Prevention of Recurrence of Diverticulitis - Full Text View

Sponsor:	Shire Pharmaceutical Development
Information provided by (Responsible Party):	Shire Pharmaceutical Development
ClinicalTrials.gov Identifier:	NCT00545103

Purpose

The purpose of this study is to determine whether SPD476 is effective in reducing recurrence of diverticulitis.

Condition	Intervention	Phase
Diverticulitis	Drug: SPD476, MMX™ mesalazine, 1.2g extended release tablet Drug: Placebo	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Prevention
Official Title:	A Phase III, Randomised, Double-Blind, Dose-Response, Stratified, Placebo-Controlled Study Evaluating the Safety and Efficacy of SPD476 Versus Placebo Over 104 Weeks in the Prevention of Recurrence of Diverticulitis.

Resource links provided by NLM:

MedlinePlus related topics: Diverticulosis and Diverticulitis

Drug Information available for: Mesalamine

U.S. FDA Resources

Further study details as provided by Shire Pharmaceutical Development:

Primary Outcome Measures:

Abdominal pain [ Time Frame: 104 Weeks ] [ Designated as safety issue: No ]
A 15% increase in white blood cell (WBC) count from baseline [ Time Frame: 104 Weeks ] [ Designated as safety issue: No ]
Bowel wall thickening (>5mm) and/or fat stranding as evidenced by spiral computerised axial tomography (CT) scan [ Time Frame: 104 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To compare the proportion of subjects who are CT-recurrence free up to Week 104 between each of 3 doses of SPD476 (1.2g/day QD, 2.4g/day QD, and 4.8g/day QD) and placebo QD. [ Time Frame: 26 and 52 Weeks ] [ Designated as safety issue: No ]
To evaluate the individual components of the primary endpoint for all subjects with a suspected recurrence of diverticulitis (defined as subjects who have a CT performed). [ Time Frame: 104 Weeks ] [ Designated as safety issue: No ]
To compare the proportion of subjects requiring surgical intervention for diverticular disease between each of 3 doses of SPD476 (1.2g/day QD, 2.4g/day QD, and 4.8g/day QD) and placebo QD up to Week 104. [ Time Frame: 104 Weeks ] [ Designated as safety issue: No ]
To compare the time to recurrence of diverticulitis between each of 3 doses of SPD476 (1.2g/day QD,2.4g/day QD, and 4.8g/day QD) and placebo QD in subjects who have had at least 1 previous attack of diverticulitis. [ Time Frame: Baseline, 16, 52 and 104 Weeks ] [ Designated as safety issue: No ]
To compare the time to CT-recurrence of diverticulitis between each of 3 doses of SPD476 (1.2g/day QD, 2.4g/day QD, and 4.8g/day QD) and placebo QD in subjects who have had at least 1 previous attack of diverticulitis. [ Time Frame: 104 Weeks ] [ Designated as safety issue: No ]
To assess the safety and tolerability of SPD476 1.2g/day QD, 2.4g/day QD, and 4.8g/day QD for the duration of the treatment period. [ Time Frame: 104 Weeks ] [ Designated as safety issue: Yes ]
To compare the proportion of subjects with CT-recurrence of complicated and uncomplicated diverticulitis between each of 3 doses of SPD476 (1.2g/day QD, 2.4g/day QD and 4.8g/day QD) and placebo QD up to Week 104. [ Time Frame: 104 Weeks ] [ Designated as safety issue: No ]
To compare Quality of Life (QoL) using the EQ5D and Health Utilities Index (HUI2) questionnaires between each of 3 doses of SPD476 (1.2g/day QD, 2.4g/day QD and 4.8g/day QD) and placebo QD at Baseline, and Weeks 16, 52, 78, and 104. [ Time Frame: Baseline; Weeks 16, 52, 78, and 104 ] [ Designated as safety issue: No ]
To compare lower endoscopy assessments of the sigmoid area between each of 3 doses of SPD476 (1.2g/day QD, 2.4g/day QD, and 4.8g/day QD) and placebo QD at Screening and Week 104 and/or Early Withdrawal of Treatment visits. [ Time Frame: Week 104 and/or Early Withdrawal of Treatment ] [ Designated as safety issue: No ]
To compare histology of biopsy samples between each of 3 doses of SPD476 (1.2g/day QD, 2.4g/day QD, and 4.8g/day QD) and placebo QD at Screening and Week 104 and/or Early Withdrawal of Treatment visits. [ Time Frame: Week 104 and/or Early Withdrawal of Treatment ] [ Designated as safety issue: No ]
To compare the change in C-Reactive Protein (CRP) from Baseline between each of 3 doses of SPD476 (1.2g/day QD, 2.4g/day QD, and 4.8g/day QD) and placebo QD at all study visits. [ Time Frame: 104 weeks ] [ Designated as safety issue: No ]

