Clinical Trial Results:
Efficacy and mode of action of mesalazine in the treatment of diarrhoea-predominant irritable bowel syndrome (IBS-D).
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Summary
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EudraCT number |
2010-018340-14 |
Trial protocol |
GB |
Global end of trial date |
30 May 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
27 Apr 2016
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First version publication date |
27 Apr 2016
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Other versions |
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Summary report(s) |
MIBS Synopsis |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
10085
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Additional study identifiers
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ISRCTN number |
ISRCTN76612274 | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
University of Nottingham
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Sponsor organisation address |
Lenton Lane, Nottingham, United Kingdom, NG7 2NR
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Public contact |
Robin Spiller, University of Nottingham, robin.spiller@nottingham.ac.uk
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Scientific contact |
Robin Spiller, University of Nottingham, robin.spiller@nottingham.ac.uk
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
30 May 2014
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
30 May 2014
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Global end of trial reached? |
Yes
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Global end of trial date |
30 May 2014
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To assess the effect of mesalazine on stool frequency.
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Protection of trial subjects |
n/a
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
15 Feb 2011
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United Kingdom: 136
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Worldwide total number of subjects |
136
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EEA total number of subjects |
136
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
136
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Participants will be recruited from IBS clinics at the investigator’s hospital, or from lists of patients who have previously taken part in research studies and have indicated that they would like to be contacted about future relevant research projects. In addition, we will, in conjunction with the local Primary Care Research Network, approach GPs | |||||||||
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Pre-assignment
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Screening details |
Male or Female patients aged 18-75 years able to give informed consent. Patients should all have had a colonoscopy or sigmoidoscopy within the last 12 months to exclude microscopic or any inflammatory colitis. (If not, but they have had a negative colonoscopy within 5 years and symptoms are unchanged, then a sigmoidoscopy and mucosal biopsy | |||||||||
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Pre-assignment period milestones
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Number of subjects started |
136 | |||||||||
Number of subjects completed |
136 | |||||||||
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Period 1
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Period 1 title |
Overall Trial (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst, Assessor | |||||||||
Blinding implementation details |
This is a double blind parallel study. Neither participant nor supervising doctor nor study nurse will be aware of the treatment allocation.
The randomisation will be based on a computer generated pseudo-random code using random permuted blocks of randomly varying size, created by the Nottingham Clinical Trials Unit (CTU) in accordance with their standard operating procedure (SOP) and held on a secure server. The randomisation will be stratified by the recruiting centre.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Experimental: Mesalazine Granules | |||||||||
Arm description |
2g oral granules, once a day for 1 week, then 2g oral granules, twice a day for 11 weeks | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Mesalazine
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Granules for oral suspension
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Routes of administration |
Oral use
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Dosage and administration details |
2g oral granules, once a day for 1 week, then 2g oral granules, twice a day for 11 weeks
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Investigational medicinal product name |
Mesalazine
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Granules for oral suspension
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Routes of administration |
Oral use
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Dosage and administration details |
2g oral granules, once a day for 1 week, then 2g oral granules, twice a day for 11 weeks
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Arm title
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Placebo Comparator: Placebo Granules | |||||||||
Arm description |
Placebo Comparator: Placebo Granules 2g oral granules, once a day for 1 week, then 2g oral granules, twice a day for 11 weeks | |||||||||
Arm type |
Placebo | |||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Granules for oral suspension
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Routes of administration |
Oral use
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Dosage and administration details |
Placebo
2g oral granules, once a day for 1 week, then 2g oral granules, twice a day for 11 weeks
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End points reporting groups
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Reporting group title |
Experimental: Mesalazine Granules
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Reporting group description |
2g oral granules, once a day for 1 week, then 2g oral granules, twice a day for 11 weeks | ||
Reporting group title |
Placebo Comparator: Placebo Granules
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Reporting group description |
Placebo Comparator: Placebo Granules 2g oral granules, once a day for 1 week, then 2g oral granules, twice a day for 11 weeks | ||
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End point title |
Average stool frequency during weeks 11-12 of the treatment period. | |||||||||
End point description |
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End point type |
Primary
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End point timeframe |
End of Study
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Statistical analysis title |
Stats Analysis | |||||||||
Statistical analysis description |
For descriptive purposes continuous data will be summarised in terms of the mean, standard deviation, median, lower & upper quartiles, minimum, maximum and number of observations. Categorical data will be summarised in terms of frequency counts and percentages.
Statistical modelling will be used to evaluate the primary and secondary outcomes, and safety data.
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Comparison groups |
Experimental: Mesalazine Granules v Placebo Comparator: Placebo Granules
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Number of subjects included in analysis |
136
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Analysis specification |
Post-hoc
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Analysis type |
equivalence | |||||||||
P-value |
< 0.05 | |||||||||
Method |
Regression, Linear | |||||||||
Confidence interval |
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Adverse events information
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Timeframe for reporting adverse events |
In accordance with the Clinical Trials Statutory Instrument 2004 No. 1031
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Adverse event reporting additional description |
Reference Safety Information: MEDRA coding dictionary used. Expectedness definitions taken from UK regulations.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
1
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Reporting groups
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Reporting group title |
Unrelated
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Reporting group description |
Unrelated to IMP | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Possibly related
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Reporting group description |
Serious adverse reaction which possibly may be related to IMP | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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25 Nov 2010 |
1) Protocol (version 2.0, 25 Nov 2010)
a) We have altered inclusion criteria 2 to include any inflammatory colitis, not just microscopic colitis.
b) Addition of faecal tryptases as a mechanistic secondary endpoint. The analysis of faecal tryptases was already mentioned in the objectives, but omitted by mistake from the endpoints. Addition of a new secondary endpoint detailing polymorphic DNA analysis of participants with details about sampling and storage of the DNA also added.
c) Change of manufacturer from MIA(IMP)19162 to MIA(IMP)17136. This involves the labelling and final assembly of blinding supplies. Several references to the license holder have been amended.
d) Expand abbreviation (NUH – Nottingham University Hospitals NHS Trust)
e) Addition of details of the Rome III questionnaire and the post-infectious IBS-D questionnaire.
2) Daily Symptom and Stool Diary (version 2.0, 25 Nov 2010)
We have altered the layout of this document and changed the scale from which the participants must score their symptoms. We have not detailed the changes below but instead submitted the whole document for review.
3) Post-Infectious IBS-D Criteria
Participants will complete 4 questions to help sub-type them with or without post-infectious IBS-D. This is a new document so we have not detailed the changes below but instead submitted the new document in whole.
4) Patient information sheet (version 2.0, 25 Nov 2010)
Details regarding the collection, analysis and future use of a DNA sample have been added.
5) Consent Form (version 2.0, 25 Nov 2010)
Optional consent for a DNA sample to be collected, analysed and store for future use has been added. Reference to the new version of the PIS has changed
7) Simplified IMP-D (version 1.1, 25 Nov 2010)
We have changed the contact details for one of the manufacturer’s. The previous were unable to fulfil their commitment. (We have also submitted, to the CA only, a copy of the new manufacturer’s license.)
8) Initial |
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05 May 2011 |
Altered inclusion criteria 2 to include colonoscopy or sigmoidoscopy, not just colonoscopy. b) Altered inclusion criteria 5 whereby patients with stool frequency of 3 or more per day for 2 or more days per week during the screening phase are eligible to be included into the study. Previously, part of eligibility into the study was patient with average stool frequency of 3 or more per day during the screening phase. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
