<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03008460</url>
  </required_header>
  <id_info>
    <org_study_id>F-FR-58800-003</org_study_id>
    <secondary_id>2016-002265-60</secondary_id>
    <nct_id>NCT03008460</nct_id>
  </id_info>
  <brief_title>Efficacy, Safety and Tolerability of Eziclen®/Izinova® Versus Klean-prep® on Bowel Cleansing in Adolescents Undergoing Colonoscopy</brief_title>
  <acronym>EASYKID</acronym>
  <official_title>Efficacy, Safety and Tolerability of a Bowel Cleansing Preparation (Eziclen/Izinova®) in Paediatric Subjects Undergoing Colonoscopy: a Phase III, Multicentre, Randomised, Comparative Study Versus Klean-Prep® (PEG-Electrolytes), Administered on the Day Before Colonoscopy, Investigator-blinded, Non-inferiority in Adolescents of 12 to 17 Years of Age (Inclusive) &gt;40 kg</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ipsen</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ipsen</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of the protocol is to demonstrate that Eziclen®/Izinova®, an osmotic&#xD;
      sulphate-based laxative preparation given on the day before colonoscopy has non-inferior&#xD;
      efficacy to Klean-Prep® (polyethylene glycol (PEG)-electrolytes) on colon cleansing in&#xD;
      adolescents aged 12 to 17 years (inclusive) with a body weight &gt;40 kg, scheduled to undergo a&#xD;
      colonoscopy for a routinely accepted diagnostic indication.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 15, 2017</start_date>
  <completion_date type="Actual">June 29, 2020</completion_date>
  <primary_completion_date type="Actual">February 24, 2020</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>Single (Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of Subjects With Successful Overall Colon Preparation, Assessed With the Cleansing Score (4-point Scale)</measure>
    <time_frame>At Day 2 (colonoscopy visit)</time_frame>
    <description>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:&#xD;
4 (Excellent) = No more than small bits of adherent faeces/fluid&#xD;
3 (Good) = Small amounts of faeces or fluid not interfering with examination&#xD;
2 (Fair) = Enough faeces or fluid to prevent a completely reliable examination&#xD;
1 (Poor) = Large amounts of faecal residue, additional cleansing required.&#xD;
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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mean Colon Cleansing Score (4-point Scale)</measure>
    <time_frame>At Day 2 (colonoscopy visit)</time_frame>
    <description>The Cleansing Score was determined by the blinded colonoscopist, based on a 4-point scale as follows:&#xD;
4 (Excellent) = No more than small bits of adherent faeces/fluid&#xD;
3 (Good) = Small amounts of faeces or fluid not interfering with examination&#xD;
2 (Fair) = Enough faeces or fluid to prevent a completely reliable examination&#xD;
1 (Poor) = Large amounts of faecal residue, additional cleansing required.&#xD;
The adjusted mean score was estimated using a 2-way analysis of variance (ANOVA), including treatment and country as covariates.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Boston Bowel Preparation Scale (BBPS) Global Score and BBPS Scores by Colon Segment</measure>
    <time_frame>At Day 2 (colonoscopy visit)</time_frame>
    <description>The BBPS score for each colon segment (left, transverse, right) was determined by the blinded colonoscopist as follows:&#xD;
0 = Unprepared colon segment with mucosa not seen due to solid stool that cannot be cleared&#xD;
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&#xD;
2 = Minor amount of residual staining, small fragments of stool and/or opaque liquid, but mucosa of segment seen well&#xD;
3 = Entire mucosa of segment seen well with no residual staining, small fragments of stool and/or opaque liquid.&#xD;
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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Subjects With Need for Rescue Treatment</measure>
    <time_frame>At Day 2 (colonoscopy visit, before colonoscopy)</time_frame>
    <description>The percentage of subjects who needed rescue treatment (saline enema) prior to colonoscopy because of inadequate preparation intake was assessed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Subjects With Need for Nasogastric Tube To Complete Preparation</measure>
    <time_frame>At Day 1 (treatment visit)</time_frame>
    <description>The percentage of subjects who needed placement of a nasogastric tube to achieve administration of the complete preparation was assessed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Subjects With Colonoscopy Procedure Documented as Completed</measure>
    <time_frame>At Day 2 (colonoscopy visit)</time_frame>
    <description>The percentage of subjects with a complete colonoscopy, defined as a procedure that reached the caecum, was assessed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Median Time to Caecal Intubation</measure>
    <time_frame>From colonoscope introduction to caecal intubation, assessed on Day 2 (colonoscopy visit)</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Duration of Examination</measure>
    <time_frame>From caecum intubation to withdrawal of the colonoscope, assessed on Day 2 (colonoscopy visit)</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Score for Overall Treatment Acceptability, Assessed Using Treatment Acceptability Questionnaire</measure>
    <time_frame>At Day 1 (treatment visit)</time_frame>
    <description>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:&#xD;
1 = Very badly accepted/unacceptable&#xD;
2 = Badly but accepted&#xD;
3 = Neither good nor bad&#xD;
4 = Well accepted&#xD;
5 = Very well accepted.&#xD;
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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Overall Treatment Compliance</measure>
    <time_frame>At Day 1 (treatment visit)</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Subject Tolerability Total Score, Assessed Using a Symptom Scale</measure>
    <time_frame>At Day 1 (treatment visit)</time_frame>
    <description>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:&#xD;
1 = No symptom&#xD;
2 = Mild&#xD;
3 = Bothersome&#xD;
4 = Distressing&#xD;
5 = Severely distressing symptoms.&#xD;
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.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Median Time to Clear Effluent</measure>
    <time_frame>From first intake of prescription to first clear watery stool, assessed on Day 1 (treatment visit) and Day 2 (colonoscopy visit)</time_frame>
    <description>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.</description>
  </other_outcome>
  <other_outcome>
    <measure>Mean Time Between Last Intake of Fluids and Start of Colonoscopy Procedure</measure>
    <time_frame>From end of treatment administration to start of colonoscopy, assessed on Day 1 (treatment visit) and Day 2 (colonoscopy visit)</time_frame>
    <description>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.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">250</enrollment>
  <condition>Digestive System Disease</condition>
  <arm_group>
    <arm_group_label>Eziclen®/Izinova®</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Klean-Prep®</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Eziclen®/Izinova®</intervention_name>
    <description>Oral solution taken the evening before the colonoscopy</description>
    <arm_group_label>Eziclen®/Izinova®</arm_group_label>
    <other_name>Suprep®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Klean-Prep®</intervention_name>
    <description>Oral solution taken the evening before the colonoscopy</description>
    <arm_group_label>Klean-Prep®</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Provision of signed informed consent form to participate in the study obtained from&#xD;
             the adolescent's parent(s)/ legal representative and a signed assent form from the&#xD;
             adolescent according to local law&#xD;
&#xD;
          -  Male or female subjects between 12 to 17 years of age (inclusive)&#xD;
&#xD;
          -  Body weight more than 40 kg&#xD;
&#xD;
