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

• Sponsor: Warner Chilcott (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00073021
• Collaborator: (none)
• Enrollment: 386
• Locations: 57
• Arms: 2
• Duration (Months): 36
• Patients Per Site: 6.8
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Ulcerative Colitis	Drug: Asacol 800 mg (mesalamine); Drug: Asacol 400 mg (mesalamine)	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 386 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: Sep 1, 2000
• Actual Primary Completion Date: Sep 1, 2003
• Actual Study Completion Date: Sep 1, 2003

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Percentage of Treatment Success Patients at Week 6, ITT (Intent to Treat) Population [6 Weeks]

   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)

Secondary Outcome Measures

1. Change From Baseline in Ulcerative Colitis Disease Activity Index (UCDAI) at Week 6, ITT Population [6 weeks]

   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]

2. Percentage of Participants Whose Rectal Bleeding & Sigmoidoscopy Score Both Improved From Baseline to Week 6, ITT Population [6 Weeks]

   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)

3. Percentage of Patients Whose Sigmoidoscopy Score Improved From Baseline to Week 6, ITT Population [6 Weeks]

   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)

4. Percentage of Patients With an Improvement in Stool Frequency, ITT Population, Week 6 [6 Weeks]

   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

5. Percentage of Patients With Improvement in Rectal Bleeding, ITT Population, Week 6 [6 Weeks]

   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. Percentage of Patients With Improvement in Patient's Functional Assessment (PFA), ITT Population, Week 6 [6 Weeks]

   PFA - 0=generally well, 1=fair, 2=poor, 3=terrible

7. Percentage of Patients With Improvement in Physician Global Assessment (PGA)Score, ITT Population, Week 6 [6 Weeks]

   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.

8. Mean Change From Baseline in Total Inflammatory Bowel Disease Questionnaire (IBDQ) at Week 3, All Randomized Patients [3 Weeks]

   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.

9. Mean Change From Baseline in Total Inflammatory Bowel Disease Questionnaire (IBDQ) at Week 6, All Randomized Patients [6 Weeks]

   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.

10. Percentage of Patients With Moderate, Left-Sided Disease at Baseline Classified as Treatment Success at Week 6, All Randomized Patients [6 Weeks]

    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)

