E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 | 10045365 |
E.1.2 | Term | Ulcerative colitis |
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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 show superiority of methotrexate vs placebo in inducing steroid-free remission in steroid-dependent ulcerative colitis Success at the 16th and the 24th week of treatment is the main criteria. The success is measured by: - Remission according to a Mayo Disease Activity Index £ 2 with no items >1* (see appendix 3), and - complete stop of prednisone or prednisolone for 7 days or more. and - no other immunosuppressive or colectomy between inclusion and the 24th week |
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E.2.2 | Secondary objectives of the trial |
Success on the 16th week Success on the 24th week Clinical remission on each visit The clinical part of the MAYO DAI (ruling out the endoscopy according to appendix 3) and the SEO index will be calculated on each visit. A Seo index score <150 determines the clinical remission. Steroid cumulative dose in both groups at 16th and 24th weeks. CRP measurements on each visit Side effects in both groups Correlation between responses, tolerance to methotrexate |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Between 18 and 75 years of age. 2.UC diagnosed according to the Lennard-Jones criteria (Appendix 1) with endoscopic colorectal lesions, whatever their extension may be. 3.A Mayo Disease Activity Index £ 4, with no item >1 for the clinical part of the score and from 0 to 2 for the endoscopic part at the time of inclusion. Steroid-dependence defined by at least 1 unsuccessful attempt to stop systemic steroid therapy during the last 12 weeks. Steroid therapy might have been completely stopped if it has been restarted within the last 30 days. 4.To be receiving a treatment of prednisone at a dose between 10 and 40mg, stable for at least 2 weeks at the time of inclusion. 5. Under an adequate contraception for male or female subjects of childbearing potential: mechanic methods of contraception (condom, female condom, diaphragm, spermicidal gel) and oral contraception started at least 15 days before inclusion. |
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E.4 | Principal exclusion criteria |
1. Indication to a colectomy. 2. Alcoholism (more than 21 glasses per week for male subjects and 14 glasses per week for female subjects). 1 glass corresponds to 3 cl of strong alcohol, 10 cl glass of wine or a half pint of beer. 3. Pregnant or breast-feeding female subjects. 4. No efficacious contraception. 5. NSAIDS or cotrimoxazole intake upon inclusion, or probenecide intake within 1 month prior to inclusion. 6. Anti-TNFa treatment within 2 months prior to inclusion. 7. Azathioprine, mercaptopurine, cyclosporin or thalidomide within 1 month prior to inclusion. 8. Modification of mesalazine or olsalazine dosage within 1 month prior to inclusion. 9. Chronic (broncho) pneumopathy. 10. Renal failure (creatininaemia > upper limit of normal laboratory values limit). 11. Liver disease apart from primary sclerosing cholangitis. 12. Unexplained rise higher than twice the normal level for transaminases, alkaline phosphatases and/or bilirubin. 13. Folate level < normal level. 14. Infection by HIV, HBV (except in case of positive antibodies anti-HBs), HCV with serologies not older than 3 months. 15. Past history of malignant condition (including leukaemia, lymphoma and myelodysplasia) except for baso-cellular cutaneous cancers. 16. Obesity (BMI>30). 17. Diabetes mellitus. 18. Known hypersensitivity to methotrexate. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Success at the 16th and the 24th week of treatment is the main criteria. The success is measured by: - Remission according to a Mayo Disease Activity Index £ 2 with no items >1. |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 | 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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 | Yes |
E.8.1.5 | Parallel group | No |
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 | Yes |
E.8.2.3 | Other | No |
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 | 6 |
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 | 36 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 36 |