| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| 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 |
|
| E.1.1.1 | Medical condition in easily understood language |
Children who have been prescribed a colonoscopy.
|
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| E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10010007 |
| E.1.2 | Term | Colonoscopy |
| E.1.2 | System Organ Class | 10022891 - Investigations |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
The primary objective 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.
|
|
| E.2.2 | Secondary objectives of the trial |
The secondary objectives are:
- To compare efficacy of Eziclen®/Izinova® versus Klean-Prep® on overall and segmental cleansing and colonoscopy quality indicators
- To assess compliance with preparation administration in both study arms
- To compare safety, acceptability and tolerability of Eziclen®/Izinova®versus Klean- Prep® |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Subject MUST satisfy all of the following entry criteria before being allowed to participate in the study:
(1) Provision of signed informed consent form (ICF) 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
(2) Male or female subjects between 12 to 17 years of age (inclusive)
(3) Body weight more than 40 kg
(4) Female of childbearing potential must have a negative pregnancy test
(5) 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)
(6) 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
(7) 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
(8) In the investigator’s judgement, subject is able and willing to follow study procedures including drug administration and response to questionnaires |
|
| E.4 | Principal exclusion criteria |
If any of the following apply, the subject MUST NOT enter/continue in the study:
(1) 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
(2) Subject with known or suspected inflammatory bowel disease (Crohn’s disease, ulcerative colitis) in moderate to severe active phase defined by PCDAI >30 (Crohn’s disease) or PUCAI >34 (ulcerative colitis)
(3) Subject with bowel perforation or increased risk of bowel perforation, including connective tissue disorders or recent bowel surgery
(4) Subject with previous significant gastrointestinal surgery (e.g. colostomy, colectomy, gastric bypass, stomach stapling)
(5) 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 (ACE) inhibitors judged clinically significant by the investigator
(6) Subject with a prior history or current condition of severe renal
(estimated glomerular filtration rate (eGFR) less than 30 mL/min/1.73 m2 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(7) Female subject who is pregnant or lactating
(8) Subject who has participated in another investigational drug treatment within the last 90 days before the first study visit
(9) Subject with phenylketonuria
(10) Subject with history of asthma or hypersensitivity to any ingredient of either drug product
(11) Subject for whom intake of substances likely to affect gastrointestinal motility or urinary flow rate is required
(12) Subject with requirement to take any other oral medication within 3 hours of starting the bowel preparation, as this may impact medication absorption
(13) Subject with tendency for nausea and/or vomiting
(14) Subject with impaired consciousness that predisposes them to pulmonary aspiration or who have known swallowing disorders
(15) Subject with history of major medical/psychiatric conditions that, in the judgment of the investigator, would compromise safety in the study
(16) 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
(17) 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
(18) Subject who has previous enrolment in this study or concomitant enrolment in other clinical studies |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Primary Endpoints and Evaluations:
Non-inferiority of Eziclen®/Izinova®versus Klean-Prep® in the cleansing of the colon:
Blinded overall assessment of preparation efficacy (Cleansing Score) as determined by the
colonoscopist upon completion of the examination, based on a 4-point scale:
Score // Grade // Description
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 allow full, reliable examination of the mucosa, will be considered as successful.
Primary efficacy will be assessed on the basis of preparation success or failure. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Primary end point will be assessed at Visit 2 (colonoscopy). |
|
| E.5.2 | Secondary end point(s) |
Secondary Endpoints and Evaluations:
- Need to place a nasogastric tube to complete preparation
- Time to clear effluent (from first intake of preparation), as reported by the subject
- Need for rescue treatment (saline enema) because of inadequate preparation
- Cleansing Scores assessed by the 4-point scale (poor, fair, good, excellent)
- Overall and segmental Cleansing Scores assessed by Boston Bowel Preparation Scale
(BBPS)
- Duration of intubation (from colonoscope introduction to caecal intubation)
- Duration of examination, measured by colonoscope withdrawal time from caecum
- Procedure documented as completed (procedures that reached the caecum)
- Treatment compliance: volumes of fluids measured by the caregiver and reported in
the treatment questionnaire of subject’s leaflet during treatment administration
- Treatment acceptability, assessed by Treatment Acceptability Questionnaire completed by caregiver or subject at the time of intake using a 5-point scale questionnaire to be filled in by the subject immediately after dosing
Very badly accepted/unacceptable // Subject showed great displeasure, compromising use of formulation
Badly but accepted // Subject showed displeasure with dosing but could be coaxed to take complete dose
Neither good nor bad // Subject showed no apparent displeasure and with little effort was coaxed to take complete dose
Well accepted // Subject appeared to enjoy the formulation and with little coaxing ingested complete dose
Very well accepted // Subject appeared eager and ingested complete without special coaxing
Safety and tolerability:
- Collection of adverse events (AEs) (for up to 30 days following the day of
colonoscopy)
- Tolerability by a Symptom Scale after each dose of treatment. Subjects will rate their preparation related symptoms after intake (stomach cramping, stomach bloating and
nausea) on a paediatric 5-point scale, ranging from 1=no symptoms to 5= severely distressing symptoms
- Description and histological examination of any colonic biopsy
specimens of mucosal lesions suspected by the investigator to have been
caused by colonic lavage
- Vital signs including body weight and physical examination
- Laboratory data: serum and urinary biochemistry (Visit 1, Visit 2, Visit 4) |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Secondary end points will be assessed at Visits 1, 2, 3 and 4. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | Yes |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 26 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 1 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 1 |
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