          -  Female of childbearing potential must have a negative pregnancy test&#xD;
&#xD;
          -  If female, and of child-bearing potential, subject must use an acceptable form of&#xD;
             birth control (hormonal birth control, intrauterine device (IUD), double-barrier&#xD;
             method, or depot contraceptive)&#xD;
&#xD;
          -  Routinely accepted indication for undergoing colonoscopy, including but not limited to&#xD;
             polyposis coli diagnosis or surveillance, gastrointestinal bleeding, unexplained&#xD;
             diarrhoea or constipation, surveillance of inflammatory bowel disease or confirmation&#xD;
             of mucosal healing, abdominal pain, abnormal endosonography or manometry, anaemia of&#xD;
             unknown aetiology, cancer surveillance&#xD;
&#xD;
          -  In the investigator's judgment, the parent(s)/legal representative are/is mentally&#xD;
             competent to provide informed consent for the subject to participate in the study&#xD;
&#xD;
          -  In the investigator's judgement, subject is able and willing to follow study&#xD;
             procedures including drug administration and response to questionnaires&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subject with known or suspected ileus, gastrointestinal obstruction, gastric retention&#xD;
             (gastroparesis), rectal impaction, toxic colitis, severe ulcerative colitis or toxic&#xD;
             megacolon, advanced carcinoma, swallowing disorders&#xD;
&#xD;
          -  Subject with known or suspected inflammatory bowel disease (Crohn's disease,&#xD;
             ulcerative colitis) in moderate to severe active phase defined by Paediatric Crohn's&#xD;
             Disease Activity Index (PCDAI) &gt;30 or Paediatric Ulcerative Colitis Index (PUCAI) &gt;34&#xD;
&#xD;
          -  Subject with bowel perforation or increased risk of bowel perforation, including&#xD;
             connective tissue disorders or recent bowel surgery&#xD;
&#xD;
          -  Subject with previous significant gastrointestinal surgery (e.g. colostomy, colectomy,&#xD;
             gastric bypass, stomach stapling)&#xD;
&#xD;
          -  Subject with uncontrolled pre-existing electrolyte abnormalities, or with electrolyte&#xD;
             abnormalities based on Visit 1 laboratory results such as hypernatremia, hyponatremia,&#xD;
             hyperphosphatemia, hypokalaemia, hypocalcaemia, uncorrected dehydration, or secondary&#xD;
             to the use of medications such as diuretics or angiotensin converting enzyme&#xD;
             inhibitors judged clinically significant by the investigator&#xD;
&#xD;
          -  Subject with a prior history or current condition of severe renal (estimated&#xD;
             glomerular filtration rate (GFR) less than 30 mL/min/1.73 m^2 as calculated by using&#xD;
             the Schwartz bedside equation* [Schwartz et al, 2009]**), liver (ascites, Child-Pugh&#xD;
             C), cardiac insufficiency (including congestive heart failure all grades) or&#xD;
             hyperuricemia&#xD;
&#xD;
             *The estimated GFR will be calculated in patients with elevated creatinine at baseline&#xD;
&#xD;
             **Schwartz GJ and Work DF. Measurement and Estimation of GFR in Children and&#xD;
             Adolescents. Clin J Am Soc Nephrol. 2009; 4: 1832-1843&#xD;
&#xD;
          -  Female subject who is pregnant or lactating&#xD;
&#xD;
          -  Subject who has participated in another investigational drug treatment within the last&#xD;
             90 days before the first study visit&#xD;
&#xD;
          -  Subject with phenylketonuria&#xD;
&#xD;
          -  Subject with history of asthma or hypersensitivity to any ingredient of either drug&#xD;
             product&#xD;
&#xD;
          -  Subject for whom intake of substances likely to affect gastrointestinal motility or&#xD;
             urinary flow rate is required&#xD;
&#xD;
          -  Subject with requirement to take any other oral medication within 3 hours of starting&#xD;
             the bowel preparation, as this may impact medication absorption&#xD;
&#xD;
          -  Subject with tendency for nausea and/or vomiting&#xD;
&#xD;
          -  Subject with impaired consciousness that predisposes them to pulmonary aspiration or&#xD;
             who have known swallowing disorders&#xD;
&#xD;
          -  Subject with history of major medical/psychiatric conditions that, in the judgment of&#xD;
             the investigator, would compromise safety in the study&#xD;
&#xD;
          -  Subject with mental or psychiatric condition rendering the subject unable to&#xD;
             understand the nature, scope and possible consequences of the study, and/or evidence&#xD;
             of an uncooperative attitude&#xD;
&#xD;
          -  Subject with a condition that, in the opinion of the investigator, might increase the&#xD;
             risk to the subject or decrease the chance of obtaining satisfactory data needed to&#xD;
             achieve the objectives of the study&#xD;
&#xD;
          -  Subject who has previous enrolment in this study or concomitant enrolment in other&#xD;
             clinical studies&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>12 Years</minimum_age>
    <maximum_age>17 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ipsen Medical Director</last_name>
    <role>Study Director</role>
    <affiliation>Ipsen Consumer Healthcare</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Fakultní nemocnice Královské Vinohrady</name>
      <address>
        <city>Praha</city>
        <zip>100 34</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Všeobecná fakultní nemocnice v Praze</name>
      <address>
        <city>Praha</city>
        <zip>128 08</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Université de Picardie Jules Verne</name>
      <address>
        <city>Amiens</city>
        <zip>80054</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Femme Mère-Enfant</name>
      <address>
        <city>Bron</city>
        <zip>69677</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Necker Enfants Malades</name>
      <address>
        <city>Paris</city>
        <zip>75015</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Uniklinikum Essen</name>
      <address>
        <city>Essen</city>
        <zip>45147</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Evang Krankenhaus Hamm</name>
      <address>
        <city>Hamm</city>
        <zip>59063</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Leipzig, Klinik und Poliklinik für Kinder- und Jugendmedizin</name>
      <address>
        <city>Leipzig</city>
        <zip>04103</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinikum Ulm</name>
      <address>
        <city>Ulm</city>
        <zip>89075</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>HELIOS Klinikum Wuppertal</name>
      <address>
        <city>Wuppertal</city>
        <zip>42283</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ORN Santobono-Pausilipon Padiglione Santobono</name>
      <address>
        <city>Napoli</city>
        <zip>680 122</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale &quot;Spirito Santo&quot; U.D.C.</name>
      <address>
        <city>Pescara</city>
        <zip>65125</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliero-Universitaria Sant'Andrea</name>
      <address>
        <city>Roma</city>
        <zip>00189</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AMC Emma kinderziekenhuis</name>
      <address>
        <city>Amsterdam</city>
        <zip>1105 AZ</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Maasstad ziekenhuis</name>
      <address>
        <city>Rotterdam</city>
        <zip>3079 DZ</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Copernicus Podmiot Leczniczy Sp. z.o.o</name>
      <address>
        <city>Gdańsk</city>
        <zip>80-803</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Samodzielny Publiczny Szpital Kliniczny Nr 6 Śląskiego</name>
      <address>
        <city>Katowice</city>
        <zip>40-752</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Uniwersytecki Szpital Dziecięcy w Krakowie</name>
      <address>
