E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Polyp and adenoma detection during colonoscopy |
|
E.1.1.1 | Medical condition in easily understood language |
Abnormal growth of tissue detection during colonoscopy |
|
E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Diagnosis [E01] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Evaluation of the histologically proven adenoma and carcinoma detection rate in patients undergoing a full colonoscopy with and without mucosal contrast enhancement, obtained with 200 mg of Methylene Blue MMX® tablets. The lack of mucosal contrast, obtained with placebo tablets is equivalent to a standard white light colonoscopy endoscopic procedure- the current standard of care. |
|
E.2.2 | Secondary objectives of the trial |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Males or females, aged between 50 and 75. • Outpatients scheduled for screening or surveillance colonoscopy for polyps or colorectal cancer. • Able to comprehend the full nature and purpose of the study, including possible risks and side effects. • 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.
|
|
E.4 | Principal exclusion criteria |
• Patients at high risk of colorectal cancer e.g. ulcerative colitis • Previous medical history of, or suspected hypersensitivity to, the Methylene Blue and/or formulations' ingredients. • Previous medical history of, or suspected hypersensitivity to, the PEG based bowel cleansing preparation and/or bowel cleansing formulations' ingredients. • Previous medical history of gastrointestinal obstruction or perforation, toxic megacolon, major colonic resection, severe diverticulitis, heart failure (Class III or IV), serious cardiovascular disease, ulcerative colitis or Crohn’s disease. • ALT, AST, GGT, Bilirubin, Creatinine or Urea greater than 2.5 x the upper limit for normal range, based on local laboratory testing. • The presence of serious cardiovascular disease, including very large abdominal aortic aneurysms (particularly if they are symptomatic), patients who are immediately postoperative, and patients who have suffered recent myocardial infarction (within 3 weeks), pulmonary embolism, or are currently hemodynamically unstable. • The presence of liver disease with coagulopathy • A history of anaemia (previously recorded haemoglobin of less than 10mg/dL) within the last 30 days prior to enrollment. • Known evidence of glucose-6-phosphate deficiency, • Known deficiency of NADPH reductase • Treatment within 5 weeks prior to randomisation with Fluoxetine (Prozac). • Concurrent treatment, or previous treatment within 2 weeks with any of the prohibited psychiatric medications that may interact with Methylene Blue as listed under Prohibited medications; Selective Serotonin Reuptake Inhibitors (SSRI), Serotonin-Norepinepherine Reuptake Inhibitors (SNRI’s), listed Tricyclic anti-depressants or Monoamine oxidase A inhibitors. • Current enrollment in any other clinical trial, or previous enrollment in a clinical trial within the last 30 days. • Other medical condition that in the investigators opinion would make the administration of the study drug or procedures hazardous to the subject. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary end-point of this study is to assess the detection efficacy of chromoendoscopy performed with 200mg Methylene Blue MMX® 25 mg tablets versus placebo tablets (white light endoscopy) in terms of the proportion of subjects with at least one histologically proven Adenoma or Carcinoma.
Adenoma is defined as a histologically proven Vienna Grade 3 to 4.2 or a histologically proven traditional serrated adenoma (TSA), or a histologically proven sessile serrated adenoma (SSA),-Histologically proven Carcinomacarcinoma is defined as Vienna Grade 4.3 to 5b.
The Vienna Classification will be made by blinded central laboratory pathologists who will review slides prepared from an additional tissue section of each paraffin embedded specimen prepared at the local site laboratory in accordance with the histology charter. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
The secondary endpoints will be evaluated in all study groups, i.e. 200mg, 100mg MMX and placebo groups.
Secondary end-points of this study are the following: > False positive rate between treatment and placebo control arms; the rate being defined as the proportion of patients with no histologically confirmed Adenoma or Carcinoma within any of the subjects excised lesions and the subject having undergone at least one excision (see 16.3) > Proportion of subjects with at least one histologically proven Adenoma; > Proportion of subjects with at least one histologically proven Carcinoma. > Number of histologically proven Adenomas Vienna categories 3, 4.1 and 4.2 or a histologically proven traditional serrated adenoma (TSA), or a histologically proven sessile serrated adenoma (SSA)) and Carcinomas (Vienna categories 4.3, 4.4, 5.a and 5.b) detected per subject. > Number of histologically proven hyperplastic polyps, fibroblastic polyps and mixed polyps detected per subject; > Adverse events; > Vital signs during colonoscopy (Systolic blood pressure, Diastolic blood pressure, Heart rate and Oxygen saturation); > Renal and liver function tests (Creatinine, Urea, AST, GGT, ALT and Total Bilirubin) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 11 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Belgium |
Canada |
Germany |
Italy |
Lithuania |
Netherlands |
United Kingdom |
United States |
|
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |