Safety and Efficacy of Two Different Doses of Asacol in the Treatment of Moderately Active Ulcerative Colitis

Study Overview
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Brief Summary
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This study is a prospective clinical study to evaluate the safety and efficacy of two different doses of Asacol for the treatment of moderately active ulcerative colitis. In addition, a new tablet formulation will be evaluated at one of the two doses.

Official Title
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A Double-Blind, Randomized, 6-Week, Parallel-Group Design Clinical Trial to Assess Safety and Efficacy of Asacol 4.8 g/Day (800 mg Tablet) Versus Asacol 2.4 g/Day (400 mg Tablet) for the Treatment of Moderately Active Ulcerative Colitis

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Drug: Asacol 800 mg (mesalamine)
* Drug: Asacol 400 mg (mesalamine)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: male or female between 18 and 75 years of age; have a confirmed diagnosis of ulcerative colitis with the extent varying from proctitis to pancolitis; currently demonstrating moderately active disease Exclusion Criteria: Patients will be excluded from admission to the study if they have/are: a history of allergy or hypersensitivity to salicylates or aminosalicylates; a history of extensive small bowel resection (>1/2 the length of the small intestine) causing short bowel syndrome; current renal or hepatic disease; participated in any drug or device clinical study within 30 days of entry; currently enrolled in any other clinical study; received any oral, intravenous, intramuscular, or rectally administered corticosteroids within 1 month prior to the Baseline Visit; received any other topical rectal therapy during the week prior to the Screening Visit; received immunomodulatory therapy including, but not limited to, 6-mercaptopurine, azathioprine, cyclosporine, or methotrexate within 3 months prior to the Baseline Visit; received a dose of mesalamine-containing compound by any route from which more than 1.6 g/day of mesalamine was available within 1 week prior to the Screening Visit (NOTE: 4 g/day of sulfasalazine and 4.5 g/day of balsalazide are equivalent to 1.6 g/day of mesalamine); received antibiotics, other than topical antibiotics, within 1 week prior to the Screening Visit; received aspirin (except for cardioprotective reasons up to a maximum dose of 325 mg/day) or NSAIDs within 1 week prior to the Baseline Visit; if female, positive pregnancy test, or lactating.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Asacol 2.4 g/day<br>Asacol (2.4 g/day) | Drug: Asacol 400 mg (mesalamine)<br>* tablets, 2.4 g/day for 6 weeks, 2 - 400 mg Asacol tablets and 2 placebo tablets 3 times daily<br>|
| Experimental: Asacol 4.8 g/day<br>Asacol (4.8 g/day) | Drug: Asacol 800 mg (mesalamine)<br>* tablets, 4.8 g/day for 6 weeks, 2 - 800 mg Asacol tablets and 2 placebo tablets 3 times daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Treatment Success Patients at Week 6, ITT (Intent to Treat) Population | Treatment success defined as complete response (PGA score 0 and complete resolution of stool frequency, rectal bleeding, PFA (patient's functional assessment), normal sigmoidoscopy) or partial response (improvement from baseline PGA and improvement in 1 clinical assessment [stool frequency, rectal bleeding, PFA, sigmoidoscopy] and no worsening in any other clinical assessments) | 6 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Ulcerative Colitis Disease Activity Index (UCDAI) at Week 6, ITT Population | UCDAI - sum of clinical assessment scores (stool frequency score [0=normal, 1=1-2 stools > normal/day, 2=3-4 stools > normal/day, 3=5 or more stools > normal/day], rectal bleeding score [0=no blood seen, 1=streaks of blood with stool less than half of the time, 2=obvious blood with stool most of the time, 3=blood alone passed and PGA score [0=quiescent disease, 1=mild, 2=moderate, 3=severe]) and sigmoidoscopy score [0=normal, 1=mild, 2=moderate, 3=severe] | 6 weeks | 
