Efficacy and Safety of Two Doses of SPD476 (Mesalazine) 2.4g and 4.8g Once Daily, With Reference to Asacol 0.8g Three Times Daily in Subjects With Acute, Mild to Moderate Ulcerative Colitis

A Phase III, Randomized, Multi-Centre, Double-blind, Double Dummy, Parallel Group, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Two Doses of SPD476 (Mesalazine) 2.4g and 4.8g Once Daily, With Reference to ASACOL 0.8g Three Times Daily, in Subjects With Mild to Moderate Ulcerative Colitis

The primary objective of the study was to compare the percentage of subjects in remission after 8 weeks of treatment with SPD476, 2.4 g/day once daily vs placebo and SPD476 4.8 g/day once daily versus placebo

Study Overview

• Status: Completed
• Conditions: Ulcerative Colitis
• Intervention / Treatment: Drug: SPD476 is a polymeric matrix formulation that displays both delayed- and extended-release of mesalazine; Drug: Mesalazine

• Study Type: Interventional
• Enrollment (Actual): 343
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Bonheiden, Belgium
    • Imelda General Hospital Dept of Gastroenterology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• newly diagnosed or relapsing mild to moderate UC (score of 4-10 (inclusive) on the UC-DAI scale, with a sigmoidoscopy score of => 1 and a PGA <=2) with compatible histology
• females eligible if post--menopausal, surgically sterile or if they had a negative urine pregnancy test at screening and were on adequate contraception

Exclusion Criteria:

• subjects with relapsing UC who were in relapse for > 6 weeks prior to baseline
• subjects who relapsed on maintenace therapy with doses of mesalazine => 2g/day
• subjects who had unsuccessfully treated their current relapse with steroids or a mesalazine dose of > 2g/day
• subjects with Crohn's disease, proctitis, bleeding disorders, active peptic ulcer disease, previous colonic surgery, or those at an immediate risk of toxic megacolon or a stool culture positive for enteric pathogens
• subjects who had used systemic or rectal steroids within the last 4 weeks, immunosuppressants wihtin the last 6 weeks or anti-inflammatory drugs on a repeat basis within 7 days prior to the baseline visit
• subjects with hypersensitivity to salicylates and subjects with moderate/severe renal impairment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of subjects in remission (UC-DAI score <=1, with scores of 0 for rectal bleeding and stool frequency and a sigmoidoscopy score reduction of 1 point or more from baseline)	8 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Clinical improvement as defined by a drop of => 3 points from baseline in the overall UC-DAI score	8 weeks
Change from baseine in UC-DAI score, symptoms, sigmoidscopy score, and PGA	8 weeks
Clinical remission defined as subjects who scored 0 for both the total stool frequency and the total rectal bleeding score	8 weeks
Treatment failure defined as unchanged, worsened missing or imcomplete UC-DAI score	8 weeks

Collaborators and Investigators

• Sponsor: Shire

Publications and helpful links

General Publications

• Kamm MA, Sandborn WJ, Gassull M, Schreiber S, Jackowski L, Butler T, Lyne A, Stephenson D, Palmen M, Joseph RE. Once-daily, high-concentration MMX mesalamine in active ulcerative colitis. Gastroenterology. 2007 Jan;132(1):66-75; quiz 432-3. doi: 10.1053/j.gastro.2006.10.011. Epub 2006 Oct 12.

Helpful Links

• FDA Recall Information
• FDA-approved labelling information, US only

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 4, 2003
• Primary Completion (ACTUAL): October 20, 2004
• Study Completion (ACTUAL): October 20, 2004

Study Registration Dates

• First Submitted: October 23, 2007
• First Submitted That Met QC Criteria: October 23, 2007
• First Posted (ESTIMATE): October 24, 2007

Study Record Updates

• Last Update Posted (ACTUAL): June 11, 2021
• Last Update Submitted That Met QC Criteria: June 8, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Mesalamine
• Other Study ID Numbers: SPD476-302