<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/NCT03749252</url>
  </required_header>
  <id_info>
    <org_study_id>GDX-44-007</org_study_id>
    <secondary_id>2018-001516-30</secondary_id>
    <nct_id>NCT03749252</nct_id>
  </id_info>
  <brief_title>Pharmacokinetics, Safety and Efficacy of P03277 in Pediatric Patients Undergoing Central Nervous System Contrast-enhanced MRI</brief_title>
  <official_title>Pharmacokinetics, Safety and Efficacy of a New Gadolinium-based Contrast Agent, P03277, in Pediatric Patients From 2 to 17 Years of Age Undergoing Central Nervous System Contrast-enhanced MRI</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Guerbet</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Guerbet</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a pharmacokinetics (PK), open-label, uncontrolled, multicenter phase II trial with&#xD;
      age-staggered approach.&#xD;
&#xD;
      The primary objective is to evaluate the PK profile of gadopiclenol in plasma following&#xD;
      single IV injection of 0.05 mmol/kg body weight (BW) in pediatric population aged from 2 to&#xD;
      17 years undergoing CNS contrast-enhanced MRI (CNS cohort).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A population PK approach and an age-down staggered approach will be used. Patients will be&#xD;
      recruited into 3 predefined age groups: 12-17, 7-11 and 2-6 years. The inclusions will start&#xD;
      with the older group (Adolescents, 12-17 years), followed by Preadolescents (7-11 years) and&#xD;
      finally Young Children (2-6 years of age).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 6, 2018</start_date>
  <completion_date type="Actual">August 10, 2020</completion_date>
  <primary_completion_date type="Actual">December 18, 2019</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Elimination Half-life</measure>
    <time_frame>4 blood samples per patient were taken post-injection for PK analysis, one within each window: 1 min to 20 min, 30 min to 45 min, 2 to 3 hours and 7 to 8 hours</time_frame>
    <description>P03277 pharmacokinetic parameters in plasma were determined from the population PK model.&#xD;
This outcome was assessed only for the CNS cohort.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Total Clearance</measure>
    <time_frame>4 blood samples per patient were taken post-injection for PK analysis, one within each window: 1 min to 20 min, 30 min to 45 min, 2 to 3 hours and 7 to 8 hours</time_frame>
    <description>P03277 pharmacokinetic parameters in plasma were determined from the population PK model.&#xD;
This outcome was assessed only for the CNS cohort.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Central Volume of Distribution</measure>
    <time_frame>4 blood samples per patient were taken post-injection for PK analysis, one within each window: 1 min to 20 min, 30 min to 45 min, 2 to 3 hours and 7 to 8 hours</time_frame>
    <description>P03277 pharmacokinetic parameters in plasma were determined from the population PK model.&#xD;
This outcome was assessed only for the CNS cohort.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Peripheral Volume of Distribution</measure>
    <time_frame>4 blood samples per patient were taken post-injection for PK analysis, one within each window: 1 min to 20 min, 30 min to 45 min, 2 to 3 hours and 7 to 8 hours</time_frame>
    <description>P03277 pharmacokinetic parameters in plasma were determined from the population PK model.&#xD;
This outcome was assessed only for the CNS cohort.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Curve</measure>
    <time_frame>4 blood samples per patient were taken post-injection for PK analysis, one within each window: 1 min to 20 min, 30 min to 45 min, 2 to 3 hours and 7 to 8 hours</time_frame>
    <description>P03277 pharmacokinetic parameters in plasma were determined from the population PK model.&#xD;
This outcome was assessed only for the CNS cohort.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Simulated Concentrations 10 Minutes Post-injection</measure>
    <time_frame>10 minutes post-injection</time_frame>
    <description>P03277 pharmacokinetic parameters in plasma were determined from the population PK model.&#xD;
This outcome was assessed only for the CNS cohort.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Simulated Concentrations 20 Minutes Post-injection</measure>
    <time_frame>20 minutes post-injection</time_frame>
    <description>P03277 pharmacokinetic parameters in plasma were determined from the population PK model.&#xD;
This outcome was assessed only for the CNS cohort.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Simulated Concentrations 30 Minutes Post-injection</measure>
    <time_frame>30 minutes post-injection</time_frame>
    <description>P03277 pharmacokinetic parameters in plasma were determined from the population PK model.&#xD;
This outcome was assessed only for the CNS cohort.</description>
  </primary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">80</enrollment>