        <city>Kraków</city>
        <zip>30-663</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Uniwersytecki Dziecięcy Szpital Kliniczny im. L. Zamenhofa w Białymstoku</name>
      <address>
        <city>Lublin</city>
        <zip>20-093</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Uniwersytecki Szpital Dziecięcy w Lublinie</name>
      <address>
        <city>Lublin</city>
        <zip>20-093</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instytut &quot;Pomnik - Centrum Zdrowia Dziecka&quot;</name>
      <address>
        <city>Warszawa</city>
        <zip>04-730</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Samodzielny Publiczny Szpital Kliniczny Nr 1 we Wrocławiu</name>
      <address>
        <city>Wrocław</city>
        <zip>50-369</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Samodzielny Publiczny Szpital Kliniczny Nr 1</name>
      <address>
        <city>Zabrze</city>
        <zip>41-800</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instytut Centrum Zdrowia Matki Polki</name>
      <address>
        <city>Łódź</city>
        <zip>93-338</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Czechia</country>
    <country>France</country>
    <country>Germany</country>
    <country>Italy</country>
    <country>Netherlands</country>
    <country>Poland</country>
  </location_countries>
  <verification_date>March 2021</verification_date>
  <study_first_submitted>December 30, 2016</study_first_submitted>
  <study_first_submitted_qc>December 30, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 2, 2017</study_first_posted>
  <results_first_submitted>January 28, 2021</results_first_submitted>
  <results_first_submitted_qc>March 1, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">March 2, 2021</results_first_posted>
  <last_update_submitted>March 1, 2021</last_update_submitted>
  <last_update_submitted_qc>March 1, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 2, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Bowel preparation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Digestive System Diseases</mesh_term>
    <mesh_term>Gastrointestinal Diseases</mesh_term>
  </condition_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>March 2, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/60/NCT03008460/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>August 25, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/60/NCT03008460/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <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.</recruitment_details>
      <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.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Eziclen®/Izinova®</title>
          <description>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).</description>
        </group>
        <group group_id="P2">
          <title>Klean-Prep®</title>
          <description>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).</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="126"/>
                <participants group_id="P2" count="124"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="119"/>
                <participants group_id="P2" count="110"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="14"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Protocol deviation</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Study drug not dispensed</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>COVID-19 pandemic - consent withdrawn</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>End of study visit outside permitted time window</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The intention-to-treat (ITT) population included all randomised subjects who received even a partial dose of study drug.</population>
      <group_list>
        <group group_id="B1">
          <title>Eziclen®/Izinova®</title>
          <description>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).</description>
        </group>
        <group group_id="B2">
          <title>Klean-Prep®</title>
          <description>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).</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="125"/>
            <count group_id="B2" value="116"/>
            <count group_id="B3" value="241"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="125"/>
                    <count group_id="B2" value="116"/>
                    <count group_id="B3" value="241"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="15.1" spread="1.6"/>
                    <measurement group_id="B2" value="15.3" spread="1.6"/>
                    <measurement group_id="B3" value="15.2" spread="1.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="125"/>
                    <count group_id="B2" value="116"/>
                    <count group_id="B3" value="241"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="60"/>
                    <measurement group_id="B2" value="47"/>
                    <measurement group_id="B3" value="107"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="65"/>
                    <measurement group_id="B2" value="69"/>
                    <measurement group_id="B3" value="134"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race and Ethnicity Not Collected</title>
          <population>Race and Ethnicity were not collected from any participant.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>France</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="125"/>
                    <count group_id="B2" value="116"/>
                    <count group_id="B3" value="241"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Germany</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="125"/>
                    <count group_id="B2" value="116"/>
                    <count group_id="B3" value="241"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Italy</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="125"/>
                    <count group_id="B2" value="116"/>
                    <count group_id="B3" value="241"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Netherlands</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="125"/>
                    <count group_id="B2" value="116"/>
                    <count group_id="B3" value="241"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="20"/>
                    <measurement group_id="B3" value="40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Poland</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="125"/>
                    <count group_id="B2" value="116"/>
                    <count group_id="B3" value="241"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="70"/>
                    <measurement group_id="B2" value="65"/>
                    <measurement group_id="B3" value="135"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Czechia</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="125"/>
                    <count group_id="B2" value="116"/>
                    <count group_id="B3" value="241"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Subjects With Successful Overall Colon Preparation, Assessed With the Cleansing Score (4-point Scale)</title>
        <description>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:&#xD;
4 (Excellent) = No more than small bits of adherent faeces/fluid&#xD;
3 (Good) = Small amounts of faeces or fluid not interfering with examination&#xD;
2 (Fair) = Enough faeces or fluid to prevent a completely reliable examination&#xD;
1 (Poor) = Large amounts of faecal residue, additional cleansing required.&#xD;
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.</description>
        <time_frame>At Day 2 (colonoscopy visit)</time_frame>
        <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.</population>
        <group_list>
          <group group_id="O1">
            <title>Eziclen®/Izinova®</title>
            <description>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).</description>
          </group>
          <group group_id="O2">
            <title>Klean-Prep®</title>
