Efficacy, Safety and Tolerability of Eziclen®/Izinova® Versus Klean-prep® on Bowel Cleansing in Adolescents Undergoing Colonoscopy

Blinded overall assessment of preparation efficacy (Cleansing Score) was determined by the colonoscopist upon completion of the examination, based on a 4-point scale as follows:

• 4 (Excellent) = No more than small bits of adherent faeces/fluid
• 3 (Good) = Small amounts of faeces or fluid not interfering with examination
• 2 (Fair) = Enough faeces or fluid to prevent a completely reliable examination
• 1 (Poor) = Large amounts of faecal residue, additional cleansing required.

Only perfect preparations graded as excellent (4) or good (3), which allowed full, reliable examination of the mucosa were considered as successful. The adjusted percentage of subjects with a successful preparation was determined using a logistic regression model, including treatment and country as covariates.

The Cleansing Score was determined by the blinded colonoscopist, based on a 4-point scale as follows:

• 4 (Excellent) = No more than small bits of adherent faeces/fluid
• 3 (Good) = Small amounts of faeces or fluid not interfering with examination
• 2 (Fair) = Enough faeces or fluid to prevent a completely reliable examination
• 1 (Poor) = Large amounts of faecal residue, additional cleansing required.

The adjusted mean score was estimated using a 2-way analysis of variance (ANOVA), including treatment and country as covariates.

The BBPS score for each colon segment (left, transverse, right) was determined by the blinded colonoscopist as follows:

• 0 = Unprepared colon segment with mucosa not seen due to solid stool that cannot be cleared
• 1 = Portion of mucosa of the segment seen, but other areas of the colon segment not well seen due to staining, residual stool and/or opaque liquid
• 2 = Minor amount of residual staining, small fragments of stool and/or opaque liquid, but mucosa of segment seen well
• 3 = Entire mucosa of segment seen well with no residual staining, small fragments of stool and/or opaque liquid.

Each segment score ranged from 0-3. Global score was sum of the 3 segment scores and ranged from 0-9 (worst to best). Successful colon cleansing was defined as a global BBPS score ≥6. The adjusted mean score was estimated using a 2-way ANOVA, including treatment and country as covariates.

The percentage of subjects who needed rescue treatment (saline enema) prior to colonoscopy because of inadequate preparation intake was assessed.

The percentage of subjects who needed placement of a nasogastric tube to achieve administration of the complete preparation was assessed.

The percentage of subjects with a complete colonoscopy, defined as a procedure that reached the caecum, was assessed.

The time to caecal intubation was defined as the time from colonoscope introduction to caecal intubation, estimated using the Kaplan-Meier product limit method. In the event the procedure did not reach the caecum, the subject was censored at time of withdrawal of colonoscope.

The duration of examination for colonoscopy (in minutes) was measured by the difference between the time of caecum intubation and the time of withdrawal of the colonoscope. The adjusted mean duration of examination was estimated using a 2-way ANOVA, including treatment and country as covariates. Subjects for whom the caecum was not reached were excluded from the analysis.

The Treatment Acceptability Questionnaire was completed by the caregiver or subject after the subject ended the intake of preparation. Subject acceptability was rated as follows:

• 1 = Very badly accepted/unacceptable
• 2 = Badly but accepted
• 3 = Neither good nor bad
• 4 = Well accepted
• 5 = Very well accepted.

Overall acceptability score is the average of scores from the 2 doses ranging from 1 - 5 (worst to best). The adjusted mean score was estimated using a 2-way ANOVA, including treatment and country as covariates.

Treatment compliance according the instructions of use provided in the prescription was assessed as the percentage of volume of fluid taken relative to the planned volume of fluid to be taken (measured by the caregiver and reported in the treatment questionnaire of subject's leaflet during treatment administration). Overall treatment compliance was derived from the total volumes of fluid (i.e. preparation + hydration for Eziclen®/Izinova® and preparation only for Klean-Prep®) and was assessed for dose 1, dose 2 and globally (accounting for both doses). The adjusted mean overall treatment compliance (%) was estimated using a 2-way ANOVA, including treatment and country as covariates.

Tolerability was assessed using a Symptom Scale after each dose of treatment for stomach cramping, stomach bloating and nausea on a paediatric 5-point scale as follows:

• 1 = No symptom
• 2 = Mild
• 3 = Bothersome
• 4 = Distressing
• 5 = Severely distressing symptoms.

The total tolerability score is the sum of the scores for the 3 symptoms ranging from 3 to 15 (best to worst). Mean total tolerability scores after dose 1 and dose 2 are presented.

The time to clear effluent, as reported by the subject, was defined as the time between first intake of prescription and first clear watery stool, estimated using the Kaplan-Meier product limit method. In the event of no clear watery stools, subjects with colonoscopy were censored at the time of colonoscope introduction, and subjects without colonoscopy were censored at time of start of treatment + 12 hours. Although time to clear effluent was pre-specified as a secondary endpoint in the study protocol, in a change to the planned analysis, it was subsequently analysed and reported as an 'other' efficacy endpoint.

The time between the end of treatment administration (on Day 1) and the start of colonoscopy (on Day 2) was determined. The adjusted mean time between the last intake of fluids and the start of colonoscopy procedure was estimated using a 2-way ANOVA, including treatment and country as covariates.