Prevention of Recurrence of Diverticulitis

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.

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

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

Secondary 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: 104 weeks
    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
    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
    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
    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
    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
    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
    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: 104 weeks
    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: 104 weeks
    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: 104 weeks
    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
    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 Investigator: Shire Pharmaceutical Development Industry

Overall Clinical Trial Officials and Contacts

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

Information obtained from ClinicalTrials.gov on February 12, 2012

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