11. Percentage of Treatment Success Patients at Week 3, ITT Population [3 Weeks]

    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)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic Scottsdale	Scottsdale	Arizona	United States	85259
2	AGMG Clinical Research	Anaheim	California	United States	92801
3	Research Site	Los Angeles	California	United States	90067
4	Community Clinical Trials	Orange	California	United States	38305
5	AGMG Clinical Research	Orange	California	United States	92869
6	Research Site	Sacramento	California	United States	95825
7	Sharp Rees-Stealy Medical Group	San Diego	California	United States	92123
8	Research Site	Arvada	Colorado	United States	80002
9	Research Site	Englewood	Colorado	United States	80110
10	Center for Medical Research, LLC	Manchester	Connecticut	United States	06040
11	Center for GI Disorders	Hollywood	Florida	United States	33021
12	Research Site	Maitland	Florida	United States	32789
13	Advanced Gastroenterology Associates	Palm Harbor	Florida	United States	34684
14	Research Site	Zephyrhills	Florida	United States	33540
15	Southeast Research Associates	Marietta	Georgia	United States	30067
16	University of Chicago Medical Center	Chicago	Illinois	United States	60637
17	GI Research	Metairie	Louisiana	United States	70001
18	Louisiana Research Center	Shreveport	Louisiana	United States	71103
19	Digestive Disorders Associates	Annapolis	Maryland	United States	21401
20	Research Site	Baltimore	Maryland	United States	21215
21	Digestive Disease Associates	Baltimore	Maryland	United States	21229
22	Metropolitan Gastroenterology Group	Chevy Chase	Maryland	United States	20815
23	Brigham & Women's Hospital	Boston	Massachusetts	United States	02115
24	Henry Ford Hospital	Detroit	Michigan	United States	48202
25	Mayo Clinic	Rochester	Minnesota	United States	55905
26	PharmaTrials, Inc.	Hillsborough	New Jersey	United States	08844
27	Research Site	Forest Hills	New York	United States	11375
28	Long Island Clinical Research Associates	Great Neck	New York	United States	11021
29	Research Site	New York	New York	United States	10128
30	Carolinas Digestive Health Associates	Charlotte	North Carolina	United States	28262
31	Research Site	Raleigh	North Carolina	United States	27612
32	Research Site	Statesville	North Carolina	United States	28677
33	Consultants for Clinical Research	Cincinnati	Ohio	United States	45219
34	Research Site	Cincinnati	Ohio	United States	45267
35	Research Site	Columbus	Ohio	United States	43215
36	GI & Liver Consultants	Dayton	Ohio	United States	45440
37	Research Site	Oklahoma City	Oklahoma	United States	73190
38	Research Site	Tulsa	Oklahoma	United States	74135
39	West Hills Gastroenterology Group	Portland	Oregon	United States	97225
40	Research Site	Altoona	Pennsylvania	United States	16602
41	Research Site	Hanover	Pennsylvania	United States	17331
42	Regional Research Institute	Jackson	Tennessee	United States	38305
43	Research Site	Austin	Texas	United States	78705
44	Research Site	Dallas	Texas	United States	75246
45	Research Site	Houston	Texas	United States	77030
46	Houston Medical Research Associates	Houston	Texas	United States	77090
47	Research Site	Temple	Texas	United States	76508
48	Research Site	Ogden	Utah	United States	84405
49	Charlottesville Medical Research	Charlottesville	Virginia	United States	22902
50	Research Site	Fairfax	Virginia	United States	22031
51	Research Site	Fredricksburg	Virginia	United States	22401
52	Richmond GI Research	Richmond	Virginia	United States	23226
53	Research Site	Spokane	Washington	United States	99207
54	Wisconsin Center for Advanced Research	Milwaukee	Wisconsin	United States	53207
55	Research Site	Richmond	British Columbia	Canada	V7C 5L9
56	Research Site	Toronto	Ontario	Canada	M5B 1W8
57	University of Puerto Rico, School of Medicine	San Juan		Puerto Rico	00935

Sponsors and Collaborators

• Warner Chilcott

Investigators

• Study Director: Piotr Krzeski, MD, Procter and Gamble

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Warner Chilcott
• ClinicalTrials.gov Identifier: NCT00073021
• Other Study ID Numbers: 2000082
• First Posted: Nov 17, 2003
• Last Update Posted: Jun 29, 2015
• Last Verified: Jun 1, 2015

• Additional relevant MeSH terms: Colitis; Colitis, Ulcerative; Ulcer; Mesalamine

Study Results

Participant Flow

Recruitment Details	Recruitment began Feb. 28, 2001. Randomized 386 patients of which 117 had mild disease and 268 had moderate disease at baseline. Analysis only includes patients with moderate disease at baseline.

Arm/Group Title	Asacol 2.4 g/Day	Asacol 4.8 g/Day
Arm/Group Description	Two 400 mg Asacol tablets and 2 placebo tablets (matching 800 mg formulation) taken 3 times daily (morning, midday, evening).	Two 800 mg Asacol tablets and 2 placebo tablets (matching 400 mg formulation) taken 3 times daily (morning, midday, evening).
Period Title: Overall Study
STARTED	139	129
COMPLETED	113	113
NOT COMPLETED	26	16

Baseline Characteristics

Arm/Group Title	Asacol 2.4 g/Day	Asacol 4.8 g/Day	Total
Arm/Group Description	Two 400 mg Asacol tablets and 2 placebo tablets (matching 800 mg formulation) taken 3 times daily (morning, midday, evening).	Two 800 mg Asacol tablets and 2 placebo tablets (matching 400 mg formulation) taken 3 times daily (morning, midday, evening).	Total of all reporting groups
Overall Participants	139	129	268
Age, Customized (Number) [Number]
18 - 64 years	126 90.6%	118 91.5%	244 91%
>= 65 years	13 9.4%	11 8.5%	24 9%
Sex: Female, Male (Count of Participants)
Female	77 55.4%	75 58.1%	152 56.7%
Male	62 44.6%	54 41.9%	116 43.3%
Race/Ethnicity, Customized (Number) [Number]
Caucasian	108 77.7%	96 74.4%	204 76.1%
Black or African American	11 7.9%	14 10.9%	25 9.3%
Asian (Indian)	1 0.7%	2 1.6%	3 1.1%
Asian (Oriental)	1 0.7%	3 2.3%	4 1.5%
Hispanic	16 11.5%	11 8.5%	27 10.1%
Multi-racial/other	2 1.4%	3 2.3%	5 1.9%

