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

Study Overview
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Brief Summary
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The purpose of the protocol is to demonstrate that Eziclen®/Izinova®, an osmotic sulphate-based laxative preparation given on the day before colonoscopy has non-inferior efficacy to Klean-Prep® (polyethylene glycol (PEG)-electrolytes) on colon cleansing in adolescents aged 12 to 17 years (inclusive) with a body weight >40 kg, scheduled to undergo a colonoscopy for a routinely accepted diagnostic indication.

Official Title
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Efficacy, Safety and Tolerability of a Bowel Cleansing Preparation (Eziclen/Izinova®) in Paediatric Subjects Undergoing Colonoscopy: a Phase III, Multicentre, Randomised, Comparative Study Versus Klean-Prep® (PEG-Electrolytes), Administered on the Day Before Colonoscopy, Investigator-blinded, Non-inferiority in Adolescents of 12 to 17 Years of Age (Inclusive) >40 kg

Conditions
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Digestive System Disease

Intervention / Treatment
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* Drug: Eziclen®/Izinova®
* Drug: Klean-Prep®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of signed informed consent form to participate in the study obtained from the adolescent's parent(s)/ legal representative and a signed assent form from the adolescent according to local law Male or female subjects between 12 to 17 years of age (inclusive) Body weight more than 40 kg Female of childbearing potential must have a negative pregnancy test If female, and of child-bearing potential, subject must use an acceptable form of birth control (hormonal birth control, intrauterine device (IUD), double-barrier method, or depot contraceptive) Routinely accepted indication for undergoing colonoscopy, including but not limited to polyposis coli diagnosis or surveillance, gastrointestinal bleeding, unexplained diarrhoea or constipation, surveillance of inflammatory bowel disease or confirmation of mucosal healing, abdominal pain, abnormal endosonography or manometry, anaemia of unknown aetiology, cancer surveillance In the investigator's judgment, the parent(s)/legal representative are/is mentally competent to provide informed consent for the subject to participate in the study In the investigator's judgement, subject is able and willing to follow study procedures including drug administration and response to questionnaires Exclusion Criteria: Subject with known or suspected ileus, gastrointestinal obstruction, gastric retention (gastroparesis), rectal impaction, toxic colitis, severe ulcerative colitis or toxic megacolon, advanced carcinoma, swallowing disorders Subject with known or suspected inflammatory bowel disease (Crohn's disease, ulcerative colitis) in moderate to severe active phase defined by Paediatric Crohn's Disease Activity Index (PCDAI) >30 or Paediatric Ulcerative Colitis Index (PUCAI) >34 Subject with bowel perforation or increased risk of bowel perforation, including connective tissue disorders or recent bowel surgery Subject with previous significant gastrointestinal surgery (e.g. colostomy, colectomy, gastric bypass, stomach stapling) Subject with uncontrolled pre-existing electrolyte abnormalities, or with electrolyte abnormalities based on Visit 1 laboratory results such as hypernatremia, hyponatremia, hyperphosphatemia, hypokalaemia, hypocalcaemia, uncorrected dehydration, or secondary to the use of medications such as diuretics or angiotensin converting enzyme inhibitors judged clinically significant by the investigator Subject with a prior history or current condition of severe renal (estimated glomerular filtration rate (GFR) less than 30 mL/min/1.73 m^2 as calculated by using the Schwartz bedside equation* [Schwartz et al, 2009]**), liver (ascites, Child-Pugh C), cardiac insufficiency (including congestive heart failure all grades) or hyperuricemia *The estimated GFR will be calculated in patients with elevated creatinine at baseline **Schwartz GJ and Work DF. Measurement and Estimation of GFR in Children and Adolescents. Clin J Am Soc Nephrol. 2009; 4: 1832-1843 Female subject who is pregnant or lactating Subject who has participated in another investigational drug treatment within the last 90 days before the first study visit Subject with phenylketonuria Subject with history of asthma or hypersensitivity to any ingredient of either drug product Subject for whom intake of substances likely to affect gastrointestinal motility or urinary flow rate is required Subject with requirement to take any other oral medication within 3 hours of starting the bowel preparation, as this may impact medication absorption Subject with tendency for nausea and/or vomiting Subject with impaired consciousness that predisposes them to pulmonary aspiration or who have known swallowing disorders Subject with history of major medical/psychiatric conditions that, in the judgment of the investigator, would compromise safety in the study Subject with mental or psychiatric condition rendering the subject unable to understand the nature, scope and possible consequences of the study, and/or evidence of an uncooperative attitude Subject with a condition that, in the opinion of the investigator, might increase the risk to the subject or decrease the chance of obtaining satisfactory data needed to achieve the objectives of the study Subject who has previous enrolment in this study or concomitant enrolment in other clinical studies

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Eziclen®/Izinova®<br> | Drug: Eziclen®/Izinova®<br>* Oral solution taken the evening before the colonoscopy<br>* Other names: Suprep®;|
| Active Comparator: Klean-Prep®<br> | Drug: Klean-Prep®<br>* Oral solution taken the evening before the colonoscopy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects With Successful Overall Colon Preparation, Assessed With the Cleansing Score (4-point Scale) | 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. | At Day 2 (colonoscopy visit) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Colon Cleansing Score (4-point Scale) | 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. | At Day 2 (colonoscopy visit) | 
| Mean Boston Bowel Preparation Scale (BBPS) Global Score and BBPS Scores by Colon Segment | 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. | At Day 2 (colonoscopy visit) | 
| Percentage of Subjects With Need for Rescue Treatment | The percentage of subjects who needed rescue treatment (saline enema) prior to colonoscopy because of inadequate preparation intake was assessed. | At Day 2 (colonoscopy visit, before colonoscopy) | 
| Percentage of Subjects With Need for Nasogastric Tube To Complete Preparation | The percentage of subjects who needed placement of a nasogastric tube to achieve administration of the complete preparation was assessed. | At Day 1 (treatment visit) | 
| Percentage of Subjects With Colonoscopy Procedure Documented as Completed | The percentage of subjects with a complete colonoscopy, defined as a procedure that reached the caecum, was assessed. | At Day 2 (colonoscopy visit) | 
| Median Time to Caecal Intubation | 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. | From colonoscope introduction to caecal intubation, assessed on Day 2 (colonoscopy visit) | 
| Mean Duration of Examination | 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. | From caecum intubation to withdrawal of the colonoscope, assessed on Day 2 (colonoscopy visit) | 
| Mean Score for Overall Treatment Acceptability, Assessed Using Treatment Acceptability Questionnaire | 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. | At Day 1 (treatment visit) | 
| Mean Overall Treatment Compliance | 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. | At Day 1 (treatment visit) | 
| Mean Subject Tolerability Total Score, Assessed Using a Symptom Scale | 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. | At Day 1 (treatment visit) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bowel preparation