Trial Outcomes & Findings for Neoplasia Detection With Methylene Blue MMX Tablets in Patients With UC Undergoing Colonoscopy (NCT NCT01520324)

NCT ID: NCT01520324

Last Updated: 2019-02-08

Results Overview

Rate of intraepithelial neoplasiae detection in the whole colon.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 53 participants
• Primary outcome timeframe: During colonscopy (usually <15 min) and subsequent histological analysis
• Results posted on: 2019-02-08

Participant Flow

This study recruited patients with a diagnosis of ulcerative colitis dating not less than 8 years.

This was an exploratory, non-comparative study with no randomization. All subjects were allocated to receive Selg 1000® 4 L bowel preparation, the day before colonoscopy. All study subjects were allocated to receive 200 mg of Methylene Blue MMX® tablets during and at the end of the intake of bowel cleansing preparation.

Participant milestones

Measure	Patients With UC Undergoing Colonoscopy oral delivery mucosal stain: 200mg methylene blue MMX tablet taken prior to colonoscopy
Overall Study STARTED	53
Overall Study COMPLETED	52
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Measure	Patients With UC Undergoing Colonoscopy oral delivery mucosal stain: 200mg methylene blue MMX tablet taken prior to colonoscopy
Overall Study Subject discontinued (moderate illness)	1

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	Patients With UC Undergoing Colonoscopy n=52 Participants oral delivery mucosal stain: 200mg methylene blue MMX tablet taken prior to colonoscopy
Age, Continuous Age	45.9 Years STANDARD_DEVIATION 9.7 • n=52 Participants
Sex: Female, Male Female	22 Participants n=52 Participants
Sex: Female, Male Male	30 Participants n=52 Participants
Height	168.9 cm STANDARD_DEVIATION 8.4 • n=52 Participants
Body weight	70.04 kg STANDARD_DEVIATION 9.57 • n=52 Participants

PRIMARY outcome

Timeframe: During colonscopy (usually <15 min) and subsequent histological analysis

Rate of intraepithelial neoplasiae detection in the whole colon.

Outcome measures

Measure	Full Analysis Set (FAS) n=52 Participants All enrolled subjects, who received at least one dose of the test investigational medicinal product and had at least one evaluation of the number of detected neoplasiae.
Detected Intraepithelial Neoplasia	0.2 Number of detected IN Standard Deviation 0.5

PRIMARY outcome

Timeframe: During colonscopy (usually <15 min) and subsequent histological analysis

The rate of intraepithelial neoplasiae detection in the whole colon is summarised along with the number and percentage of subjects affected. The number and percentage of false and true negative and of false and true positive findings of intraepithelial neoplasiae are also listed.

Outcome measures

Measure	Full Analysis Set (FAS) n=52 Participants All enrolled subjects, who received at least one dose of the test investigational medicinal product and had at least one evaluation of the number of detected neoplasiae.
Intraepithelial Neoplasia (IN) Detection Rate (True Positive Findings)	7.7 percentage of true pos. findings of IN

PRIMARY outcome

Timeframe: During colonscopy (usually <15 min) and subsequent histological analysis

The rate of intraepithelial neoplasiae detection in the whole colon is summarised along with the number and percentage of subjects affected. The number and percentage of false and true negative and of false and true positive findings of intraepithelial neoplasiae are also listed.

Outcome measures

Measure	Full Analysis Set (FAS) n=52 Participants All enrolled subjects, who received at least one dose of the test investigational medicinal product and had at least one evaluation of the number of detected neoplasiae.
Intraepithelial Neoplasia (IN) Detection Rate (False Positive Findings)	7.7 percentage of false pos. findings of IN

PRIMARY outcome

Timeframe: During colonscopy (usually <15 min) and subsequent histological analysis

The rate of intraepithelial neoplasiae detection in the whole colon is summarised along with the number and percentage of subjects affected. The number and percentage of false and true negative and of false and true positive findings of intraepithelial neoplasiae are also listed.

