E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Ulceration and inflammation of the bowel |
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E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045365 |
E.1.2 | Term | Ulcerative colitis |
E.1.2 | System Organ Class | 100000004856 |
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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 objective of this study is to compare the percentage of subjects in complete (clinical and endoscopic) remission after 12 months of maintenance treatment with 2.4g/day MMX mesalamine/mesalazine given once daily (QD) between subjects who were in complete remission and subjects who were in partial remission at the end of 8 weeks acute treatment with 4.8g/day MMX mesalamine/mesalazine given QD. |
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E.2.2 | Secondary objectives of the trial |
1. To compare the percentage of subjects in clinical remission at 12 months between subjects who were in complete remission and subjects who were in partial remission at the end of 8 weeks acute treatment.
2. To compare the time to relapse between subjects who were in complete remission and subjects who were in partial remission at the end of 8 weeks acute treatment.
3. To compare the percentage of subjects who achieve or maintain mucosal healing (endoscopy score ≤1) at 12 months between subjects who were in complete remission and subjects who were in partial remission at the end of 8 weeks acute treatment.
4. To assess the improvement in symptoms at 3 and 8 weeks of acute treatment.
5. To assess the percentage of subjects who achieve complete remission at the end of 8 weeks acute treatment.
6. To assess the safety and tolerability of MMX mesalamine/mesalazine. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects meeting all of the criteria listed below at screening may be included in the study:
1. Adults aged 18 years or older.
2. Male, or non-pregnant, non-lactating female who agrees to comply with any applicable contraceptive requirements of the protocol.
3. Diagnosis of active mild to moderate UC (acute flare or suspected newly diagnosed with a total score of 4‑10 inclusive on the modified UC-DAI with an endoscopy score of ³1 and a PGA of ≤2).* The original diagnosis of UC must be established by sigmoidoscopy or colonoscopy and have compatible histology (performed prior to screening). An endoscopy with biopsies taken for confirmatory histology will be performed during the screening period for suspected newly diagnosed subjects only.
4. Stable maintenance therapy of 5-ASA ≤3.2g/day (excluding MMX mesalamine/mesalazine), if 5-ASA is being taken at the onset of acute flare. Stable maintenance therapy is defined as no change in dose, or no initiation of 5-ASA, from the onset of the acute flare through baseline. |
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E.4 | Principal exclusion criteria |
Subjects are excluded from the study if any of the following criteria are met at screening:
1. Severe UC (assessed by PGA =3).*
2. Acute flare with onset >6 weeks prior to Baseline (Visit 0) while on maintenance
therapy. There is no limit to the onset of flare prior to Baseline (Visit 0) if the flare is
untreated.
3. Acute flare while on maintenance MMX mesalamine/mesalazine (LIALDA®, MEZAVANT®, MEZAVANT® XL,MEZAVANT® LP).
4. Unsuccessfully treated current acute flare using steroids or 5-ASA doses >3.2g/day.
5. Acute flare on a 5-ASA maintenance therapy of >3.2g/day.
6. Systemic or rectal steroids use within the 4 weeks prior to screening or immunosuppressants within the last 6 weeks prior to screening.
7. History of biologic (anti-TNF agent) use.
8. Antibiotic use or repeated use (>3 consecutive days of use at doses above the prescribed over-the-counter dose) of any anti-inflammatory drugs, including non-steroidal anti-inflammatory drugs such as aspirin, COX-2 inhibitors or ibuprofen, within 7 days prior to screening. However, prophylactic use of a stable dose of aspirin up to 325mg/day for cardiac disease is permitted.
9. Current or recurrent disease, other than UC, that could affect the colon, the action, absorption, or disposition of the investigational medicinal product, or clinical or laboratory assessments.
* The symptom parameters of the modified UC-DAI (rectal bleeding and stool frequency) will be assessed at screening and Baseline (Visit 0). Endoscopy scores will be obtained at Baseline (Visit 0) to confirm eligibility, except in the case of suspected newly diagnosed subjects only, where endoscopy with biopsies taken for both confirmatory histology and for central laboratory assessment will be performed during the screening period. For all subjects (including suspected newly diagnosed subjects), the PGA, assessment of subject’s symptoms, and calculation of total UC-DAI score will be performed at Baseline (Visit 0) |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is to compare the proportion of subjects in complete (clinical and endoscopic) remission after 12 months of maintenance treatment with 2.4g/day MMX mesalamine/mesalazine given QD between subjects who were in complete remission and subjects who were in partial remission at the end of 8 weeks acute treatment with 4.8g/day MMX mesalamine/mesalazine given QD.
Complete (clinical and endoscopic) remission is defined as a modified UC-DAI ≤1 with a score of 0 for rectal bleeding and stool frequency and at least a 1-point reduction in
endoscopy score from baseline (Visit 0).
Partial remission is defined as a modified UC-DAI ≤3 with a combined stool frequency and rectal bleeding score of ≤1 and not in complete remission. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Efficacy
1. To compare the proportion of subjects in clinical remission (stool frequency and rectal bleeding scores equal to 0) at 12 months between subjects who were in complete remission and subjects who were in partial remission at the end of 8 weeks acute treatment.
2. To compare the time to relapse (the need for alternative treatment for UC [including surgery]) between subjects who were in complete remission and subjects who were in partial remission at the end of 8 weeks acute treatment.
3. To compare the proportion of subjects who achieve or maintain mucosal healing (endoscopy score less than or equal to 1) at 12 months between subjects who were in complete remission and subjects who were in partial remission at the end of 8 weeks acute treatment.
4. To assess the improvement in symptoms (rectal bleeding and stool frequency) from Baseline (Visit 0) to Weeks 3 and 8 weeks of acute treatment. Improvement is defined as at least a 1 point reduction in the symptom score from Baseline (Visit 0) to each assessment point.
5. To assess the proportion of subjects who achieve complete remission at the end of 8 weeks acute treatment.
Safety
To assess the safety and tolerability of MMX mesalamine/mesalazine throughout the study.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
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 | No |
E.8.1.1 | Randomised | No |
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 | 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 | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 38 |
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 | No |
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 |
Canada |
Colombia |
India |
Poland |
Russian Federation |
South Africa |
United States |
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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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Last visit of last subject undergoing treatment |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 14 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 14 |