Outcome Measures

1. Primary Outcome

Title	Percentage of Treatment Success Patients at Week 6, ITT (Intent to Treat) Population
Description	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)
Time Frame	6 Weeks

Outcome Measure Data

Analysis Population Description

ITT Population with Moderate Disease [PGA = 2] at Baseline

Arm/Group Title	Asacol 2.4 g/Day	Asacol 4.8 g/Day
Arm/Group Description	Two 400 mg Asacol tablets and 2 placebo tablets (matching 800 mg formulation) taken 3 times daily (morning, midday, evening).	Two 800 mg Asacol tablets and 2 placebo tablets (matching 400 mg formulation) taken 3 times daily (morning, midday, evening).
Measure Participants	130	124
Number [Percentage of Participants]	59.2 42.6%	71.8 55.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Asacol 2.4 g/Day, Asacol 4.8 g/Day
	Comments	It was assumed that true rate of improvement for 2.4 g/day treatment group is 40% and for the 4.8 g/day group is 60%. To detect a true difference of 20% between these 2 groups with 2-sided test, type I error of 0.05 (alpha = 0.05), and power of 80%, 120 patients with moderately active ulcerative colitis were required per group to complete the study.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0357
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Difference in Success Rates
	Estimated Value	12.543
	Confidence Interval	(2-Sided) 95%; 0.96 to 24.12
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline in Ulcerative Colitis Disease Activity Index (UCDAI) at Week 6, ITT Population
Description	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]
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

ITT Population with Moderate Disease [PGA = 2] at Baseline.

Arm/Group Title	Asacol 2.4 g/Day	Asacol 4.8 g/Day
Arm/Group Description	Two 400 mg Asacol tablets and 2 placebo tablets (matching 800 mg formulation) taken 3 times daily (morning, midday, evening).	Two 800 mg Asacol tablets and 2 placebo tablets (matching 400 mg formulation) taken 3 times daily (morning, midday, evening).
Measure Participants	130	124
Mean (Standard Error) [Scores on a Scale]	-3.2 (0.27)	-3.7 (0.27)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Asacol 2.4 g/Day, Asacol 4.8 g/Day
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1594
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Difference Between Means
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 95%; -1.28 to 0.21
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Asacol 2.4 g/Day
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Compared to baseline
	Method	t-test, 2 sided
	Comments	The 2-sample t-test will be used to examine the treatment effect.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Asacol 4.8 g/Day
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Compared to baseline
	Method	t-test, 2 sided
	Comments	Teh 2-sample t-test will be used to examine the treatment effect.

3. Secondary Outcome

Title	Percentage of Participants Whose Rectal Bleeding & Sigmoidoscopy Score Both Improved From Baseline to Week 6, ITT Population
Description	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)
Time Frame	6 Weeks

Outcome Measure Data

Analysis Population Description

ITT Patients with Moderate Disease [PGA=2] at Baseline. Percentage of patients whose rectal bleeding AND sigmoidoscopy scores BOTH improved from baseline at Week 6

Arm/Group Title	Asacol 2.4 g/Day	Asacol 4.8 g/Day
Arm/Group Description	Two 400 mg Asacol tablets and 2 placebo tablets (matching 800 mg formulation) taken 3 times daily (morning, midday, evening).	Two 800 mg Asacol tablets and 2 placebo tablets (matching 400 mg formulation) taken 3 times daily (morning, midday, evening).
Measure Participants	130	124
Number [Percentage of Participants]	59.8 43%	63.6 49.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Asacol 2.4 g/Day, Asacol 4.8 g/Day
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5774
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Difference in Success Rates
	Estimated Value	3.75
	Confidence Interval	(2-Sided) 95%; -9.43 to 16.93
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Percentage of Patients Whose Sigmoidoscopy Score Improved From Baseline to Week 6, ITT Population
Description	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)
Time Frame	6 Weeks