Outcome measures

Measure	Full Analysis Set (FAS) n=52 Participants All enrolled subjects, who received at least one dose of the test investigational medicinal product and had at least one evaluation of the number of detected neoplasiae.
Intraepithelial Neoplasia (IN) Detection Rate (True Negative Findings)	78.8 percentage of true neg. findings of IN

PRIMARY outcome

Timeframe: During colonscopy (usually <15 min) and subsequent histological analysis

The rate of intraepithelial neoplasiae detection in the whole colon is summarised along with the number and percentage of subjects affected. The number and percentage of false and true negative and of false and true positive findings of intraepithelial neoplasiae are also listed.

Outcome measures

Measure	Full Analysis Set (FAS) n=52 Participants All enrolled subjects, who received at least one dose of the test investigational medicinal product and had at least one evaluation of the number of detected neoplasiae.
Intraepithelial Neoplasia (IN) Detection Rate (False Negative Findings)	5.8 percentage of false neg. findings of IN

SECONDARY outcome

Timeframe: During colonscopy (usually <15 min) and subsequent histological analysis

The inflammation conditions of the mucosa were evaluated during the colonoscopy and, afterwards, in the bioptic specimens.

Rachmilewitz EI and Saverymuttu scores were used to assess inflammation. Rachmilewitz's scoring system for endoscopic index (EI) measures granulation scattering reflected light, vascular pattern, vulnerability of mucose and mucosal damage on a scoring scale of 0 to 4 from normal to damaged.

Saverymuttu's scoring system for enteric specimens assesses disease activity in the bowel by rating histological changes in enterocytes, crypts, lamina propria mononuclear cells and lamina propria neutrophils.

The average score for histological changes in individual biopsy specimens was summed and converted into a grade from 1 to 4, increasing in severity.

Outcome measures

Measure	Full Analysis Set (FAS) n=52 Participants All enrolled subjects, who received at least one dose of the test investigational medicinal product and had at least one evaluation of the number of detected neoplasiae.
The Extent and Severity of the Inflamed Mucosa Rachmilewitz EI	2.1 Rachmilewitz and Saverymuttu scores Standard Deviation 3.0
The Extent and Severity of the Inflamed Mucosa Saverymuttu grade	1.1 Rachmilewitz and Saverymuttu scores Standard Deviation 1.0

SECONDARY outcome

Timeframe: During colonscopy (usually <15 min) and subsequent histological analysis

The mucosal staining efficacy of Methylene Blue MMX® tablets was assessed in all 4 examined colonic regions (ascending, transverse and descending colon and rectosigmoid).

The staining efficacy in each colon region was assessed scoring the observed staining percentage as reported below:

0. no staining

1. traces (poor traces in colon mucosa)

2. detectable (at least the 25% of colon mucosa is stained)

3. acceptable (at least the 50% of colon mucosa is stained)

4. good (at least the 75% of colon mucosa is stained)

5. overstained (the 100% of the colon mucosa is over stained)

Outcome measures

Measure	Full Analysis Set (FAS) n=52 Participants All enrolled subjects, who received at least one dose of the test investigational medicinal product and had at least one evaluation of the number of detected neoplasiae.
The Mucosal Staining Efficacy of Methylene Blue MMX® Tablets After a Total Oral Dose of 200 mg Administered During and at the End of the Intake of the Bowel Cleansing Preparation. Ascending colon	3.4 Staining score Standard Deviation 1.0
The Mucosal Staining Efficacy of Methylene Blue MMX® Tablets After a Total Oral Dose of 200 mg Administered During and at the End of the Intake of the Bowel Cleansing Preparation. Transverse colon	3.0 Staining score Standard Deviation 0.9
The Mucosal Staining Efficacy of Methylene Blue MMX® Tablets After a Total Oral Dose of 200 mg Administered During and at the End of the Intake of the Bowel Cleansing Preparation. Descending colon	2.9 Staining score Standard Deviation 1.1
The Mucosal Staining Efficacy of Methylene Blue MMX® Tablets After a Total Oral Dose of 200 mg Administered During and at the End of the Intake of the Bowel Cleansing Preparation. Rectosigmoid	2.8 Staining score Standard Deviation 1.1

SECONDARY outcome

Timeframe: During colonscopy (usually <15 min)

The Boston Bowel Preparation Score (BBPS) was used to rate colon cleansing quality. Each of the following 3 regions was rated: right, mid and rectosigmoid colon. The following 4-point scale (0-3) was used.

