Once Daily (OD) Versus Three Times Daily (TID) Dosing With Mesalazine Granules for Prevention of Recurrence of Ulcerative Colitis (UC)

Study Overview
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Brief Summary
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This study intends to study the efficacy and tolerability of once daily 3.0 g mesalazine granules vs. once daily 1.5 g mesalazine granules vs. three times daily 0.5 g mesalazine granules for maintenance of remission in patients with ulcerative colitis

Official Title
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Double-blind, Double-dummy, Randomised, Multicentre, 12-months, Comparative Study of the Efficacy and Tolerability of Once Daily 3.0 g Mesalazine Granules vs. Once Daily 1.5 g Mesalazine Granules vs. Three Times Daily 0.5 g Mesalazine Granules for Maintenance of Remission in Patients With Ulcerative Colitis

Conditions
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Colitis, Ulcerative, Recurrence

Intervention / Treatment
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* Drug: mesalamine granules
* Drug: mesalamine granules
* Drug: mesalamine granules


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent, Men or women aged 18 to 75 years, Historically confirmed diagnosis of ulcerative colitis by endoscopy and histology, Patient being in remission, defined (according to Rachmilewitz) as: Clinical Activity Index (CAI) <= 4, and Endoscopic Index (EI) < 4, Extent of inflammation during last acute episode was >15 cm beyond the anal margin, Last acute episode ended within 3 months prior to study entry. Exclusion Criteria: Crohn's disease, Prior bowel resection leading to diarrhoea, Toxic megacolon, Gastric or duodenal ulcer, Haemorrhagic diathesis, Presence of symptomatic organic disease of the gastrointestinal tract (with the exception of haemorrhoids or hiatal hernia), Active colorectal cancer or a history of colorectal cancer, Serious other secondary illnesses of an acute or chronic nature, Asthma, Severe impairment of renal (e.g., serum creatinine > 1.5 mg/dl) and/or liver functions (e.g., serum transaminase [ALT and/or AST] or alkaline phosphatase >=2x upper limit of normal [ULN]), Application of immunosuppressants within 3 months and/or corticosteroids (oral, intravenous [IV] or topical rectal) within 30 days prior to baseline, Application of non-steroidal anti-inflammatory drugs (NSAIDs) as long term treatment (i.e. > 6 weeks), other than acetylsalicylic acid (<= 350 mg/day), or paracetamol, Known intolerance/hypersensitivity to salicylic acid and its derivatives or to any of the other constituents of the study drugs, Well-founded doubt about the patient's cooperation, Existing or intended pregnancy, breast-feeding, Women of child-bearing potential without adequate contraceptive protection, e.g., hormonal contraception, intrauterine device (IUD), double-barrier method of contraception (e.g., use of a condom and spermicide), partner has undergone vasectomy and subject is in monogamous relationship. The investigator is responsible for determining whether the subject has adequate birth control for study participation, Participation in another clinical trial within the last 30 days,simultaneous participation in another clinical trial, or previous participation in this trial.

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 3.0g OD<br> | Drug: mesalamine granules<br>* 3.0g mesalamine in the morning, 0.5g placebo at lunch, 0.5g placebo in the evening;<br>* Other names: Mesalazine;|
| Experimental: 1.5g OD<br> | Drug: mesalamine granules<br>* 1.5g mesalamine and 1.5g placebo in the morning, 0.5g placebo at lunch, 0.5g placebo in the evening;<br>* Other names: Mesalazine;|
| Active Comparator: 0.5g TID<br> | Drug: mesalamine granules<br>* 0.5g mesalamine and 2.5g placebo in the morning, 0.5g mesalamine at lunch, 0.5g mesalamine in the evening<br>* Other names: Mesalazine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients still in clinical remission at the final/withdrawal examination, with clinical relapse defined as a CAI >4 with an increase of ≥3 points from baseline. |  | week 52 or premature withdrawal | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to relapse |  | within 52 weeks | 
| Proportion of patients in endoscopical remission, defined as a mucosal appearance score of ≤ 1 at final/withdrawal examination. |  | week 52 or premature withdrawal | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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maintenance, 5-ASA, mesalamine, mesalazine, ulcerative colitis