Outcome Measure Data

Analysis Population Description

ITT Population with Moderate Disease [PGA=2] at Baseline

Arm/Group Title	Asacol 2.4 g/Day	Asacol 4.8 g/Day
Arm/Group Description	Two 400 mg Asacol tablets and 2 placebo tablets (matching 800 mg formulation) taken 3 times daily (morning, midday, evening).	Two 800 mg Asacol tablets and 2 placebo tablets (matching 400 mg formulation) taken 3 times daily (morning, midday, evening).
Measure Participants	130	124
Number [Percentage of Participants]	69.0 49.6%	75.2 58.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Asacol 2.4 g/Day, Asacol 4.8 g/Day
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2991
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Difference in Success Rates
	Estimated Value	6.19
	Confidence Interval	(2-Sided) 95%; -5.47 to 17.86
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Percentage of Patients With an Improvement in Stool Frequency, ITT Population, Week 6
Description	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
Time Frame	6 Weeks

Outcome Measure Data

Analysis Population Description

ITT Patients with Moderate Disease [PGA=2] at Baseline

Arm/Group Title	Asacol 2.4 g/Day	Asacol 4.8 g/Day
Arm/Group Description	Two 400 mg Asacol tablets and 2 placebo tablets (matching 800 mg formulation) taken 3 times daily (morning, midday, evening).	Two 800 mg Asacol tablets and 2 placebo tablets (matching 400 mg formulation) taken 3 times daily (morning, midday, evening).
Measure Participants	130	124
Number [Percentage of Participants]	71.3 51.3%	74.0 57.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Asacol 2.4 g/Day, Asacol 4.8 g/Day
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6543
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Difference in Success Rates
	Estimated Value	2.74
	Confidence Interval	(2-Sided) 95%; -9.25 to 14.73
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Percentage of Patients With Improvement in Rectal Bleeding, ITT Population, Week 6
Description	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)
Time Frame	6 Weeks

Outcome Measure Data

Analysis Population Description

ITT Population with Moderate Disease [PGA=2] at Baseline

Arm/Group Title	Asacol 2.4 g/Day	Asacol 4.8 g/Day
Arm/Group Description	Two 400 mg Asacol tablets and 2 placebo tablets (matching 800 mg formulation) taken 3 times daily (morning, midday, evening).	Two 800 mg Asacol tablets and 2 placebo tablets (matching 400 mg formulation) taken 3 times daily (morning, midday, evening).
Measure Participants	130	124
Number [Percentage of Participants]	77.5 55.8%	78.5 60.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Asacol 2.4 g/Day, Asacol 4.8 g/Day
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8542
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Difference in Success Rates
	Estimated Value	1.05
	Confidence Interval	(2-Sided) 95%; -10.19 to 12.29
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Percentage of Patients With Improvement in Patient's Functional Assessment (PFA), ITT Population, Week 6
Description	PFA - 0=generally well, 1=fair, 2=poor, 3=terrible
Time Frame	6 Weeks

Outcome Measure Data

Analysis Population Description

ITT Population with Moderate Disease [PGA=2] at Baseline

Arm/Group Title	Asacol 2.4 g/Day	Asacol 4.8 g/Day
Arm/Group Description	Two 400 mg Asacol tablets and 2 placebo tablets (matching 800 mg formulation) taken 3 times daily (morning, midday, evening).	Two 800 mg Asacol tablets and 2 placebo tablets (matching 400 mg formulation) taken 3 times daily (morning, midday, evening).
Measure Participants	130	124
Number [Percentage of Participants]	70.5 50.7%	69.6 54%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Asacol 2.4 g/Day, Asacol 4.8 g/Day
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8859
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Difference in Success Rates
	Estimated Value	-0.96
	Confidence Interval	(2-Sided) 95%; -14.09 to 12.17
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Percentage of Patients With Improvement in Physician Global Assessment (PGA)Score, ITT Population, Week 6
Description	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.
Time Frame	6 Weeks