| Percentage of Participants Whose Rectal Bleeding & Sigmoidoscopy Score Both Improved From Baseline to Week 6, ITT Population | Rectal Bleeding - 0=no blood seen, 1=streaks of blood w/stool less than half of the time, 2=obvious blood w/stool most of the time, 3=blood alone passed Sigmoidoscopy Assessment Score - 0=normal (intact vascular pattern, no friability or granularity), 1=mild (erythema, diminished or absent vascular markings; mild granularity; friability), 2=moderate (marked erythema, granularity; absent vascular markings; bleeds with minimal trauma; no ulcerations) 3=severe (spontaneous bleeding, ulcerations) | 6 Weeks | 
| Percentage of Patients Whose Sigmoidoscopy Score Improved From Baseline to Week 6, ITT Population | Sigmoidoscopy Assessment Score (0=normal intact vascular pattern, no friability or granularity, 1=mild erythema; diminished or absent vascular markings; mild granularity; friability, 2=moderate marked erythema, granularity; absent vascular markings; bleeds with minimal trauma; no ulcerations, 3=severe spontaneous bleeding, ulcerations) | 6 Weeks | 
| Percentage of Patients With an Improvement in Stool Frequency, ITT Population, Week 6 | 0=Normal stool frequency per day, 1=1-2 stools greater than normal per day, 2=3-4 stools greater than normal per day, 3=5 or more stools greater than normal per day | 6 Weeks | 
| Percentage of Patients With Improvement in Rectal Bleeding, ITT Population, Week 6 | Rectal Bleeding (0=no blood seen, 1=streaks of blood with stool less than half of the time, 2=obvious blood with stool most of the time, 3=blood alone passed) | 6 Weeks | 
| Percentage of Patients With Improvement in Patient's Functional Assessment (PFA), ITT Population, Week 6 | PFA - 0=generally well, 1=fair, 2=poor, 3=terrible | 6 Weeks | 
| Percentage of Patients With Improvement in Physician Global Assessment (PGA)Score, ITT Population, Week 6 | PGA -Physician's Global Assessment - 0=quiescent disease (all parameters 0), 1=mild disease (parameters mostly 1's) 2=moderate (parameters mostly 2's), 3=severe (parameters mostly 3's) [parameters: combination of stool frequency, rectal bleeding, PFA & sigmoidoscopy findings] If scoring equal default to physician judgement. | 6 Weeks | 
| Mean Change From Baseline in Total Inflammatory Bowel Disease Questionnaire (IBDQ) at Week 3, All Randomized Patients | IBDQ-32 questions divided into 4 categories: bowel, systemic, emotional and social. Each question graded with the following responses: 1-more than ever before, 2-extremely frequently, 3-very frequently, 4-moderate increase in frequency, 5-some increase in frequency, 6-slight increase in frequency or 7-not at all/normal; 1/worst thru 7/best. Scoring 32 - 224 - higher score better. | 3 Weeks | 
| Mean Change From Baseline in Total Inflammatory Bowel Disease Questionnaire (IBDQ) at Week 6, All Randomized Patients | IBDQ-32 questions divided into 4 categories: bowel, systemic, emotional and social. Each question graded with the following responses: 1-more than ever before, 2-extremely frequently, 3-very frequently, 4-moderate increase in frequency, 5-some increase in frequency, 6-slight increase in frequency or 7-not at all/normal; 1/worst thru 7/best. Scoring 32-224 - higher score better. | 6 Weeks | 
| Percentage of Patients With Moderate, Left-Sided Disease at Baseline Classified as Treatment Success at Week 6, All Randomized Patients | Treatment success defined as complete response (PGA score 0 and complete resolution of stool frequency, rectal bleeding, PFA (patient's functional assessment), normal sigmoidoscopy) or partial response (improvement from baseline PGA and improvement in 1 clinical assessment [stool frequency, rectal bleeding, PFA, sigmoidoscopy] and no worsening in any other clinical assessments) | 6 Weeks | 
| Percentage of Treatment Success Patients at Week 3, ITT Population | Treatment success defined as complete response (PGA score 0 and complete resolution of stool frequency, rectal bleeding, PFA (patient's functional assessment), normal sigmoidoscopy) or partial response (improvement from baseline PGA and improvement in 1 clinical assessment [stool frequency, rectal bleeding, PFA, sigmoidoscopy] and no worsening in any other clinical assessments) | 3 Weeks |