Multicentre, controlled, randomized, investigator-blinded, comparative study of oral mesalazine 4g per day once daily versus 4g per day in two divided doses in patients with active ulcerative colitis. - MOTUS

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2008-000045-59-GB
• Date of registration: 15/07/2008
• Prospective Registration: Yes
• Primary sponsor: Ferring Pharmaceuticals Ltd.
• Public title: Multicentre, controlled, randomized, investigator-blinded, comparative study of oral mesalazine 4g per day once daily versus 4g per day in two divided doses in patients with active ulcerative colitis. - MOTUS
• Scientific title: Multicentre, controlled, randomized, investigator-blinded, comparative study of oral mesalazine 4g per day once daily versus 4g per day in two divided doses in patients with active ulcerative colitis. - MOTUS
• Date of first enrolment: 17/03/2009
• Target sample size: 398
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-000045-59
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: yes Double blind: no Parallel group: yes Cross over: no Other: yes Other trial design description: Single blind: Investigator blinded. If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: Same IMP, the comparator is the reference regimen 4g per day in 2 divided doses (BID)

Countries of recruitment

Belgium, France, Netherlands, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
•Aged over 18 years.
•Newly diagnosed or relapsing mild to moderate ulcerative colitis with disease extension beyond rectum (of at least 12-18 cm from the anorectal junction). All patients must have had at least one total colonoscopy in their disease history (within the previous 5 years).
•Disease activity will be assessed within 15 days before inclusion and according to the ulcerative colitis disease activity index (UC-DAI) score. The UC-DAI score will be from 3 to 8 (mild: 3-5 or moderate: 6-8).
•Men or non pregnant women.
•Women with childbearing potential must be using a contraceptive method judged effective by the investigator.
•Oral maintenance treatment with azathioprine or 6-mercaptopurine (taken for at least 6 months and continued at the same dose throughout the study) is permitted.
•Informed consent given.
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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
•Proctitis (less than 12-18 cm from the anorectal junction).
•Previous colonic surgery.
•Previously failed to respond to steroids within the previous year.
•Non-response to rectal 5-ASA therapy or to oral 5-ASA therapy at a dose > 3/day for induction of remission within the previous year.
•Current relapse lasting more than 6 weeks. For the patient recently diagnosed, the period of 6 weeks runs from the endoscopic diagnosis (from what patient says).
•Severe/fulminant ulcerative colitis.
•Evidence of other forms of inflammatory bowel disease or infectious disease.
•Allergy to aspirin or salicylate derivatives.
•The following treatment will be forbidden during the study (if present at selection, a wash-out will be necessary):
- Loperamide and other antidiarrheal agents, mucilages, antibiotics: 1 week wash-out.
- Oral steroids: 4 week wash-out.
- Rectal steroids: 2 week wash-out
- Repeated treatment (> 3days of use) of non steroidal anti-inflammatory drugs
(NSAID) oral or rectal route: 1 week wash-out (aspirin =325 mg/day used for
cardioprotection is allowed).
- Sulfasalazine > 4g/day or mesalazine or 4-ASA at a higher dose than what it is
permitted in the local formulary or standard care for maintenance treatment: 4
week wash-out.
- Immunomodulating/suppressing drugs: 3 month for wash out (except for
patients maintained on azathioprine or 6-mercaptopurine).
•Known significant hepatic or renal function abnormalities.
•Moderate/severe abnormal renal, hepatic or blood count tests defined as: creatinine plasma value > 1.5 x ULN or white blood cells < 3500/mm3 or > 15000/mm3 or platelets < 100000/mm3 or > 800000/mm3 or ASAT/ALAT > 3 x ULN or GGT/Alkalin Phosphatases > 3x ULN (Primary Sclerosing Cholangitis is not an exclusion criteria).
•History or physical examination findings indicative of active alcohol or drug abuse.
•Pregnancy or breast-feeding.
•History of disease, including mental/emotional disorder, that might interfere with their participation in the study.
•Participation in another clinical study in the last 3 months.
•Inability to comply with the protocol requirements.
•Inability to fill in the diary cards.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Patients with mild to moderate active ulcerative colitis
MedDRA version: 9.1 Level: LLT Classification code 10058816 Term: Colitis ulcerative acute episode

Intervention(s)

Product Name: Pentasa 2g sachet prolonged release granules (95%)
Pharmaceutical Form: Granules
INN or Proposed INN: MESALAZINE
CAS Number: 89576
Concentration unit: g gram(s)
Concentration type: equal
Concentration number: 2-

Primary Outcome(s)

Secondary Objective: •Compliance
•Clinical remission at week 4 and week 8
•Clinical variables improvement (stool frequency and bloody stools) at week 4, 8 and 12 separately
•Treatment failure rates at week 4 and week 8
•Time to remission according patient’s diary (normal stool frequency and cessation of bleeding)
•Time to cessation of bleeding
•Improvement at week 4 and 8 based on UC-DAI score
•Endoscopic assessment at week 0 and week 8
•Acceptability of the treatment
•Safety
•Proportion of patients staying in clinical remission at week 12.

Main Objective: To demonstrate that oral mesalazine 4g per day once daily (QD) is non-inferior to the reference regimen, mesalazine 4g per day in two divided doses (BID) (2g x 2 per day), in patients with active ulcerative colitis treated for 8 weeks, in terms of remission evaluated with the UC-DAI score and defined as =1. Both groups (4g QD and 2gx2) will receive an enema containing 1g of mesalazine at bedtime during the initial 4 weeks.

Primary end point(s): Primary efficacy criterion:
- Remission after 8 weeks of treatment, defined on the basis of the UC-DAI score =1.

Secondary efficacy variables
- Compliance at W8.
- Clinical remission at week 4, 8 and 12 defined as normalization of stool frequency, disappearance of bleeding stools and no active disease at Physician Global Assessment (PGA).
- Treatment failure rates at W4 and W8 defined as the need for other treatment than those allowed by the protocol. Treatment failure will be counted as non-remission.
- Clinical variables (stool frequency and bloody stools) at week 4, 8 and 12 separately
- Time of cessation of bleeding, defined as the time between the first dose of study medication and the first bleeding-free day
- Time to remission according patient’s diary (normal stools frequency and cessation of bleeding)
- Improvement at week 4 and week 8 based on UC-DAI score
- Endoscopic assessment at week 0 and at week 8
- Acceptability of the treatment at W4 and W8
- Safety

Secondary ID(s)

2008-000045-59-FR

Pentasa FE 999907 CS06