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

NCT ID: NCT00737789

Last Updated: 2015-03-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

206 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-11-30

Study Completion Date

2010-06-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Ulcerative Colitis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Investigators

Study Groups

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Mesalazine once/day

Participants received 4g oral Mesalazine once a day (2 sachets of prolonged release granules) for 8 weeks during the induction period. In addition, participants received a liquid enema of 1g Mesalazine once a day at bedtime for the first 4 weeks. Participants who were in remission at Week 8 received oral mesalazine 2g once daily (1 sachet/day) for an additional 4 weeks (maintenance period).

Group Type EXPERIMENTAL

Mesalazine slow-release granules

Intervention Type DRUG

Mesalazine 2g Sachet prolonged release granules, administered orally.

Mesalazine liquid enema

Intervention Type DRUG

1g mesalazine liquid enema, administered topically once a day in the evening.

Mesalazine twice/day

Participants received oral mesalazine 4 g per day in two divided doses (1 sachet prolonged release granules twice a day) for 8 weeks during the induction period. In addition, participants received a liquid enema of 1g Mesalazine once a day at bedtime for the first 4 weeks. Participants who were in remission at Week 8 received oral Mesalazine 2g (one sachet) once a day for an additional 4 weeks (maintenance period).

Group Type ACTIVE_COMPARATOR

Mesalazine slow-release granules

Intervention Type DRUG

Mesalazine 2g Sachet prolonged release granules, administered orally.

Mesalazine liquid enema

Intervention Type DRUG

1g mesalazine liquid enema, administered topically once a day in the evening.

Interventions

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Mesalazine slow-release granules

Mesalazine 2g Sachet prolonged release granules, administered orally.

Intervention Type DRUG

Mesalazine liquid enema

1g mesalazine liquid enema, administered topically once a day in the evening.

Intervention Type DRUG

Other Intervention Names

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Pentasa

Eligibility Criteria

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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 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

* 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.
* 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ferring Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Development Support

Role: STUDY_DIRECTOR

Ferring Pharmaceuticals

Locations

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O.L.Vrouwziekenhuis Campus Aalst

Aalst, , Belgium

Site Status

C.H.U. Saint-Pierre

Brussels, , Belgium

Site Status

Saint Luc University Hospital

Brussels, , Belgium

Site Status

Universitair Ziekenhuis Brussel

Brussels, , Belgium

Site Status

U.Z. Antwerpen

Edegem, , Belgium

Site Status

University Hospital Gasthuisberg

Leuven, , Belgium

Site Status

Clinique Esquirol-St Hilaire

Agen, , France

Site Status

Investigational site

Albi, , France

Site Status

Investigational site

Amiens, , France

Site Status

Centre Hospitalier Avignon

Avignon, , France

Site Status

Centre Hospitalier Bethune

Béthune, , France

Site Status

Investigational site

Bourgoin, , France

Site Status

Investigational site

Brest, , France

Site Status

Clinique Jean-Villar

Bruges, , France

Site Status

Clinique Saint Martin - 18 rue Rocquemonts

Caen, , France

Site Status

Clinique Saint Martin

Caen, , France

Site Status

Investigational site

Caluire-et-Cuire, , France

Site Status

Investigational site

Carcassonne, , France

Site Status

Clinique du Parc

Castelnau-le-Lez, , France

Site Status

Investigational site

Chambray-lès-Tours, , France

Site Status

Centre Médical République

Clermont-Ferrand, , France

Site Status

Investigational site

Clichy, , France

Site Status

Clinique des Cèdres

Cornebarrieu, , France

Site Status

Centre Hospitalier Intercommunal

Créteil, , France

Site Status

Investigational site

Dunkirk, , France

Site Status

Centre Hospitalier Universitaire Albert MICHALON

Grenoble, , France

Site Status

Investigational site

Grenoble, , France

Site Status

Investigational site

Hazebroucq, , France

Site Status

Investigational site

Irigny, , France

Site Status

Investigational site

Istres, , France

Site Status

Centre Hospitalier Lagny

Lagny, , France

Site Status

Investigational site

Le Mans, , France

Site Status

Investigational site - 23 bis, place Sébastol

Lille, , France

Site Status

Investigational site - 60 rue Jean Bart

Lille, , France

Site Status

Clinique de la Sauvegarde

Lyon, , France

Site Status

Investigational site - 186 avenue de la Rose

Marseille, , France

Site Status

Investigational site - 23 Cours Gouffé

Marseille, , France

Site Status

Investigational site

Miramas, , France

Site Status

CH Le raincy-Montfermeil

Montfermeil, , France

Site Status

Investigational site

Nancy, , France

Site Status

Hôpital L'Archet 2

Nice, , France

Site Status

Investigational site - 127 boulevard St Germain

Paris, , France

Site Status

Investigational site - 72 rue Archeveau

Paris, , France

Site Status

Investigational site - 91 rue Caulaincourt

Paris, , France

Site Status

Investigational site

Perpignan, , France

Site Status

Clinique Saint Martin

Pessac, , France

Site Status

Hôpital de Lyon Sud

Pierre-Bénite, , France

Site Status

Investigational site

Reims, , France

Site Status

Centre Hospitalier Privé

Saint-Grégoire, , France

Site Status

Investigational site - 140 avenue Lwoff

Saint-Priest, , France

Site Status

Investigational site

Saint-Quentin, , France

Site Status

Investigational site

Strasbourg, , France

Site Status

Clinique Saint Jean Languedoc - 20 route de Revel

Toulouse, , France

Site Status

Clinique Saint Jean-Languedoc

Toulouse, , France

Site Status

Centre FUTURA MEDICA

Verquigneul, , France

Site Status

Groupe Hospitalier les Portes du Sud

Vénissieux, , France

Site Status

Kennemer Gasthuis, loc. EG

Haarlem, , Netherlands

Site Status

Streekziekenhuis Midden Twente

Hengelo, , Netherlands

Site Status

IJsselmeer Ziekenhuis Loc. Lelystad, Poli MDL

Lelystad, , Netherlands

Site Status

Mumc / Azm

Maastricht, , Netherlands

Site Status

Haga Ziekenhuis, loc.Rode Kruis

The Hague, , Netherlands

Site Status

TweeSteden Ziekenhuis

Tilburg, , Netherlands

Site Status

Isala Klinieken, loc. Sophia

Zwolle, , Netherlands

Site Status

Bristol Royal Infirmary

Bristol, , United Kingdom

Site Status

Addenbrooke's Hospital

Cambridge, , United Kingdom

Site Status

Royal Victoria Infirmary

Newcastle, , United Kingdom

Site Status

Countries

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Belgium France Netherlands United Kingdom

References

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Flourie B, Hagege H, Tucat G, Maetz D, Hebuterne X, Kuyvenhoven JP, Tan TG, Pierik MJ, Masclee AA, Dewit O, Probert CS, Aoucheta D; MOTUS study investigators. Randomised clinical trial: once- vs. twice-daily prolonged-release mesalazine for active ulcerative colitis. Aliment Pharmacol Ther. 2013 Apr;37(8):767-75. doi: 10.1111/apt.12266. Epub 2013 Mar 4.

Reference Type DERIVED
PMID: 23451806 (View on PubMed)

Other Identifiers

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EudractCT No 2008-000045-59

Identifier Type: -

Identifier Source: secondary_id

Pentasa FE999907 CS06

Identifier Type: -

Identifier Source: org_study_id

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