            <description>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).</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Subjects With Successful Overall Colon Preparation, Assessed With the Cleansing Score (4-point Scale)</title>
          <description>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:&#xD;
4 (Excellent) = No more than small bits of adherent faeces/fluid&#xD;
3 (Good) = Small amounts of faeces or fluid not interfering with examination&#xD;
2 (Fair) = Enough faeces or fluid to prevent a completely reliable examination&#xD;
1 (Poor) = Large amounts of faecal residue, additional cleansing required.&#xD;
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.</description>
          <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.</population>
          <units>adjusted percentage of subjects</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="125"/>
                <count group_id="O2" value="116"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="71.42" lower_limit="56.33" upper_limit="82.89"/>
                    <measurement group_id="O2" value="79.03" lower_limit="65.34" upper_limit="88.28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Analysis of the treatment difference (Eziclen®/Izinova® minus Klean-Prep®) was performed using a logistic regression model, including treatment and country as covariates.</groups_desc>
            <non_inferiority_type>Non-Inferiority</non_inferiority_type>
            <non_inferiority_desc>Non-inferiority would be demonstrated if the lower limit of the 95% confidence interval of the adjusted treatment difference was higher than -15%.</non_inferiority_desc>
            <p_value>0.0907</p_value>
            <p_value_desc>P-value for non-inferiority was estimated from the adjusted treatment difference.</p_value_desc>
            <method>Regression, Logistic</method>
            <param_type>Adjusted treatment difference</param_type>
            <param_value>-7.61</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-18.45</ci_lower_limit>
            <ci_upper_limit>3.24</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Colon Cleansing Score (4-point Scale)</title>
        <description>The Cleansing Score was determined by the blinded colonoscopist, based on a 4-point scale as follows:&#xD;
4 (Excellent) = No more than small bits of adherent faeces/fluid&#xD;
3 (Good) = Small amounts of faeces or fluid not interfering with examination&#xD;
2 (Fair) = Enough faeces or fluid to prevent a completely reliable examination&#xD;
1 (Poor) = Large amounts of faecal residue, additional cleansing required.&#xD;
The adjusted mean score was estimated using a 2-way analysis of variance (ANOVA), including treatment and country as covariates.</description>
        <time_frame>At Day 2 (colonoscopy visit)</time_frame>
        <population>The ITT population included all randomised subjects who received even a partial dose of study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Eziclen®/Izinova®</title>
            <description>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).</description>
          </group>
          <group group_id="O2">
            <title>Klean-Prep®</title>
            <description>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).</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Colon Cleansing Score (4-point Scale)</title>
          <description>The Cleansing Score was determined by the blinded colonoscopist, based on a 4-point scale as follows:&#xD;
4 (Excellent) = No more than small bits of adherent faeces/fluid&#xD;
3 (Good) = Small amounts of faeces or fluid not interfering with examination&#xD;
2 (Fair) = Enough faeces or fluid to prevent a completely reliable examination&#xD;
1 (Poor) = Large amounts of faecal residue, additional cleansing required.&#xD;
The adjusted mean score was estimated using a 2-way analysis of variance (ANOVA), including treatment and country as covariates.</description>
          <population>The ITT population included all randomised subjects who received even a partial dose of study drug.</population>
          <units>scores on a scale</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="125"/>
                <count group_id="O2" value="116"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.83" lower_limit="2.67" upper_limit="2.99"/>
                    <measurement group_id="O2" value="3.02" lower_limit="2.85" upper_limit="3.18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Analysis of the treatment difference (Eziclen®/Izinova® minus Klean-Prep®) was performed using a 2-way ANOVA, including treatment and country as covariates.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.0428</p_value>
            <method>ANOVA</method>
            <param_type>Adjusted treatment difference</param_type>
            <param_value>-0.18</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.36</ci_lower_limit>
            <ci_upper_limit>-0.01</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Boston Bowel Preparation Scale (BBPS) Global Score and BBPS Scores by Colon Segment</title>
        <description>The BBPS score for each colon segment (left, transverse, right) was determined by the blinded colonoscopist as follows:&#xD;
0 = Unprepared colon segment with mucosa not seen due to solid stool that cannot be cleared&#xD;
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&#xD;
2 = Minor amount of residual staining, small fragments of stool and/or opaque liquid, but mucosa of segment seen well&#xD;
3 = Entire mucosa of segment seen well with no residual staining, small fragments of stool and/or opaque liquid.&#xD;
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.</description>
        <time_frame>At Day 2 (colonoscopy visit)</time_frame>
        <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.</population>
        <group_list>
          <group group_id="O1">
            <title>Eziclen®/Izinova®</title>
            <description>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).</description>
          </group>
          <group group_id="O2">
            <title>Klean-Prep®</title>
            <description>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).</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Boston Bowel Preparation Scale (BBPS) Global Score and BBPS Scores by Colon Segment</title>
          <description>The BBPS score for each colon segment (left, transverse, right) was determined by the blinded colonoscopist as follows:&#xD;
0 = Unprepared colon segment with mucosa not seen due to solid stool that cannot be cleared&#xD;
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&#xD;
2 = Minor amount of residual staining, small fragments of stool and/or opaque liquid, but mucosa of segment seen well&#xD;
3 = Entire mucosa of segment seen well with no residual staining, small fragments of stool and/or opaque liquid.&#xD;
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.</description>
          <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.</population>
          <units>scores on a scale</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="125"/>
                <count group_id="O2" value="116"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Left colon</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="124"/>
                    <count group_id="O2" value="116"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.05" lower_limit="1.89" upper_limit="2.22"/>
                    <measurement group_id="O2" value="2.12" lower_limit="1.95" upper_limit="2.29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Transverse colon</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="124"/>
                    <count group_id="O2" value="115"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.25" lower_limit="2.10" upper_limit="2.40"/>
                    <measurement group_id="O2" value="2.33" lower_limit="2.18" upper_limit="2.48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Right colon</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="123"/>
                    <count group_id="O2" value="115"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.92" lower_limit="1.74" upper_limit="2.09"/>
