Efficacy and Safety of Asacol™ 4.8 g/Day (800 mg Tablets) for the Treatment of Active Ulcerative Colitis

Study Overview
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Brief Summary
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The primary objective of the study is to determine the efficacy of Asacol™ 4.8 g/day (800 mg tablets) to induce clinical and endoscopic remission after 6 weeks of treatment compared to placebo in subjects with active ulcerative colitis (UC).

Detailed Description
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The 800 mg Asacol™ tablets from Tillotts Pharma AG are being marketed in over 30 countries, mainly in Europe and Asia. Approved dosages for the treatment of active UC are between 2.4 and 4.8 g/day in analogy to the approved 400 mg dosage form. The present trial is planned to generate efficacy data to support the safe use of a 4.8 g/day dose of the 800 mg dosage form in a well defined population of patients with mildly to moderately active UC. In keeping with the EMEA UC guideline the study will have a placebo-controlled 6 weeks induction treatment. After 6 weeks, treatment success will be evaluated using the modified UC disease activity index as primary efficacy measurement.

Official Title
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A Randomized Placebo-Controlled Double-Blind Study to Evaluate the Efficacy and Safety of Asacol™ 4.8 g/Day (800 mg Tablets) for the Treatment of Active Ulcerative Colitis

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Drug: Mesalamin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: (1) Male or non-pregnant, non-lactating females, 18 years of age or older. (2) Documented diagnosis of UC with disease extending at least 15 cm from the anal verge. (3) Active UC defined by: (a) modified UC-DAI score of 4-10 with (b) sigmoidoscopy component score ≥ 2 and (c) rectal bleeding component score ≥ 1 (4) Ability of subject to participate fully in all aspects of this clinical trial. (5) Written informed consent must be obtained and documented. Exclusion Criteria: Severe UC defined by the following criteria: ³6 bloody stools daily with one or more of the following: oral temperature > 37.8°C or > 100.0°F pulse > 90/min hemoglobin < 10 g/dL Previously failed treatment with a mesalazine dose of > 2.0 g/day. Current relapse lasting > 6 weeks in the opinion of the investigator. Treatment with 5-ASA at a dose of >2.0g/day within 1 week prior to randomisation Treatment with systemic or rectal steroids within 4 weeks prior to randomization. Treatment with immunosuppressants within 6 weeks prior to randomization. Treatment with infliximab or other biologics within 3 months prior to randomization. Treatment with systemic antibiotics for UC within 7 days prior to randomization. Treatment with probiotics within 7 days prior to randomization. Treatment with anti-diarrheals within 7 days prior to randomization. Treatment with nicotine patch within 7 days prior to randomization. Received any investigational drug within 30 days prior to randomization. History of colectomy or partial colectomy. History of definite dysplasia in colonic biopsies. Crohn's disease. Known bleeding disorders. Immediate or significant risk of toxic megacolon. Hypersensitivity to salicylates, aspirin, sulfasalazine or 5-ASA. Serum creatinine > 1.5 times the upper limit of the normal range. AST, ALT, total bilirubin or alkaline phosphatase > 2 times the upper limit of the normal range. Serious underlying disease other than UC which in the opinion of the investigator may interfere with the subject's ability to participate fully in the study. History of alcohol or drug abuse which in the opinion of the investigator may interfere with the subject's ability to comply with the study procedures. Stools positive for clostridium difficile. Pregnant or lactating women. Prior enrolment in the current study and had received study treatment.

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mesalamin<br>4.8g Mesalamin (800mg tablet) | Drug: Mesalamin<br>* 4.8g/day, 800 mg tablets<br>* Other names: Asacol;|
| Placebo Comparator: Placebo<br>4.8g Placebo to Mesalamin (800 mg tablet) | Drug: Mesalamin<br>* 4.8g/day, 800 mg tablets<br>* Other names: Asacol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To Achieve Clinical Remission in Subjects With Active Ulcerative Colitis (UC). | Clinical remission defined as stool frequency score of 0, rectal bleeding score of 0, no urgency | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Remission | Clinical remission defined as a score of 0 for stool frequency, 0 for rectal bleeding and no urgency | 10 weeks | 
| Endoscopic Remission | Endoscopic remission is defined as a sigmoidoscopy score of 1 or less | 6 weeks | 
| Endoscopic Remission | Endoscopic remission is defined as a sigmoidoscopy score of 1 or less | 10 weeks | 
| Improvement | Improvement is defined as a reduction of at least 3 points from baseline in the modified UC-DAI score. (minumum 3, maximum 7, higher absolute UC-DAI scores indicate more severe disease) | 6 weeks | 
| Improvement | Improvement is defined as a reduction of at least 3 points from baseline in the modified UC-DAI score. (minumum 3, maximum 7, higher absolute UC-DAI scores indicate more severe disease) | 10 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mesalamine, Asacol, Ulcerative colitis, induction therapy, acute disease, mild to moderate, Active Ulcerative Colitis (mild to moderate)