Outcome Measure Data

Analysis Population Description

ITT Population with Moderate Disease [PGA=2] at Baseline

Arm/Group Title	Asacol 2.4 g/Day	Asacol 4.8 g/Day
Arm/Group Description	Two 400 mg Asacol tablets and 2 placebo tablets (matching 800 mg formulation) taken 3 times daily (morning, midday, evening).	Two 800 mg Asacol tablets and 2 placebo tablets (matching 400 mg formulation) taken 3 times daily (morning, midday, evening).
Measure Participants	130	124
Number [Percentage of Participants]	73.5 52.9%	83.2 64.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Asacol 2.4 g/Day, Asacol 4.8 g/Day
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0758
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Difference in Success Rates
	Estimated Value	9.73
	Confidence Interval	(2-Sided) 95%; -0.94 to 20.40
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Mean Change From Baseline in Total Inflammatory Bowel Disease Questionnaire (IBDQ) at Week 3, All Randomized Patients
Description	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.
Time Frame	3 Weeks

Outcome Measure Data

Analysis Population Description

All Randomized Patients with Moderate Disease[PGA=2] at Baseline. Questionnaire analyzable if patient answered 28 of 32 for total, 8/10 for bowel, 3/5 for systemic, 10/12 for emotional, 3/5 for social.

Arm/Group Title	Asacol 2.4 g/Day	Asacol 4.8 g/Day
Arm/Group Description	Two 400 mg Asacol tablets and 2 placebo tablets (matching 800 mg formulation) taken 3 times daily (morning, midday, evening).	Two 800 mg Asacol tablets and 2 placebo tablets (matching 400 mg formulation) taken 3 times daily (morning, midday, evening).
Measure Participants	139	129
Mean (Standard Error) [Scores on a Scale]	30.4 (2.84)	29.8 (2.60)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Asacol 2.4 g/Day, Asacol 4.8 g/Day
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8308
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Asacol 2.4 g/Day
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Compared to baseline
	Method	t-test, 2 sided
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Asacol 4.8 g/Day
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Compared to baseline.
	Method	t-test, 2 sided
	Comments

10. Secondary Outcome

Title	Mean Change From Baseline in Total Inflammatory Bowel Disease Questionnaire (IBDQ) at Week 6, All Randomized Patients
Description	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.
Time Frame	6 Weeks

Outcome Measure Data

Analysis Population Description

All Randomized Patients with Moderate Disease [PGA=2] at Baseline. Questionnaire analyzable if patient answered 28 of 32 for total, 8/10 for bowel, 3/5 for systemic, 10/12 for emotional, 3/5 for social.

Arm/Group Title	Asacol 2.4 g/Day	Asacol 4.8 g/Day
Arm/Group Description	Two 400 mg Asacol tablets and 2 placebo tablets (matching 800 mg formulation) taken 3 times daily (morning, midday, evening).	Two 800 mg Asacol tablets and 2 placebo tablets (matching 400 mg formulation) taken 3 times daily (morning, midday, evening).
Measure Participants	139	129
Mean (Standard Error) [Scores on a Scale]	43.1 (3.5)	40.4 (3.08)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Asacol 2.4 g/Day, Asacol 4.8 g/Day
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5340
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Asacol 2.4 g/Day
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Compared to baseline
	Method	t-test, 2 sided
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Asacol 4.8 g/Day
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Compared to baseline
	Method	t-test, 2 sided
	Comments

11. Secondary Outcome

Title	Percentage of Patients With Moderate, Left-Sided Disease at Baseline Classified as Treatment Success at Week 6, All Randomized Patients
Description	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)
Time Frame	6 Weeks

Outcome Measure Data

Analysis Population Description

All Randomized Patients with Moderate Disease [PGA=2] at Baseline. Left Sided Disease = proctitis, proctosigmoiditis or left-sided colitis

Arm/Group Title	Asacol 2.4 g/Day	Asacol 4.8 g/Day
Arm/Group Description	Two 400 mg Asacol tablets and 2 placebo tablets (matching 800 mg formulation) taken 3 times daily (morning, midday, evening).	Two 800 mg Asacol tablets and 2 placebo tablets (matching 400 mg formulation) taken 3 times daily (morning, midday, evening).
Measure Participants	105	97
Number [Percentage of Participants]	60.0 43.2%	71.1 55.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Asacol 2.4 g/Day, Asacol 4.8 g/Day
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0966
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Difference in Success Rates
	Estimated Value	11.1
	Confidence Interval	(2-Sided) 95%; -1.87 to 24.14
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

