Prevention of Recurrence of Diverticulitis

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

Official Title
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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.

Conditions
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Diverticulitis

Intervention / Treatment
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* Drug: SPD476, MMX™ mesalazine, 1.2g extended release tablet
* Drug: SPD476, MMX™ mesalazine, 2.4g extended release tablet
* Drug: SPD476, MMX™ mesalazine, 4.8g extended release tablet
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SPD476 (1.2 g)<br> | Drug: SPD476, MMX™ mesalazine, 1.2g extended release tablet<br>* SPD476 1.2g administered Once Daily (QD)<br>* Other names: LIALDA;|
| Experimental: SPD476 (2.4 g)<br> | Drug: SPD476, MMX™ mesalazine, 2.4g extended release tablet<br>* SPD476 2.4g administered Once Daily (QD)<br>* Other names: LIALDA;|
| Experimental: SPD476 (4.8 g)<br> | Drug: SPD476, MMX™ mesalazine, 4.8g extended release tablet<br>* SPD476 4.8g administered Once Daily (QD)<br>* Other names: LIALDA;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo administered Once Daily (QD)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of Subjects Without Recurrence of Diverticulitis | Recurrence of diverticulitis is defined as the presence of each and all of the following 3 items: 1) abdominal pain, 2) a 15% increase in white blood cell count from baseline, 3) bowel wall thickening (>5 mm) and/or fat stranding as evidenced by spiral computerized axial tomography (CT) scan; OR surgical intervention for diverticular disease. Withdrawals are considered as recurrences. | up to 104 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of Subjects Who Are CT-Recurrence Free of Diverticulitis | CT-recurrence of diverticulitis is defined as: a positive spiral CT scan for diverticulitis showing, at a minimum, fat stranding with or without bowel wall thickening >5 mm or surgical intervention for diverticular disease. Withdrawals considered as CT-recurrences. | up to 104 weeks | 
| Number of CT Scans Performed Within 7 Days of Suspected Recurrence of Diverticulitis That Were Positive | A positive CT scan was defined as a CT scan that showed bowel wall thickening (>5 mm) and/or fat stranding as read by the central reader. | up to 104 Weeks | 
| Number of CT Scans Performed Within 7 Days of Suspected Recurrence of Diverticulitis That Were Negative | A negative CT scan was defined as a CT scan that did not show bowel wall thickening (>5 mm) and/or fat stranding as read by the central reader. | up to 104 weeks | 
| Number of CT Scans Performed More Than 7 Days From Suspected Recurrence of Diverticulitis That Were Positive | A positive CT scan was defined as a CT scan that showed bowel wall thickening (>5 mm) and/or fat stranding as read by the central reader. | up to 104 weeks | 
| Number of CT Scans Performed More Than 7 Days From Suspected Recurrence of Diverticulitis That Were Negative | A negative CT scan was defined as a CT scan that did not show bowel wall thickening (>5 mm) and/or fat stranding as read by the central reader. | up to 104 weeks | 
| Percent of Subjects Requiring Surgery for Diverticulitis |  | up to 104 Weeks |