                    <measurement group_id="O2" value="2.16" lower_limit="1.98" upper_limit="2.34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Global score</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="123"/>
                    <count group_id="O2" value="115"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.25" lower_limit="5.86" upper_limit="6.63"/>
                    <measurement group_id="O2" value="6.61" lower_limit="6.21" upper_limit="7.01"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Left colon:&#xD;
Analysis of the treatment difference (Eziclen®/Izinova® minus Klean-Prep®) was performed using a 2-way ANOVA, including treatment and country as covariates.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.4676</p_value>
            <method>ANOVA</method>
            <param_type>Adjusted treatment difference</param_type>
            <param_value>-0.07</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.25</ci_lower_limit>
            <ci_upper_limit>0.12</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Transverse colon:&#xD;
Analysis of the treatment difference (Eziclen®/Izinova® minus Klean-Prep®) was performed using a 2-way ANOVA, including treatment and country as covariates.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.3076</p_value>
            <method>ANOVA</method>
            <param_type>Adjusted treatment difference</param_type>
            <param_value>-0.09</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.25</ci_lower_limit>
            <ci_upper_limit>0.08</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Right colon:&#xD;
Analysis of the treatment difference (Eziclen®/Izinova® minus Klean-Prep®) was performed using a 2-way ANOVA, including treatment and country as covariates.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.0155</p_value>
            <method>ANOVA</method>
            <param_type>Adjusted treatment difference</param_type>
            <param_value>-0.24</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.44</ci_lower_limit>
            <ci_upper_limit>-0.05</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Global score:&#xD;
Analysis of the treatment difference (Eziclen®/Izinova® minus Klean-Prep®) was performed using a 2-way ANOVA, including treatment and country as covariates.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.0975</p_value>
            <method>ANOVA</method>
            <param_type>Adjusted treatment difference</param_type>
            <param_value>-0.36</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.79</ci_lower_limit>
            <ci_upper_limit>0.07</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Subjects With Need for Rescue Treatment</title>
        <description>The percentage of subjects who needed rescue treatment (saline enema) prior to colonoscopy because of inadequate preparation intake was assessed.</description>
        <time_frame>At Day 2 (colonoscopy visit, before colonoscopy)</time_frame>
        <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).</population>
        <group_list>
          <group group_id="O1">
            <title>Eziclen®/Izinova®</title>
            <description>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).</description>
          </group>
          <group group_id="O2">
            <title>Klean-Prep®</title>
            <description>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).</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Subjects With Need for Rescue Treatment</title>
          <description>The percentage of subjects who needed rescue treatment (saline enema) prior to colonoscopy because of inadequate preparation intake was assessed.</description>
          <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).</population>
          <units>percentage of subjects</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="124"/>
                <count group_id="O2" value="116"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20.2" lower_limit="13.1" upper_limit="27.2"/>
                    <measurement group_id="O2" value="14.7" lower_limit="8.2" upper_limit="21.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Analysis was performed using Cochran-Mantel-Haenszel (CMH) chi-square method (using the general association statistic), stratified on country.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.2428</p_value>
            <method>CMH chi-square</method>
            <param_type>Adjusted treatment difference rate</param_type>
            <param_value>1.3847</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.8</ci_lower_limit>
            <ci_upper_limit>2.4</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Subjects With Need for Nasogastric Tube To Complete Preparation</title>
        <description>The percentage of subjects who needed placement of a nasogastric tube to achieve administration of the complete preparation was assessed.</description>
        <time_frame>At Day 1 (treatment visit)</time_frame>
        <population>The ITT population included all randomised subjects who received even a partial dose of study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Eziclen®/Izinova®</title>
            <description>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).</description>
          </group>
          <group group_id="O2">
            <title>Klean-Prep®</title>
            <description>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).</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Subjects With Need for Nasogastric Tube To Complete Preparation</title>
          <description>The percentage of subjects who needed placement of a nasogastric tube to achieve administration of the complete preparation was assessed.</description>
          <population>The ITT population included all randomised subjects who received even a partial dose of study drug.</population>
          <units>percentage of subjects</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="125"/>
                <count group_id="O2" value="116"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.2" lower_limit="2.7" upper_limit="11.7"/>
                    <measurement group_id="O2" value="31.0" lower_limit="22.6" upper_limit="39.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Analysis was performed using CMH chi-square method (using the general association statistic), stratified on country.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <method>CMH chi-square</method>
            <param_type>Adjusted treatment difference rate</param_type>
            <param_value>24.0219</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>12.6</ci_lower_limit>
            <ci_upper_limit>45.9</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Subjects With Colonoscopy Procedure Documented as Completed</title>
        <description>The percentage of subjects with a complete colonoscopy, defined as a procedure that reached the caecum, was assessed.</description>
        <time_frame>At Day 2 (colonoscopy visit)</time_frame>
        <population>The ITT population included all randomised subjects who received even a partial dose of study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Eziclen®/Izinova®</title>
            <description>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).</description>
          </group>
          <group group_id="O2">
            <title>Klean-Prep®</title>
            <description>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).</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Subjects With Colonoscopy Procedure Documented as Completed</title>
          <description>The percentage of subjects with a complete colonoscopy, defined as a procedure that reached the caecum, was assessed.</description>
          <population>The ITT population included all randomised subjects who received even a partial dose of study drug.</population>
          <units>percentage of subjects</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="125"/>
                <count group_id="O2" value="116"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="96.8" lower_limit="93.7" upper_limit="99.9"/>
