Effect of Oral Administration of Methylene Blue MMX Tablets on Double Stranded DNA

Primary Objective: To evaluate the effect of oral 200 mg Methylene Blue MMX® tablets, (administered as 8 x 25 mg), prior to endoscopy, on double-stranded DNA breaks in colonic biopsy samples assessed by histone γH2AX analysis, compared to control biopsies collected during standard white light colonoscopy without the prior use of Methylene Blue MMX®.

Secondary Objectives : To evaluate the safety and tolerability of oral Methylene Blue MMX® tablets.. To evaluate the staining score for colonoscopy obtained with oral Methylene Blue MMX® tablets . Time to reach the caecum during colonoscopy and withdrawal time from caecum to exit.

Inclusion criteria

• Males or females, aged between 18 and 75.
• Outpatients scheduled for screening or surveillance colonoscopy
• Subjects must be identified as having the clinical requirement for second colonoscopy within 2weeks of the initial colonoscopy.
• Women of childbearing potential must use at least one reliable method of contraception, be surgically sterilised or be abstinent.
• For female subjects, a negative serum pregnancy test is required before Methylene Blue MMX® tablets are dispensed to the subject.
• Post menopausal patients need to have a period of greater than 1year since last menstrual period.
• Subjects must be able to comprehend the full nature and purpose of the study, including possible risks and side effects.
• Subjects must be able to co-operate with the investigator and to comply with the requirements of the entire study.
• Signed written informed consent prior to inclusion in the study.

Exclusion criteria

• No Pregnant or lactating women, or women undergoing fertility treatment.
• No previous medical history of, or suspected hypersensitivity to the Methylene Blue and/or this formulations ingredients.
• No previous medical history of, or suspected hypersensitivity to the PEG based bowel cleansing preparation and/or this formulations ingredients.
• No previous medical history of gastrointestinal obstruction or perforation, toxic megacolon, major colonic resection, severe diverticulitis, heart failure (Class III or IV), serious cardiovascular disease.
• No ALT, AST, GGT, Bilirubin, Creatinine or Urea greater than 2.5 x the upper limit for normal, based on local laboratory testing.
• No clinical alarm symptoms or history of anaemia (previously recorded haemoglobin of less than 10mg/dL) or frank blood in the stool within the last 30 days prior to enrolment.
• No known deficiency of glucose-6-phosphate dehydrogenase.
• No known deficiency of NADPH reductase.
• No treatment within 5 weeks prior to randomisation with Fluoxetine (Prozac).
• No concurrent treatment, or previous treatment within 2 weeks with any of the prohibited psychiatric medications that may interact with Methylene Blue as listed in the Prohibited Medications section; Selective Serotonin Reuptake Inhibitors (SSRI), Serotonin-Norepinepherine Reuptake Inhibitors (SNRI's), listed Tricyclic anti-depressants or Monoamine oxidase A inhibitors.
• No concurrent treatment with anticoagulants, or antiaggregants, inducing an INR > 1.5.
• No current enrolment in any other clinical trial, or previous enrolment in a clinical trial within the last 30 days.
• No other medical condition that in the investigators opinion would make the administration of the study drug or procedures hazardous to the subject.

Exclusion criteria

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