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Mesalazine 4g Once Daily Versus 4g in Two Divided Doses in Active Ulcerative Colitis.
This study is not yet open for participant recruitment.
Verified by Ferring Pharmaceuticals, August 2008
Sponsored by: Ferring Pharmaceuticals
Information provided by: Ferring Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00737789
  Purpose

The purpose of this study is to demonstrate that mesalazine po 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 (UC) treated for 8 weeks, in terms of remission evaluated with the UC-DAI score and defined as less than or equal to 1. Both groups (4g QD and 2gx2) will receive an enema containing 1g of mesalazine at bedtime during the initial 4 weeks.


Condition Intervention Phase
Ulcerative Colitis
Drug: Mesalazine
Phase III

Genetics Home Reference related topics: Crohn disease
MedlinePlus related topics: Ulcerative Colitis
Drug Information available for: Mesalamine
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized, Single Blind (Investigator), Active Control, Parallel Assignment, Efficacy Study
Official Title: Multicentre, Controlled, Randomised, Investigator-Blinded, Comparative Study of Oral Mesalazine 4g Once Daily Versus Mesalazine 4g in Two Divided Doses in Patients With Active Ulcerative Colitis.

Further study details as provided by Ferring Pharmaceuticals:

Primary Outcome Measures:
  • Primary efficacy criterion: remission after 8 weeks of treatment, defined on the basis of the UC-DAI score less than or equal to 1 [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Compliance [ Time Frame: 12 Weeks ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 398
Study Start Date: September 2008
Estimated Study Completion Date: March 2010
Estimated Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
T: Experimental

Mesalazine Test regimen: Pentasa (mesalazine) 2g Sachet prolonged release granules (95%) 4g/day po once daily (QD.) for 8 weeks.

Plus an enema containing 1g of mesalazine at bedtime during the initial 4 weeks.

Follow-up period: 4 weeks Pentasa (mesalazine) 2g Sachet prolonged release granules (95%) 2g/day po once daily (1 sachet/day)

Drug: Mesalazine
T, Test QD, 01 T, Test QD, 02
C: Active Comparator

Mesalazine Reference regimen: Pentasa (mesalazine) 2g Sachet prolonged release granules (95%) 4g (2g x 2)/day po (BID.) for 8 weeks.

Plus an enema containing 1g of mesalazine at bedtime during the initial 4 weeks.

Follow-up period: 4 weeks Pentasa (mesalazine) 2g Sachet prolonged release granules (95%) 2g/day po once daily (1 sachet/day).

Drug: Mesalazine
C, Comparator BID, 01 C, Comparator BID, 02

Detailed Description:

A key element in therapeutic response in UC is treatment compliance. In daily practice, compliance of UC patients with 5-ASA treatment appears mediocre, particularly in maintenance therapy. Poor or non-existent compliance affects not only treatment response but also disease progression.

An inverse relationship has been found between the number of daily doses prescribed and treatment compliance. Thus, reduction to a single daily dose of mesalazine is a major factor likely to significantly increase treatment compliance

Reducing the dosing rate to a single daily dose for 8 weeks constitutes a simple method of improving treatment compliance but it is necessary to demonstrate at least equivalent efficacy compared to the twice daily dosing which is the reference regimen. This study is designed to show that mesalazine 4 g. once daily is at least as effective as mesalazine 4 g. in two divided doses per day in patients with mild to moderate ulcerative colitis after 8 weeks of treatment with a better compliance. To improve remission, both groups will receive an enema during the first 4 weeks, as usually done in current practice.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Patients will be included if they comply with the following inclusion criteria determined at baseline, prior to first drug administration:

  • 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 on the 7 days before inclusion and according to 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 at stable dose and continued at the same dose throughout the study) is permitted.
  • Informed consent given.

Exclusion Criteria:

The patients will not be included in the study if one of the following exclusion criteria is fulfilled at baseline, prior to first drug administration:

  • 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 > 3g/day for induction of remission within the previous year.
  • Current relapse lasting more than 6 weeks (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 weeks wash-out.
  • Rectal steroids: 2 weeks 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 is permitted in the local formulary or standard care for maintenance treatment: 4 weeks wash-out
  • Immunomodulating/suppressing drugs: 3 month for wash out (except for patients maintained on azathioprine or 6-mercaptopurine -see above).
  • 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/Alkaline Phosphatase's > 3 x 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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00737789

Contacts
Contact: Sylvie Forestier, MD +33149088516

Locations
France, Gentilly
Ferring SAS
7 rue Jean-Baptiste Clement, Gentilly, France, 94250
Sponsors and Collaborators
Ferring Pharmaceuticals
Investigators
Principal Investigator: Bernard Flourie, Pr Centre Hospitalier Lyon Sud
  More Information

Responsible Party: Ferring SAS ( Dr. Sylvie Forestier )
Study ID Numbers: Pentasa FE 999907 CS06, EudractCT No 2008-000045-59
Study First Received: August 19, 2008
Last Updated: August 19, 2008
ClinicalTrials.gov Identifier: NCT00737789  
Health Authority: France: Afssaps - French Health Products Safety Agency

Study placed in the following topic categories:
Digestive System Diseases
Mesalamine
Gastrointestinal Diseases
Ulcer
Colonic Diseases
Inflammatory Bowel Diseases
Colitis, Ulcerative
Intestinal Diseases
Gastroenteritis
Colitis

Additional relevant MeSH terms:
Anti-Inflammatory Agents
Pathologic Processes
Sensory System Agents
Analgesics, Non-Narcotic
Therapeutic Uses
Physiological Effects of Drugs
Anti-Inflammatory Agents, Non-Steroidal
Peripheral Nervous System Agents
Analgesics
Antirheumatic Agents
Central Nervous System Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 14, 2009