Colon Staining in Preparation for Colonoscopy
Conditions
Brief summary
To describe and evaluate the mucosal staining efficacy of Methylene Blue MMX® tablets after total oral doses of 150 or 200 mg in patients undergoing a full colonoscopy for various reasons.
Detailed description
Objectives: To describe and evaluate the mucosal staining efficacy of Methylene Blue MMX® tablets after total oral doses of 150 or 200 mg in patients undergoing a full colonoscopy for various reasons. Primary end-point(s): To evaluate the mucosal staining efficacy of Methylene Blue MMX® tablets after total oral doses of 150 or 200 mg. Secondary end-point(s): Bowel cleansing quality evaluated according to the validated Boston Bowel Preparation Scale (BBPS) after intake of 150 or 200 mg of Methylene Blue MMX® tablets during the intake of the bowel cleansing preparation. To collect data about safety and tolerability of Methylene Blue MMX® tablets after administration of single oral doses of 150 or 200 mg. Methodology: Open label, staining efficacy exploratory study.
Interventions
DRUGMethylene Blue MMX 25 mg modified release tablets
Methylene Blue MMX 25 mg modified release tablets administered with a full dose regimen of a 4-L PEG-based bowel cleansing preparation.
Sponsors
Cross S.A.
Cosmo Technologies Ltd
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Masking description
None. Open label
Intervention model description
Open label, staining efficacy exploratory study.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
1. Sex: males and females; 2. Age:18 to 70 years; 3. Colonoscopy: out-patients with indication for colonoscopy including faecal occult blood test positive colorectal cancer screening, polypectomy follow-up and inflammatory bowel disease check; 4. Contraception: either sterile subjects or subjects practising at least one reliable methods of contraception or in post-menopausal status for at least 1 year; 5. Informed Consent: signed written informed consent prior to inclusion in the study.
Exclusion criteria
1. Pregnancy: pregnant or lactating women or at a risk of becoming pregnant; 2. Allergy: known or suspected hypersensitivity to the active principle and/or formulations' ingredients; history of anaphylaxis to drugs or allergic reactions in general; 3. Diseases: known or suspected gastrointestinal obstruction or perforation, toxic megacolon, major colonic resection, inflammatory bowel diseases in active phase, severe diverticulosis with diverticulitis, heart failure (Class III or IV), serious cardiovascular disease, severe liver failure, end-stage renal insufficiency, any other relevant disease that might interfere with the aim of the study. 4. Comprehension: inability to comprehend the full nature and purpose of the study and unwillingness to co-operate with the Investigator and to comply with the requirements of the entire study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of Mucosal Staining Efficacy | One day- mucosal staining efficacy is assessed during the colonoscopy procedure | Mucosal staining efficacy of Methylene Blue MMX tablets after total oral doses of 150 or 200 mg. Methylene blue staining efficacy was assessed by scoring the observed percentage of staining as reported below for each colon region (AC, TC, DC, RES) 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. \- over stained ( the 100% of the colon mucosa is over stained) After scoring (SC) separately each colonic segment, the total staining score (TSC) was also calculated and the number of regions with an SC\>2 (NSA) was determined. For each patient, the best effective TSC was set at 16, when SC=4 was detected in all 4 regions. SC=5 detected in any region and TSC\>16, both denoting an overstaining of the mucosa, were defined as suboptimal results in colon staining. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability of Methylene Blue MMX as Determined by AEs | Until study completion (until 2 days after dose) | Safety and tolerability of Methylene Blue MMX® tablets after administration of total oral doses of 150 or 200 mg.AEs were assessed throughout the study. |
| Safety and Tolerability of Methylene Blue MMX as Determined by Heart Rate | until study completion (until 2 days after dose) | incidence of treatment emergent by measurement of vital signs (heart rate) to determine Safety and Tolerability of Methylene Blue MMX |
| Safety and Tolerability of Methylene Blue MMX as Determined by Vital Signs (Blood Pressure) | until study completion (until 2 days after dose) | safety and tolerability of Methylene Blue MMX reviewed by incidence of treatment emergent by measurement of vital signs (blood pressure) |
| Safety and Tolerability of Methylene Blue MMX as Determined Body Weight. | until study completion (until 2 days after dose) | safety and tolerability of Methylene Blue MMX in relation to incidence of treatment emergent by body weight. |
