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.”

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

Study Type: Interventional

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

Study Primary Completion Date: December 2010

Intervention(s) in this Clinical Trial

• Drug: SPD476, MMX™ mesalazine, 1.2g extended release tablet
  • 1.2g SPD476/day QD
• Drug: placebo
  • placebo
• Drug: SPD476, MMX™ mesalazine, 1.2g extended release tablet
  • 2.4g SPD476/day QD
• Drug: SPD476, MMX™ mesalazine, 1.2g extended release tablet
  • 4.8g SPD476/day QD

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
• Experimental: 2
• Experimental: 3
• Placebo Comparator: 4

Primary Measures

• Changes in predefined lab parameters
  • Time Frame: 104 Weeks
    Safety Issue?: No
• Time to presence of predefined symptoms of diverticulitis
  • Time Frame: 104 Weeks
    Safety Issue?: No

Secondary Measures

• Proportion of subjects without recurrence of diverticulitis between 3 doses of SPD476 and placebo
  • Time Frame: 26 and 52 Weeks
    Safety Issue?: No
• Evaluate the subgroup classifications of diverticulitis between 3 doses of SPD476 and placebo
  • Time Frame: 104 Weeks
    Safety Issue?: No
• Proportion of subjects requiring surgical intervention for diverticular disease up to 104 weeks post baseline between 3 doses of SPD476 and placebo QD
  • Time Frame: 104 Weeks
    Safety Issue?: No
• Quality of Life (QoL)questionnaires between treatment groups
  • Time Frame: Baseline, 16, 52 and 104 Weeks
    Safety Issue?: No
• To assess the safety and tolerability of SPD476 at 3 different doses
  • Time Frame: 104 Weeks
    Safety Issue?: Yes
• Endoscopy of the sigmoid colon between treatment groups
  • Time Frame: 104 Weeks
    Safety Issue?: No
• Histology of biopsy samples between treatment groups
  • Time Frame: 104 Weeks
    Safety Issue?: No

Inclusion Criteria:

• 1. Males and females =>18yrs of age.
• 2. 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.
• 3. An episode of acute diverticulitis that resolved without colonic resection.
• 4. Confirmation of diverticulosis via endoscopic evaluation of the sigmoid colon with at least three diverticula noted.

Exclusion Criteria:

• 1. Previous colorectal surgery, including surgical intervention for diverticular disease (with the exception of haemorrhoidectomy, colonic removal of polyps, and appendectomy)
• 2. Active peptic ulcer disease
• 3. History of or current presence of inflammatory bowel disease (IBD)
• 4. Subjects with active irritable bowel syndrome (IBS) requiring ongoing medication
• 5. Allergy or hypersensitivity to aspirin or related compounds
• 6. Allergy to radiologic contrast agents
• 7. Use of another Investigational product within 30 days of Baseline
• 8. Use of antibiotic therapy within 4 weeks of Baseline
• 9. 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
• 10. Use of systemic or rectal steroids within 6 weeks of Baseline. Use of inhaled or nasal steroids is acceptable
• 11. Use of anti-inflammatory drugs, (NSIADs, COX-2 inhibitors) including aspirin (except for cardiac prophylaxis) and ibuprofen, on a regular and ongoing basis
• 12. History of alcohol or other substance abuse within the previous year
• 13. Active or recent history of endometriosis or dysmenorrhoea within 6 months prior to Baseline
• 14. Females who are lactating

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Shire Pharmaceutical Development

Overall Clinical Trial Officials and Contacts

Prof. Michael Kamm Principal Investigator St. Vincent’s Hospital.  

Overall Contact: Shire Call Centre +1 866 842 5335 

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00545740

Study ID Number: SPD476-313

ClinicalTrials.gov Identifier: NCT00545740

Health Authority: United States: Food and Drug Administration