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

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

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.

Study Overview

• Status: Completed
• Conditions: Ulcerative Colitis
• Intervention / Treatment: Drug: Asacol 400 mg (mesalamine); Drug: Asacol 800 mg (mesalamine)

• Study Type: Interventional
• Enrollment (Actual): 386
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Richmond, British Columbia, Canada, V7C 5L9
      • Research Site
  • Ontario
    • Toronto, Ontario, Canada, M5B 1W8
      • Research Site
• Puerto Rico
  • San Juan, Puerto Rico, 00935
    • University of Puerto Rico, School of Medicine
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic Scottsdale
  • California
    • Anaheim, California, United States, 92801
      • AGMG Clinical Research
    • Los Angeles, California, United States, 90067
      • Research Site
    • Orange, California, United States, 38305
      • Community Clinical Trials
    • Orange, California, United States, 92869
      • AGMG Clinical Research
    • Sacramento, California, United States, 95825
      • Research Site
    • San Diego, California, United States, 92123
      • Sharp Rees-Stealy Medical Group
  • Colorado
    • Arvada, Colorado, United States, 80002
      • Research Site
    • Englewood, Colorado, United States, 80110
      • Research Site
  • Connecticut
    • Manchester, Connecticut, United States, 06040
      • Center for Medical Research, LLC
  • Florida
    • Hollywood, Florida, United States, 33021
      • Center for GI Disorders
    • Maitland, Florida, United States, 32789
      • Research Site
    • Palm Harbor, Florida, United States, 34684
      • Advanced Gastroenterology Associates
    • Zephyrhills, Florida, United States, 33540
      • Research Site
  • Georgia
    • Marietta, Georgia, United States, 30067
      • Southeast Research Associates
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
  • Louisiana
    • Metairie, Louisiana, United States, 70001
      • GI Research
    • Shreveport, Louisiana, United States, 71103
      • Louisiana Research Center
  • Maryland
    • Annapolis, Maryland, United States, 21401
      • Digestive Disorders Associates
    • Baltimore, Maryland, United States, 21215
      • Research Site
    • Baltimore, Maryland, United States, 21229
      • Digestive Disease Associates
    • Chevy Chase, Maryland, United States, 20815
      • Metropolitan Gastroenterology Group
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham & Women's Hospital
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • New Jersey
    • Hillsborough, New Jersey, United States, 08844
      • PharmaTrials, Inc.
  • New York
    • Forest Hills, New York, United States, 11375
      • Research Site
    • Great Neck, New York, United States, 11021
      • Long Island Clinical Research Associates
    • New York, New York, United States, 10128
      • Research Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28262
      • Carolinas Digestive Health Associates
    • Raleigh, North Carolina, United States, 27612
      • Research Site
    • Statesville, North Carolina, United States, 28677
      • Research Site
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Consultants for Clinical Research
    • Cincinnati, Ohio, United States, 45267
      • Research Site
    • Columbus, Ohio, United States, 43215
      • Research Site
    • Dayton, Ohio, United States, 45440
      • GI & Liver Consultants
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73190
      • Research Site
    • Tulsa, Oklahoma, United States, 74135
      • Research Site
  • Oregon
    • Portland, Oregon, United States, 97225
      • West Hills Gastroenterology Group
  • Pennsylvania
    • Altoona, Pennsylvania, United States, 16602
      • Research Site
    • Hanover, Pennsylvania, United States, 17331
      • Research Site
  • Tennessee
    • Jackson, Tennessee, United States, 38305
      • Regional Research Institute
  • Texas
    • Austin, Texas, United States, 78705
      • Research Site
    • Dallas, Texas, United States, 75246
      • Research Site
    • Houston, Texas, United States, 77030
      • Research Site
    • Houston, Texas, United States, 77090
      • Houston Medical Research Associates
    • Temple, Texas, United States, 76508
      • Research Site
  • Utah
    • Ogden, Utah, United States, 84405
      • Research Site
  • Virginia
    • Charlottesville, Virginia, United States, 22902
      • Charlottesville Medical Research
    • Fairfax, Virginia, United States, 22031
      • Research Site
    • Fredricksburg, Virginia, United States, 22401
      • Research Site
    • Richmond, Virginia, United States, 23226
      • Richmond GI Research
  • Washington
    • Spokane, Washington, United States, 99207
      • Research Site
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53207
      • Wisconsin Center for Advanced Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Warner Chilcott
• Investigators: Study Director: Piotr Krzeski, MD, Procter and Gamble

Publications and helpful links

General Publications

• Orchard TR, van der Geest SA, Travis SP. Randomised clinical trial: early assessment after 2 weeks of high-dose mesalazine for moderately active ulcerative colitis - new light on a familiar question. Aliment Pharmacol Ther. 2011 May;33(9):1028-35. doi: 10.1111/j.1365-2036.2011.04620.x. Epub 2011 Mar 8.
• Lichtenstein GR, Ramsey D, Rubin DT. Randomised clinical trial: delayed-release oral mesalazine 4.8 g/day vs. 2.4 g/day in endoscopic mucosal healing--ASCEND I and II combined analysis. Aliment Pharmacol Ther. 2011 Mar;33(6):672-8. doi: 10.1111/j.1365-2036.2010.04575.x. Epub 2011 Jan 23.

Study record dates

Study Major Dates

• Study Start: September 1, 2000
• Primary Completion (Actual): September 1, 2003
• Study Completion (Actual): September 1, 2003

Study Registration Dates

• First Submitted: November 13, 2003
• First Submitted That Met QC Criteria: November 14, 2003
• First Posted (Estimate): November 17, 2003

Study Record Updates

• Last Update Posted (Estimate): June 29, 2015
• Last Update Submitted That Met QC Criteria: June 1, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Mesalamine
• Other Study ID Numbers: 2000082