  <condition>Central Nervous System Indication</condition>
  <condition>Pediatric Patients</condition>
  <condition>Body Indication</condition>
  <arm_group>
    <arm_group_label>CNS Cohort 2-6 years</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Pediatric patients aged 2-6 years undergoing CNS contrast-enhanced MRI</description>
  </arm_group>
  <arm_group>
    <arm_group_label>CNS Cohort 7-11 years</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Pediatric patients aged 7-11 years undergoing CNS contrast-enhanced MRI</description>
  </arm_group>
  <arm_group>
    <arm_group_label>CNS Cohort 12-17 years</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Pediatric patients aged 12-17 years undergoing CNS contrast-enhanced MRI</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Body Cohort 2-6 years</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Pediatric patients aged 2-6 years undergoing contrast-enhanced MRI of other body organs (head and neck, thorax, abdomen, pelvis or musculoskeletal system)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Body Cohort 7-11 years</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Pediatric patients aged 7-11 years undergoing contrast-enhanced MRI of other body organs (head and neck, thorax, abdomen, pelvis or musculoskeletal system)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Body Cohort 12-17 years</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Pediatric patients aged 12-17 years undergoing contrast-enhanced MRI of other body organs (head and neck, thorax, abdomen, pelvis or musculoskeletal system)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>P03277</intervention_name>
    <description>A dose of 0.05 mmol/kg body weight (0.1 mL/kg body weight) of P03277 will be administered to each patient in a single intravenous injection.</description>
    <arm_group_label>Body Cohort 12-17 years</arm_group_label>
    <arm_group_label>Body Cohort 2-6 years</arm_group_label>
    <arm_group_label>Body Cohort 7-11 years</arm_group_label>
    <arm_group_label>CNS Cohort 12-17 years</arm_group_label>
    <arm_group_label>CNS Cohort 2-6 years</arm_group_label>
    <arm_group_label>CNS Cohort 7-11 years</arm_group_label>
    <other_name>gadopiclenol</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        To be included in the study, the patient had to meet all the following criteria:&#xD;
&#xD;
          1. Female or male pediatric patient aged 2 to 17 years,&#xD;
&#xD;
          2. Patient with known or suspected lesion(s) scheduled to undergo routine&#xD;
             contrast-enhanced MRI of CNS or of other organs including at least one organ among&#xD;
             head and neck, thorax, abdomen, pelvis or musculoskeletal system (including&#xD;
             extremities),&#xD;
&#xD;
          3. Patient whose parent(s) or legal guardian having read the information, provided their&#xD;
             consent to patient's participation in writing by dating and signing the informed&#xD;
             consent prior to any trial related procedure being conducted,&#xD;
&#xD;
          4. Patient with capacity of understanding who received age- and maturity-appropriate&#xD;
             information and provided his/her assent to participate in the trial (as required by&#xD;
             national regulations),&#xD;
&#xD;
          5. Patient affiliated to national health insurance according to local regulatory&#xD;
             requirements.&#xD;
&#xD;
        Non-inclusion Criteria:&#xD;
&#xD;
        Patients could not be included in the study if they presented with one or more of the&#xD;
        following non-inclusion criteria:&#xD;
&#xD;
          1. Patient planned for treatment or procedure (e.g., surgery) that would prevent&#xD;
             obtaining the required blood samples or performing other trial procedures between the&#xD;
             screening visit and up to 1 day after gadopiclenol administration,&#xD;
&#xD;
          2. Patient undergoing treatment or procedure (e.g., diuretics, clinically significant&#xD;
             blood loss or blood transfusion) preceding or subsequent to gadopiclenol&#xD;
             administration that would alter gadopiclenol PK parameters,&#xD;
&#xD;
          3. Patient with acute or chronic renal insufficiency defined as estimated Glomerular&#xD;
             Filtration Rate (eGFR) out of age-adjusted normal ranges (eGFR calculated with bedside&#xD;
             Schwartz equation),&#xD;
&#xD;
          4. Patients referred for MR Angiography,&#xD;
&#xD;
          5. Patient with history of bleeding disorder,&#xD;
&#xD;
          6. Patient with known severe liver disease,&#xD;
&#xD;
          7. Patient with known cardiac disease (e.g., heart rhythm anomalies, long QT syndrome),&#xD;
&#xD;
          8. Patient with any clinically significant abnormal 12-lead ECG that in the&#xD;
             Investigator's opinion would affect the safety evaluation or place the patient at&#xD;
             risk,&#xD;
&#xD;
