Digestive System Disease
Conditions
Keywords
Bowel preparation
Brief summary
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.
Interventions
Oral solution taken the evening before the colonoscopy
DRUGKlean-Prep®
Oral solution taken the evening before the colonoscopy
Sponsors
Ipsen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Years to 17 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With Successful Overall Colon Preparation, Assessed With the Cleansing Score (4-point Scale) | At Day 2 (colonoscopy visit) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Colon Cleansing Score (4-point Scale) | At Day 2 (colonoscopy visit) | 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. |
| Mean Boston Bowel Preparation Scale (BBPS) Global Score and BBPS Scores by Colon Segment | At Day 2 (colonoscopy visit) | 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. |
| Percentage of Subjects With Need for Rescue Treatment | At Day 2 (colonoscopy visit, before colonoscopy) | The percentage of subjects who needed rescue treatment (saline enema) prior to colonoscopy because of inadequate preparation intake was assessed. |
| Percentage of Subjects With Need for Nasogastric Tube To Complete Preparation | At Day 1 (treatment visit) | The percentage of subjects who needed placement of a nasogastric tube to achieve administration of the complete preparation was assessed. |
| Percentage of Subjects With Colonoscopy Procedure Documented as Completed | At Day 2 (colonoscopy visit) | The percentage of subjects with a complete colonoscopy, defined as a procedure that reached the caecum, was assessed. |
| Mean Overall Treatment Compliance | At Day 1 (treatment visit) | 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. |
| Mean Subject Tolerability Total Score, Assessed Using a Symptom Scale | At Day 1 (treatment visit) | 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. |
| Median Time to Caecal Intubation | From colonoscope introduction to caecal intubation, assessed on Day 2 (colonoscopy visit) | 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. |
| Mean Duration of Examination | From caecum intubation to withdrawal of the colonoscope, assessed on Day 2 (colonoscopy visit) | 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. |
| Mean Score for Overall Treatment Acceptability, Assessed Using Treatment Acceptability Questionnaire | At Day 1 (treatment visit) | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Median Time to Clear Effluent | From first intake of prescription to first clear watery stool, assessed on Day 1 (treatment visit) and Day 2 (colonoscopy visit) | 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. |
| Mean Time Between Last Intake of Fluids and Start of Colonoscopy Procedure | From end of treatment administration to start of colonoscopy, assessed on Day 1 (treatment visit) and Day 2 (colonoscopy visit) | 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. |
Countries
Czechia, France, Germany, Italy, Netherlands, Poland
Participant flow
Recruitment details
This study was conducted in adolescents (aged 12 to 17 years inclusive) who were undergoing a colonoscopy for a routinely accepted diagnostic indication. Subjects were randomised 1:1 to Eziclen®/Izinova® (¾ of adult dose; 750 millilitres \[mL\] of preparation plus 1500 mL of water) or Klean-Prep® (70 mL/kilogram \[kg\]; maximum of 4000 mL). Subjects were randomised at 22 study centres in 6 countries.
Pre-assignment details
The study consisted of a 1-day enrolment (Day 1, baseline) and investigator-blind label dosing period, a colonoscopy (Day 2) and a 30-day follow-up period (Day 32 \[-5/+15, i.e. Day 27 to Day 47\]). Subjects were expected to participate in the study for a minimum of 27 days and up to 47 days.