| Bowel Cleansing Quality-Boston Bowel Preparation Score | One day- bowel cleansing quality is assessed during the colonoscopy procedure | Bowel cleansing quality evaluated according to the validated Boston Bowel Preparation Scale (BBPS). Colon was divided into 4 target regions: ascending colon (AC), transverse colon (TC), descending colon (DC) and rectosigmoid (RES). Methylene blue staining efficacy was assessed scoring the observed staining percentage as reported below for each colon region: 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. \- over stained ( the 100% of the colon mucosa is over stained) |
| Safety and Tolerability of Methylene Blue MMX as Determined by Vital Signs (Oxygen Saturation in Peripheral Blood) | until study completion (until 2 days after dose) | safety and tolerability of Methylene Blue MMX reviewed by incidence of treatment emergent by measurement of vital signs (Oxygen Saturation in peripheral blood) |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Methylene Blue MMX 150mg Patients under going Colonoscpy taking Methylene Blue-MMX tablets equivalent to 150 mg | 24 |
| Methylene Blue MMX 200mg Patients under going Colonoscpy taking Methylene Blue-MMX tablets equivalent to 200 mg | 88 |
| Total | 112 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 0 | 2 |
Baseline characteristics
| Characteristic | Methylene Blue MMX 150mg | Methylene Blue MMX 200mg | Total |
|---|---|---|---|
| Age, Continuous | 50.4 years STANDARD_DEVIATION 11 | 55.6 years STANDARD_DEVIATION 11.2 | 54.5 years STANDARD_DEVIATION 11.3 |
| Body Weight | 68 Kg STANDARD_DEVIATION 13.3 | 70.6 Kg STANDARD_DEVIATION 14.2 | 69 Kg STANDARD_DEVIATION 14 |
| Height | 166.5 Centimetres STANDARD_DEVIATION 8.4 | 168.5 Centimetres STANDARD_DEVIATION 8.7 | 167.4 Centimetres STANDARD_DEVIATION 8.7 |
| Sex: Female, Male Female | 11 Participants | 35 Participants | 46 Participants |
| Sex: Female, Male Male | 13 Participants | 53 Participants | 66 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 24 | 2 / 88 |
| serious Total, serious adverse events | 0 / 24 | 0 / 88 |
Outcome results
Primary
Evaluation of Mucosal Staining Efficacy
Mucosal staining efficacy of Methylene Blue MMX tablets after total oral doses of 150 or 200 mg. Methylene blue staining efficacy was assessed by scoring the observed percentage of staining as reported below for each colon region (AC, TC, DC, RES) 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. \- over stained ( the 100% of the colon mucosa is over stained) After scoring (SC) separately each colonic segment, the total staining score (TSC) was also calculated and the number of regions with an SC\>2 (NSA) was determined. For each patient, the best effective TSC was set at 16, when SC=4 was detected in all 4 regions. SC=5 detected in any region and TSC\>16, both denoting an overstaining of the mucosa, were defined as suboptimal results in colon staining.
Time frame: One day- mucosal staining efficacy is assessed during the colonoscopy procedure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| A (Dose:150mg) | Evaluation of Mucosal Staining Efficacy | 6.8 scores on a scale | Standard Deviation 4 |
| B (Dose:150mg) | Evaluation of Mucosal Staining Efficacy | 2.3 scores on a scale | Standard Deviation 2.4 |
| C (Dose:150mg) | Evaluation of Mucosal Staining Efficacy | 8.1 scores on a scale | Standard Deviation 3.6 |
| D (Dose:200mg) | Evaluation of Mucosal Staining Efficacy | 7.0 scores on a scale | Standard Deviation 5 |
| E (Dose:200mg) | Evaluation of Mucosal Staining Efficacy | 9.8 scores on a scale | Standard Deviation 4.1 |
| F (Dose:200mg) | Evaluation of Mucosal Staining Efficacy | 10.5 scores on a scale | Standard Deviation 4.1 |
| G (Dose 200mg) | Evaluation of Mucosal Staining Efficacy | 10.5 scores on a scale | Standard Deviation 7.8 |
| H (Dose:200mg) | Evaluation of Mucosal Staining Efficacy | 10.0 scores on a scale | Standard Deviation 3.2 |
| I (Dose:200mg) | Evaluation of Mucosal Staining Efficacy | 11.4 scores on a scale | Standard Deviation 3.8 |
| J (Dose:200mg) | Evaluation of Mucosal Staining Efficacy | 11.6 scores on a scale | Standard Deviation 3.5 |
Secondary
Bowel Cleansing Quality-Boston Bowel Preparation Score
Bowel cleansing quality evaluated according to the validated Boston Bowel Preparation Scale (BBPS). Colon was divided into 4 target regions: ascending colon (AC), transverse colon (TC), descending colon (DC) and rectosigmoid (RES). Methylene blue staining efficacy was assessed scoring the observed staining percentage as reported below for each colon region: 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. \- over stained ( the 100% of the colon mucosa is over stained)
Time frame: One day- bowel cleansing quality is assessed during the colonoscopy procedure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| A (Dose:150mg) | Bowel Cleansing Quality-Boston Bowel Preparation Score | 5.4 Colon cleansing score | Standard Deviation 1.7 |
| B (Dose:150mg) | Bowel Cleansing Quality-Boston Bowel Preparation Score | 5.4 Colon cleansing score | Standard Deviation 1.1 |
| C (Dose:150mg) | Bowel Cleansing Quality-Boston Bowel Preparation Score | 5.4 Colon cleansing score | Standard Deviation 1.2 |
Secondary
Safety and Tolerability of Methylene Blue MMX as Determined Body Weight.
