Ulcerative Colitis MedDRA version: 14.1 Level: LLT Classification code 10045365 Term: Ulcerative colitis System Organ Class: 100000004856
Conditions
Interventions
Trade Name: Mezavant XL Gastro-resistant, prolonged release tablets
Product Name: Mezavant XL
Product Code: SPD476
Pharmaceutical Form: Gastro-resistant
Sponsors
Shire Development LLC
Eligibility
Sex/Gender
All
Inclusion criteria
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. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 338 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
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)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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.; Secondary Objective: 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. ;Timepoint(s) of evaluation of this end point: 29 December 2012; 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 | — |
Secondary
| Measure | Time frame |
|---|---|
| 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. ;Timepoint(s) of evaluation of this end point: 29 December 2012 | — |
Countries
Belgium, Canada, Colombia, Czech Republic, France, Germany, Hungary, India, Ireland, Poland, Russian Federation, South Africa, Spain, United Kingdom, United States
Contacts
Public ContactMedical Communications
Shire Pharmaceuticals Ltd
Outcome results
None listed