                    <measurement group_id="O2" value="96.6" lower_limit="93.2" upper_limit="99.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Analysis was performed using CMH chi-square method (using the general association statistic), stratified on country.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.9257</p_value>
            <method>CMH chi-square</method>
            <param_type>Adjusted treatment difference rate</param_type>
            <param_value>1.0022</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.0</ci_lower_limit>
            <ci_upper_limit>1.1</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Median Time to Caecal Intubation</title>
        <description>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.</description>
        <time_frame>From colonoscope introduction to caecal intubation, assessed on Day 2 (colonoscopy visit)</time_frame>
        <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.</population>
        <group_list>
          <group group_id="O1">
            <title>Eziclen®/Izinova®</title>
            <description>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).</description>
          </group>
          <group group_id="O2">
            <title>Klean-Prep®</title>
            <description>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).</description>
          </group>
        </group_list>
        <measure>
          <title>Median Time to Caecal Intubation</title>
          <description>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.</description>
          <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.</population>
          <units>minutes</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="123"/>
                <count group_id="O2" value="115"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.0" lower_limit="10.0" upper_limit="15.0"/>
                    <measurement group_id="O2" value="15.0" lower_limit="12.0" upper_limit="15.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Duration of Examination</title>
        <description>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.</description>
        <time_frame>From caecum intubation to withdrawal of the colonoscope, assessed on Day 2 (colonoscopy visit)</time_frame>
        <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).</population>
        <group_list>
          <group group_id="O1">
            <title>Eziclen®/Izinova®</title>
            <description>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).</description>
          </group>
          <group group_id="O2">
            <title>Klean-Prep®</title>
            <description>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).</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Duration of Examination</title>
          <description>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.</description>
          <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).</population>
          <units>minutes</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="119"/>
                <count group_id="O2" value="111"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14.77" lower_limit="12.63" upper_limit="16.92"/>
                    <measurement group_id="O2" value="15.70" lower_limit="13.50" upper_limit="17.90"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Analysis of the treatment difference (Eziclen®/Izinova® minus Klean-Prep®) was performed using a 2-way ANOVA, including treatment and country as covariates.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.4459</p_value>
            <method>ANOVA</method>
            <param_type>Adjusted treatment difference</param_type>
            <param_value>-0.93</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-3.32</ci_lower_limit>
            <ci_upper_limit>1.47</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Score for Overall Treatment Acceptability, Assessed Using Treatment Acceptability Questionnaire</title>
        <description>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:&#xD;
1 = Very badly accepted/unacceptable&#xD;
2 = Badly but accepted&#xD;
3 = Neither good nor bad&#xD;
4 = Well accepted&#xD;
5 = Very well accepted.&#xD;
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.</description>
        <time_frame>At Day 1 (treatment visit)</time_frame>
        <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).</population>
        <group_list>
          <group group_id="O1">
            <title>Eziclen®/Izinova®</title>
            <description>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).</description>
          </group>
          <group group_id="O2">
            <title>Klean-Prep®</title>
            <description>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).</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Score for Overall Treatment Acceptability, Assessed Using Treatment Acceptability Questionnaire</title>
          <description>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:&#xD;
1 = Very badly accepted/unacceptable&#xD;
2 = Badly but accepted&#xD;
3 = Neither good nor bad&#xD;
4 = Well accepted&#xD;
5 = Very well accepted.&#xD;
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.</description>
          <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).</population>
          <units>scores on a scale</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="125"/>
                <count group_id="O2" value="110"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.93" lower_limit="2.65" upper_limit="3.21"/>
                    <measurement group_id="O2" value="2.22" lower_limit="1.92" upper_limit="2.51"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Analysis of the treatment difference (Eziclen®/Izinova® minus Klean-Prep®) was performed using a 2-way ANOVA, including treatment and country as covariates.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <method>ANOVA</method>
            <param_type>Adjusted treatment difference</param_type>
            <param_value>0.71</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.40</ci_lower_limit>
            <ci_upper_limit>1.03</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Overall Treatment Compliance</title>
        <description>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.</description>
        <time_frame>At Day 1 (treatment visit)</time_frame>
        <population>The ITT population included all randomised subjects who received even a partial dose of study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Eziclen®/Izinova®</title>
            <description>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).</description>
          </group>
          <group group_id="O2">
            <title>Klean-Prep®</title>
            <description>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).</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Overall Treatment Compliance</title>
          <description>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.</description>
          <population>The ITT population included all randomised subjects who received even a partial dose of study drug.</population>
          <units>adjusted percentage of fluid volume (mL)</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="125"/>
                <count group_id="O2" value="116"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Dose 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="96.74" lower_limit="94.19" upper_limit="99.30"/>
                    <measurement group_id="O2" value="95.52" lower_limit="92.90" upper_limit="98.13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dose 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="93.53" lower_limit="89.24" upper_limit="97.81"/>
                    <measurement group_id="O2" value="87.14" lower_limit="82.76" upper_limit="91.53"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Global</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="96.82" lower_limit="93.32" upper_limit="100.31"/>
                    <measurement group_id="O2" value="89.34" lower_limit="85.74" upper_limit="92.93"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Dose 1:&#xD;
Analysis of the treatment difference (Eziclen®/Izinova® minus Klean-Prep®) was performed using a 2-way ANOVA, including treatment and country as covariates.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.3945</p_value>
