Primary objective:To demonstrate that Eziclen, given on the day before colonoscopy has non-inferior efficacy to Klean-Prep on colon cleansing in adolescents aged 12 to 17 years (inclusive) with a body weight > 40 kg, scheduled to undergo a…
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Source
Brief title
Condition
- Gastrointestinal therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary Endpoints and Evaluations concerning efficacy:
Non-inferiority of Eziclen versus Klean-Prep in the cleansing of the colon.
This is determined by the blinded colonoscopist upon finalization of the scopy,
by completion of a questionnaire (Cleansing Score) that is based on a 4-point
scale (Poor, Fair, Good, Excellent cleaning).
Only perfect bowel cleansing (graded as 4 or 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.
Secondary outcome
Secondary endpoints and evaluations concerning efficacy:
* 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;
* Procedures documented as completed (procedures that reached the caecum);
* Treatment compliance: volumes ingested as measured by research staff;
* Treatment acceptability, assessed by questionnaire completed by research
staff or subject at the time of intake (unacceptable; badly but accepted;
neither good nor bad; well accepted; very well accepted).
Secondary endpoints and evaluations concerning safety and tolerability:
* Collection of adverse events for up to 30 days following the day of
colonoscopy:
- Diagnosis or diagnostic findings made at colonoscopy will be reported as such
and will not be reported as AEs unless the investigator
observes mucosal lesions that he/she suspects to be related or possibly
related to the colonic lavage. Such lesions will be biopsied. In this
situation only, description of the colonoscopy findings and
histological examination results will be reported as AEs.
* 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 5-point scale (ranging from no symptoms to severely
distressing symptoms);
* Description and histological examination of any colonic biopsy specimens of
mucosal lesions suspected to have been caused by colonic lavage;
* Vital signs including body weight and physical examination;
* Laboratory data (serum and urinary biochemistry) collected at visit 1, day 2
(colonoscopy) and visit 4.
Background summary
A wide variety of bowel cleansing preparations prior to a colonoscopy are used
in children. These preparations are often poorly accepted due to their
unpleasant salty taste and the large volume to be ingested over a relatively
short period. As a consequence the preparation may not be taken completely.
This affects the quality of the colonoscopy. If the intestine is not completely
cleaned, the examination may be incomplete or may last longer because the
doctor additionally needs to clean during the examination. It might even that
the procedure needs to be repeated. A good preparation is particularly
important in children as the examination is conducted under general anaesthesia.
Eziclen, the treatment under investigation in this study, is approved in adult
patients and on the market in Europe since 2014. It is not yet approved in
children. The study is conducted at the request of the European Health
Authorities in order to allow prescription of Eziclen to children.
Study objective
Primary objective:
To demonstrate that Eziclen, given on the day before colonoscopy has
non-inferior efficacy to Klean-Prep 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.
Secondary objectives:
* To compare efficacy of Eziclen 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 versus
Klean-Prep.
Study design
This is a multicentre, phase III, randomized, comparative study between Eziclen
and Klean-prep, administered as bowel preparation to adolescents on the day
prior to colonoscopy. The investigator will be blinded.
Patients (both male and female and > 40 kg) will be randomized to Eziclen or
Klean-prep in a 1:1 ratio.
Patients will be hospitaliozed from (Visit 1, day 1) to completion of
colonoscopy (Visit 2, day 2). The duration of the study for each subject will
be maximal 47 days:
* Baseline (Visit 1) and treatment administration;
* Colonoscopy (Visit 2) on day 2;
* Phone contact (Visit 3) at Day 4 ±1 day;
* End of Treatment visit (Visit 4) on day 32 (-5/+15 days).
Intervention
In this study, half of the children (i.e. around 125) will receive the study
drug (Eziclen) and the other half will receive the comparator treatment
(Klean-Prep).
Eziclen is administered as a one-day treatment on the evening before the
colonoscopy is performed. The total ingested volume of the Eziclen solution is
750 mL plus 1500 mL water (2250 mL in total). This is 3/4 of the dosis that is
used in adults.
Klean-Prep is also administered as a one-day treatment on the evening prior to
the colonoscopy takes place in a dose of 70 mL/kg body weight. Depending on
his/her weight, the patient will need to drink a volume between 2800 to 4000
mL.
At study visit 1,2 and 4, about 5.5 mL of blood will be collected for safety
testing.
Study burden and risks
Eziclen is, in contrast to Klean-prep, not yet authorized to use for bowel
preparation in children. This study is conducted as part of the pediatric
investigation plan (PIP) to get this marketing authorisation. The dose of
Eziclen used in this study will be 3/4 of the dose that is used in adults.
Klean-prep is used as bowel preparation for children in the Netherlands.
Klean-prep and Eziclen have a comparable safety profile. The expected outcome
after ingestion is watery diarrhoea.
In adult patients, the most frequently reported adverse reactions for Eziclen
(in at least 1 out of 10 patients) are gastrointestinal symptoms such as
feeling sick (nausea), being sick (vomiting), abdominal discomfort, cramping or
pain, abdominal bloating or distension.
The most common side effects for Klean-prep include gastrointestinal symptoms
such as nausea, vomiting, abdominal pain, anal discomfort, abdominal swelling
and flatulence.
Recently, a study with Eziclen has been conducted in 29 adolescent patients.
The adverse reactions observed were similar in nature to what has been observed
in adult patients. Adolescent patients experienced slightly more nausea and
vomiting. Reports of preparation related symptoms were generally low with both
preparations. More than 75% of subjects reported their symptoms as *none* or
*mild*.
During the study, three blood samples are collected (about 16.5 mL in total).
Blood sampling may cause pain, discomfort, swelling, bruising (hematoma),
fainting or extremely rarely, infection from the needle puncture site. The use
of an anaesthetic patch will limit or avoid discomfort and pain. But also may
be associated with transient local reactions such as swelling, redness or
burning sensation.
The colonoscopy is conducted by using general anaesthesia and if necessary a
nasogastric tube can be placed. It might also necessary to administer a
clyster. These procedures are standard procedures for a colonoscopy.
quai Georges Gorse 65
Boulogne-Billancourt 92100
FR
quai Georges Gorse 65
Boulogne-Billancourt 92100
FR
Listed location countries
Age
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
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
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
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In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2016-002265-60-NL |
| CCMO | NL59332.018.17 |