Efficacy, Safety and Tolerability of Eziclen®/Izinova® Ve... | NCT03008460

NCT03008460

ID	Type	Description	Link
2016-002265-60	EudraCT Number

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Label	Type	Description	Intervention Names
Eziclen®/Izinova®	Experimental		Drug: Eziclen®/Izinova®
Klean-Prep®	Active Comparator		Drug: Klean-Prep®

Name	Type	Description	Arm Group Labels	Other Names
Eziclen®/Izinova®	Drug	Oral solution taken the evening before the colonoscopy	Eziclen®/Izinova®

Outcomes Module

Primary Outcomes

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 Outcomes

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.

Other Outcomes

Measure	Description	Time Frame
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.

Eligibility Module

Eligibility Criteria

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

Contacts/Locations Module

Name	Affiliation	Role
Ipsen Medical Director	Ipsen Consumer Healthcare	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Fakultní nemocnice Královské Vinohrady		Prague		100 34	Czechia
Všeobecná fakultní nemocnice v Praze

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
36821851	Derived	Socha P, Posovszky C, Szychta M, Viscogliosi F, Martemucci L, Grzybowska-Chlebowczyk U, Perrot V, Kornowski A, Benninga MA; EASYKID Study Group. Phase III Randomized Non-Inferiority Study of OSS Versus PEG + Electrolyte Colonoscopy Preparation in Adolescents. J Pediatr Gastroenterol Nutr. 2023 May 1;76(5):652-659. doi: 10.1097/MPG.0000000000003745. Epub 2023 Feb 22.

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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).

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Mar 2, 2020	Nov 24, 2020

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

FG000126 subjects
FG001124 subjects

The intention-to-treat (ITT) population included all randomised subjects who received even a partial dose of study drug.

Arm/Group Information

ID	Title	Description
BG000	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).
BG001	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).
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	OG00071.42(56.33 to 82.89) OG00179.03(65.34 to 88.28)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Analysis of the treatment difference (Eziclen®/Izinova® minus Klean-Prep®) was performed using a logistic regression model, including treatment and country as covariates.	Regression, Logistic		0.0907	P-value for non-inferiority was estimated from the adjusted treatment difference.	Adjusted treatment difference	-7.61			2-Sided	95	-18.45	3.24					Non-Inferiority	Non-inferiority would be demonstrated if the lower limit of the 95% confidence interval of the adjusted treatment difference was higher than -15%.

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.

The ITT population included all randomised subjects who received even a partial dose of study drug.

Posted

Mean

95% Confidence Interval

scores on a scale

At Day 2 (colonoscopy visit)

ID	Title	Description
OG000	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).
OG001	Klean-Prep®

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.

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.

Posted

Mean

95% Confidence Interval

scores on a scale

At Day 2 (colonoscopy visit)

ID	Title	Description
OG000	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).

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.

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).

Posted

Number

95% Confidence Interval

percentage of subjects

At Day 2 (colonoscopy visit, before colonoscopy)

ID	Title	Description
OG000	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).
OG001	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).

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.

The ITT population included all randomised subjects who received even a partial dose of study drug.

Posted

Number

95% Confidence Interval

percentage of subjects

At Day 1 (treatment visit)

ID	Title	Description
OG000	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).
OG001	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).

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.

The ITT population included all randomised subjects who received even a partial dose of study drug.

Posted

Number

95% Confidence Interval

percentage of subjects

At Day 2 (colonoscopy visit)

ID	Title	Description
OG000	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).
OG001	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).

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.

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.

Posted

Median

95% Confidence Interval

minutes

From colonoscope introduction to caecal intubation, assessed on Day 2 (colonoscopy visit)

ID	Title	Description
OG000	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).
OG001	Klean-Prep®

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.

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).

Posted

Mean

95% Confidence Interval

minutes

From caecum intubation to withdrawal of the colonoscope, assessed on Day 2 (colonoscopy visit)

ID	Title	Description
OG000	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).
OG001	Klean-Prep®

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.

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).

Posted

Mean

95% Confidence Interval

scores on a scale

At Day 1 (treatment visit)

ID	Title	Description
OG000	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).

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.

The ITT population included all randomised subjects who received even a partial dose of study drug.

Posted

Mean

95% Confidence Interval

adjusted percentage of fluid volume (mL)

At Day 1 (treatment visit)

ID	Title	Description
OG000	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).
OG001

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.

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).

Posted

Mean

Standard Deviation

scores on a scale

At Day 1 (treatment visit)

ID	Title	Description
OG000	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).
OG001

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.

The ITT population included all randomised subjects who received even a partial dose of study drug.

Posted

Median

95% Confidence Interval

hours

From first intake of prescription to first clear watery stool, assessed on Day 1 (treatment visit) and Day 2 (colonoscopy visit)

ID	Title	Description
OG000	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).

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.

The ITT population included all randomised subjects who received even a partial dose of study drug.

Posted

Mean

95% Confidence Interval

hours

From end of treatment administration to start of colonoscopy, assessed on Day 1 (treatment visit) and Day 2 (colonoscopy visit)

ID	Title	Description
OG000	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).
OG001	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).

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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).	0	124	4	124	111	124
EG001	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).	0	117	3	117	105	117

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Abdominal pain	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment		EG0001 events1 affected124 at risk EG0010 events0 affected117 at risk
Crohn's disease	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	Diagnostic finding at colonoscopy, reported as non-related TEAE and related to the indication for colonoscopy.	EG0002 events2 affected124 at risk EG0011 events1 affected117 at risk
Intestinal polyp	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment		EG0001 events1 affected124 at risk EG0010 events0 affected117 at risk
Intestinal stenosis	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment		EG0001 events1 affected124 at risk EG0010 events0 affected117 at risk
Drug hypersensitivity	Immune system disorders	MedDRA 23.0	Systematic Assessment		EG0000 events0 affected124 at risk EG0011 events1 affected117 at risk
Blood creatine phosphokinase increased	Investigations	MedDRA 23.0	Systematic Assessment		EG0000 events0 affected124 at risk EG0011 events1 affected117 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Nausea	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment		EG000123 events90 affected124 at risk EG001115 events84 affected117 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment		EG00091 events67 affected124 at risk EG001107 events77 affected117 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment		EG00083 events64 affected124 at risk EG00184 events64 affected117 at risk
Vomiting	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment		EG00011 events11 affected124 at risk EG00111 events10 affected117 at risk
Crohn's disease	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	Diagnostic finding at colonoscopy, reported as non-related TEAE and related to the indication for colonoscopy.	EG0009 events9 affected124 at risk EG0012 events2 affected117 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment		EG0006 events6 affected124 at risk EG0013 events3 affected117 at risk
Colitis ulcerative	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	Diagnostic finding at colonoscopy, reported as non-related TEAE and related to the indication for colonoscopy.	EG0001 events1 affected124 at risk EG0016 events6 affected117 at risk
Gastritis	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment		EG0004 events4 affected124 at risk EG0013 events3 affected117 at risk
Headache	Nervous system disorders	MedDRA 23.0	Systematic Assessment		EG0009 events9 affected124 at risk EG0012 events2 affected117 at risk

ID	Term
D004066	Digestive System Diseases

ID	Term
C112283	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).