            <method>ANOVA</method>
            <param_type>Adjusted treatment difference rate</param_type>
            <param_value>1.22</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.60</ci_lower_limit>
            <ci_upper_limit>4.05</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Dose 2:&#xD;
Analysis of the treatment difference (Eziclen®/Izinova® minus Klean-Prep®) was performed using a 2-way ANOVA, including treatment and country as covariates.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.0085</p_value>
            <method>ANOVA</method>
            <param_type>Adjusted treatment difference rate</param_type>
            <param_value>6.38</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.65</ci_lower_limit>
            <ci_upper_limit>11.12</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Global:&#xD;
Analysis of the treatment difference (Eziclen®/Izinova® minus Klean-Prep®) was performed using a 2-way ANOVA, including treatment and country as covariates.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.0036</p_value>
            <method>ANOVA</method>
            <param_type>Adjusted treatment difference rate</param_type>
            <param_value>7.48</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>2.46</ci_lower_limit>
            <ci_upper_limit>12.50</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Subject Tolerability Total Score, Assessed Using a Symptom Scale</title>
        <description>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:&#xD;
1 = No symptom&#xD;
2 = Mild&#xD;
3 = Bothersome&#xD;
4 = Distressing&#xD;
5 = Severely distressing symptoms.&#xD;
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.</description>
        <time_frame>At Day 1 (treatment visit)</time_frame>
        <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).</population>
        <group_list>
          <group group_id="O1">
            <title>Eziclen®/Izinova®</title>
            <description>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).</description>
          </group>
          <group group_id="O2">
            <title>Klean-Prep®</title>
            <description>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).</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Subject Tolerability Total Score, Assessed Using a Symptom Scale</title>
          <description>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:&#xD;
1 = No symptom&#xD;
2 = Mild&#xD;
3 = Bothersome&#xD;
4 = Distressing&#xD;
5 = Severely distressing symptoms.&#xD;
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.</description>
          <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).</population>
          <units>scores on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="124"/>
                <count group_id="O2" value="117"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Dose 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="124"/>
                    <count group_id="O2" value="117"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.48" spread="2.42"/>
                    <measurement group_id="O2" value="6.34" spread="2.78"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dose 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="122"/>
                    <count group_id="O2" value="113"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.93" spread="2.58"/>
                    <measurement group_id="O2" value="6.71" spread="3.07"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Median Time to Clear Effluent</title>
        <description>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.</description>
        <time_frame>From first intake of prescription to first clear watery stool, assessed on Day 1 (treatment visit) and Day 2 (colonoscopy visit)</time_frame>
        <population>The ITT population included all randomised subjects who received even a partial dose of study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Eziclen®/Izinova®</title>
            <description>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).</description>
          </group>
          <group group_id="O2">
            <title>Klean-Prep®</title>
            <description>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).</description>
          </group>
        </group_list>
        <measure>
          <title>Median Time to Clear Effluent</title>
          <description>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.</description>
          <population>The ITT population included all randomised subjects who received even a partial dose of study drug.</population>
          <units>hours</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="125"/>
                <count group_id="O2" value="116"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.3" lower_limit="3.5" upper_limit="5.3"/>
                    <measurement group_id="O2" value="4.8" lower_limit="3.8" upper_limit="5.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Mean Time Between Last Intake of Fluids and Start of Colonoscopy Procedure</title>
        <description>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.</description>
        <time_frame>From end of treatment administration to start of colonoscopy, assessed on Day 1 (treatment visit) and Day 2 (colonoscopy visit)</time_frame>
        <population>The ITT population included all randomised subjects who received even a partial dose of study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Eziclen®/Izinova®</title>
            <description>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).</description>
          </group>
          <group group_id="O2">
            <title>Klean-Prep®</title>
            <description>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).</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Time Between Last Intake of Fluids and Start of Colonoscopy Procedure</title>
          <description>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.</description>
          <population>The ITT population included all randomised subjects who received even a partial dose of study drug.</population>
          <units>hours</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="125"/>
                <count group_id="O2" value="116"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15.30" lower_limit="14.72" upper_limit="15.88"/>
                    <measurement group_id="O2" value="14.25" lower_limit="13.65" upper_limit="14.84"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Analysis of the treatment difference (Eziclen®/Izinova® minus Klean-Prep®) was performed using 2-way ANOVA, including treatment and country as covariates.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.0015</p_value>
            <method>ANOVA</method>
            <param_type>Adjusted treatment difference</param_type>
            <param_value>1.05</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.41</ci_lower_limit>
            <ci_upper_limit>1.69</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Treatment-emergent adverse events (TEAEs) were collected from Day 1 up to Day 32 (30 days [-5+/15] after colonoscopy).</time_frame>
      <desc>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).</desc>
      <group_list>
        <group group_id="E1">
          <title>Eziclen®/Izinova®</title>
          <description>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).</description>
        </group>
        <group group_id="E2">
          <title>Klean-Prep®</title>
          <description>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).</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 23.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="124"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="117"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="124"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="117"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="124"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="117"/>
              </event>
              <event>
                <sub_title>Crohn's disease</sub_title>
