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 |
A bowel disease that is characterized by inflammation with ulcer formation in the lining of colon (large intestine) |
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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 | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10058816 |
E.1.2 | Term | Colitis ulcerative acute episode |
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 |
To demonstrate the efficacy of mesalamine 2 g extended release granules (sachet) once daily (QD) compared to placebo in the maintenance of remission of ulcerative colitis (UC) |
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E.2.2 | Secondary objectives of the trial |
- To evaluate the efficacy of mesalamine 2 g extended release granules (sachet) utilizing the Clinical and Endoscopic Response Score subsets, and frequency of treatment failures - To assess health-related quality of life - To assess the incidence and severity of adverse events |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Satisfied one of the following criteria for enrollment into the trial: a. Met the remission criteria at Week 8 of Study 000174 (Pathway 1) or b. Did not meet the remission criteria during Study 000174 and agreed to an additional 8 weeks of open-label treatment with mesalamine 4 g/day QD, after which met the remission criteria (Pathway 2) or c. Subjects not currently enrolled in Study 000174 and currently treated with medications for UC and currently in remission <1 year based on clinical and endoscopic evaluation (rectal bleeding score of 0 and stool frequency scores of 0 and 1, with endoscopic score of 0 or 1 in Clinical and Endoscopic Response Score; i.e., clinical and endoscopic remission). The duration of prior remission must be less <1 year and include a history of flare (defined as escalation of medical therapy[ies]), and/or documented episode of recurrent rectal bleeding accompanied by abdominal pain and increased stool number that required medical intervention) (Pathway 3 – de novo) 2. Signed informed consent obtained before any trial-related procedures 3. Male or nonpregnant female subjects aged 18 to 75 years 4. Extent of colonic involvement historically confirmed (i.e., flexible sigmoidoscopy/colonoscopy report, colonoscopy report, biopsy reading) within past 12 months 5. Estimated creatinine clearance ≥ 60 mL/min 6. Females of childbearing potential must agree to use an adequate contraception during the course of the trial. Accepted forms of contraception are: i.e., implants, injectables, hormonal intrauterine device, combined hormonal contraceptives, sexual abstinence, and vasectomized sexual partner. Sterilized or postmenopausal women may also participate. Women must have a negative serum pregnancy test result at screening and negative urine pregnancy test result on baseline/randomization. |
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E.4 | Principal exclusion criteria |
1. Evidence of other forms of inflammatory bowel disease 2. Infectious disease (including human immunodeficiency virus [HIV], hepatitis B virus [HBV], or hepatitis C virus [HCV]) 3. Disease limited to proctitis <15 cm 4. Short bowel syndrome 5. Prior colon resection surgery 6. History of severe/fulminant UC 7. Intolerant or allergic to aspirin or salicylate derivatives 8. Taking the following treatments: a. Aspirin within 7 days prior to Visit 1 (except for cardioprotective reasons - maximum dose 325 mg/day) b. Loperamide and other antidiarrheal agents, mucilages, antibiotics (metronidazole and ciprofloxacin), nonsteroidal anti-inflammatory drugs (NSAIDs), nicotine patch within 1 week c. Corticosteroids (oral, intravenous, or intramuscular) within the previous month d. Immunomodulating/suppressing drugs within the previous 6 weeks e. Use of rectal formulations (5-ASA, steroids) within 7 days prior to Visit 1 f. History of biologics (e.g., Remicade) 9. Pathway 3 – de novo only: mesalamine use within 72 hours prior to Visit 1 10. ALT; AST ≥3 x upper limit of normal (ULN) or severe liver impairment 11. Clinically significant hematological function abnormalities 12. Known alcohol or drug abuse 13. Women who are pregnant or nursing 14. History of or known malignancy (Note: Adequately treated (i.e. cured) basal cell carcinoma and cervical intraepithelial neoplasia (CIN) or carcinoma in situ of the cervix with no evidence of recurrence within the previous 5 years can be included) 15. History of bleeding disorders, active gastric or active duodenal ulcers, autoimmune diseases, or mental/emotional disorders that would interfere with participation in the trial 16. Participation in a clinical trial with administration of another investigational medicinal product within the previous 30 days (except for Study 000174) 17. Unable to comply with the requirements of the protocol 18. Unable to complete the subject daily diary or follow data-capturing procedures |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the proportion of subjects in remission, defined by the Clinical and Endoscopic Response Score based on a modified 9 point Mayo Score.
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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) |
1. The proportion of subjects in clinical remission at Months 2, 4, and 6 2. Time to relapse, defined as number of days from randomization to the day of withdrawal due to escalation of therapy 3. The change from baseline in the health-related quality of life |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary endpoints will be evaluated at pre-specified timepoints indicated in section E.5.2. |
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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 | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | 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.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 22 |
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 |
Belgium |
Bulgaria |
Canada |
Hungary |
Latvia |
Mexico |
Russian Federation |
Serbia |
Switzerland |
Ukraine |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |