E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Active, mild to moderate ulcerative colitis |
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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 | 18.1 |
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 efficacy of mesalamine 4 g extended release granules (sachet) once daily (QD) in the induction of clinical and endoscopic remission versus placebo in subjects with active, mild to moderate ulcerative colitis (UC) |
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E.2.2 | Secondary objectives of the trial |
- To evaluate the efficacy of mesalamine 4 g extended release granules (sachet) using the Clinical and Endoscopic Response Score and the Clinical Response Score subset
- To assess health-related quality of life
- To assess the incidence and severity of adverse events |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or nonpregnant female subjects aged 18 to 75 years
2. Newly diagnosed or recurrent mild to moderate UC as defined by Modified Mayo score of ≥4 but not >10 and a score of ≥2 for flexible sigmoidoscopy
3. Extent of colonic involvement as confirmed by flexible sigmoidoscopy; colonoscopy performed only if flexible sigmoidoscopy cannot establish the upper border of UC involvement
4. Negative stool test at screening to rule out parasites, bacterial pathogens, and Clostridium difficile. Subjects who test positive for Clostridium difficile can be rescreened if treated and Clostridium difficile negative for 2 consecutive 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 at Visit 1 (baseline/randomization)
7. Signed informed consent obtained before any trial-related procedures |
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E.4 | Principal exclusion criteria |
1. Use of oral 5-ASA products at a dose >2.5 g/day or topical rectal 5-ASA within the past 7 days
2. Disease limited to proctitis <15 cm
3. Short bowel syndrome
4. Prior colon resection surgery
5. History of severe/fulminant UC
6. Evidence of other forms of inflammatory bowel disease
7. Infectious disease (including human immunodeficiency virus [HIV], hepatitis B virus [HBV], or hepatitis C virus [HCV])
8. Intolerant or allergic to aspirin or salicylate derivatives
9. Taking the following treatments:
a. Aspirin within the past 7 days (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 months
e. Use of rectal formulations (5-ASA, steroids) within <7 days
f. History of biologics (e.g., Remicade)
10. ALT; AST >3 x upper limit of normal (ULN)
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 basal cell carcinoma can be included)
15. History of bleeding disorders, active gastric or active duodenal ulcers, autoimmune diseases, or mental/emotional disorders, that would interfere with their participation in the trial
16. Participation in another clinical trial in the last 30 days
17. Unable to comply with the requirements of the protocol
18. Unable to complete the subject electronic 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 with 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 |
|
E.5.2 | Secondary end point(s) |
Key secondary endpoints:
1. The proportion of subjects with remission in the primary endpoint and the Physician’s Global Assessment (PGA) at Week 8
2. Time to cessation of rectal bleeding
Secondary endpoints:
1. The proportion of subjects in clinical remission at Weeks 2, 4, and 8
2. Time to normal stool pattern
3. The change from baseline in the health-related quality of life
4. Safety assessed by incidence and severity of AEs |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Key secondary endpoints:
1- Week 8
2- From randomization to the first day of 3 consecutive days with a rectal bleeding score of 0.
Secondary endpoints:
1- Weeks 2,4 and 8
2- From randomization to the first day of 3 consecutive days with a stool frequency score of 0
3- From baseline to each scheduled assessment of the health-related quality of life
4- From Signing of informed consent |
|
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 |
|
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 | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 33 |
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 |
Canada |
Czech Republic |
Hungary |
Israel |
Poland |
Russian Federation |
Slovakia |
Switzerland |
Ukraine |
United States |
|
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
|
|
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 | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |