Ulcerative ColitisPhase 3NCT00737789
Mesalazine 4g Once Daily Versus 4g in Two Divided Doses in Active Ulcerative Colitis.
A Phase 3 study testing Mesalazine slow-release granules and Mesalazine liquid enema in people with Ulcerative Colitis, run by Ferring Pharmaceuticals at 66 sites in 4 countries.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Ulcerative Colitis
- What is being tested?
- Mesalazine slow-release granules and Mesalazine liquid enema
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 206 participants
- Where
- 66 sitesin 4 countries
- Study dates
- Nov 2008to Jun 2010
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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).
Show all 24Show fewer
- 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.
Trial locations and contacts
66 sites in 4 countries.
66 sites in 4 countries
France50 sites
Clinique Esquirol-St Hilaire
Agen
Investigational site
Albi
Investigational site
Amiens
Centre Hospitalier Avignon
Avignon
Centre Hospitalier Bethune
Béthune
Investigational site
Bourgoin
Investigational site
Brest
Clinique Jean-Villar
Bruges
Clinique Saint Martin - 18 rue Rocquemonts
Caen
Clinique Saint Martin
Caen
Investigational site
Caluire-et-Cuire
Investigational site
Carcassonne
Clinique du Parc
Castelnau-le-Lez
Investigational site
Chambray-lès-Tours
Centre Médical République
Clermont-Ferrand
Investigational site
Clichy
Clinique des Cèdres
Cornebarrieu
Centre Hospitalier Intercommunal
Créteil
Investigational site
Dunkirk
Centre Hospitalier Universitaire Albert MICHALON
Grenoble
Investigational site
Grenoble
Investigational site
Hazebroucq
Investigational site
Irigny
Investigational site
Istres
Centre Hospitalier Lagny
Lagny
Investigational site
Le Mans
Investigational site - 23 bis, place Sébastol
Lille
Investigational site - 60 rue Jean Bart
Lille
Clinique de la Sauvegarde
Lyon
Investigational site - 186 avenue de la Rose
Marseille
Investigational site - 23 Cours Gouffé
Marseille
Investigational site
Miramas
CH Le raincy-Montfermeil
Montfermeil
Investigational site
Nancy
Hôpital L'Archet 2
Nice
Investigational site - 127 boulevard St Germain
Paris
Investigational site - 72 rue Archeveau
Paris
Investigational site - 91 rue Caulaincourt
Paris
Investigational site
Perpignan
Clinique Saint Martin
Pessac
Hôpital de Lyon Sud
Pierre-Bénite
Investigational site
Reims
Centre Hospitalier Privé
Saint-Grégoire
Investigational site - 140 avenue Lwoff
Saint-Priest
Investigational site
Saint-Quentin
Investigational site
Strasbourg
Clinique Saint Jean Languedoc - 20 route de Revel
Toulouse
Clinique Saint Jean-Languedoc
Toulouse
Groupe Hospitalier les Portes du Sud
Vénissieux
Centre FUTURA MEDICA
Verquigneul
Netherlands7 sites
Kennemer Gasthuis, loc. EG
Haarlem
Streekziekenhuis Midden Twente
Hengelo
IJsselmeer Ziekenhuis Loc. Lelystad, Poli MDL
Lelystad
Mumc / Azm
Maastricht
Haga Ziekenhuis, loc.Rode Kruis
The Hague
TweeSteden Ziekenhuis
Tilburg
Isala Klinieken, loc. Sophia
Zwolle
Belgium6 sites
O.L.Vrouwziekenhuis Campus Aalst
Aalst
C.H.U. Saint-Pierre
Brussels
Saint Luc University Hospital
Brussels
Universitair Ziekenhuis Brussel
Brussels
U.Z. Antwerpen
Edegem
University Hospital Gasthuisberg
Leuven
United Kingdom3 sites
Bristol Royal Infirmary
Bristol
Addenbrooke's Hospital
Cambridge
Royal Victoria Infirmary
Newcastle
About this 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.
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.
Read the detailed 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.