          9. Patient with electrolyte or fluid imbalance that at Investigator's judgment presents&#xD;
             undue risk assessed within 1 month prior to gadopiclenol administration,&#xD;
&#xD;
         10. Patient undergoing a change in chemotherapy within 1 day prior to or 1 day after&#xD;
             gadopiclenol administration,&#xD;
&#xD;
         11. Patient who received any other contrast agent for CT and/or MRI within 1 week prior to&#xD;
             or 1 week after gadopiclenol administration,&#xD;
&#xD;
         12. Patient with contraindication for MRI such as iron metal implants (e.g., aneurysm&#xD;
             clips, pacemaker),&#xD;
&#xD;
         13. Patient with history of anaphylactoid or anaphylactic reaction to any allergen&#xD;
             including drugs,&#xD;
&#xD;
         14. Patient with history of hypersensitivity caused by any contrast media / agents&#xD;
             (iodinated or gadolinium-based),&#xD;
&#xD;
         15. Patient with known contraindication(s) to the use of any GBCA,&#xD;
&#xD;
         16. Pregnant or breast-feeding female patient (female patient with childbearing potential&#xD;
             [who experienced menarche] must have a negative urine pregnancy test within 24 hours&#xD;
             prior to gadopiclenol administration and must be using medically approved&#xD;
             contraception* if sexually active),&#xD;
&#xD;
         17. Patient with anticipated, current or past condition (medical, psychological, social or&#xD;
             geographical) that would compromise the patient's safety or her/his ability to&#xD;
             participate to the whole trial,&#xD;
&#xD;
         18. Patient unlikely to comply with the protocol, e.g., uncooperative attitude of&#xD;
             parent(s) or legal guardian, inability to return for follow-up visits and unlikelihood&#xD;
             of completing the trial,&#xD;
&#xD;
         19. Having participated in a clinical trial and having received any investigational&#xD;
             product within 7 days prior to gadopiclenol administration or planned during the&#xD;
             trial,&#xD;
&#xD;
         20. Patient previously included in this trial,&#xD;
&#xD;
         21. Patient related to the Investigator or any other trial staff or relative directly&#xD;
             involved in the trial conduct.&#xD;
&#xD;
               -  medically approved contraception methods include: female sterilization, use of&#xD;
                  oral, injected or implanted hormonal methods of contraception or other forms of&#xD;
                  hormonal contraception that have comparable efficacy (failure rate &lt;1%), for&#xD;
                  example hormone vaginal ring or transdermal hormone contraception, placement of&#xD;
                  an Intrauterine Device (IUD) or Intrauterine System (IUS), barrier methods of&#xD;
                  contraception (condom or occlusive cap (diaphragm or cervical/vault caps) with&#xD;
                  spermicidal foam/gel/film/cream/ vaginal suppository).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>2 Years</minimum_age>
    <maximum_age>17 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Elżbieta Jurkiewicz, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Instytut Pomnik</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>MHAT Central Onco Hospital Ltd</name>
      <address>
        <city>Plovdiv</city>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acibadem City Clinic Tokuda Hospital</name>
      <address>
        <city>Sofia</city>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MHAT Dr. Stoyan Kirkovich</name>
      <address>
        <city>Stara Zagora</city>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Semmelweis Egyetem II. sz Gyermekgyogyaszati Klinika</name>
      <address>
        <city>Budapest</city>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Markhot Ferenc Oktatokorhaz es Rendelointezet</name>
      <address>
        <city>Eger</city>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>B.-A.-Z. Megyei Korhaz Gyermek-Egeszsegugyi Kozpont</name>
      <address>
        <city>Miskolc</city>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Szpital Uniwersytecki nr 1 w Bydgoszczy im. dr Jurasza, Oddział Kliniczny Chirurgii Ogólnej i Onkologicznej Dzieci i Młodzieży</name>
      <address>
        <city>Bydgoszcz</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Uniwersytecki Szpital Dziecięcy w Lublinie</name>
      <address>
        <city>Lublin</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinika Chirurgii Dziecięcej</name>
      <address>
        <city>Rzeszów</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instytut &quot;Pomnik -Centrum Zdrowia Dziecka&quot;</name>
      <address>
        <city>Warsaw</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Zakład Radiologii PediatrycznejSamodzielny Publ. Dziecięcy Szp. Kliniczny w Warszawie</name>
      <address>
        <city>Warsaw</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instytut Centrum Zdrowia Matki Polki</name>