Enrollment:	592
Study Start Date:	December 2007
Study Completion Date:	November 2011
Primary Completion Date:	November 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1	Drug: SPD476, MMX™ mesalazine, 1.2g extended release tablet SPD476 1.2g administered Once Daily (QD) Other Name: LIALDA
Experimental: 2	Drug: SPD476, MMX™ mesalazine, 1.2g extended release tablet SPD476 2.4g administered Once Daily (QD) Other Name: LIALDA
Experimental: 3	Drug: SPD476, MMX™ mesalazine, 1.2g extended release tablet SPD476 4.8g administered Once Daily (QD) Other Name: LIALDA
Placebo Comparator: 4	Drug: Placebo Placebo

Eligibility

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

Criteria

Inclusion Criteria:

Males and females =>18yrs of age.
If female of childbearing potential (FOCP), has demonstrated a negative beta HCG (human chorionic gonadotropin) serum pregnancy test, and agrees to comply with any applicable contraceptive requirements of the protocol
An episode of acute diverticulitis that resolved without colonic resection.
Confirmation of diverticulosis via endoscopic evaluation of the sigmoid colon with at least three diverticula noted

Exclusion Criteria:

Previous colorectal surgery, including surgical intervention for diverticular disease (with the exception of haemorrhoidectomy, colonic removal of polyps, and appendectomy)
Active peptic ulcer disease
History of or current presence of inflammatory bowel disease (IBD)
Subjects with active irritable bowel syndrome (IBS) requiring ongoing medication
Allergy or hypersensitivity to aspirin or related compounds
Allergy to radiologic contrast agents
Use of another Investigational product within 30 days of Baseline
Use of antibiotic therapy within 4 weeks of Baseline
Within 14 days of Baseline, use of prebiotic, probiotic or 5-ASA medications, as well as drugs active at the 5HT-receptor or anti-spasmodic agents
Use of systemic or rectal steroids within 6 weeks of Baseline. Use of inhaled or nasal steroids is acceptable
Use of anti-inflammatory drugs, (NSIADs, COX-2 inhibitors) including aspirin (except for cardiac prophylaxis) and ibuprofen, on a regular and ongoing basis
History of alcohol or other substance abuse within the previous year
Active or recent history of endometriosis or dysmenorrhoea within 6 months prior to Baseline
Females who are lactating

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00545103

Show 131 Study Locations

Sponsors and Collaborators

Shire Pharmaceutical Development

Investigators

Principal Investigator:

Jeffrey B. Raskin, M.D.

University of Miami Miller School of Medicine

More Information

No publications provided

Responsible Party:	Shire Pharmaceutical Development
ClinicalTrials.gov Identifier:	NCT00545103 History of Changes
Other Study ID Numbers:	SPD476-314
Study First Received:	October 16, 2007
Last Updated:	December 8, 2011
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Diverticulitis
Recurrence
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Disease Attributes
Pathologic Processes
Mesalamine
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic

Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on February 09, 2012