- Conditions
- Ulcerative Colitis
- Being tested
- Mesalazine slow-release granules, Mesalazine liquid enema
- Medical subject headings
- Colitis, Ulcerative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mesalazine slow-release granulesDrug
Also called Pentasa
Mesalazine 2g Sachet prolonged release granules, administered orally.
Mesalazine liquid enemaDrug
1g mesalazine liquid enema, administered topically once a day in the evening.
| Study group | Role | What they receive |
|---|---|---|
| Mesalazine once/day | Experimental | 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). Receives: Drug: Mesalazine slow-release granules; Drug: Mesalazine liquid enema |
| Mesalazine twice/day | Active comparator | 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). Receives: Drug: Mesalazine slow-release granules; Drug: Mesalazine liquid enema |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary efficacy criterion: remission after 8 weeks of treatment, defined on the basis of the UC-DAI score less than or equal to 1
Measured: 12 weeks
Secondary outcomes (9)
Compliance
Measured: Week 8
Clinical remission
Measured: At week 4, week 8 and week 12
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.
Measured: At week 4 and week 8
Clinical variables (stool frequency and bloody stools)
Measured: At week 4, 8 and 12 separately
Time to remission according to patient's diary (normal stool frequency and cessation of bleeding)
Measured: At week 4 and week 8
Time to cessation of bleeding
Measured: At week 4, week 8 and week 12
Improvement - based on UC-DAI score
Measured: At week 4 and 8
Endoscopic assessment
Measured: At week 0 and week 8
Safety
Measured: At week 0, week 4, week 8 and week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Aug 2008 (estimated)
- Study startNov 2008
- Primary completionJun 2010
- Study completionJun 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Ulcerative ColitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 206 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ferring Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Development Support, Study director, Ferring Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00737789
- Sponsor's protocol ID
- Pentasa FE999907 CS06
- Other IDs
- EudractCT No 2008-000045-59
- Status last verified
- Mar 2015
- First submitted
- 19 Aug 2008
- Last updated
- 4 Mar 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 23451806
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT00737789
- Acronym / sponsor ID
- Pentasa FE999907 CS06
- Conditions
- Ulcerative Colitis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 206 participants (actual)
- Lead sponsor
- Ferring PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Nov 2008
- Primary completion
- Jun 2010 (actual)
- Study completion
- Jun 2010 (actual)
- First posted
- 20 Aug 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Mesalazine once/day | Experimental | Drug: Mesalazine slow-release granules, Drug: Mesalazine liquid enemaParticipants 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). |
| Mesalazine twice/day | Active comparator | Drug: Mesalazine slow-release granules, Drug: Mesalazine liquid enemaParticipants 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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (24 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Mesalazine slow-release granulesAlso: PentasaMesalazine 2g Sachet prolonged release granules, administered orally. | Drug | Mesalazine once/day, Mesalazine twice/day |
| Mesalazine liquid enema1g mesalazine liquid enema, administered topically once a day in the evening. | Drug | Mesalazine once/day, Mesalazine twice/day |
Primary outcome
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
9 secondary outcomes
Compliance
Time frame: Week 8
Clinical remission
Time frame: At week 4, week 8 and week 12
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.
Time frame: At week 4 and week 8
Clinical variables (stool frequency and bloody stools)
Time frame: At week 4, 8 and 12 separately
Time to remission according to patient's diary (normal stool frequency and cessation of bleeding)
Time frame: At week 4 and week 8
Time to cessation of bleeding
Time frame: At week 4, week 8 and week 12
Improvement - based on UC-DAI score
Time frame: At week 4 and 8
Endoscopic assessment
Time frame: At week 0 and week 8
Safety
Time frame: At week 0, week 4, week 8 and week 12
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2015.
- Derived from this study: PubMed 23451806Flourie 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Development Support study director
Ferring Pharmaceuticals
66 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Mesalazine slow-release granules and Mesalazine liquid enema in people with Ulcerative Colitis, run by Ferring Pharmaceuticals at 66 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Mar 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 66 sites in France, Netherlands, Belgium, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00737789, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2015.