Efficacy and Safety of Asacol™ 4.8 g/Day (800 mg Tablets) for the Treatment of Active Ulcerative Colitis

The 800 mg Asacol™ tablets from Tillotts Pharma AG are being marketed in over 30 countries, mainly in Europe and Asia. Approved dosages for the treatment of active UC are between 2.4 and 4.8 g/day in analogy to the approved 400 mg dosage form. The present trial is planned to generate efficacy data to support the safe use of a 4.8 g/day dose of the 800 mg dosage form in a well defined population of patients with mildly to moderately active UC. In keeping with the EMEA UC guideline the study will have a placebo-controlled 6 weeks induction treatment. After 6 weeks, treatment success will be evaluated using the modified UC disease activity index as primary efficacy measurement.

Inclusion criteria

(1) Male or non-pregnant, non-lactating females, 18 years of age or older. (2) Documented diagnosis of UC with disease extending at least 15 cm from the anal verge.

(3) Active UC defined by:

(a) modified UC-DAI score of 4-10 with (b) sigmoidoscopy component score ≥ 2 and (c) rectal bleeding component score ≥ 1 (4) Ability of subject to participate fully in all aspects of this clinical trial.

(5) Written informed consent must be obtained and documented.

Exclusion criteria

• Severe UC defined by the following criteria:

³6 bloody stools daily with one or more of the following:

• oral temperature > 37.8°C or > 100.0°F
• pulse > 90/min
• hemoglobin < 10 g/dL
• Previously failed treatment with a mesalazine dose of > 2.0 g/day.
• Current relapse lasting > 6 weeks in the opinion of the investigator.
• Treatment with 5-ASA at a dose of >2.0g/day within 1 week prior to randomisation
• Treatment with systemic or rectal steroids within 4 weeks prior to randomization.
• Treatment with immunosuppressants within 6 weeks prior to randomization.
• Treatment with infliximab or other biologics within 3 months prior to randomization.
• Treatment with systemic antibiotics for UC within 7 days prior to randomization.
• Treatment with probiotics within 7 days prior to randomization.
• Treatment with anti-diarrheals within 7 days prior to randomization.
• Treatment with nicotine patch within 7 days prior to randomization.
• Received any investigational drug within 30 days prior to randomization.
• History of colectomy or partial colectomy.
• History of definite dysplasia in colonic biopsies.
• Crohn's disease.
• Known bleeding disorders.
• Immediate or significant risk of toxic megacolon.
• Hypersensitivity to salicylates, aspirin, sulfasalazine or 5-ASA.
• Serum creatinine > 1.5 times the upper limit of the normal range.
• AST, ALT, total bilirubin or alkaline phosphatase > 2 times the upper limit of the normal range.
• Serious underlying disease other than UC which in the opinion of the investigator may interfere with the subject's ability to participate fully in the study.
• History of alcohol or drug abuse which in the opinion of the investigator may interfere with the subject's ability to comply with the study procedures.
• Stools positive for clostridium difficile.
• Pregnant or lactating women.
• Prior enrolment in the current study and had received study treatment.