safety and tolerability of Methylene Blue MMX in relation to incidence of treatment emergent by body weight.
Time frame: until study completion (until 2 days after dose)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| A (Dose:150mg) | Safety and Tolerability of Methylene Blue MMX as Determined Body Weight. | 67.2 Kg | Standard Deviation 13 |
| B (Dose:150mg) | Safety and Tolerability of Methylene Blue MMX as Determined Body Weight. | 71.3 Kg | Standard Deviation 15.9 |
| C (Dose:150mg) | Safety and Tolerability of Methylene Blue MMX as Determined Body Weight. | 67.4 Kg | Standard Deviation 13 |
| D (Dose:200mg) | Safety and Tolerability of Methylene Blue MMX as Determined Body Weight. | 71.2 Kg | Standard Deviation 15.8 |
Secondary
Safety and Tolerability of Methylene Blue MMX as Determined by AEs
Safety and tolerability of Methylene Blue MMX® tablets after administration of total oral doses of 150 or 200 mg.AEs were assessed throughout the study.
Time frame: Until study completion (until 2 days after dose)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| A (Dose:150mg) | Safety and Tolerability of Methylene Blue MMX as Determined by AEs | 3 Participants |
| B (Dose:150mg) | Safety and Tolerability of Methylene Blue MMX as Determined by AEs | 3 Participants |
| C (Dose:150mg) | Safety and Tolerability of Methylene Blue MMX as Determined by AEs | 0 Participants |
| D (Dose:200mg) | Safety and Tolerability of Methylene Blue MMX as Determined by AEs | 0 Participants |
| E (Dose:200mg) | Safety and Tolerability of Methylene Blue MMX as Determined by AEs | 0 Participants |
| F (Dose:200mg) | Safety and Tolerability of Methylene Blue MMX as Determined by AEs | 0 Participants |
Secondary
Safety and Tolerability of Methylene Blue MMX as Determined by Heart Rate
incidence of treatment emergent by measurement of vital signs (heart rate) to determine Safety and Tolerability of Methylene Blue MMX
Time frame: until study completion (until 2 days after dose)
Population: Safety population: the safety population was defined as all enrolled subjects who received at least one dose of the study drug. This population was used for safety evaluation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| A (Dose:150mg) | Safety and Tolerability of Methylene Blue MMX as Determined by Heart Rate | 73.9 beats per minute (BPM) | Standard Deviation 10.6 |
| B (Dose:150mg) | Safety and Tolerability of Methylene Blue MMX as Determined by Heart Rate | 75.2 beats per minute (BPM) | Standard Deviation 15.1 |
| C (Dose:150mg) | Safety and Tolerability of Methylene Blue MMX as Determined by Heart Rate | 74.3 beats per minute (BPM) | Standard Deviation 10.9 |
| D (Dose:200mg) | Safety and Tolerability of Methylene Blue MMX as Determined by Heart Rate | 75.3 beats per minute (BPM) | Standard Deviation 15.1 |
| E (Dose:200mg) | Safety and Tolerability of Methylene Blue MMX as Determined by Heart Rate | 74.2 beats per minute (BPM) | Standard Deviation 10.9 |
| F (Dose:200mg) | Safety and Tolerability of Methylene Blue MMX as Determined by Heart Rate | 7.1 beats per minute (BPM) | Standard Deviation 15.1 |
Secondary
Safety and Tolerability of Methylene Blue MMX as Determined by Vital Signs (Blood Pressure)
safety and tolerability of Methylene Blue MMX reviewed by incidence of treatment emergent by measurement of vital signs (blood pressure)
Time frame: until study completion (until 2 days after dose)
Population: Safety population: the safety population was defined as all enrolled subjects who received at least one dose of the study drug. This population was used for safety evaluation
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| A (Dose:150mg) | Safety and Tolerability of Methylene Blue MMX as Determined by Vital Signs (Blood Pressure) | Diastolic Blood Pressure(mmHg) | 74.7 mmHg | Standard Deviation 8.1 |
