Strategies in Maintenance for Patients Receiving Long-term Therapy (S.I.M.P.L.E.) With MMX (Multi-Matrix System) Mesalamine for Ulcerative Colitis (UC)

Study Overview
=================
Brief Summary
-----------------
To evaluate the percentage of subjects with clinical recurrence of UC at 6 months using MMX mesalamine once daily.

Official Title
-----------------
A Phase IV, Multi-center, Open-label Study to Assess Clinical Recurrence Related to Compliance With Treatment With MMX Mesalamine 2.4g/Day Given Once Daily for the Maintenance of Quiescent Ulcerative Colitis (UC)

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

Intervention / Treatment
-----------------
* Drug: MMX Mesalamine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria - Acute Phase: Male and female subjects aged at least 18 years with active mild to moderate UC may enter the Acute Phase of the study. Must have a previous diagnosis of UC confirmed by histology and endoscopy or radiology. Males or non-pregnant, non-lactating FOCP who have a negative serum pregnancy test prior to entering the study and who are using adequate forms of contraception for the duration of the study. General medical assessment must be satisfactory and there must not be clinically significant and relevant abnormalities. Subject must have had >2 acute episodes of UC (a documented episode of increased bowel frequency with rectal blood loss for which UC therapy was intensified) in their medical history. Subjects who have relapsed on maintenance therapy after 2 weeks with doses of mesalamine at: a. <2.0g/day, will be allowed into the Acute Phase at 2.4g/day QD, or b. between 2.0g/day - 3.0g/day will be allowed into the Acute Phase at 4.8g/day QD. Inclusion Criteria - Maintenance Phase: Subjects determined to be quiescent at study entry on prior oral mesalamine therapy will be eligible to enter directly into the Maintenance Phase. UC must have been considered to be quiescent, with scores of zero for both rectal bleeding and bowel movements. Exclusion Criteria - Acute Phase: Subjects who have been in relapse for >6 weeks. Female subjects who are pregnant or lactating, including females with a positive pregnancy test at screening. Subjects must not have used another investigational agent within the last 30 days prior to enrollment. Subjects who have unsuccessfully treated their current relapse with steroids or a mesalamine dose of >2.0 g/day. Subjects who have relapsed on maintenance therapy with doses of mesalamine >2.0g/day. If the subject had a recent dose reduction from 2.0g/day to less than or equal to 2.0g/day and relapsed within 2 weeks of that dose reduction, the subject will not be eligible. Subjects who have used systemic or rectal steroids within the last 4 weeks prior to Baseline, immunosuppressants within the last 6 weeks, antibiotic use within the last 7 days or chronic use of any anti-inflammatory drugs within 7 days prior to Baseline. Subjects with hypersensitivity to salicylates/aspirin are excluded. Subjects with moderate or severe hepatic impairment. Subjects with Crohn's Disease, proctitis (where the extent of inflammation is less than or equal to 15cm), short bowel syndrome, bleeding disorders, or active peptic ulcer disease. Subjects with asthma are excluded only if they are known to be mesalamine-sensitive. Subjects with a positive stool culture for enteric pathogens (including Salmonella, Shigella, Yersinia, Aeromonas, Plesiomonas or Campylobacter) are excluded, as are those with C. difficile toxin present or with ova or parasites as detected by microscopy. Subjects who have a history of previous colonic surgery. Subjects with moderate or severe renal impairment are contra-indicated for treatment with mesalamine compounds and are excluded from the study. Subjects with current or recurrent disease that could affect the colon, the action, absorption or disposition of the study drug, or clinical or laboratory assessments. Subjects with current or relevant previous history of serious, severe or unstable (acute or progressive) physical or psychiatric illness, any medical disorder that may require treatment or make the patient unlikely to fully complete the study, or any condition that presents undue risk from the study drug or procedures. Subjects with a history of alcohol or other substance abuse within the previous year. Subjects who withdrew from a mesalamine trial due to a possibly or probably related severe AE or SAE are not eligible to enter this study. Exclusion Criteria - Maintenance Phase (in addition to above inclusion for the Acute Phase): Subjects who have withdrawn from the Acute Phase before study visit A3. Subjects with severe UC according to the PGA.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MMX Mesalamine<br> | Drug: MMX Mesalamine<br>* MMX™ mesalamine 2.4g/day to 4.8g/day once-daily (QD) (two to four 1.2g tablets MMX™ mesalamine, dosed QD,respectively).<br>* Other names: Lialda;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Recurrence of Ulcerative Colitis (UC) During the Maintenance Phase at 6 Months | Clinical recurrence is defined as 4 or more bowel movements per day above the subject's normal frequency and associated with any of the following: urgency, abdominal pain, or rectal bleeding. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Recurrence of UC During the Maintenance Phase at 12 Months | Clinical recurrence is defined as 4 or more bowel movements per day above the subject's normal frequency and associated with any of the following: urgency, abdominal pain, or rectal bleeding. | 12 Months | 
| Clinical Recurrence of UC During the Maintenance Phase Associated With Subject Compliance at 6 Months | Clinical recurrence is defined as 4 or more bowel movements per day above the subject's normal frequency and associated with any of the following: urgency, abdominal pain, or rectal bleeding. Compliance is a subject's adherence to a recommended course of treatment and for this study is calculated: [(Sum of days' supplies dispensed) divided by (Sum of days in all refill intervals)] x 100. | 6 Months | 
| Clinical Recurrence of UC During the Maintenance Phase Associated With Subject Compliance at 12 Months | Clinical recurrence is defined as 4 or more bowel movements per day above the subject's normal frequency and associated with any of the following: urgency, abdominal pain, or rectal bleeding. Compliance is a subject's adherence to a recommended course of treatment and for this study is calculated: (Sum of days' supplies dispensed) divided by (Sum of days in all refill intervals) x 100. | 12 months | 
| Quiescent UC During the Maintenance Phase at 12 Months | Quiescent UC is defined as scores of 0 for both rectal bleeding and bowel movements. Rectal bleeding is assessed on a scale from 0-3 (0 = no rectal bleeding, 1 = streaks of blood, 2 = obvious blood, 3 = mostly blood). Bowel movements are 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). | 12 Months | 
| Endoscopic Remission of UC During the Maintenance Phase at 12 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]. | 12 Months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
ulcerative colitis, compliance, mesalamine, clinical study, clinical trial, clinical research, maintenance, long term, uc study, uc trial, uc research, open label, once a day, once, daily, daily dosing, simple, oral