Clinical Trial Results:
Colonic lesion staining and flagging efficacy of methylene blue administered as MMX® 25 mg modified release tablets to patients receiving a split dose regimen of bowel cleansing preparation for colonoscopy
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Summary
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EudraCT number |
2017-003505-17 |
Trial protocol |
IT |
Global end of trial date |
28 Feb 2019
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Results information
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Results version number |
v1(current) |
This version publication date |
29 Dec 2022
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First version publication date |
29 Dec 2022
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Other versions |
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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 |
CB-17-01/15
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
Cosmo Technologies Ltd
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Sponsor organisation address |
Riverside II, Sir John Rogerson’s Quay, Dublin, Ireland,
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Public contact |
Diego Scanniffio, CROSS Research SA, 0041 916300510, diego.scanniffio@croalliance.com
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Scientific contact |
Diego Scanniffio, CROSS Research SA, 0041 916300510, diego.scanniffio@croalliance.com
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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 |
28 Feb 2019
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
28 Feb 2019
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Global end of trial reached? |
Yes
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Global end of trial date |
28 Feb 2019
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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 evaluate the colonic lesion staining and flagging efficacy of single 200 mg oral doses of Methylene Blue MMX® 25 mg tablets administered to patients undergoing colonoscopy, in association with a high volume split dose regimen of bowel preparation, or a low volume split dose regimen of bowel preparation. Bowel cleansing quality will also be evaluated according to the validated Boston Bowel Preparation Scale (BBPS) after the intake of the bowel cleansing preparation and of a total dose of 200 mg of Methylene Blue MMX® 25 mg tablets administered the day before the colonoscopy procedure, with bowel preparation or water indicated volumes.
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Protection of trial subjects |
Subjects were followed for safety and tolerability assessments: adverse events, vital signs, and physical examination.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
28 Feb 2018
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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 |
Italy: 100
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Worldwide total number of subjects |
100
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EEA total number of subjects |
100
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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) |
65
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From 65 to 84 years |
35
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85 years and over |
0
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Recruitment
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Recruitment details |
According to the study plan, the investigator included in the study and randomised 100 subjects. | ||||||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
Outpatients scheduled for colonoscopy were informed about the aims, procedures, benefits and possible risks of the study prior to signing the informed consent form for inclusion in the trial. Screening/Enrolment Visit window: Day -30 to Day -3. | ||||||||||||||||||||||||||||||
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Period 1
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Period 1 title |
Treatment Period - overall study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||||||||||||||||
Blinding implementation details |
This was an open trial and no masking procedure was applied.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Group A (Test treatment 1 - T1) | ||||||||||||||||||||||||||||||
Arm description |
High volume split dose regimen bowel preparation (Selg-Esse®) along with 8 Methylene Blue MMX® 25 mg modified release tablets according to a 3+3+2 intake schedule. | ||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Methylene Blue MMX® modified release tablets
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
An oral dose of 200 mg of Methylene Blue MMX® 25 mg modified release tablets was administered during bowel cleansing preparation administered the day before the colonoscopy procedure. IMP was administered according to a 3+3+2 intake schedule.
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Investigational medicinal product name |
4-L, PEG-based bowel cleansing preparation (Selg-Esse®)
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder for oral solution
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Routes of administration |
Oral use
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Dosage and administration details |
Dose: The content of 4 bags dissolved in 4L of water.
In the evening before the colonoscopy, the subjects receiving the high volume split dose drank 250 mL of solution (Selg-Esse®) every 15 min up to approximately 2 L (up to 1 h and 45 min from the start of the intake), according to the investigator's or deputy's instructions. Then the subjects drank the remaining volume of the bowel cleansing preparation (2 L) in the morning of the colonoscopy day at the same rate (i.e. approximately 250 mL/15 min) until they completed the intake of the whole volume.
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Arm title
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Group B (Test treatment 2 - T2) | ||||||||||||||||||||||||||||||
Arm description |
High volume split dose regimen bowel preparation (Selg-Esse®) along with 8 Methylene Blue MMX® 25 mg modified release tablets according to a 4+4 intake schedule. | ||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Methylene Blue MMX® modified release tablets
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
An oral dose of 200 mg of Methylene Blue MMX® 25 mg modified release tablets was administered during bowel cleansing preparation administered the day before the colonoscopy procedure. IMP was administered according to a 4+4 intake schedule.
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Investigational medicinal product name |
4-L, PEG-based bowel cleansing preparation (Selg-Esse®)
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder for oral solution
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Routes of administration |
Oral use
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Dosage and administration details |
Dose: The content of 4 bags dissolved in 4L of water.
In the evening before the colonoscopy, the subjects receiving the high volume split dose drank 250 mL of solution (Selg-Esse®) every 15 min up to approximately 2 L (up to 1 h and 45 min from the start of the intake), according to the investigator's or deputy's instructions. Then the subjects drank the remaining volume of the bowel cleansing preparation (2 L) in the morning of the colonoscopy day at the same rate (i.e. approximately 250 mL/15 min) until they completed the intake of the whole volume.
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Arm title
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Group C (Test treatment 3 - T3) | ||||||||||||||||||||||||||||||
Arm description |
Low volume split dose regimen bowel preparation 1 (Izinova®) along with 8 Methylene Blue MMX® 25 mg modified release tablets according to a 3+3+2 intake schedule. | ||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Methylene Blue MMX® modified release tablets
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
An oral dose of 200 mg of Methylene Blue MMX® 25 mg modified release tablets was administered during bowel cleansing preparation administered the day before the colonoscopy procedure. IMP was administered according to a 3+3+2 intake schedule.
