E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with mild to moderate ulcerative colitis |
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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 demonstrate that mesalazine po 4 g per day once daily (QD.) is non-inferior to the reference regimen, mesalazine 4 g 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 1 g 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 (stools frequency and blood stools) at week 4, 8 and 12 seperately * Treatment failure rates at W4 and W8 * Time to remission according patient's diary (normal stools frequency and cessation of bleeding) * Time to cessation of bleeding * Improvement at week 4 and 8 based on UC-DAI score * Endoscopic assessment at W0 and W8 * Acceptability of the treatment * Safety * Proportion of patients stayin in clinical remission at week 12. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Age 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 7 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-mecraptopurine (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 |
- proctitits (less than 12-18 cm from the anorectal junction - previous colonic surgery. - previous failed to respond to steroids within the previous year. - Non-response to rectal 5-ASA therapy or to oral 5-ASA therapy at dose > 3/day for induction of remission within the previous year. - Current relapse lasting more than 6 weeks (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 (metronidazole) and ciproflocacin): 1 week wash-out. * Oral steroids: 4 weeks wash-out. * Rectal steroids: 2 weeks wash-out * Repeated treatment (> 3 days of use) of non-steroidal anti-inflammatory drugs (NSAID) oral or rectal route: 1 week wash-out (aspirin </= 325 mg per day used for cardioprotection is allowed. * Sulfasalzine > 4g 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 weeks wash-out. * Immunomodulating/suppressing drugs: 3 month for wash-out (except for patients maintained on azathioprine or 6-mercaptopuring-see above) - Known significant hepatic or renal function abnormalities. - Moderate/severe abnormal renal, hepatic or blood count tests defineda 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 > 3 x 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. - Seocndary efficacy variables °Compliance at W8 °Clinical remission at W4, W8 and W12 °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 °Clincal variables (stool frequency and bloody stools) at week 4, 8 and 12 seperately ° Time of cessation of bleeding ° 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 week 4 and week 8 ° Safety |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Information not present in EudraCT |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
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 | No |
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 |
investigator blinded, patient opened |
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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 regiment 4 gper day in 2 idvided 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 | 12 |
E.8.9.1 | In the Member State concerned days | 88 |
E.8.9.2 | In all countries concerned by the trial months | 12 |
E.8.9.2 | In all countries concerned by the trial days | 88 |