      <address>
        <city>Łódź</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>II. Detská klinika SZU, Detská fakultná nemocnica s poliklinikou Banská Bystrica</name>
      <address>
        <city>Banská Bystrica</city>
        <country>Slovakia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinika detí a dorastu JLF UK a UNM, Univerzitná nemocnica Martin</name>
      <address>
        <city>Martin</city>
        <country>Slovakia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Faculty hospital Nitra, Clinic of neonates, children and adolescents</name>
      <address>
        <city>Nitra</city>
        <country>Slovakia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's City Clinical Hospital</name>
      <address>
        <city>Dnipro</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Bulgaria</country>
    <country>Hungary</country>
    <country>Poland</country>
    <country>Slovakia</country>
    <country>Ukraine</country>
  </location_countries>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>November 20, 2018</study_first_submitted>
  <study_first_submitted_qc>November 20, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 21, 2018</study_first_posted>
  <results_first_submitted>March 29, 2022</results_first_submitted>
  <results_first_submitted_qc>May 5, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">June 1, 2022</results_first_posted>
  <disposition_first_submitted>August 25, 2020</disposition_first_submitted>
  <disposition_first_submitted_qc>May 5, 2022</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">June 1, 2022</disposition_first_posted>
  <last_update_submitted>May 5, 2022</last_update_submitted>
  <last_update_submitted_qc>May 5, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">June 1, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <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>April 24, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/52/NCT03749252/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>January 27, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/52/NCT03749252/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>CNS &amp; Body Cohorts 2-6 Years</title>
          <description>Pediatric patients aged 2-6 years undergoing CNS or Body contrast-enhanced MRI&#xD;
P03277: A dose of 0.05 mmol/kg body weight (0.1 mL/kg body weight) of P03277 will be administered to each patient in a single intravenous injection.</description>
        </group>
        <group group_id="P2">
          <title>CNS &amp; Body Cohorts 7-11 Years</title>
          <description>Pediatric patients aged 7-11 years undergoing CNS or Body contrast-enhanced MRI&#xD;
P03277: A dose of 0.05 mmol/kg body weight (0.1 mL/kg body weight) of P03277 will be administered to each patient in a single intravenous injection.</description>
        </group>
        <group group_id="P3">
          <title>CNS &amp; Body Cohorts 12-17 Years</title>
          <description>Pediatric patients aged 12-17 years undergoing CNS or Body contrast-enhanced MRI&#xD;
P03277: A dose of 0.05 mmol/kg body weight (0.1 mL/kg body weight) of P03277 will be administered to each patient in a single intravenous injection.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="26"/>
                <participants group_id="P2" count="23"/>
                <participants group_id="P3" count="31"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="26"/>
                <participants group_id="P2" count="23"/>
                <participants group_id="P3" count="31"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>All patients who received gadopiclenol administration and underwent CNS or Body MRI</population>
      <group_list>
        <group group_id="B1">
          <title>CNS &amp; Body Cohorts 2-6 Years</title>
          <description>Pediatric patients aged 2-6 years undergoing CNS or Body contrast-enhanced MRI&#xD;
P03277: A dose of 0.05 mmol/kg body weight (0.1 mL/kg body weight) of P03277 will be administered to each patient in a single intravenous injection.</description>
        </group>
        <group group_id="B2">
          <title>CNS &amp; Body Cohorts 7-11 Years</title>
          <description>Pediatric patients aged 7-11 years undergoing CNS or Body contrast-enhanced MRI&#xD;
P03277: A dose of 0.05 mmol/kg body weight (0.1 mL/kg body weight) of P03277 will be administered to each patient in a single intravenous injection.</description>
        </group>
        <group group_id="B3">
          <title>CNS &amp; Body Cohorts 12-17 Years</title>
          <description>Pediatric patients aged 12-17 years undergoing CNS or Body contrast-enhanced MRI&#xD;
P03277: A dose of 0.05 mmol/kg body weight (0.1 mL/kg body weight) of P03277 will be administered to each patient in a single intravenous injection.</description>
        </group>
        <group group_id="B4">
          <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="26"/>
            <count group_id="B2" value="23"/>
            <count group_id="B3" value="31"/>
