Canadian Active & Maintenance Modified Pentasa Study

Study Overview
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Brief Summary
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The purpose of this study is to demonstrate that the new modified oral extended-release Pentasa® 500mg tablet is at least as efficacious as the currently marketed Pentasa® 500mg tablet in active mild to moderate Ulcerative Colitis (UC) and also in maintenance of quiescent disease.

Detailed Description
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A multi-centre, randomized, double-blind, non-inferiority trial comparing the efficacy and safety of a new modified oral extended release Pentasa® (mesalamine) 500 mg tablet to the currently marketed Pentasa® (mesalamine) 500 mg tablet in subjects with active mild to moderate ulcerative colitis treated with 4 g/day for 8 weeks and in maintenance of remission of ulcerative colitis in subjects treated with 2 g/day for 24 weeks. The study involves male or non-pregnant female subjects aged 18 to 75 years. Subjects were randomised on entry into the trial, and if they were in remission at the end of the 8-week Active Phase or the 4-week Run-in Phase, they were eligible for enrolment into the 24-week Maintenance Phase, remaining on the original randomised treatment.

Official Title
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A Multicentre, Randomised, Double-blind, Non-inferiority Trial Comparing the Efficacy and Safety of a New Modified Oral Extended Release Pentasa® (Mesalamine) 500 mg Tablet to the Currently Marketed Pentasa® (Mesalamine) 500 mg Tablet in Subjects With Active Mild to Moderate Ulcerative Colitis Treated With 4 g/Day for 8 Weeks and in Maintenance of Remission of Ulcerative Colitis in Subjects Treated With 2 g/Day for 24 Weeks

Conditions
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Active Ulcerative Colitis, Remission of Ulcerative Colitis

Intervention / Treatment
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* Drug: 5-ASA (5-Aminosalicylate)
* Drug: 5-ASA (5-Aminosalicylate)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for Active phase: Newly diagnosed or recurrent, mild to moderate Ulcerative Colitis patients. Extent of colonic involvement confirmed within the past 36 months UCDAI score of at least 3 but not greater than 8 and a score of at least 1 for endoscopy Screening tests to rule out any abnormalities in stool, heart or kidney. Male or non-pregnant females between 18 to 75 years. Women of childbearing potential to use efficacious contraception as judged by the investigator. Written informed consent given. Inclusion Criteria for Maintenance phase: Newly recruited subjects with documented mild to moderate UC entering the Run-in Phase: in clinical remission for at least 1 month and for a maximum of 3 years, and receiving 5-ASA 1.4 to 2.5 g/day for maintenance of quiescent disease Subjects from Active Phase: meeting remission criteria after the 8-week active period Extent of colonic involvement confirmed within the past 36 months by colonoscopy In complete remission at entry into the Maintenance Phase, defined as i) a score of 0 or 1 for stool frequency; ii) a score of 0 for rectal bleeding; iii) a score of 0 for endoscopy findings; and iv) a Physician's Global Assessment (PGA) score of 0 or 1 Screening tests to rule out any abnormalities in stool, heart or kidney. Exclusion Criteria: Use of 5-ASA products at a dose >2.5g/day within 7 days prior to entry. Proctitis, short bowel syndrome, prior bowel surgery, severe UC, other forms of Inflammatory Bowel Disease Infectious diseases, parasites, bacterial pathogens Allergy to aspirin or salicylate Liver or kidney abnormalities Alcohol or drug abuse Pregnancy Cancer Bleeding disorders, ulcers, autoimmune diseases Mental disorders Participation in clinical trial in last 30 days Inability to fill in diary cards / comply with protocol requirements

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 |
| --- | --- |
| Experimental: Pentasa® modified extended release<br>5-ASA (5-Aminosalicylate) | Drug: 5-ASA (5-Aminosalicylate)<br>* 500 mg tablet (modified extended release)<br>* Other names: mesalamine;|
| Active Comparator: Pentasa®<br>5-ASA (5-Aminosalicylate) | Drug: 5-ASA (5-Aminosalicylate)<br>* 500 mg tablet<br>* Other names: mesalamine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Active Phase: Proportion of Active Subjects Achieving Overall Improvement | Overall improvement is defined as either a complete remission or a clinical response to therapy as measured by the Ulcerative Colitis Disease Activity Index (UCDAI). Complete remission is defined as: i) a score of 0 or 1 for stool frequency; ii) a score of 0 for rectal bleeding; iii) a score of 0 for endoscopy findings and iv) a Physician's Global Assessment (PGA) score of 0 or 1. A clinical response to therapy in the active disease phase is defined as i) improvement in the baseline PGA score; ii) improvement in endoscopy findings and in at least one other clinical assessment (stool frequency, rectal bleeding); iii) no worsening in any other clinical assessment; iv) a decrease of 2 or more points on the UCDAI score. | From baseline to week 8 | 
| Maintenance Phase: Proportion of Subjects Experiencing Relapse | Relapse is defined as a UCDAI score of at least 3 and a score of at least 1 for endoscopy | Up to week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of Adverse Events | Safety dataset represents all patients in all study phases exposed to study drug at anytime during study. Safety dataset was a combination of the active, run-in and maintenance phases and therefore it is not possible to report the adverse events per phase. | From baseline to week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ulcerative Colitis, 5-Aminosalicylate