Colon Staining Efficacy of Single Oral Doses of Methylene Blue MMX

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.

• Methylene Blue MMX 25 mg modified release tablets (Drug): Methylene Blue MMX 25 mg modified release tablets administered with a full dose regimen of a 4-L PEG-based bowel cleansing preparation.

Primary outcomes

• 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 outcomes

• 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 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 (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)
• 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)

Sex: All, ages: 18 Years to 70 Years, accepts healthy volunteers

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.

Participant flow

Outcome results

• Evaluation of Mucosal Staining Efficacy (Primary), Mean, scores on a scale: A (Dose:150mg) 6.8 +/- 4.0; B (Dose:150mg) 2.3 +/- 2.4; C (Dose:150mg) 8.1 +/- 3.6; D (Dose:200mg) 7.0 +/- 5.0; E (Dose:200mg) 9.8 +/- 4.1; F (Dose:200mg) 10.5 +/- 4.1; G (Dose 200mg) 10.5 +/- 7.8; H (Dose:200mg) 10.0 +/- 3.2; I (Dose:200mg) 11.4 +/- 3.8; J (Dose:200mg) 11.6 +/- 3.5
• Safety and Tolerability of Methylene Blue MMX as Determined by Vital Signs (Blood Pressure) (Secondary), Mean, mmHg: Pre Colonoscopy - 150mg Dose 122.6 +/- 14.6; Pre Colonoscopy- 200mg Dose 124.3 +/- 17.7; During Colonoscopy- 150mg Dose 122.6 +/- 14.6; During Colonoscopy- 200mg Dose 124.3 +/- 17.7; Post Colonoscopy- 150mg Dose 122.7 +/- 14.5; Post Colonoscopy- 200mg Dose 124.2 +/- 17.7
• Safety and Tolerability of Methylene Blue MMX as Determined by AEs (Secondary), Count of participants, Participants: Pre Colonoscopy - 150mg Dose 3; Pre Colonoscopy- 200mg Dose 3; During Colonoscopy- 150mg Dose 0; During Colonoscopy- 200mg Dose 0; Post Colonoscopy- 150mg Dose 0; Post Colonoscopy- 200mg Dose 0
• Safety and Tolerability of Methylene Blue MMX as Determined by Heart Rate (Secondary), Mean, beats per minute (BPM): Pre Colonoscopy - 150mg Dose 73.9 +/- 10.6; Pre Colonoscopy- 200mg Dose 75.2 +/- 15.1; During Colonoscopy - 150mg Dose 74.3 +/- 10.9; During Colonoscopy- 200mg Dose 75.3 +/- 15.1; Post Colonoscopy- 150mg Dose 74.2 +/- 10.9; Post Colonoscopy- 200mg Dose 7.1 +/- 15.1
• Safety and Tolerability of Methylene Blue MMX as Determined by Vital Signs (Oxygen Saturation in Peripheral Blood) (Secondary), Mean, percentage of saturation: Pre Colonoscopy - 150mg Dose 98.4 +/- 1.8; Pre Colonoscopy- 200mg Dose 98.7 +/- 6.6; During Colonoscopy- 150mg Dose 98.4 +/- 1.8; During Colonoscopy- 200mg Dose 98.8 +/- 6.5; Post Colonoscopy- 150mg Dose 98.4 +/- 1.8; Post Colonoscopy- 200mg Dose 98.8 +/- 6.5
• Safety and Tolerability of Methylene Blue MMX as Determined Body Weight. (Secondary), Mean, Kg: Visit 1-Screening 150mL 67.2 +/- 13.0; Visit 1-Screening 200mL 71.3 +/- 15.9; Visit 2-Final 150mL 67.4 +/- 13.0; Visit 2-Final 200mL 71.2 +/- 15.8
• Bowel Cleansing Quality-Boston Bowel Preparation Score (Secondary), Mean, Colon cleansing score: 150 mg Methylene Blue-MMX Tablets 5.4 +/- 1.7; 200 mg Methylene Blue-MMX Tablets 5.4 +/- 1.1; Overall 5.4 +/- 1.2

Adverse events

Other adverse events by term