| A (Dose:150mg) | Safety and Tolerability of Methylene Blue MMX as Determined by Vital Signs (Blood Pressure) | Systolic Blood Pressure (mmHg) | 122.6 mmHg | Standard Deviation 14.6 |
| B (Dose:150mg) | Safety and Tolerability of Methylene Blue MMX as Determined by Vital Signs (Blood Pressure) | Diastolic Blood Pressure(mmHg) | 74.0 mmHg | Standard Deviation 11.9 |
| B (Dose:150mg) | Safety and Tolerability of Methylene Blue MMX as Determined by Vital Signs (Blood Pressure) | Systolic Blood Pressure (mmHg) | 124.3 mmHg | Standard Deviation 17.7 |
| C (Dose:150mg) | Safety and Tolerability of Methylene Blue MMX as Determined by Vital Signs (Blood Pressure) | Systolic Blood Pressure (mmHg) | 122.6 mmHg | Standard Deviation 14.6 |
| C (Dose:150mg) | Safety and Tolerability of Methylene Blue MMX as Determined by Vital Signs (Blood Pressure) | Diastolic Blood Pressure(mmHg) | 74.9 mmHg | Standard Deviation 8.2 |
| D (Dose:200mg) | Safety and Tolerability of Methylene Blue MMX as Determined by Vital Signs (Blood Pressure) | Systolic Blood Pressure (mmHg) | 124.3 mmHg | Standard Deviation 17.7 |
| D (Dose:200mg) | Safety and Tolerability of Methylene Blue MMX as Determined by Vital Signs (Blood Pressure) | Diastolic Blood Pressure(mmHg) | 74.0 mmHg | Standard Deviation 11.9 |
| E (Dose:200mg) | Safety and Tolerability of Methylene Blue MMX as Determined by Vital Signs (Blood Pressure) | Systolic Blood Pressure (mmHg) | 122.7 mmHg | Standard Deviation 14.5 |
| E (Dose:200mg) | Safety and Tolerability of Methylene Blue MMX as Determined by Vital Signs (Blood Pressure) | Diastolic Blood Pressure(mmHg) | 75 mmHg | Standard Deviation 8.2 |
| F (Dose:200mg) | Safety and Tolerability of Methylene Blue MMX as Determined by Vital Signs (Blood Pressure) | Diastolic Blood Pressure(mmHg) | 74.0 mmHg | Standard Deviation 11.9 |
| F (Dose:200mg) | Safety and Tolerability of Methylene Blue MMX as Determined by Vital Signs (Blood Pressure) | Systolic Blood Pressure (mmHg) | 124.2 mmHg | Standard Deviation 17.7 |
Secondary
Safety and Tolerability of Methylene Blue MMX as Determined by Vital Signs (Oxygen Saturation in Peripheral Blood)
safety and tolerability of Methylene Blue MMX reviewed by incidence of treatment emergent by measurement of vital signs (Oxygen Saturation in peripheral blood)
Time frame: until study completion (until 2 days after dose)
Population: Safety population: the safety population was defined as all enrolled subjects who received at least one dose of the study drug. This population was used for safety evaluation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| A (Dose:150mg) | Safety and Tolerability of Methylene Blue MMX as Determined by Vital Signs (Oxygen Saturation in Peripheral Blood) | 98.4 percentage of saturation | Standard Deviation 1.8 |
| B (Dose:150mg) | Safety and Tolerability of Methylene Blue MMX as Determined by Vital Signs (Oxygen Saturation in Peripheral Blood) | 98.7 percentage of saturation | Standard Deviation 6.6 |
| C (Dose:150mg) | Safety and Tolerability of Methylene Blue MMX as Determined by Vital Signs (Oxygen Saturation in Peripheral Blood) | 98.4 percentage of saturation | Standard Deviation 1.8 |
| D (Dose:200mg) | Safety and Tolerability of Methylene Blue MMX as Determined by Vital Signs (Oxygen Saturation in Peripheral Blood) | 98.8 percentage of saturation | Standard Deviation 6.5 |
| E (Dose:200mg) | Safety and Tolerability of Methylene Blue MMX as Determined by Vital Signs (Oxygen Saturation in Peripheral Blood) | 98.4 percentage of saturation | Standard Deviation 1.8 |
| F (Dose:200mg) | Safety and Tolerability of Methylene Blue MMX as Determined by Vital Signs (Oxygen Saturation in Peripheral Blood) | 98.8 percentage of saturation | Standard Deviation 6.5 |