Clinical trial NCT00708656: The Colitis Once Daily Asacol Study
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Ulcerative Colitis
Keywords: IBD
Colitis
UC
Lead sponsor: Cardiff and Vale University Health Board
Sponsor class: OTHER_GOV
Collaborators: name: Procter and Gamble
First posted: 2008-07-02
Enrollment: 213
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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).

Eligibility criteria: 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

Primary outcomes:
measure: To assess whether a once daily dose of three 800mg tablets of mesalazine (Asacol®) in the morning is equivalent to mesalazine (Asacol®) given as 800mg three times daily in preventing relapse over a 12 month period.
timeFrame: At relapse or 12 month follow up
Secondary outcomes:
measure: To assess equivalence in terms of safety
timeFrame: 12 months
measure: To assess equivalence in terms of time to relapse
timeFrame: 12 months
measure: To assess equivalence in terms of progression of disease (measured by Mayo score)
timeFrame: 12 months
Other outcomes:
Locations:
city: Barnsley
country: United Kingdom
facility: Barnsley District General Hospital
city: Basingstoke
country: United Kingdom
facility: North Hampshire Hospital
city: Birmingham
country: United Kingdom
facility: Birmingham Heartlands Hospital
city: Birmingham
country: United Kingdom
facility: Selly Oak Hospital
city: Bishop Auckland
country: United Kingdom
facility: Bishop Auckland General Hospital
city: Blackpool
country: United Kingdom
facility: Blackpool Victoria Hospital
city: Bodelwyddan
country: United Kingdom
facility: Glan Clwyd Hospital
city: Boston
country: United Kingdom
facility: Pilgrim Hospital
city: Brighton
country: United Kingdom
facility: Princess Royal Hospital
city: Brighton
country: United Kingdom
facility: Royal Sussex County Hospital
city: Bristol
country: United Kingdom
facility: Bristol Royal Infirmary
city: Cardiff
country: United Kingdom
facility: Llandough Hospital
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales
city: Carlisle
country: United Kingdom
facility: Cumberland Infirmary
city: Coventry
country: United Kingdom
facility: Walsgrave Hospital
city: Derby
country: United Kingdom
facility: Derby City General Hospital
city: Doncaster
country: United Kingdom
facility: Dr M Al-Najjar
city: Dudley
country: United Kingdom
facility: Russells Hall Hospital
city: Durham
country: United Kingdom
facility: University Hospital of North Durham
city: Glasgow
country: United Kingdom
facility: Stobhill Hospital
city: Gloucester
country: United Kingdom
facility: Gloucester Royal Hospital
city: Hartlepool
country: United Kingdom
facility: University Hospital of Hartlepool
city: Hull
country: United Kingdom
facility: Hull Royal Infirmary
city: Llantrisant
country: United Kingdom
facility: Royal Glamorgan Hospital
city: Louth
country: United Kingdom
facility: County Hospital
city: Luton
country: United Kingdom
facility: Luton & Dunstable Hospital
city: Macclesfield
country: United Kingdom
facility: Macclesfield District General Hospital
city: Melrose
country: United Kingdom
facility: Borders General Hospital
city: Merthyr Tydfil
country: United Kingdom
facility: Prince Charles Hospital
city: Norwich
country: United Kingdom
facility: Norfolk and Norwich University Hospitals NHS Foundation Trust
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
city: Poole
country: United Kingdom
facility: Poole General Hospital
city: Portsmouth
country: United Kingdom
facility: Queen Alexandra Hospital
city: Reading
country: United Kingdom
facility: Royal Berkshire Hospital
city: Rotherham
country: United Kingdom
facility: Rotherham District General Hospital
city: Sheffield
country: United Kingdom
facility: Royal Hallamshire Hospital
city: Stockton on Tees
country: United Kingdom
facility: University Hospital of North Tees & University Hospital of Hartlepool
city: Truro
country: United Kingdom
facility: Royal Cornwall Hospital
city: Welwyn Garden City
country: United Kingdom
facility: Queen Elizabeth II Hospital
city: Wolverhampton
country: United Kingdom
facility: New Cross Hospital
city: Worcester
country: United Kingdom
facility: Alexandra Hospital
city: Worcester
country: United Kingdom
facility: Worcester Royal Infirmary
city: Worthing
country: United Kingdom
facility: Worthing Hospital
city: Yeovil
country: United Kingdom
facility: Yeovil District Hospital
city: York
country: United Kingdom
facility: York District Hospital
Study officials:
affiliation: Cardiff and Vale University Health Board
name: Dr A B Hawthorne
role: PRINCIPAL_INVESTIGATOR
affiliation: Bristol Royal Infirmary
name: Professor C Probert
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gillespie D, Farewell D, Barrett-Lee P, Casbard A, Hawthorne AB, Hurt C, Murray N, Probert C, Stenson R, Hood K. The use of randomisation-based efficacy estimators in non-inferiority trials. Trials. 2017 Mar 9;18(1):117. doi: 10.1186/s13063-017-1837-3.