Trial Outcomes & Findings for Mesalamine 4 g Sachet for the Induction of Remission in Active, Mild to Moderate Ulcerative Colitis (UC) (NCT NCT02522767)

A total of 71 sites in 10 countries (Bulgaria, Canada, Hungary, Latvia, Mexico, Russia, Serbia, Switzerland, Ukraine, and United States) recruited subjects to this trial between October 2015 to November 2017, the last subject completed last visit in April 2018.

A total of 411 subjects were screened, of which 228 subjects were randomized in a 1:1 ratio to either mesalamine or placebo group (114 subjects each), for 8 weeks double-blind treatment. Subjects who completed 8 weeks but failed to meet the defined criteria for remission received open-label treatment with mesalamine for additional 8 weeks.

Mesalamine 4 g Sachet for the Induction of Remission in Active, Mild to Moderate Ulcerative Colitis (UC)

The proportion of subjects with remission was defined by the Clinical and Endoscopic Response Score: 0 for rectal bleeding; 0 or 1 with at least 1 point decrease from baseline for stool frequency; 0 or 1 for endoscopic score. The Clinical and Endoscopic Response Score ranged between 0-9, higher scores indicating greater disease severity. This score had two components: Clinical Response which assessed subject's symptoms and ranged between 0-6, and Endoscopic Response which assessed objective evidence of inflammation and ranged between 0-3. Further, the Clinical Response component included two subscales: stool frequency and rectal bleeding (each ranged between 0-3 each) obtained from subjects' daily records. The Endoscopic Response component had one subscale: flexible sigmoidoscopy/colonoscopy (ranging between 0-3).

The Modified Mayo score was calculated as the sum of the Clinical and Endoscopic Response Score (Range: 0-9, and the standard PGA score (range: 0-3; normal \[score=0\], mild disease \[score=1\], moderate disease \[score=2\], severe disease \[score=3\]). The statistical test was to be conducted only if the primary analysis was significant.

Defined as time in days from randomization to the first day of 3 consecutive days with a rectal bleeding score of 0, based on subject's daily diary. The statistical test was to be conducted only if the primary analysis was significant.

Defined as an Endoscopic Response Score of 0 or 1, with at least a 1 point reduction from baseline in the endoscopic score at Week 8.

Defined as a score of 0 for rectal bleeding and 0 or 1 with at least 1 point decrease from baseline for stool frequency in the Clinical Response Score subset.

Defined as time in days from randomization to the first day of 3 consecutive days with a stool frequency score of 0, based on subject daily diary.

Defined as change from baseline in rectal bleeding score at Week 2, 4, and 8 based on subject daily diary. Rectal Bleeding Score is graded 0-3, where 0 is best.

The adjusted mean changes in serum CRP levels from baseline and their difference between treatment groups are presented for each time point.

The adjusted mean change from baseline in fecal calprotectin levels at Week 8 are presented.

The change from baseline to Week 2, 4, and 8 in Inflammatory Bowel Disease Questionnaire (IBDQ) scores. The adjusted changes from baseline and their differences between treatment groups are presented. The IBDQ is an instrument used to assess quality of life in adult patients with UC. Subjects were asked to recall symptoms and QoL from last two weeks and to rate each item on a 7- point Likert score (higher scores equate to higher QoL).

An adverse event (AE) is defined as any untoward medical occurrence in a subject taking part in a clinical trial. A 'treatment-emergent AE (TEAE)' is defined as an AE which occurs in the time interval from initial dosing (investigational medicinal product \[IMP\] intake) to the end of treatment visit. Proportion of subjects with any TEAE (serious or non-serious) are presented.

The proportion of subjects with intensity of AEs (classified as mild, moderate or severe) are presented.

Proportion of subjects with markedly abnormal changes from baseline in hematology values are presented. \>= greater than equal to; \<= less than equal to.

Proportion of subjects with markedly abnormal changes from baseline values in coagulation laboratory values are presented. INR= International normalized ratio.

Proportion of subjects with markedly abnormal changes in serum chemistry laboratory values are presented. ALT= Alanine aminotransferase; AST= Aspartate aminotransferase; BUN= Blood urea nitrogen; GGT= Gamma glutamyl transferase.