Assessing the Safety/Efficacy of Asacol® Given Every 12 Hours to Children and Adolescents for the Maintenance of Remission of Ulcerative Colitis

Study Overview
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Brief Summary
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The purpose of this study is to determine whether low dose Asacol® (27 mg/kg - 71 mg/kg) and high dose Asacol® (53 mg/kg - 118 mg/kg) are safe and effective when dosed as 400 mg delayed-release tablets given twice daily for 26 weeks to children and adolescents for the maintenance of remission of ulcerative colitis.

Official Title
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A Randomized, Double-blind, Parallel-group Study to Assess the Safety and Efficacy of Asacol® (1.2 to 4.8g/Day) 400 mg Delayed-release Tablets Given Twice Daily for 26 Weeks to Children and Adolescents for the Maintenance of Remission of Ulcerative Colitis

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Drug: Asacol 400 mg
* Drug: Asacol 400 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: male or female between the ages of 5 and 17 years, inclusive, at the time of the first dose of study medication; have a documented history of UC that has been successfully maintained in complete remission for at least 1 month prior to study entry have a baseline PUCAI score < 10 have a body weight no less than 17 kg and no more than 90 kg have a history of at least 1 active episode or relapse in the last 12 months have taken a stable maintenance dose of oral mesalamine (or equivalent oral 5-ASA dose) for at least 1 month prior to entry in the study. Stable is defined as the same dose for the last month. maintained complete remission, as defined, throughout the 30-day run-in phase. Note:ONLY applies to those patients who complete the 6-week treatment in complete remission from Study 2007017 and immediately roll-over to the 30-day run-in phase are female patients who are pre-menarchal or have a negative urine pregnancy test and, if sexually active, practice acceptable contraception (e.g., abstinence; oral, intramuscular, or implanted hormonal contraception [at least 3 months prior to enrollment] Exclusion Criteria: have a history of allergy or hypersensitivity to salicylates, aminosalicylates, or any component of the Asacol tablet have a significant co-existing illness or other condition(s), including but not limited to cancer or significant organic or psychiatric disease on medical history or physical examination, that, in the judgment of the Investigator, contraindicate(s) administration of the study drug and/or any study procedures have a history or presence of any condition causing malabsorption or an effect on gastrointestinal motility or history of extensive small bowel resection (greater than one half the length of the small intestine) causing short bowel syndrome any condition causing malabsorption or an effect on gastrointestinal motility have current renal disease, or a screening blood urea nitrogen (BUN) or creatinine value that is > 1.5 times the upper limit of the age appropriate normal have a documented history of or current hepatic disease, or liver function tests (alanine transaminase [ALT], aspartate transaminase [AST], total bilirubin) that are > 2 times the upper limit of normal have a history of pancreatitis have undergone treatment with any oral, intravenous, intramuscular, or rectally administered corticosteroids (including budesonide) within 30 days prior to the Screening visit have undergone treatment with any rectal mesalamine therapy within 30 days prior to the screening visit have undergone treatment with immunomodulatory therapy including, but not limited to: rosiglitazone, 6-mercaptopurine or azathioprine, cyclosporine, or methotrexate within 90 days prior to Screening visit have undergone treatment with biologic therapy including, but not limited to: infliximab,adalimumab, certolizumab or other biologic treatment of ulcerative colitis within 90 days prior to Screening visit have undergone treatment with antibiotics (other than topical antibiotics) including metronidazole within 7 days prior to the Screening visit have undergone treatment with aspirin or other nonsteroidal anti-inflammatory drugs NSAIDs) within 7 days prior to the Screening visit have undergone treatment with any antidiarrheals and/or antispasmodics within 30 days of the Screening visit have a stool examination positive for Clostridium difficile (C. difficile), bacterial pathogens, or ova and parasites. Note: Because normal gut flora may vary by geography, the Medical Monitor should be consulted before excluding a patient with a stool sample that is positive for C. difficile, bacterial pathogens or ova and parasites.

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 17 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: High Dose<br>2.0 - 4.8 g/day Asacol dependent on body weight | Drug: Asacol 400 mg<br>* 17-33kg = 3 Asacol 400mg AM & 2 Asacol 400mg PM; 33-<54kg = 5 Asacol 400 mg AM & 4 Asacol 400mg PM; 54-<90kg = 6 Asacol 400mg AM & PM<br>* Other names: mesalamine; 5-aminosalicylic acid; 5-ASA; mesalazine;|
| Experimental: Low Dose<br>1.2 - 2.4 g/day Asacol dependent upon body weight | Drug: Asacol 400 mg<br>* 17-<33kg = 2 Asacol 400mg & 1 placebo AM, 1 Asacol 400mg & 1 placebo PM; 33-<54kg = 3 Asacol 400mg & 2 placebo AM, 2 Asacol 400mg & 2 placebo PM; 54-<90kg = 3 Asacol 400mg & 3 placebo AM & PM<br>* Other names: mesalamine; 5-aminosalicylic acid; 5-ASA; mesalazine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment Success PUCAI (Pediatric Ulcerative Colitis Activity Index), mITT/Modified Intent to Treat Population | PUCAI Score (0-85, sum of scores for each): abdominal pain (0/5/10 - no pain/ignored/not ignored), rectal bleeding (0/10/20/30 - none, small amount <50% of stools, small amount most stools, large amount >50%), stool consistency (0/5/10 - formed, partially formed, completely formed), # stools/24 hrs. (0/5/10/15 - 0-2/3-5/6-8/>8), nocturnal bowel/any diarrhea causing wakening (0/10 - no/yes), activity level (0/5/10 - no limitation/occ limitation, severe restrictions). Remission <10, Mild 10-34, Moderate 35-64, Severe 65-85. Remission defined as Treatment Success. | Week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment Success PUCAI Amended Endpoint (5 Point Scale Abdominal Pain), mITT | PUCAI Score (0-85, sum of scores for each) abdominal pain (0/2.5/5/7.5/10 - no pain/very mild/mild/moderate/severe), rectal bleeding (0/10/20/30 - none, small amount <50% of stools, small amount most stools, large amount >50%), stool consistency (0/5/10 - formed, partially formed, completely formed), # stools/24 hrs. (0/5/10/15 - 0-2/3-5/6-8/>8), nocturnal bowel/any diarrhea causing wakening (0/10 - no/yes), activity level (0/5/10 - no limitation/occ limitation, severe restrictions). Remission <10, Mild 10-34, Moderate 35-64, Severe 65-85. Remission is Treatment Success. | Week 26 |