            <count group_id="B4" value="80"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3.8" spread="1.3"/>
                    <measurement group_id="B2" value="8.8" spread="1.2"/>
                    <measurement group_id="B3" value="14.3" spread="1.6"/>
                    <measurement group_id="B4" value="9.3" spread="4.6"/>
                  </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>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="19"/>
                    <measurement group_id="B4" value="39"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="12"/>
                    <measurement group_id="B4" value="41"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="26"/>
                    <measurement group_id="B2" value="23"/>
                    <measurement group_id="B3" value="31"/>
                    <measurement group_id="B4" value="80"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="26"/>
                    <measurement group_id="B2" value="23"/>
                    <measurement group_id="B3" value="31"/>
                    <measurement group_id="B4" value="80"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Elimination Half-life</title>
        <description>P03277 pharmacokinetic parameters in plasma were determined from the population PK model.&#xD;
This outcome was assessed only for the CNS cohort.</description>
        <time_frame>4 blood samples per patient were taken post-injection for PK analysis, one within each window: 1 min to 20 min, 30 min to 45 min, 2 to 3 hours and 7 to 8 hours</time_frame>
        <population>All patients of the CNS cohort who received gadopiclenol administration except one patient, whose PK blood samples were assessed out of stability period</population>
        <group_list>
          <group group_id="O1">
            <title>CNS Cohort 2-6 Years</title>
            <description>Pediatric patients aged 2-6 years undergoing CNS contrast-enhanced MRI&#xD;
P03277: A dose of 0.05 mmol/kg body weight (0.1 mL/kg body weight) of P03277 will be administered to each patient in a single intravenous injection.</description>
          </group>
          <group group_id="O2">
            <title>CNS Cohort 7-11 Years</title>
            <description>Pediatric patients aged 7-11 years undergoing CNS contrast-enhanced MRI&#xD;
P03277: A dose of 0.05 mmol/kg body weight (0.1 mL/kg body weight) of P03277 will be administered to each patient in a single intravenous injection.</description>
          </group>
          <group group_id="O3">
            <title>CNS Cohort 12-17 Years</title>
            <description>Pediatric patients aged 12-17 years undergoing CNS contrast-enhanced MRI&#xD;
P03277: A dose of 0.05 mmol/kg body weight (0.1 mL/kg body weight) of P03277 will be administered to each patient in a single intravenous injection.</description>
          </group>
        </group_list>
        <measure>
          <title>Elimination Half-life</title>
          <description>P03277 pharmacokinetic parameters in plasma were determined from the population PK model.&#xD;
This outcome was assessed only for the CNS cohort.</description>
          <population>All patients of the CNS cohort who received gadopiclenol administration except one patient, whose PK blood samples were assessed out of stability period</population>
          <units>hours</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="20"/>
                <count group_id="O3" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.29" lower_limit="0.69" upper_limit="3.38"/>
                    <measurement group_id="O2" value="1.48" lower_limit="0.83" upper_limit="3.20"/>
                    <measurement group_id="O3" value="1.77" lower_limit="1.00" upper_limit="3.57"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Total Clearance</title>
        <description>P03277 pharmacokinetic parameters in plasma were determined from the population PK model.&#xD;
This outcome was assessed only for the CNS cohort.</description>
        <time_frame>4 blood samples per patient were taken post-injection for PK analysis, one within each window: 1 min to 20 min, 30 min to 45 min, 2 to 3 hours and 7 to 8 hours</time_frame>
        <population>All patients of the CNS cohort who received gadopiclenol administration except one patient, whose PK blood samples were assessed out of stability period</population>
        <group_list>
          <group group_id="O1">
            <title>CNS Cohort 2-6 Years</title>
            <description>Pediatric patients aged 2-6 years undergoing CNS contrast-enhanced MRI&#xD;
P03277: A dose of 0.05 mmol/kg body weight (0.1 mL/kg body weight) of P03277 will be administered to each patient in a single intravenous injection.</description>
          </group>
          <group group_id="O2">
            <title>CNS Cohort 7-11 Years</title>
            <description>Pediatric patients aged 7-11 years undergoing CNS contrast-enhanced MRI&#xD;
P03277: A dose of 0.05 mmol/kg body weight (0.1 mL/kg body weight) of P03277 will be administered to each patient in a single intravenous injection.</description>
