Ulcerative Colitis
Conditions
Brief summary
The purpose of this study was to demonstrate that mesalazine 4g orally per day once daily (QD) is non-inferior to the reference regimen, mesalazine 4g per day in two divided doses (BID) (2g x 2 per day), in patients with active ulcerative colitis (UC) treated for 8 weeks, in terms of remission evaluated with the Ulcerative Colitis Disease Activity Index (UC-DAI) score and defined as less than or equal to 1. Both groups (4g QD and 2gx2) received an enema containing 1g of mesalazine at bedtime during the initial 4 weeks. Participants in remission at week 8 received an additional 4 weeks of maintenance therapy with 2g oral mesalazine once a day. Participants who did not achieve remission at Week 8 completed the study at week 8.
Detailed description
A key element in therapeutic response in UC is treatment compliance. In daily practice, compliance of UC patients with 5-Amino Salicylic Acid (5-ASA) treatment appears mediocre, particularly in maintenance therapy. Poor or non-existent compliance affects not only treatment response but also disease progression. An inverse relationship has been found between the number of daily doses prescribed and treatment compliance. Thus, reduction to a single daily dose of mesalazine is a major factor likely to significantly increase treatment compliance. Reducing the dosing rate to a single daily dose for 8 weeks constitutes a simple method of improving treatment compliance but it is necessary to demonstrate at least equivalent efficacy compared to the twice daily dosing which is the reference regimen. This study was designed to show that mesalazine 4g once daily is at least as effective as mesalazine 4g in two divided doses per day in patients with mild to moderate ulcerative colitis after 8 weeks of treatment with a better compliance. To improve remission, both groups received an enema during the first 4 weeks, as usually done in current practice.
Interventions
DRUGMesalazine slow-release granules
Mesalazine 2g Sachet prolonged release granules, administered orally.
DRUGMesalazine liquid enema
1g mesalazine liquid enema, administered topically once a day in the evening.
Sponsors
Ferring Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Patients will be included if they comply with the following inclusion criteria determined at baseline, prior to first drug administration: * Aged over 18 years. * Newly diagnosed or relapsing mild to moderate ulcerative colitis with disease extension beyond rectum (of at least 12-18 cm from the anorectal junction). All patients must have had at least one total colonoscopy in their disease history (within the previous 5 years). * Disease activity will be assessed on the 15 days before inclusion and according to ulcerative colitis disease activity index (UC-DAI) score. The UC-DAI score will be from 3 to 8 (mild: 3-5 or moderate: 6-8). * Men or non pregnant women. * Women with childbearing potential must be using a contraceptive method judged effective by the investigator. * Oral maintenance treatment with azathioprine or 6-mercaptopurine (taken for at least 6 months at stable dose and continued at the same dose throughout the study) is permitted. * Informed consent given.
Exclusion criteria
The patients will not be included in the study if one of the following
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary efficacy criterion: remission after 8 weeks of treatment, defined on the basis of the UC-DAI score less than or equal to 1 | 12 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Clinical remission | At week 4, week 8 and week 12 |
| Treatment failure is defined as need of other treatment (ie steroids, immunosuppressive or immunomodulating drugs) than those allowed by the protocol, as judged by investigator. Treatment failure will be counted as non-remission. | At week 4 and week 8 |
| Clinical variables (stool frequency and bloody stools) | At week 4, 8 and 12 separately |
| Time to remission according to patient's diary (normal stool frequency and cessation of bleeding) | At week 4 and week 8 |
| Compliance | Week 8 |
| Improvement - based on UC-DAI score | At week 4 and 8 |
| Endoscopic assessment | At week 0 and week 8 |
| Safety | At week 0, week 4, week 8 and week 12 |
| Time to cessation of bleeding | At week 4, week 8 and week 12 |
Countries
Belgium, France, Netherlands, United Kingdom
Outcome results
None listed