Participants by arm
| Arm | Count |
|---|---|
| Eziclen®/Izinova® Subjects received Eziclen®/Izinova® oral sulphate salt solution, administered as ¾ of the adult dose, as a 1-day regimen on the evening of the day before colonoscopy (Day 1). The 750 mL preparation was administered in 2 half doses as follows: the first half of preparation (375 mL) was drunk slowly in 30 minutes to 1 hour, followed by 750 mL of water over the next hour. Approximately 2 hours after starting the first half of preparation, the second half (375 mL) was drunk slowly in 30 minutes to 1 hour, followed by 750 mL of water over the next hour. Overall total volume (preparation + water) was 2250 mL (1125 mL per dose). | 125 |
| Klean-Prep® Subjects received Klean-Prep® oral solution, administered as a 70 mL/kg dose (calculated based on subject's weight) as a 1-day regimen on the evening of the day before colonoscopy (Day 1). The whole solution was administered in 2 half doses (1 litre per hour), with a 1-hour pause between the 2 half doses. Approximately 2 hours after starting the first half of preparation, the second half was drunk. The maximum global volume administered was 4000 mL (2000 mL per dose). | 116 |
| Total | 241 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | COVID-19 pandemic - consent withdrawn | 1 | 0 |
| Overall Study | End of study visit outside permitted time window | 0 | 1 |
| Overall Study | Lost to Follow-up | 1 | 3 |
| Overall Study | Protocol deviation | 0 | 2 |
| Overall Study | Study drug not dispensed | 0 | 1 |
| Overall Study | Withdrawal by Subject | 5 | 6 |
Baseline characteristics
| Characteristic | Klean-Prep® | Total | Eziclen®/Izinova® |
|---|---|---|---|
| Age, Continuous | 15.3 years STANDARD_DEVIATION 1.6 | 15.2 years STANDARD_DEVIATION 1.6 | 15.1 years STANDARD_DEVIATION 1.6 |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment Czechia | 3 participants | 6 participants | 3 participants |
| Region of Enrollment France | 9 participants | 18 participants | 9 participants |
| Region of Enrollment Germany | 11 participants | 24 participants | 13 participants |
| Region of Enrollment Italy | 8 participants | 18 participants | 10 participants |
| Region of Enrollment Netherlands | 20 participants | 40 participants | 20 participants |
| Region of Enrollment Poland | 65 participants | 135 participants | 70 participants |
| Sex: Female, Male Female | 47 Participants | 107 Participants | 60 Participants |
| Sex: Female, Male Male | 69 Participants | 134 Participants | 65 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 124 | 0 / 117 |
| other Total, other adverse events | 111 / 124 | 105 / 117 |
| serious Total, serious adverse events | 4 / 124 | 3 / 117 |
Outcome results
Primary
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.
Time frame: At Day 2 (colonoscopy visit)
Population: The modified intention-to-treat population included all randomised subjects who received even a partial dose of study drug and produced a primary efficacy assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Eziclen®/Izinova® | Percentage of Subjects With Successful Overall Colon Preparation, Assessed With the Cleansing Score (4-point Scale) | 71.42 adjusted percentage of subjects |
| Klean-Prep® | Percentage of Subjects With Successful Overall Colon Preparation, Assessed With the Cleansing Score (4-point Scale) | 79.03 adjusted percentage of subjects |
Comparison: Analysis of the treatment difference (Eziclen®/Izinova® minus Klean-Prep®) was performed using a logistic regression model, including treatment and country as covariates.p-value: 0.090795% CI: [-18.45, 3.24]Regression, Logistic
Secondary
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.
Time frame: At Day 2 (colonoscopy visit)
Population: The ITT population included all randomised subjects who received even a partial dose of study drug. Only subjects with data available for each specified parameter were included in the analysis.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Eziclen®/Izinova® | Mean Boston Bowel Preparation Scale (BBPS) Global Score and BBPS Scores by Colon Segment | Left colon | 2.05 scores on a scale |
| Eziclen®/Izinova® | Mean Boston Bowel Preparation Scale (BBPS) Global Score and BBPS Scores by Colon Segment | Transverse colon | 2.25 scores on a scale |
| Eziclen®/Izinova® | Mean Boston Bowel Preparation Scale (BBPS) Global Score and BBPS Scores by Colon Segment | Right colon | 1.92 scores on a scale |
| Eziclen®/Izinova® | Mean Boston Bowel Preparation Scale (BBPS) Global Score and BBPS Scores by Colon Segment | Global score | 6.25 scores on a scale |
| Klean-Prep® | Mean Boston Bowel Preparation Scale (BBPS) Global Score and BBPS Scores by Colon Segment | Global score | 6.61 scores on a scale |
| Klean-Prep® | Mean Boston Bowel Preparation Scale (BBPS) Global Score and BBPS Scores by Colon Segment | Left colon | 2.12 scores on a scale |
| Klean-Prep® | Mean Boston Bowel Preparation Scale (BBPS) Global Score and BBPS Scores by Colon Segment | Right colon | 2.16 scores on a scale |
| Klean-Prep® | Mean Boston Bowel Preparation Scale (BBPS) Global Score and BBPS Scores by Colon Segment | Transverse colon | 2.33 scores on a scale |
Comparison: Left colon:~Analysis of the treatment difference (Eziclen®/Izinova® minus Klean-Prep®) was performed using a 2-way ANOVA, including treatment and country as covariates.p-value: 0.467695% CI: [-0.25, 0.12]ANOVA
Comparison: Transverse colon:~Analysis of the treatment difference (Eziclen®/Izinova® minus Klean-Prep®) was performed using a 2-way ANOVA, including treatment and country as covariates.p-value: 0.307695% CI: [-0.25, 0.08]ANOVA
Comparison: Right colon:~Analysis of the treatment difference (Eziclen®/Izinova® minus Klean-Prep®) was performed using a 2-way ANOVA, including treatment and country as covariates.p-value: 0.015595% CI: [-0.44, -0.05]ANOVA
Comparison: Global score:~Analysis of the treatment difference (Eziclen®/Izinova® minus Klean-Prep®) was performed using a 2-way ANOVA, including treatment and country as covariates.p-value: 0.097595% CI: [-0.79, 0.07]ANOVA
Secondary
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.
