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

This study has been completed.

First Received: October 23, 2007 Last Updated: May 5, 2009 History of Changes

Sponsored by:	Shire Pharmaceutical Development
Information provided by:	Shire Pharmaceutical Development
ClinicalTrials.gov Identifier:	NCT00548574

Purpose

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

Condition	Intervention	Phase
Ulcerative Colitis	Drug: SPD476 is a polymeric matrix formulation that displays both delayed- and extended-release of mesalazine Drug: Mesalazine	Phase III

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

Resource links provided by NLM:

Genetics Home Reference related topics: Crohn disease

MedlinePlus related topics: Ulcerative Colitis

Drug Information available for: Mesalamine

U.S. FDA Resources

Further study details as provided by Shire Pharmaceutical Development:

Primary Outcome Measures:

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) [ Time Frame: 8 weeks ]

Secondary Outcome Measures:

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

Enrollment:	343
Study Start Date:	December 2003
Study Completion Date:	July 2005

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00548574

Locations

Belgium
Imelda General Hospital Dept of Gastroenterology
Bonheiden, Belgium

Sponsors and Collaborators

Shire Pharmaceutical Development

Investigators

Principal Investigator:

Professor Michael Kamm

St Marks Hospital, London, UK

More Information

Additional Information:

Synopsis of study results This link exits the ClinicalTrials.gov site

FDA-approved labelling information, US only This link exits the ClinicalTrials.gov site

FDA Recall information This link exits the ClinicalTrials.gov site

FDA Medical Product Safety Alerts This link exits the ClinicalTrials.gov site

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. Epub 2006 Oct 12.

Study ID Numbers:	SPD476-302
Study First Received:	October 23, 2007
Last Updated:	May 5, 2009
ClinicalTrials.gov Identifier:	NCT00548574 History of Changes
Health Authority:	France: Institutional Ethical Committee

Study placed in the following topic categories:

Anti-Inflammatory Agents
Gastrointestinal Diseases
Mesalamine
Ulcer
Colonic Diseases
Inflammatory Bowel Diseases
Colitis, Ulcerative
Intestinal Diseases

Digestive System Diseases
Analgesics, Non-Narcotic
Anti-Inflammatory Agents, Non-Steroidal
Peripheral Nervous System Agents
Analgesics
Antirheumatic Agents
Gastroenteritis
Colitis

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Gastrointestinal Diseases
Mesalamine
Ulcer
Physiological Effects of Drugs
Colonic Diseases
Inflammatory Bowel Diseases
Colitis, Ulcerative
Intestinal Diseases
Pharmacologic Actions
Digestive System Diseases

Pathologic Processes
Sensory System Agents
Analgesics, Non-Narcotic
Therapeutic Uses
Anti-Inflammatory Agents, Non-Steroidal
Peripheral Nervous System Agents
Analgesics
Antirheumatic Agents
Gastroenteritis
Central Nervous System Agents
Colitis

ClinicalTrials.gov processed this record on July 02, 2009