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

Condition(s) targeted: Ulcerative Colitis

Intervention: SPD476 is a polymeric matrix formulation that displays both delayed- and extended-release of mesalazine (Drug); Mesalazine (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: Shire Pharmaceutical Development

Official(s) and/or principal investigator(s):
Professor Michael Kamm, Principal Investigator, Affiliation: St Marks Hospital, London, UK

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

Official title: 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

Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: 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)

Secondary outcome:

Clinical improvement as defined by a drop of => 3 points from baseline in the overall UC-DAI score

Change from baseine in UC-DAI score, symptoms, sigmoidscopy score, and PGA

Clinical remission defined as subjects who scored 0 for both the total stool frequency and the total rectal bleeding score

Treatment failure defined as unchanged, worsened missing or imcomplete UC-DAI score

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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

Imelda General Hospital Dept of Gastroenterology, Bonheiden, Belgium

Synopsis of study results

FDA-approved labelling information, US only

FDA Recall information

FDA Medical Product Safety Alerts

Starting date: December 2003
Ending date: July 2005
Last updated: November 9, 2007