Time frame: At Day 2 (colonoscopy visit)
Population: The ITT population included all randomised subjects who received even a partial dose of study drug.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Eziclen®/Izinova® | Mean Colon Cleansing Score (4-point Scale) | 2.83 scores on a scale |
| Klean-Prep® | Mean Colon Cleansing Score (4-point Scale) | 3.02 scores on a scale |
Comparison: Analysis of the treatment difference (Eziclen®/Izinova® minus Klean-Prep®) was performed using a 2-way ANOVA, including treatment and country as covariates.p-value: 0.042895% CI: [-0.36, -0.01]ANOVA
Secondary
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.
Time frame: From caecum intubation to withdrawal of the colonoscope, assessed on Day 2 (colonoscopy visit)
Population: The ITT population included all randomised subjects who received even a partial dose of study drug. Only subjects with data available were included in the analysis (6 subjects in the Eziclen®/Izinova® group and 5 subjects in the Klean-Prep® group had missing data so are not included in the overall number analysed).
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Eziclen®/Izinova® | Mean Duration of Examination | 14.77 minutes |
| Klean-Prep® | Mean Duration of Examination | 15.70 minutes |
Comparison: Analysis of the treatment difference (Eziclen®/Izinova® minus Klean-Prep®) was performed using a 2-way ANOVA, including treatment and country as covariates.p-value: 0.445995% CI: [-3.32, 1.47]ANOVA
Secondary
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.
Time frame: At Day 1 (treatment visit)
Population: The ITT population included all randomised subjects who received even a partial dose of study drug.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Eziclen®/Izinova® | Mean Overall Treatment Compliance | Dose 1 | 96.74 adjusted percentage of fluid volume (mL) |
| Eziclen®/Izinova® | Mean Overall Treatment Compliance | Dose 2 | 93.53 adjusted percentage of fluid volume (mL) |
| Eziclen®/Izinova® | Mean Overall Treatment Compliance | Global | 96.82 adjusted percentage of fluid volume (mL) |
| Klean-Prep® | Mean Overall Treatment Compliance | Dose 1 | 95.52 adjusted percentage of fluid volume (mL) |
| Klean-Prep® | Mean Overall Treatment Compliance | Dose 2 | 87.14 adjusted percentage of fluid volume (mL) |
| Klean-Prep® | Mean Overall Treatment Compliance | Global | 89.34 adjusted percentage of fluid volume (mL) |
Comparison: Dose 1:~Analysis of the treatment difference (Eziclen®/Izinova® minus Klean-Prep®) was performed using a 2-way ANOVA, including treatment and country as covariates.p-value: 0.394595% CI: [-1.6, 4.05]ANOVA
Comparison: Dose 2:~Analysis of the treatment difference (Eziclen®/Izinova® minus Klean-Prep®) was performed using a 2-way ANOVA, including treatment and country as covariates.p-value: 0.008595% CI: [1.65, 11.12]ANOVA
Comparison: Global:~Analysis of the treatment difference (Eziclen®/Izinova® minus Klean-Prep®) was performed using a 2-way ANOVA, including treatment and country as covariates.p-value: 0.003695% CI: [2.46, 12.5]ANOVA
Secondary
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.
Time frame: At Day 1 (treatment visit)
Population: The ITT population included all randomised subjects who received even a partial dose of study drug. Only subjects with data available were included in the analysis (6 subjects in the Klean-Prep® group had missing data so are not included in the overall number analysed).
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Eziclen®/Izinova® | Mean Score for Overall Treatment Acceptability, Assessed Using Treatment Acceptability Questionnaire | 2.93 scores on a scale |
| Klean-Prep® | Mean Score for Overall Treatment Acceptability, Assessed Using Treatment Acceptability Questionnaire | 2.22 scores on a scale |
Comparison: Analysis of the treatment difference (Eziclen®/Izinova® minus Klean-Prep®) was performed using a 2-way ANOVA, including treatment and country as covariates.p-value: <0.000195% CI: [0.4, 1.03]ANOVA
Secondary
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.
