CB-17-01/08

Cosmo Technologies Ltd

Riverside 2, 49 Sir John Rogerson's Quay, Grand Canal Dock, Dublin,, Dublin, Ireland, D02 KV60

Study Management Unit, CROSS S.A., +41 916300510, corporate@croalliance.com

Study Management Unit, CROSS S.A., +41 916300510, corporate@croalliance.com

No

No

No

Final

17 Apr 2015

Yes

09 Dec 2014

Yes

09 Dec 2014

No

Evaluation of the effect of a total oral dose of 200 mg of Methylene Blue MMX® tablets on colonic epithelial double-stranded DNA during a full chromoendoscopy in comparison with a standard white light colonoscopy without use of Methylene Blue MMX®.

The colonoscopic exam will be performed according to the standard procedure protocols of the clinic. Blood samples will be collected at Visits 1 and 2 for renal and liver function measurement (creatinine, urea, AST, γ-GT, ALT, total bilirubin, haemoglobin). For patients with abnormal hepatic and renal function post-colonoscopy, a follow-up blood sample will be collected within two weeks after colonoscopy.

15 Apr 2013

No

No

Italy: 13

13

13

0

0

0

0

0

0

6

7

0

Enrolment (overall period)

Non-randomised - controlled

Not applicable

Methylene blue MMX® modified release tablets

MB-MMX

Tablet

Oral use

The patients will receive a 4-L PEG-based bowel cleansing preparation, following the instructions enclosed with the product, starting in the afternoon before the 2nd colonoscopy. The patients, who will receive the bowel cleansing preparation according to a full dose regimen, will start the intake in the afternoon before the colonoscopy day and shall drink at least 250 mL of solution every 15 min, so that the intake is complete 4 h after. The subjects, who will receive the bowel cleansing preparation according to a split dose regimen, will start to drink 250 mL of solution every 15 min in the evening before the colonoscopy day up to approximately 2 or 3 L according to the investigator instructions. The remaining quantity of bowel cleansing preparation will be then drunk in the morning of the colonoscopy day at the same rate, until the intake is complete. During the intake of the bowel cleansing preparation, a total oral dose of 200 mg will be taken by each subject.

Enrolment

Safety set

Safety Set: all subjects who will receive at least one dose of the IMP. This analysis set will be used for safety analyses.

FAS

Full Analysis Set (FAS): all included subjects, who will receive at least one dose of the IMP and will have at least one biopsy for the evaluation of the level of γH2AX. This analysis set will be used for the primary analysis

Per Protocol Set

Per Protocol Set (PP): all included subjects who will fulfil the study protocol requirements in terms of IMP intake and collection of primary analysis data and without major deviations that may affect study results. This analysis set will be used for sensitivity analyses

Enrolled Set

Enrolled Set: all screened subjects. This analysis set will be used for demographic, baseline and background characteristics

Methylene Blue

Safety set

Safety Set: all subjects who will receive at least one dose of the IMP. This analysis set will be used for safety analyses.

FAS

Full Analysis Set (FAS): all included subjects, who will receive at least one dose of the IMP and will have at least one biopsy for the evaluation of the level of γH2AX. This analysis set will be used for the primary analysis

Per Protocol Set

Per Protocol Set (PP): all included subjects who will fulfil the study protocol requirements in terms of IMP intake and collection of primary analysis data and without major deviations that may affect study results. This analysis set will be used for sensitivity analyses

Enrolled Set

Enrolled Set: all screened subjects. This analysis set will be used for demographic, baseline and background characteristics

Evaluation, by histone γH2AX analysis, of the effect of a total oral dose of 200 mg of Methylene Blue MMX® tablets on colonic epithelial double-stranded DNA in colonic biopsy samples collected during chromoendoscopy as compared to control biopsies collect. At both colonoscopies, the γH2AX assay was negative for all the colonic regions, for all the analysed subjects (N=10, safety set). The occurrence of any DNA double strand damage could be excluded at each of the performed colonoscopies on the basis of the γH2AX analysis result.

Primary

Following the colonoscopy.

The statistical analysis was performed using SAS® version 9.3 (TS1M1). The data documented in this trial and the clinical parameters measured were described using classic descriptive statistics for quantitative variables and frequencies for qualitative variables.

Methylene Blue v Safety set

20

Pre-specified

On average, the staining quality of the colonic mucosa was acceptable (i.e. at least the 50% of colon mucosa is stained=score 3) in the ascending, transverse and descending colon both in terms of mean and of median SC. On average, the staining quality of rectosigmoid was detectable (i.e. at least the 25% of colon mucosa is stained=score 2). The majority of subjects (40.0% of the subjects) had NSA of 2 regions. The frequency of NSA of 3 or 4 regions was 20.0% (2 subjects each). TSC had a mean ± SD of 11.0±3.4.

Secondary

Following the colonoscopy

During the study

No serious AEs (SAEs) occurred throughout the study. Eight (8) out of the 10 subjects (80%) in the safety set experienced at least one TEAE, for a total of 13 TEAEs. The investigator judged only one of the 13 reported TEAEs as unrelated to the treatment in 1 subject (10%). One PTAE occurred during the study.

17.1

Pre-Treatment-emergent adverse events

Treatment Emergent Adverse Event