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Investigational medicinal product name |
Izinova®
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Concentrate for oral solution
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Routes of administration |
Oral use
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Dosage and administration details |
Dose: The content of each bottle was diluted in water, using the cup provided, to a total volume of approximately 0.5 L for each bottle: one bottle for the evening administration (day 1) and one bottle for the morning administration (day 2). A total volume of 1 L of solution + 2 L of water was drunk.
In the evening before the colonoscopy, the subjects receiving the low volume split dose of bowel preparation 1 drank 250 mL of solution (Izinova®) every 15 min up to 0.5 mL, followed by 250 mL of water every 15 min up to an additional 1 L (1.5 L total liquid intake), according to the investigator's or deputy's instructions. The same regimen was followed in the morning of the colonoscopy day up to an overall solution/water volume of 3 L.
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Arm title
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Group D (Test treatment 4 - T4) | ||||||||||||||||||||||||||||||
Arm description |
Low volume split dose regimen bowel preparation 2 (Moviprep®) along with 8 Methylene Blue MMX® 25 mg modified release tablets according to a 3+3+2 intake schedule. | ||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Methylene Blue MMX® modified release tablets
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
An oral dose of 200 mg of Methylene Blue MMX® 25 mg modified release tablets was administered during bowel cleansing preparation administered the day before the colonoscopy procedure. IMP was administered according to a 3+3+2 intake schedule.
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Investigational medicinal product name |
Moviprep®
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder for oral solution
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Routes of administration |
Oral use
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Dosage and administration details |
Dose: The content of 1 'sachet A' and 1 'sachet B' were dissolved together in water to make 1 L of solution. One (1) L was prepared for the evening (day 1) and 1 L for the morning (day 2) administration. A total volume of 2 L of solution + 250 mL of water were drunk.
In the evening before the colonoscopy, the subjects receiving the low volume split dose of bowel preparation 2 (Group D; T4) drank 250 mL of solution (Moviprep®) every 15 min up to 1 L, followed by 250 mL of water (1.25 L total liquid intake), according to the investigator's or deputy's instructions. The same regimen (but without the 250 mL of water) was followed in the morning of the colonoscopy day up to an overall solution/water volume of 2.25 L.
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Baseline characteristics reporting groups
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Reporting group title |
Treatment Period - overall study
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Group A (Test treatment 1 - T1)
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Reporting group description |
High volume split dose regimen bowel preparation (Selg-Esse®) along with 8 Methylene Blue MMX® 25 mg modified release tablets according to a 3+3+2 intake schedule. | ||
Reporting group title |
Group B (Test treatment 2 - T2)
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Reporting group description |
High volume split dose regimen bowel preparation (Selg-Esse®) along with 8 Methylene Blue MMX® 25 mg modified release tablets according to a 4+4 intake schedule. | ||
Reporting group title |
Group C (Test treatment 3 - T3)
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Reporting group description |
Low volume split dose regimen bowel preparation 1 (Izinova®) along with 8 Methylene Blue MMX® 25 mg modified release tablets according to a 3+3+2 intake schedule. | ||
Reporting group title |
Group D (Test treatment 4 - T4)
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Reporting group description |
Low volume split dose regimen bowel preparation 2 (Moviprep®) along with 8 Methylene Blue MMX® 25 mg modified release tablets according to a 3+3+2 intake schedule. | ||
Subject analysis set title |
Full Analysis Set
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
all randomised patients, who received at least one dose of the IMP and had at least one post-randomisation assessment of the primary efficacy data. This analysis set was used for the primary efficacy analysis.
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Subject analysis set title |
Safety Set
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
All patients who received at least one dose of the IMP. Patients who took only the bowel preparation were not included in the safety set. This analysis set was used for the safety analyses.
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Subject analysis set title |
Per Protocol
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
all randomised patients who fulfilled the study protocol requirements in terms of IMP intake and collection of primary efficacy data and with no
major deviations that could affect study results. This analysis set was used for sensitivity analyses;
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End point title |
Colonic lesion staining and flagging efficacy of Methylene Blue MMX® 25 mg modified release tablets [1] | ||||||||||||||||||||||||||||||||||||||||
End point description |
To evaluate the colonic lesion staining and flagging efficacy of Methylene Blue MMX® 25 mg modified release tablets after a total oral dose of 200 mg in association with a high volume or a low volume split dose regimen of bowel cleansing preparation or a low volume split dose regimen of bowel cleansing preparation or water.
Staining quality observed in each region on the 0-4 scale.
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End point type |
Primary
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End point timeframe |
Evaluated on Day 2 (Day of Colonoscopy)
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Could not be entered |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||
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End point title |
Bowel cleansing quality according to the validated Boston Bowel Preparation Scale (BBPS) [2] | ||||||||||||||||||||||||||||||||||||||||
End point description |
To evaluate the bowel cleansing quality according to the validated Boston Bowel Preparation Scale (BBPS) after the intake of the high volume or the low volume split dose regimen bowel cleansing preparation and of a total dose of 200 mg of Methylene Blue MMX® 25 mg modified release tablets administered during the intake of the bowel cleansing preparation or water.
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End point type |
Primary
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End point timeframe |
Evaluated at D2 (Colonoscopy Day)
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Could not be entered |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Throughout the study
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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 |
22.0
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Reporting groups
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Reporting group title |
Group A (Test treatment 1 - T1)
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||
Reporting group title |
Group B (Test treatment 2 - T2)
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||
Reporting group title |
Group C (Test treatment 3 - T3)
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||
Reporting group title |
Group D (Test treatment 4 - T4)
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
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 | |||