Title	Percentage of Treatment Success Patients at Week 3, ITT Population
Description	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)
Time Frame	3 Weeks

Outcome Measure Data

Analysis Population Description

ITT Patients with Moderate Disease [PGA = 2] at Baseline

Arm/Group Title	Asacol 2.4 g/Day	Asacol 4.8 g/Day
Arm/Group Description	Two 400 mg Asacol tablets and 2 placebo tablets (matching 800 mg formulation) taken 3 times daily (morning, midday, evening).	Two 800 mg Asacol tablets and 2 placebo tablets (matching 400 mg formulation) taken 3 times daily (morning, midday, evening).
Measure Participants	130	124
Number [Percentage of Participants]	51.5 37.1%	61.3 47.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Asacol 2.4 g/Day, Asacol 4.8 g/Day
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1173
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Difference in Success Rates
	Estimated Value	9.75
	Confidence Interval	(2-Sided) 95%; -2.39 to 21.89
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	6 week treatment period for each subject, February 28, 2001 thru April 15 2004
Arm/Group Title	Asacol 2.4 g/Day		Asacol 4.8 g/Day
Arm/Group Description	Two 400 mg Asacol tablets and 2 placebo tablets (matching 800 mg formulation) taken 3 times daily (morning, midday, evening).		Two 800 mg Asacol tablets and 2 placebo tablets (matching 400 mg formulation) taken 3 times daily (morning, midday, evening).
All Cause Mortality
	Asacol 2.4 g/Day		Asacol 4.8 g/Day
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Asacol 2.4 g/Day		Asacol 4.8 g/Day
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/139 (2.9%)		1/129 (0.8%)
Cardiac disorders
Pericarditis	0/139 (0%)	0	1/129 (0.8%)	1
Gastrointestinal disorders
Nausea	1/139 (0.7%)	1	0/129 (0%)	0
Vomiting	1/139 (0.7%)	1	0/129 (0%)	0
Increased Diarrhea	1/139 (0.7%)	1	0/129 (0%)	0
Abdominal Cramping	1/139 (0.7%)	1	0/129 (0%)	0
Exacerbation of Ulcerative Colitis	1/139 (0.7%)	1	0/129 (0%)	0
Pancreatitis	1/139 (0.7%)	1	0/129 (0%)	0
Hepatobiliary disorders
Cholecystitis	1/139 (0.7%)	1	0/129 (0%)	0
Musculoskeletal and connective tissue disorders
Shoulder/Chest Pain	0/139 (0%)	0	1/129 (0.8%)	1
Renal and urinary disorders
Nephritis	1/139 (0.7%)	1	0/129 (0%)	0
Other (Not Including Serious) Adverse Events
	Asacol 2.4 g/Day		Asacol 4.8 g/Day
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	72/195 (36.9%)		81/191 (42.4%)
Gastrointestinal disorders
Pain, Abdominal	11/195 (5.6%)		7/191 (3.7%)
Diarrhea	6/195 (3.1%)		8/191 (4.2%)
Nausea	5/195 (2.6%)		5/191 (2.6%)
Rectal Disorder	5/195 (2.6%)		5/191 (2.6%)
Dyspepsia	5/195 (2.6%)		4/191 (2.1%)
Colitis Ulcer	3/195 (1.5%)		5/191 (2.6%)
Flatulence	6/195 (3.1%)		2/191 (1%)
General disorders
Fever	4/195 (2.1%)		4/191 (2.1%)
Asthenia	3/195 (1.5%)		4/191 (2.1%)
Infections and infestations
Infection	5/195 (2.6%)		9/191 (4.7%)
Flu Syndrome	5/195 (2.6%)		4/191 (2.1%)
Nervous system disorders
Headache	15/195 (7.7%)		16/191 (8.4%)
Respiratory, thoracic and mediastinal disorders
Rhinitis	7/195 (3.6%)		1/191 (0.5%)
Cough Increased	6/195 (3.1%)		1/191 (0.5%)
Sinusitis	5/195 (2.6%)		1/191 (0.5%)
Bronchitis	1/195 (0.5%)		4/191 (2.1%)
Skin and subcutaneous tissue disorders
Rash	4/195 (2.1%)		2/191 (1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.