The Colitis Once Daily Asacol Study

A Randomized, Single-Blind Study to Assess Efficacy and Safety of Dosing Mesalazine 800 mg Tablets (Asacol®) at 2.4 g Once Daily Versus Divided Doses 3 Times Daily for 12 Months in Maintenance of Remission of Ulcerative Colitis.

The purpose of this study is to compare the safety and effectiveness of dosing mesalazine 800 mg tablets (Asacol®) at 2.4 g once daily versus divided doses three times daily in the maintenance of remission of ulcerative colitis.

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