E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with mild to moderate active ulcerative colitis |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10058816 |
E.1.2 | Term | Colitis ulcerative acute episode |
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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 demonstrate that oral mesalazine 4g 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 treated for 8 weeks, in terms of remission evaluated with the UC-DAI score and defined as ≤1. Both groups (4g QD and 2gx2) will receive an enema containing 1g of mesalazine at bedtime during the initial 4 weeks. |
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E.2.2 | Secondary objectives of the trial |
•Compliance •Clinical remission at week 4 and week 8 •Clinical variables improvement (stool frequency and bloody stools) at week 4, 8 and 12 separately •Treatment failure rates at week 4 and week 8 •Time to remission according patient’s diary (normal stool frequency and cessation of bleeding) •Time to cessation of bleeding •Improvement at week 4 and 8 based on UC-DAI score •Endoscopic assessment at week 0 and week 8 •Acceptability of the treatment •Safety •Proportion of patients staying in clinical remission at week 12. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•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 within 15 days before inclusion and according to the 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 and continued at the same dose throughout the study) is permitted. •Informed consent given. |
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E.4 | Principal exclusion criteria |
•Proctitis (less than 12-18 cm from the anorectal junction). •Previous colonic surgery. •Previously failed to respond to steroids within the previous year. •Non-response to rectal 5-ASA therapy or to oral 5-ASA therapy at a dose > 3/day for induction of remission within the previous year. •Current relapse lasting more than 6 weeks. For the patient recently diagnosed, the period of 6 weeks runs from the endoscopic diagnosis (from what patient says). •Severe/fulminant ulcerative colitis. •Evidence of other forms of inflammatory bowel disease or infectious disease. •Allergy to aspirin or salicylate derivatives. •The following treatment will be forbidden during the study (if present at selection, a wash-out will be necessary): - Loperamide and other antidiarrheal agents, mucilages, antibiotics: 1 week wash-out. - Oral steroids: 4 week wash-out. - Rectal steroids: 2 week wash-out - Repeated treatment (> 3days of use) of non steroidal anti-inflammatory drugs (NSAID) oral or rectal route: 1 week wash-out (aspirin ≤325 mg/day used for cardioprotection is allowed). - Sulfasalazine > 4g/day or mesalazine or 4-ASA at a higher dose than what it is permitted in the local formulary or standard care for maintenance treatment: 4 week wash-out. - Immunomodulating/suppressing drugs: 3 month for wash out (except for patients maintained on azathioprine or 6-mercaptopurine). •Known significant hepatic or renal function abnormalities. •Moderate/severe abnormal renal, hepatic or blood count tests defined as: creatinine plasma value > 1.5 x ULN or white blood cells < 3500/mm3 or > 15000/mm3 or platelets < 100000/mm3 or > 800000/mm3 or ASAT/ALAT > 3 x ULN or GGT/Alkalin Phosphatases > 3x ULN (Primary Sclerosing Cholangitis is not an exclusion criteria). •History or physical examination findings indicative of active alcohol or drug abuse. •Pregnancy or breast-feeding. •History of disease, including mental/emotional disorder, that might interfere with their participation in the study. •Participation in another clinical study in the last 3 months. •Inability to comply with the protocol requirements. •Inability to fill in the diary cards. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary efficacy criterion: - Remission after 8 weeks of treatment, defined on the basis of the UC-DAI score ≤1.
Secondary efficacy variables - Compliance at W8. - Clinical remission at week 4, 8 and 12 defined as normalization of stool frequency, disappearance of bleeding stools and no active disease at Physician Global Assessment (PGA). - Treatment failure rates at W4 and W8 defined as the need for other treatment than those allowed by the protocol. Treatment failure will be counted as non-remission. - Clinical variables (stool frequency and bloody stools) at week 4, 8 and 12 separately - Time of cessation of bleeding, defined as the time between the first dose of study medication and the first bleeding-free day - Time to remission according patient’s diary (normal stools frequency and cessation of bleeding) - Improvement at week 4 and week 8 based on UC-DAI score - Endoscopic assessment at week 0 and at week 8 - Acceptability of the treatment at W4 and W8 - Safety |
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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 | No |
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 | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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 | Yes |
E.8.1.7.1 | Other trial design description |
Single blind: Investigator blinded. |
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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, the comparator is the reference regimen 4g per day in 2 divided doses (BID) |
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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.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 57 |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 23 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 23 |