          </group>
          <group group_id="O3">
            <title>CNS Cohort 12-17 Years</title>
            <description>Pediatric patients aged 12-17 years undergoing CNS contrast-enhanced MRI&#xD;
P03277: A dose of 0.05 mmol/kg body weight (0.1 mL/kg body weight) of P03277 will be administered to each patient in a single intravenous injection.</description>
          </group>
        </group_list>
        <measure>
          <title>Total Clearance</title>
          <description>P03277 pharmacokinetic parameters in plasma were determined from the population PK model.&#xD;
This outcome was assessed only for the CNS cohort.</description>
          <population>All patients of the CNS cohort who received gadopiclenol administration except one patient, whose PK blood samples were assessed out of stability period</population>
          <units>L/h/kg</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="20"/>
                <count group_id="O3" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.12" lower_limit="0.05" upper_limit="0.28"/>
                    <measurement group_id="O2" value="0.10" lower_limit="0.04" upper_limit="0.24"/>
                    <measurement group_id="O3" value="0.08" lower_limit="0.04" upper_limit="0.20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Central Volume of Distribution</title>
        <description>P03277 pharmacokinetic parameters in plasma were determined from the population PK model.&#xD;
This outcome was assessed only for the CNS cohort.</description>
        <time_frame>4 blood samples per patient were taken post-injection for PK analysis, one within each window: 1 min to 20 min, 30 min to 45 min, 2 to 3 hours and 7 to 8 hours</time_frame>
        <population>All patients of the CNS cohort who received gadopiclenol administration except one patient, whose PK blood samples were assessed out of stability period</population>
        <group_list>
          <group group_id="O1">
            <title>CNS Cohort 2-6 Years</title>
            <description>Pediatric patients aged 2-6 years undergoing CNS contrast-enhanced MRI&#xD;
P03277: A dose of 0.05 mmol/kg body weight (0.1 mL/kg body weight) of P03277 will be administered to each patient in a single intravenous injection.</description>
          </group>
          <group group_id="O2">
            <title>CNS Cohort 7-11 Years</title>
            <description>Pediatric patients aged 7-11 years undergoing CNS contrast-enhanced MRI&#xD;
P03277: A dose of 0.05 mmol/kg body weight (0.1 mL/kg body weight) of P03277 will be administered to each patient in a single intravenous injection.</description>
          </group>
          <group group_id="O3">
            <title>CNS Cohort 12-17 Years</title>
            <description>Pediatric patients aged 12-17 years undergoing CNS contrast-enhanced MRI&#xD;
P03277: A dose of 0.05 mmol/kg body weight (0.1 mL/kg body weight) of P03277 will be administered to each patient in a single intravenous injection.</description>
          </group>
        </group_list>
        <measure>
          <title>Central Volume of Distribution</title>
          <description>P03277 pharmacokinetic parameters in plasma were determined from the population PK model.&#xD;
This outcome was assessed only for the CNS cohort.</description>
          <population>All patients of the CNS cohort who received gadopiclenol administration except one patient, whose PK blood samples were assessed out of stability period</population>
          <units>L/kg</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="20"/>
                <count group_id="O3" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.12" lower_limit="0.06" upper_limit="0.26"/>
                    <measurement group_id="O2" value="0.12" lower_limit="0.06" upper_limit="0.24"/>
                    <measurement group_id="O3" value="0.11" lower_limit="0.05" upper_limit="0.24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Peripheral Volume of Distribution</title>
        <description>P03277 pharmacokinetic parameters in plasma were determined from the population PK model.&#xD;
This outcome was assessed only for the CNS cohort.</description>
        <time_frame>4 blood samples per patient were taken post-injection for PK analysis, one within each window: 1 min to 20 min, 30 min to 45 min, 2 to 3 hours and 7 to 8 hours</time_frame>
        <population>All patients of the CNS cohort who received gadopiclenol administration except one patient, whose PK blood samples were assessed out of stability period</population>
        <group_list>
          <group group_id="O1">
            <title>CNS Cohort 2-6 Years</title>
            <description>Pediatric patients aged 2-6 years undergoing CNS contrast-enhanced MRI&#xD;
P03277: A dose of 0.05 mmol/kg body weight (0.1 mL/kg body weight) of P03277 will be administered to each patient in a single intravenous injection.</description>
          </group>
          <group group_id="O2">
            <title>CNS Cohort 7-11 Years</title>