Time frame: At Day 1 (treatment visit)
Population: The safety population included all randomised subjects who received even a partial dose of study drug. Subjects were assessed according to the treatment received (1 subject randomised to the Eziclen®/Izinova® group was mistakenly administered Klean-Prep®; this subject was therefore included in the Klean-Prep® safety population).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eziclen®/Izinova® | Mean Subject Tolerability Total Score, Assessed Using a Symptom Scale | Dose 1 | 5.48 scores on a scale | Standard Deviation 2.42 |
| Eziclen®/Izinova® | Mean Subject Tolerability Total Score, Assessed Using a Symptom Scale | Dose 2 | 5.93 scores on a scale | Standard Deviation 2.58 |
| Klean-Prep® | Mean Subject Tolerability Total Score, Assessed Using a Symptom Scale | Dose 1 | 6.34 scores on a scale | Standard Deviation 2.78 |
| Klean-Prep® | Mean Subject Tolerability Total Score, Assessed Using a Symptom Scale | Dose 2 | 6.71 scores on a scale | Standard Deviation 3.07 |
Secondary
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.
Time frame: From colonoscope introduction to caecal intubation, assessed on Day 2 (colonoscopy visit)
Population: The ITT population included all randomised subjects who received even a partial dose of study drug. Note: for 2 subjects in the Eziclen®/Izinova® group and 1 subject in the Klean-Prep® group, although the procedure reached the caecum, the time was not reported and consequently, these subjects could not be included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Eziclen®/Izinova® | Median Time to Caecal Intubation | 13.0 minutes |
| Klean-Prep® | Median Time to Caecal Intubation | 15.0 minutes |
Secondary
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.
Time frame: At Day 2 (colonoscopy visit)
Population: The ITT population included all randomised subjects who received even a partial dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Eziclen®/Izinova® | Percentage of Subjects With Colonoscopy Procedure Documented as Completed | 96.8 percentage of subjects |
| Klean-Prep® | Percentage of Subjects With Colonoscopy Procedure Documented as Completed | 96.6 percentage of subjects |
Comparison: Analysis was performed using CMH chi-square method (using the general association statistic), stratified on country.p-value: 0.925795% CI: [1, 1.1]CMH chi-square
Secondary
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.
Time frame: At Day 1 (treatment visit)
Population: The ITT population included all randomised subjects who received even a partial dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Eziclen®/Izinova® | Percentage of Subjects With Need for Nasogastric Tube To Complete Preparation | 7.2 percentage of subjects |
| Klean-Prep® | Percentage of Subjects With Need for Nasogastric Tube To Complete Preparation | 31.0 percentage of subjects |
Comparison: Analysis was performed using CMH chi-square method (using the general association statistic), stratified on country.p-value: <0.000195% CI: [12.6, 45.9]CMH chi-square
Secondary
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.
Time frame: At Day 2 (colonoscopy visit, before colonoscopy)
Population: The ITT population included all randomised subjects who received even a partial dose of study drug. Only subjects with data available were included in the analysis (1 subject in the Eziclen®/Izinova® group had missing data so is not included in the overall number analysed).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Eziclen®/Izinova® | Percentage of Subjects With Need for Rescue Treatment | 20.2 percentage of subjects |
| Klean-Prep® | Percentage of Subjects With Need for Rescue Treatment | 14.7 percentage of subjects |
Comparison: Analysis was performed using Cochran-Mantel-Haenszel (CMH) chi-square method (using the general association statistic), stratified on country.p-value: 0.242895% CI: [0.8, 2.4]CMH chi-square
Other Pre-specified
Mean Time Between Last Intake of Fluids and Start of Colonoscopy Procedure
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.
Time frame: From end of treatment administration to start of colonoscopy, assessed on Day 1 (treatment visit) and Day 2 (colonoscopy visit)
Population: The ITT population included all randomised subjects who received even a partial dose of study drug.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Eziclen®/Izinova® | Mean Time Between Last Intake of Fluids and Start of Colonoscopy Procedure | 15.30 hours |
| Klean-Prep® | Mean Time Between Last Intake of Fluids and Start of Colonoscopy Procedure | 14.25 hours |
Comparison: Analysis of the treatment difference (Eziclen®/Izinova® minus Klean-Prep®) was performed using 2-way ANOVA, including treatment and country as covariates.p-value: 0.001595% CI: [0.41, 1.69]ANOVA
Other Pre-specified
Median Time to Clear Effluent
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.
Time frame: From first intake of prescription to first clear watery stool, assessed on Day 1 (treatment visit) and Day 2 (colonoscopy visit)
Population: The ITT population included all randomised subjects who received even a partial dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Eziclen®/Izinova® | Median Time to Clear Effluent | 4.3 hours |
| Klean-Prep® | Median Time to Clear Effluent | 4.8 hours |