Asacol Acute Diverticulitis(DIVA)Study

Study Overview
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Brief Summary
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The purpose of this study is to determine whether Asacol® 2.4 g/day (400 mg Mesalamine) is safe and effective in the treatment of diverticulitis.

Detailed Description
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This study is designed to evaluate the safety and efficacy of Asacol® 2.4 g/day in generally healthy, adult patients who have had an attack of acute diverticulitis. The study will evaluate the safety and efficacy of a 12 week treatment with Asacol® followed a 9 month non-treatment observation period in approximately 180 patients with acute diverticulitis.

Official Title
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A Randomized, Double-blind, Placebo-controlled Study to Assess the Safety and Efficacy of a 12 Week Treatment of Acute Diverticulitis With Asacol® 2.4 g/Day (400 mg Mesalamine Tablet), Followed by a 9 Month Treatment-free Observation Period

Conditions
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Diverticulitis

Intervention / Treatment
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* Drug: Mesalamine
* Drug: Probiotic
* Drug: Placebo
* Other: Dietary Advice
* Drug: Antibiotic for Diverticulitis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A clinical diagnosis of acute diverticulitis Female patients must be postmenopausal (at least 1 year without spontaneous menses) or surgically sterile or have a negative urine pregnancy test and practice acceptable contraception (e.g., abstinence; oral, intramuscular, or implanted hormonal contraception [at least 3 months prior to enrollment]; 2-barrier methods [e.g., condom, diaphragm, or spermicide]; intrauterine device or verbal report of partner with history of non-reversed vasectomy) Willing and able to participate in the study and provide a signed informed consent Exclusion Criteria: Presence of diverticular complications (e.g., fistula, abscess, obstruction, stenosis); Active or recent history (within 6 months) of a peptic ulcer; Prior history of irritable bowel syndrome (IBS), as determined by the Investigator; History of major abdominal surgery (as determined by the Investigator); History of GI surgery within 3 months of diagnosis of acute diverticulitis; History of immunocompromising disease, human immunodeficiency virus (HIV) infection, or acquired immunodeficiency syndrome (AIDS); If female patient, active or recent history of endometriosis or dysmenorrhea; Received a dose of a product that contains, or is metabolized to, mesalamine by any route within 4 weeks before the screening visit;

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 85 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Days 1 thru Days 10 to 14 (Visit 2): daily antibiotic therapy, dietary advice, and 6 placebo tablets (matching mesalamine) once a day. Visit 2 thru Week 12 : 1 placebo capsule (matching probiotic) and 6 placebo tablets (matching mesalamine) daily. | Drug: Placebo<br>* 6 placebo tablets for first 10 (+4) days followed by once daily placebo tablets.<br>Other: Dietary Advice<br>* Dietary advice<br>Drug: Antibiotic for Diverticulitis<br>* Physician recommended antibiotic for Diverticulitis taken for 10-14 days. Antibiotic not specified for study.<br>|
| Active Comparator: Mesalamine<br>Days 1 thru 10-14 (Visit 2): daily antibiotic therapy, dietary advice and 6 - 400 mg mesalamine tablets once a day. Visit 2 thru Week 12: 1 placebo capsule (matching probiotic) and 6 - 400 mg mesalamine tablets daily. | Drug: Mesalamine<br>* 6 - 400 mg tablets once daily<br>Other: Dietary Advice<br>* Dietary advice<br>Drug: Antibiotic for Diverticulitis<br>* Physician recommended antibiotic for Diverticulitis taken for 10-14 days. Antibiotic not specified for study.<br>|
| Active Comparator: Mesalamine & Probiotic<br>Days 1 thru 10-14 (Visit 2): daily antibiotic therapy, dietary advice and 6 - 400 mg mesalamine tablets once daily. Visit 2 thru Week 12: 1- Bifidobacterium infantis 35624 capsule and 6 - 400 mg mesalamine tablets daily | Drug: Probiotic<br>* Once capsule daily Bifidobacterium infantis 35624 added at Visit 2 (Day 10 + 4 days)<br>* Other names: Align;Other: Dietary Advice<br>* Dietary advice<br>Drug: Antibiotic for Diverticulitis<br>* Physician recommended antibiotic for Diverticulitis taken for 10-14 days. Antibiotic not specified for study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Global Symptom Score (GSS) at Week 12, Primary Efficacy Population | GSS - Abdominal Pain & Symptom Rating, scale 0-none (better) to 6-severe (worse) for each of the following categories: abdominal pain, abdominal tenderness, nausea/vomiting, bloating, constipation, diarrhea, mucus in stool, feeling urge to evacuate but no bowel movement, painful straining with bowel movement, pain/difficulty urinating. Total minimum score 0 (better), total maximum score 60 (worse). | 12 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Responders at Week 12 - ITT Population | Responder - patient whose GSS scores for all symptoms were either 0 or 1 GSS - Abdominal Pain & Symptom Rating, scale 0-none (better) to 6-severe (worse) for each of the following categories: abdominal pain, abdominal tenderness, nausea/vomiting, bloating, constipation, diarrhea, mucus in stool, feeling urge to evacuate but no bowel movement, painful straining with bowel movement, pain/difficulty urinating. Total minimum score 0 (better), total maximum score 60 (worse). | 12 Weeks | 
| Percentage of Responders at Week 52 - ITT Population | Responder - patient whose GSS scores for all symptoms were either 0 or 1 GSS - Abdominal Pain & Symptom Rating, scale 0-none (better) to 6-severe (worse) for each of the following categories: abdominal pain, abdominal tenderness, nausea/vomiting, bloating, constipation, diarrhea, mucus in stool, feeling urge to evacuate but no bowel movement, painful straining with bowel movement, pain/difficulty urinating. Total minimum score 0 (better), total maximum score 60 (worse). | 52 Weeks | 
| Change in GSS From Baseline to Week 12 - ITT Population | GSS - Abdominal Pain & Symptom Rating, scale 0-none (better) to 6-severe (worse) for each of the following categories: abdominal pain, abdominal tenderness, nausea/vomiting, bloating, constipation, diarrhea, mucus in stool, feeling urge to evacuate but no bowel movement, painful straining with bowel movement, pain/difficulty urinating. Total minimum score 0 (better), total maximum score 60 (worse). | Baseline to Week 12 | 
| Change in GSS From Baseline to Week 52 - ITT Population | GSS - Abdominal Pain & Symptom Rating, scale 0-none (better) to 6-severe (worse) for each of the following categories: abdominal pain, abdominal tenderness, nausea/vomiting, bloating, constipation, diarrhea, mucus in stool, feeling urge to evacuate but no bowel movement, painful straining with bowel movement, pain/difficulty urinating. Total minimum score 0 (better), total maximum score 60 (worse). | Baseline to Week 52 | 
| Withdrawal Due to Surgery for Diverticulitis, Percentage, ITT Population, Week 12 |  | 12 Weeks | 
| Recurrent Diverticulitis, Percentage, ITT Population, Week 12 | At least one report of recurrent diverticulitis since the last visit (prior to the Week 12 visit). | 12 Weeks | 
| Recurrent Diverticulitis, Percentage, ITT Population, Week 52 | At least one report of recurrent diverticulitis since the last visit (prior to the Week 52 visit). | 52 Weeks |