E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Ulcerative colitis is characterized by acute and chronic inflammatory changes to the mucosa and submucosa of the colon and rectum. Clinical presentations include increased stool frequency, bloody diarrhea, and abdominal or rectal pain.
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
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 terms of: • Safety • Time to relapse • Progression of disease (measured by Mayo scoring system)
To assess whether a once daily dose of three 800mg tablets of mesalazine (Asacol®) in the morning is superior to mesalazine (Asacol®) given as 800mg three times daily in terms of: • Medication compliance
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients who meet the following criteria will be eligible for study entry:
i. 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)
ii. 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 enrolment), or • using acceptable contraception (e.g., oral, intramuscular, or implanted hormonal contraception) at least 3 months prior to enrolment, 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)
iii. 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
iv. Patients taking mesalazine, sulfasalazine or other drug containing 5-ASA for 4 weeks or longer
v. Patients capable of giving written informed consent
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E.4 | Principal exclusion criteria |
The following patients will be excluded from the study:
i. Patients with Crohn’s disease.
ii. Patients with symptoms of active colitis
iii. Modified Baron sigmoidoscopy score of 2 or 3
iv. 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.
v. 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).
vi. Patients with intolerance to Asacol 400 mg or mesalazine.
vii. Women who are pregnant or lactating.
viii. Patients with known HIV infection.
ix. Patients with hepatic disease
x. Patients with renal impairment (creatinine above local reference range), or with positive urine dipstick test to blood or protein
xi. Other serious medical or psychiatric illness that in the opinion of the investigator would possibly comprise the study.
xii. Patients with problem alcohol excess or drug abuse.
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E.5 End points |
E.5.1 | Primary end point(s) |
Relapse rate over 1 year in the intention to treat population, with the study powered to detect non-inferiority of the once-daily regimen vs. the three times daily regimen.
Relapse will be defined as:
A. Typical symptoms with grade 2-3 mucosal changes (modified Baron score) or
B. If sigmoidoscopy is not possible, then any additional medication (enema, suppository, oral or intravenous steroids, enema or suppository mesalazine, or increased dose of oral mesalazine), confirmed by the investigator to be for the treatment of active ulcerative colitis)
The time of relapse will be defined as the earlier of either: a) the sigmoidoscopy showing grade 2-3 mucosal changes or b) the date of commencing treatment for active colitis.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | Yes |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
same IMP, same dose, but different dose regimen |
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E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the study is defined as the last visit of the last patient ongoing in the study. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |