A study to investigate the efficacy and safety of Mesalamine 2 g extended release granules (Sachet) for maintenance of clinical and endoscopic remission in Ulcerative Colitis

Phase 1

• Conditions: lcerative colitis; MedDRA version: 18.1Level: LLTClassification code 10058816Term: Colitis ulcerative acute episodeSystem Organ Class: 100000004856; Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

• Registration Number: EUCTR2015-002558-11-BE
• Lead Sponsor: Ferring International PharmaScience Center U.S., Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2015-11-04
• Last Update Posted: 6 November 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 260

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 (Clinical and Endoscopic Response Score of 0 or 1 and rectal bleeding and stool frequency scores of 0; 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 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 245
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 15

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 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)
9. Pathway 3 – de novo only: mesalamine use within 72 hours
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 participation in the trial
16. Participation in another clinical trial in the last 30 days (except for Study 000174)
17. Unable to comply with the requirements of the protocol
18. Unable to complete the subject electronic diary or follow data-capturing procedures

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: 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);Secondary Objective: - To evaluate the efficacy of mesalamine 2 g extended release granules (sachet) <br>- To assess health-related quality of life <br>- To assess the incidence and severity of adverse events;Primary end point(s): The primary efficacy endpoint is the proportion of subjects in remission, defined by the Clinical and Endoscopic Response Score based<br>on a modified 9 point Mayo Score.<br>;Timepoint(s) of evaluation of this end point: At 6 months

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1. The proportion of subjects in clinical remission at Months 2, 4, and 6<br>2. Time to relapse, defined as number of days from randomization to the day of withdrawal due to escalation of therapy <br>3. The change from baseline in the health-related quality of life;Timepoint(s) of evaluation of this end point: Secondary endpoints will be evaluated at pre-specified timepoints indicated in section E.5.2.