Mesalazine 4g Once Daily Versus 4g in Two Divided Doses in Active Ulcerative Colitis.

Ulcerative Colitis Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00737789
• Other study ID #: Pentasa FE999907 CS06
• Secondary ID: EudractCT No 200
• Status: Completed
• Phase: Phase 3
• First received: August 19, 2008
• Last updated: March 3, 2015
• Start date: November 2008
• Est. completion date: June 2010

Study information

• Verified date: March 2015
• Source: Ferring Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)United Kingdom: Medicines and Healthcare Products Regulatory AgencyBelgium: Federal Agency for Medicinal Products and Health ProductsNetherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial Summary

The purpose of this study was to demonstrate that mesalazine 4g orally 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 Ulcerative Colitis Disease Activity Index (UC-DAI) score and defined as less than or equal to 1. Both groups (4g QD and 2gx2) received an enema containing 1g of mesalazine at bedtime during the initial 4 weeks.

Participants in remission at week 8 received an additional 4 weeks of maintenance therapy with 2g oral mesalazine once a day. Participants who did not achieve remission at Week 8 completed the study at week 8.

Description:

A key element in therapeutic response in UC is treatment compliance. In daily practice, compliance of UC patients with 5-Amino Salicylic Acid (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 was designed to show that mesalazine 4g once daily is at least as effective as mesalazine 4g 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 received an enema during the first 4 weeks, as usually done in current practice.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 206
• Est. completion date: June 2010
• Est. primary completion date: June 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 15 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-Amino Salicylic Acid (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 (for 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 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 Upper Limit of Normal (ULN) or white blood cells < 3500/mm^3 or > 15000/mm^3 or Platelets < 100000/mm^3 or > 800000/mm^3 or aspartate aminotransferase/alanine Aminotransferase (ASAT/ALAT) > 3 x ULN or Gamma glutamyl transpeptidase (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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer
• Ulcerative Colitis

Intervention

Drug:
• Mesalazine slow-release granules
Mesalazine 2g Sachet prolonged release granules, administered orally.
• Mesalazine liquid enema
1g mesalazine liquid enema, administered topically once a day in the evening.

Locations

Country	Name	City	State
Belgium	O.L.Vrouwziekenhuis Campus Aalst	Aalst
Belgium	Saint Luc University Hospital	Brussels
Belgium	Universitair Ziekenhuis Brussel	Brussels
Belgium	C.H.U. Saint-Pierre	Bruxelles
Belgium	U.Z. Antwerpen	Edegem
Belgium	University Hospital Gasthuisberg	Leuven
France	Clinique Esquirol-St Hilaire	Agen
France	Investigational site	Albi
France	Investigational site	Amiens
France	Centre Hospitalier Avignon	Avignon
France	Centre Hospitalier Bethune	BETHUNE Cedex
France	Investigational site	Bourgoin-jallieu
France	Investigational site	Brest
France	Clinique Jean-Villar	Bruges
France	Clinique Saint Martin	CAEN Cedex 4
France	Clinique Saint Martin - 18 rue Rocquemonts	CAEN Cedex 4
France	Investigational site	Caluire Et Cuire
France	Investigational site	Carcassonne
France	Clinique du Parc	Castelnau Le Lez
France	Investigational site	Chambray les Tours
France	Centre Médical République	Clermont-ferrand
France	Investigational site	Clichy
France	Clinique des Cèdres	Cornebarrieu
France	Centre Hospitalier Intercommunal	Creteil
France	Investigational site	Dunkerque
France	Investigational site	Grenoble
France	Centre Hospitalier Universitaire Albert MICHALON	Grenoble Cedex 09
France	Investigational site	Hazebroucq
France	Investigational site	Irigny
France	Investigational site	Istres
France	Centre Hospitalier Lagny	Lagny
France	Investigational site	Le Mans
France	Investigational site - 23 bis, place Sébastol	Lille
France	Investigational site - 60 rue Jean Bart	Lille
France	Clinique de la Sauvegarde	Lyon
France	Investigational site - 186 avenue de la Rose	Marseille
France	Investigational site - 23 Cours Gouffé	Marseille
France	Investigational site	Miramas
France	CH Le raincy-Montfermeil	Montfermeil
France	Investigational site	Nancy
France	Hôpital L'Archet 2	Nice
France	Investigational site - 127 boulevard St Germain	Paris
France	Investigational site - 72 rue Archeveau	Paris
France	Investigational site - 91 rue Caulaincourt	Paris
France	Investigational site	Perpignan
France	Clinique Saint Martin	Pessac
France	Hôpital de Lyon Sud	Pierre-benite
France	Investigational site	Reims
France	Centre Hospitalier Privé	Saint Gregoire
France	Investigational site - 140 avenue Lwoff	Saint Priest
France	Investigational site	Saint Quentin
France	Investigational site	Strasbourg
France	Clinique Saint Jean Languedoc - 20 route de Revel	Toulouse
France	Clinique Saint Jean-Languedoc	Toulouse
France	Groupe Hospitalier les Portes du Sud	Venissieux
France	Centre FUTURA MEDICA	Verquigneul
Netherlands	Haga Ziekenhuis, loc.Rode Kruis	Den Haag
Netherlands	Kennemer Gasthuis, loc. EG	Haarlem
Netherlands	Streekziekenhuis Midden Twente	Hengelo
Netherlands	IJsselmeer Ziekenhuis Loc. Lelystad, Poli MDL	Lelystad
Netherlands	Mumc / Azm	Maastricht
Netherlands	TweeSteden Ziekenhuis	Tilburg
Netherlands	Isala Klinieken, loc. Sophia	Zwolle
United Kingdom	Bristol Royal Infirmary	Bristol
United Kingdom	Addenbrooke's Hospital	Cambridge
United Kingdom	Royal Victoria Infirmary	Newcastle

Sponsors (1)

Lead Sponsor	Collaborator
Ferring Pharmaceuticals

Countries where clinical trial is conducted

Belgium,  France,  Netherlands,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Primary efficacy criterion: remission after 8 weeks of treatment, defined on the basis of the UC-DAI score less than or equal to 1		12 weeks	Yes
Secondary	Compliance		Week 8	Yes
Secondary	Clinical remission		At week 4, week 8 and week 12	Yes
Secondary	Treatment failure is defined as need of other treatment (ie steroids, immunosuppressive or immunomodulating drugs) than those allowed by the protocol, as judged by investigator. Treatment failure will be counted as non-remission.		At week 4 and week 8	Yes
Secondary	Clinical variables (stool frequency and bloody stools)		At week 4, 8 and 12 separately	Yes
Secondary	Time to remission according to patient's diary (normal stool frequency and cessation of bleeding)		At week 4 and week 8	Yes
Secondary	Time to cessation of bleeding		At week 4, week 8 and week 12	Yes
Secondary	Improvement - based on UC-DAI score		At week 4 and 8	Yes
Secondary	Endoscopic assessment		At week 0 and week 8	Yes
Secondary	Safety		At week 0, week 4, week 8 and week 12	Yes