The Colitis Once Daily Asacol Study

Study design

• Multicentre, randomized, single-blind, comparator-controlled, parallel-armed study
• One year follow-up, or until relapse (whichever shorter)
• 40-60 UK centres

Subject population

• Ulcerative colitis in remission (sigmoidoscopy score of 0 or 1 with no symptoms of active disease, with no treatment for active colitis) for at least 4 weeks, and for no more than 2 years
• Taking mesalazine or sulfasalazine prior to study entry
• Patients excluded if they have Crohn's disease, symptoms of active colitis, have used corticosteroids, ciclosporin or oral/enema mesalazine in the past 4 weeks, are intolerant to mesalazine or Asacol, are pregnant or lactating, or have known HIV, hepatic disease, renal impairment or other serious medical or psychiatric illness
• Sample size 250
• Gender: male or female
• Ethnicity: no restriction
• Age: over 18

Test Product

Once daily group: Asacol® 2.4g daily given as three 800mg tablets orally qAM

Three times daily group: Asacol® 2.4g daily given as one 800mg tablet orally three times daily

Criteria for Evaluation:

Primary Outcome Variable: Relapse rate over 1 year in the intention to treat population, with the study powered to detect non-inferiority of the once-daily regimen.

Secondary Outcome Variables: assessment of superiority of the once-daily regimen, if non-inferiority is demonstrated; safety analysis; per protocol analysis of relapse rate; time course of relapse; medication compliance; changes in modified Baron sigmoidoscopy scores between trial entry and relapse/12 month; impact of various factors on relapse rate (time from last relapse at study entry, concomitant azathioprine or 6-mercaptopurine therapy; disease extent; disease duration; smoking status; age at diagnosis; previous dose of mesalazine; baseline calprotectin; baseline CRP level).

Inclusion criteria

Patients who meet the following criteria will be eligible for study entry:

• Male and female patients aged over 18 with ulcerative colitis confirmed by histology who are in remission (no symptoms of active disease, and modified Baron sigmoidoscopic score of 0 or 1)
• If female, must be (as documented in patient notes):

• postmenopausal (at least 1 year without spontaneous menses), or
• surgically sterile (tubal ligation or hysterectomy at least 6 months prior to enrollment), or
• using acceptable contraception (e.g., oral, intramuscular, or implanted hormonal contraception) at least 3 months prior to enrollment, or
• have a sexual partner with non-reversed vasectomy (with confirmed azoospermia), or
• be using 1 barrier method (e.g., condom, diaphragm, spermicide, or intra-uterine device)
• Patients whose ulcerative colitis has been in clinical remission for 4 weeks or longer, and who have had a symptomatic relapse within the past two years
• Patients taking mesalazine, sulfasalazine or other drug containing 5-ASA for 4 weeks or longer
• Patients capable of giving written informed consent

Exclusion criteria

The following patients will be excluded from the study:

• Patients with Crohn's disease
• Patients with symptoms of active colitis
• Modified Baron sigmoidoscopy score of 2 or 3
• Patients who have used oral, enema, intravenous or suppository preparations of corticosteroids, oral or intravenous ciclosporin, mesalazine enemas or suppositories within the past four weeks
• Patients taking azathioprine or 6-mercaptopurine who have altered the dose or started treatment within the past three months, (these drugs permitted in stable dose during the study)
• Patients with intolerance to Asacol 400 mg or mesalazine
• Women who are pregnant or lactating
• Patients with known HIV infection
• Patients with hepatic disease
• Patients with renal impairment (creatinine above local reference range), or with positive urine dipstick test to blood or protein
• Other serious medical or psychiatric illness that in the opinion of the investigator would possibly comprise the study
• Patients with problem alcohol excess or drug abuse