine delayed-release tablets in patients with mildly to moderately active ulcerative colitis. 

In one randomized, double-blind, multi-center trial of 158 patients (Study 1), mesalamine delayed-release doses of 1.6 g/day and 2.4 g/day for 6 weeks were compared to placebo. The scoring system for determination of treatment efficacy included assessment of stool frequency, rectal bleeding, sigmoidoscopic findings, patient’s functional assessment, and physician global assessment. At the dose of 2.4 g/day, 21 of 43 (49%) patients using mesalamine delayed-release tablets showed an improvement in sigmoidoscopic appearance of the bowel compared to 12 of 44 (27%) patients using placebo (p = 0.048). In addition, significantly more patients in mesalamine delayed-release tablets 2.4 g/day group showed improvement in rectal bleeding and stool frequency. The 1.6 g/day dose did not produce consistent evidence of effectiveness.

In a second randomized, double-blind, placebo-controlled clinical trial of 6 weeks duration in 87 (Study 2) patients, mesalamine delayed-release tablets, at a dose of 4.8 g/day, for 6 weeks, resulted in sigmoidoscopic improvement in 28 of 38 (74%) patients compared to 10 of 38 (26%) placebo patients (p less than 0.001). Also, more patients in the mesalamine delayed-release tablets 4.8 g/day group than the placebo group showed improvement in overall symptoms.

The 4.8 g/day dose is not an approved dosage for the treatment of mildly to moderately active ulcerative colitis.

Pediatrics  
The safety and effectiveness of mesalamine delayed-release 400 mg tablets in pediatric patients 5 to 17 years of age for treatment of mildly to moderately active ulcerative colitis are supported by evidence from adequate and well controlled studies of mesalamine delayed-release 400 mg tablets in adults and a single study in pediatric patients.

A randomized, double-blind, 6-week study of 2 dose levels of mesalamine delayed-release 400 mg tablets (Study 3) was conducted in 82 pediatric patients 5 to 17 years of age with mildly or moderately active ulcerative colitis. All patients were divided by weight category (17 to less than 33 kg, 33 to less than 54 kg, and 54 to 90 kg) and randomly assigned to receive a low dose (1.2, 2.0, and 2.4 g/day for the respective weight category) or a high dose (2.0, 3.6, and 4.8 g/day). Doses were administered every 12 hours. 

The proportion of patients who achieved success based on the Truncated Mayo Score (TM-Mayo) (based on the stool frequency and rectal bleeding subscores of the Mayo Score) and based on the Pediatric Ulcerative Colitis Activity Index (PUCAI) (which included assessment of abdominal pain, rectal bleeding, stool consistency and frequency, presence of nocturnal bowel movement and level of activity) was measured after 6 weeks of treatment. Success based on TM-Mayo was defined as either partial response (improvement from baseline in stool frequency or rectal bleeding subscores with no worsening in the other) or complete response (both stool frequency and rectal bleeding subscores equal 0). Success based on PUCAI was defined as either partial response (PUCAI reduction of greater than or equal to 20 points from Baseline to Week 6 with Week 6 score greater than or equal to 10) or complete response (PUCAI less than 10 at Week 6). 

There were 41 patients in the low dose group and 41 patients in the high dose group who received at least one dose of mesalamine delayed-release 400 mg tablets; 36 patients in each dose group completed the study. Patients were considered treatment failures if they did not achieve success or dropped out due to adverse reaction or lack of efficacy.

At Week 6, 73.2% of the patients in the low dose group, and 70.0% of the patients in the high dose group achieved success based on the TM-Mayo; 34.1% of the patients in the low dose group and 42.5% of the patients in the high dose group achieved complete response. At Week 6, 56.1% of the patients in the low dose group, and 55.0% of the patients in the high dose group achieved success based on the PUCAI; 46.3% of the patients in the low dose group and 42.5% of the patients in the high dose group achieved complete response. 

The high dose was not more effective than the low dose and is not an approved dosage [see Dosage and Administration (2.1)].