                <description>Diagnostic finding at colonoscopy, reported as non-related TEAE and related to the indication for colonoscopy.</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="124"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="117"/>
              </event>
              <event>
                <sub_title>Intestinal polyp</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="124"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="117"/>
              </event>
              <event>
                <sub_title>Intestinal stenosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="124"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="117"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Drug hypersensitivity</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="124"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="117"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood creatine phosphokinase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="124"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="117"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>2</frequency_threshold>
        <default_vocab>MedDRA 23.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="111" subjects_at_risk="124"/>
                <counts group_id="E2" subjects_affected="105" subjects_at_risk="117"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="123" subjects_affected="90" subjects_at_risk="124"/>
                <counts group_id="E2" events="115" subjects_affected="84" subjects_at_risk="117"/>
              </event>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <counts group_id="E1" events="91" subjects_affected="67" subjects_at_risk="124"/>
                <counts group_id="E2" events="107" subjects_affected="77" subjects_at_risk="117"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" events="83" subjects_affected="64" subjects_at_risk="124"/>
                <counts group_id="E2" events="84" subjects_affected="64" subjects_at_risk="117"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="11" subjects_affected="11" subjects_at_risk="124"/>
                <counts group_id="E2" events="11" subjects_affected="10" subjects_at_risk="117"/>
              </event>
              <event>
                <sub_title>Crohn's disease</sub_title>
                <description>Diagnostic finding at colonoscopy, reported as non-related TEAE and related to the indication for colonoscopy.</description>
                <counts group_id="E1" events="9" subjects_affected="9" subjects_at_risk="124"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="117"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="124"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="117"/>
              </event>
              <event>
                <sub_title>Colitis ulcerative</sub_title>
                <description>Diagnostic finding at colonoscopy, reported as non-related TEAE and related to the indication for colonoscopy.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="124"/>
                <counts group_id="E2" events="6" subjects_affected="6" subjects_at_risk="117"/>
              </event>
              <event>
                <sub_title>Gastritis</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="124"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="117"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="9" subjects_affected="9" subjects_at_risk="124"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="117"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The sponsor requires that reasonable opportunity be given to review the content and conclusions of any abstract, presentation, or paper before the material is submitted for publication or communicated. The sponsor will comment on the draft documents within the time period agreed in the contractual arrangements. Requested amendments will be incorporated by the author, provided they do not alter the scientific value of the material.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Ipsen Medical Director</name_or_title>
      <organization>Ipsen</organization>
      <phone>use email</phone>
      <email>clinical.trials@ipsen.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03008460
org study id: F-FR-58800-003
secondary id: 2016-002265-60
nct id: NCT03008460
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: Single (Investigator)
measure: Percentage of Subjects With Successful Overall Colon Preparation, Assessed With the Cleansing Score (4-point Scale)
time frame: At Day 2 (colonoscopy visit)
description: 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.
measure: Mean Colon Cleansing Score (4-point Scale)
time frame: At Day 2 (colonoscopy visit)
description: 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.
measure: Mean Boston Bowel Preparation Scale (BBPS) Global Score and BBPS Scores by Colon Segment
time frame: At Day 2 (colonoscopy visit)
description: 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.
measure: Percentage of Subjects With Need for Rescue Treatment
time frame: At Day 2 (colonoscopy visit, before colonoscopy)
description: The percentage of subjects who needed rescue treatment (saline enema) prior to colonoscopy because of inadequate preparation intake was assessed.
measure: Percentage of Subjects With Need for Nasogastric Tube To Complete Preparation
time frame: At Day 1 (treatment visit)
description: The percentage of subjects who needed placement of a nasogastric tube to achieve administration of the complete preparation was assessed.
measure: Percentage of Subjects With Colonoscopy Procedure Documented as Completed
time frame: At Day 2 (colonoscopy visit)
description: The percentage of subjects with a complete colonoscopy, defined as a procedure that reached the caecum, was assessed.
measure: Median Time to Caecal Intubation
time frame: From colonoscope introduction to caecal intubation, assessed on Day 2 (colonoscopy visit)
description: 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.
measure: Mean Duration of Examination
time frame: From caecum intubation to withdrawal of the colonoscope, assessed on Day 2 (colonoscopy visit)
description: 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.
measure: Mean Score for Overall Treatment Acceptability, Assessed Using Treatment Acceptability Questionnaire
time frame: At Day 1 (treatment visit)
description: 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.
measure: Mean Overall Treatment Compliance
time frame: At Day 1 (treatment visit)
description: 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.
measure: Mean Subject Tolerability Total Score, Assessed Using a Symptom Scale
time frame: At Day 1 (treatment visit)
description: 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.
measure: Median Time to Clear Effluent
time frame: From first intake of prescription to first clear watery stool, assessed on Day 1 (treatment visit) and Day 2 (colonoscopy visit)
description: 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.
measure: Mean Time Between Last Intake of Fluids and Start of Colonoscopy Procedure
time frame: From end of treatment administration to start of colonoscopy, assessed on Day 1 (treatment visit) and Day 2 (colonoscopy visit)
description: 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.
arm group label: Eziclen®/Izinova®
arm group type: Experimental
arm group label: Klean-Prep®
arm group type: Active Comparator
intervention type: Drug
intervention name: Eziclen®/Izinova®
description: Oral solution taken the evening before the colonoscopy
arm group label: Eziclen®/Izinova®
other name: Suprep®
intervention type: Drug
intervention name: Klean-Prep®
description: Oral solution taken the evening before the colonoscopy
arm group label: Klean-Prep®
criteria: 
gender: All
minimum age: 12 Years
maximum age: 17 Years
healthy volunteers: No
last name: Ipsen Medical Director
role: Study Director
affiliation: Ipsen Consumer Healthcare
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Czechia
country: France
country: Germany
country: Italy
country: Netherlands
country: Poland
responsible party type: Sponsor
mesh term: Digestive System Diseases
mesh term: Gastrointestinal Diseases
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 