0 - unprepared colon segment with mucosa not seen due to solid stool that cannot be cleared

1. - portion of mucosa of the colon segment seen, but other areas of the colon segment not well seen due to staining, residual stool and/or opaque liquid

2. - minor amount of residual staining, small fragments of stool and/or opaque liquid, but mucosa of colon segment seen well

3. - entire mucosa of colon segment seen well with no residual staining, small fragments of stool or opaque liquid.

Each region of the colon received a "segment score" from 0 to 3 and these segment scores were summed for a total BBPS score ranging from 0 to 9. Therefore, the maximum BBPS score for a perfectly clean colon, without any residual liquid, is 9 and the minimum BBPS score for an unprepared colon is 0.

Outcome measures

Measure	Full Analysis Set (FAS) n=52 Participants All enrolled subjects, who received at least one dose of the test investigational medicinal product and had at least one evaluation of the number of detected neoplasiae.
Bowel Cleansing Quality Evaluated by Boston Bowel Preparation Scale After Intake of Bowel Cleansing Formulation and of a Total Dose of 200 mg of Methylene Blue MMX Tablets Administered During and at the End of the Intake of the Bowel Cleansing Formulation Right colon	1.3 Boston bowel preparation scale (BBPS) Standard Deviation 0.5
Bowel Cleansing Quality Evaluated by Boston Bowel Preparation Scale After Intake of Bowel Cleansing Formulation and of a Total Dose of 200 mg of Methylene Blue MMX Tablets Administered During and at the End of the Intake of the Bowel Cleansing Formulation Mid colon	1.7 Boston bowel preparation scale (BBPS) Standard Deviation 0.5
Bowel Cleansing Quality Evaluated by Boston Bowel Preparation Scale After Intake of Bowel Cleansing Formulation and of a Total Dose of 200 mg of Methylene Blue MMX Tablets Administered During and at the End of the Intake of the Bowel Cleansing Formulation Rectosigmoid colon	1.7 Boston bowel preparation scale (BBPS) Standard Deviation 0.5

Adverse Events

Full Analysis Set (FAS)

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Full Analysis Set (FAS) n=53 participants at risk All enrolled subjects, who received at least one dose of the test investigational medicinal product and had at least one evaluation of the number of detected neoplasiae.
Gastrointestinal disorders Nausea	15.1% 8/53 • Number of events 8 • On the day before colonoscopy (day 1), the subjects took the investigational product at home during the intake of the bowel cleansing preparation according to the given instructions. On the following day (day 2), the patients returned to the clinic for colonoscopy. The investigator inquired the subjects about occurrence of any AE and the intake of concomitant medications. It was over these two days the AEs were monitored.
Gastrointestinal disorders Vomiting	1.9% 1/53 • Number of events 1 • On the day before colonoscopy (day 1), the subjects took the investigational product at home during the intake of the bowel cleansing preparation according to the given instructions. On the following day (day 2), the patients returned to the clinic for colonoscopy. The investigator inquired the subjects about occurrence of any AE and the intake of concomitant medications. It was over these two days the AEs were monitored.

Additional Information

Dr. Richard Jones

Cosmo Pharmaceuticals NV

Phone: +353 18170370

Email: RJones@cosmopharma.com

Results disclosure agreements

• Principal investigator is a sponsor employee Publication to be reviewed by sponsor prior to submission.
• Publication restrictions are in place

Restriction type: OTHER