Efficacy and Safety of SPD476 in Maintaining Remission in Patients With Ulcerative Colitis

Study Overview
=================
Brief Summary
-----------------
Ulcerative colitis is a disease of the large bowel (colon) and rectum in which the lining of the bowel becomes red and swollen. Over time, patients with this disease may experience acute episodes of diarrhea, rectal bleeding and abdominal pain followed by periods of time without disease symptoms. 5-ASA drugs are a standard treatment for ulcerative colitis. Mesalazine is an experimental drug designed to gradually release 5-ASA into the areas of large bowel associated with ulcerative colitis. This study will test the safety and efficacy of mesalazine in keeping ulcerative colitis in remission.

Official Title
-----------------
A Phase III, Randomized Multi-centre, Double-blind, Parallel Group, Active Comparator Study to Compare the Efficacy and Safety of SPD476 (Mesalazine)2.4g/Day Once Daily With Asacol 1.6g/Day Twice Daily in the Maintenance of Remission in Patients With Ulcerative Colitis

Conditions
-----------------
Ulcerative Colitis

Intervention / Treatment
-----------------
* Drug: SPD476
* Drug: Asacol


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: previous diagnosis of ulcerative colitis confirmed by histology that has been considered to be in remission for => 30 days female subjects must be post-menopausal, surgically or biologically sterile, or with a negative urine pregnancy test at screening and on adequate contraception Exclusion Criteria: proctitis previous resective colonic surgery Crohn's disease hypersensitivity to salicylates moderate/severe renal impairment

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SPD476<br>Mesalazine | Drug: SPD476<br>* 2.4 g/day Once Daily (QD)<br>* Other names: MMX mesalamine;|
| Active Comparator: Asacol<br> | Drug: Asacol<br>* 1.6g/day administered 800 mg Twice Daily (BID)<br>* Other names: mesalamine;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endoscopic Remission of Ulcerative Colitis (UC) at 6 Months | Endoscopic remission is defined as an endoscopy score of less than or equal to 1. Endoscopy score (mucosal appearance) ranges from 0-3 (0 = normal [intact vascular pattern; no friability or granulation], 1 = mild [erythema; decreased vascular pattern; minimal granularity], 2 = moderate [marked erythema; granularity; friability; absent vascular pattern; bleeding with minimal trauma; no ulcerations], 3 = severe [ulceration; spontaneous bleeding]. | 6 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Withdrawal Due to Relapse of UC | Relapse is defined as withdrawal from the study due to lack of efficacy. | Over 6 Months | 
| Endoscopic Remission of UC With No or Mild Symptoms at 6 Months | Endoscopic remission with no or mild symptoms is defined as an endoscopy score of less than or equal to 1 and a combined symptom score (stool frequency plus rectal bleeding) of less than or equal to 1. Endoscopy score (mucosal appearance) ranges from 0-3 (0 = normal, 1 = mild , 2 = moderate, 3 = severe). Rectal bleeding is assessed on a scale from 0-3 (0 = no rectal bleeding, 1 = streaks of blood, 2 = obvious blood, 3 = mostly blood). Stool frequency is assessed on a scale of 0-2 (0 = 0-1 more than normal per day, 1 = 2-3 more than normal per day, 2 = 4 or more than normal per day). | 6 Months | 
| Change From Baseline in Modified Ulcerative Colitis Disease Activity Index (UCDAI) Score at 6 Months | The modified UCDAI score is the sum of the scores of 4 parameters (stool frequency, rectal bleeding, endoscopy score, and physician global assessment), each scoring between 0 and 3, making 12 the worst score. | Baseline and 6 months | 
| Short Inflammatory Bowel Disease Questionnaire (SIBDQ) Total Score | Quality of life (QoL) was assessed using the SIBDQ. SIBDQ total score is calculated from the sum of 10 questions. Each question is scored on a scale from 1 (poor QoL) to 7 (good QoL) with total scores ranging from 10 to 70. Higher scores indicate better QoL. | 6 Months |