E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Ulcerative Colitis extending proximally beyond the rectum with bleeding, verified by endoscopic examination |
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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 |
The primary efficacy objective of the trial is to demonstrate that the response to the treatment, measured in terms of DAI after 4 weeks of treatment, is not inferior in BDP group, compared to the one detected in the Prednisone group. The primary safety objective is to demonstrate a better safety profile in terms of steroid toxicity and reduction of endogenous cortisol production of BDP treatment compared to Prednisone treatment after 4 weeks of treatment |
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E.2.2 | Secondary objectives of the trial |
Evaluation of efficacy of the 2 treatments in terms of improvements of disease related symptoms, general condition and disease severity, measured at week 4 and week 8; Evaluation of the overall safety profile of the two treatment regimens after 4 and 8 weeks of treatment. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Pre-inclusion criteria at screening visit: - male or female ≥ 18 and ≤ 70 years old; - women of child-bearing potential using effective contraceptive methods; - history and documented diagnosis of ulcerative colitis, dated from more than 3 months; Rectal bleeding score ≥ 1; - Stable dosage of ongoing oral mesalazine therapy (maximum dosage 3.2 g/day) For patients under treatment with other oral medication containing 5 ASA maximum allowed dosage at study entry is: balsalazide (6.7 g/day), or olsalazine (2 g/day) or sulfasalazine (3 g/day) in the last 14 days; - Able to understand and to follow the protocol; - Having given written informed consent for study participation;
Inclusion criteria at randomization (end of run-in period) - Endoscopic score ≥ 1 in one or more colon segments; - DAI score ≥ 3 and < 10; - Confirmation of rectal bleeding score ≥ 1; - Negative stool examination for infectious disease; - Absence of concomitant medications since the screening visit (especially for non authorized treatments); - Negative pregnancy test for women |
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E.4 | Principal exclusion criteria |
Exclusion criteria at screening: - Women of childbearing potential not using adequate contraceptive methods; - Pregnant women or breast-feeding women; - Severe ulcerative colitis or toxic megacolon; - Infectious Colitis; - Ischemic Colitis; - Colitis induced by drug or radiotherapy; - Chron's disease; - Major gastro-intestinal surgery other than appendectomy; - Evolutive active peptic ulcer or medical history of peptic ulcer complications; - Non compensated diabetes mellitus; - Non controlled arterial hypertension (SBP ≥ 160 mm Hg and or DBP ≥ 100 mm Hg) - Hyperthyroidism; - Medical history of concomitant cancer or other disease which, according to Investgators' opinion could interfere with the evaluation of the test drug; - Poorly controlled pulmonary infections (tubercolosis, active mycotic infections); - Patients receiving oral or injectable corticosteroids (oral budesonide included) within 30 days from screening visit, rectal corticosteroids (suppositories, enema, foams), inhaled corticosteroids in the 14 days prior to screening visit; - Change in the dose of oral Mesalazine treatment, in the 14 days prior the screening visit or at a dosage superior to 3.2 g/day or balsalazide (6.7 g/day), olsalazine (2 g/day), or sulfasalazine (3 g/day); - Patients being treated with H2-receptor antagonists or proton pump inhibitor (PPIs) in the previous 2 weeks ; - Use of immunomodulators or immunodepressants in the previous 3 months; - Patients treated with TNF-alfa antagonists in the previous 6 months; - Antibiotic treatment that cannot be stopped before randomization; - History of drug or alcohol abuse; - Patients who took part to another trial in the previous 3 months-
Exclusion criteria at randomization (end of run-in period) - Severe ulcerative colitis (DAI > 10); - Positive ova and parasitic stool examination; - Ulcerative Colitis with endoscopic store < 1 or rectal bleeding score < 1; - Ulcerative Colitis limited to the rectum; - Chron's Disease; - Significant hepatic impairment (AST or ALT twice the upper limit of normal range); - Significant renal impairment (sreum creatinine > 1.5 mg/dL); - Any abnormal laboratory test which could interfere with the protocol
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary variable will be the percentage of patients with clinical response, defined as a DAI score < 3 or reduced of at least 3 points for patients with a baseline DAI ≥ 7 after 4 weeks of treatment with test drugs. The secondary variables will be: percentage of patients with clinical response after 4 weeks of treatment without steroid-related adverse event (AEs), including cortisol levels < 5 mcg/dL (or< 150 nmol/L); percentage of patients with DAI score ≤ 1 after 4 weeks of treatment; change in DAI total score after 4 weeks of treatment; change in endoscopic store after 4 weeks of treatment; change in CAI total score after 4 and 8 weeks of treatment; changes in CRP, ESR, after 4 and 8 weeks of treatment. The primary safety variable will be the percentage of patients with adverse events related to steroidal treatment including morning serum cortisol < 5 mcg/dL (or < 150 nmol/L) during the second 4 weeks of treatment (after visit 4 to Visit 6); changes from baseline to visits after 4 and 8 weeks of treatment (from Visit 2 to 4). The secondary varables will be: percentage of patients with adverse events related to steroid treatment including morning serum cortisol < 5 mcg/dL (or < 150 nmol/L) during the second 4 weeks of treatment (after Visit 4 to Visit 6); changes from baseline to visits 4 and 8 weeks of treatment in morning cortisol level; chnges from baseline to visits after 4 and 8 weeks of treatment in laboratory test parameters; change from baseline to visit 4 and 6 in vital signs; percentage of patients with adverse events related to steroid treatment including morning serum cortisol < 5 mcg/dL (or < 150 nmol/L) during the whole treatment period |
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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 | Yes |
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) | 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 | Yes |
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) | Yes |
E.8.2.2 | Placebo | No |
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 | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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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 | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 10 |