            <description>Pediatric patients aged 7-11 years undergoing CNS contrast-enhanced MRI&#xD;
P03277: A dose of 0.05 mmol/kg body weight (0.1 mL/kg body weight) of P03277 will be administered to each patient in a single intravenous injection.</description>
          </group>
          <group group_id="O3">
            <title>CNS Cohort 12-17 Years</title>
            <description>Pediatric patients aged 12-17 years undergoing CNS contrast-enhanced MRI&#xD;
P03277: A dose of 0.05 mmol/kg body weight (0.1 mL/kg body weight) of P03277 will be administered to each patient in a single intravenous injection.</description>
          </group>
        </group_list>
        <measure>
          <title>Peripheral Volume of Distribution</title>
          <description>P03277 pharmacokinetic parameters in plasma were determined from the population PK model.&#xD;
This outcome was assessed only for the CNS cohort.</description>
          <population>All patients of the CNS cohort who received gadopiclenol administration except one patient, whose PK blood samples were assessed out of stability period</population>
          <units>L/kg</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="20"/>
                <count group_id="O3" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.06" lower_limit="0.06" upper_limit="0.06"/>
                    <measurement group_id="O2" value="0.06" lower_limit="0.06" upper_limit="0.06"/>
                    <measurement group_id="O3" value="0.06" lower_limit="0.06" upper_limit="0.06"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Area Under the Curve</title>
        <description>P03277 pharmacokinetic parameters in plasma were determined from the population PK model.&#xD;
This outcome was assessed only for the CNS cohort.</description>
        <time_frame>4 blood samples per patient were taken post-injection for PK analysis, one within each window: 1 min to 20 min, 30 min to 45 min, 2 to 3 hours and 7 to 8 hours</time_frame>
        <population>All patients of the CNS cohort who received gadopiclenol administration except one patient, whose PK blood samples were assessed out of stability period</population>
        <group_list>
          <group group_id="O1">
            <title>CNS Cohort 2-6 Years</title>
            <description>Pediatric patients aged 2-6 years undergoing CNS contrast-enhanced MRI&#xD;
P03277: A dose of 0.05 mmol/kg body weight (0.1 mL/kg body weight) of P03277 will be administered to each patient in a single intravenous injection.</description>
          </group>
          <group group_id="O2">
            <title>CNS Cohort 7-11 Years</title>
            <description>Pediatric patients aged 7-11 years undergoing CNS contrast-enhanced MRI&#xD;
P03277: A dose of 0.05 mmol/kg body weight (0.1 mL/kg body weight) of P03277 will be administered to each patient in a single intravenous injection.</description>
          </group>
          <group group_id="O3">
            <title>CNS Cohort 12-17 Years</title>
            <description>Pediatric patients aged 12-17 years undergoing CNS contrast-enhanced MRI&#xD;
P03277: A dose of 0.05 mmol/kg body weight (0.1 mL/kg body weight) of P03277 will be administered to each patient in a single intravenous injection.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Curve</title>
          <description>P03277 pharmacokinetic parameters in plasma were determined from the population PK model.&#xD;
This outcome was assessed only for the CNS cohort.</description>
          <population>All patients of the CNS cohort who received gadopiclenol administration except one patient, whose PK blood samples were assessed out of stability period</population>
          <units>mg.h/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="20"/>
                <count group_id="O3" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="403.16" spread="93.35"/>
                    <measurement group_id="O2" value="477.25" spread="105.71"/>
                    <measurement group_id="O3" value="582.30" spread="122.08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Simulated Concentrations 10 Minutes Post-injection</title>
        <description>P03277 pharmacokinetic parameters in plasma were determined from the population PK model.&#xD;
This outcome was assessed only for the CNS cohort.</description>
        <time_frame>10 minutes post-injection</time_frame>
        <population>All patients of the CNS cohort who received gadopiclenol administration except one patient, whose PK blood samples were assessed out of stability period</population>
        <group_list>
          <group group_id="O1">
            <title>CNS Cohort 2-6 Years</title>
            <description>Pediatric patients aged 2-6 years undergoing CNS contrast-enhanced MRI&#xD;
P03277: A dose of 0.05 mmol/kg body weight (0.1 mL/kg body weight) of P03277 will be administered to each patient in a single intravenous injection.</description>
          </group>
          <group group_id="O2">
            <title>CNS Cohort 7-11 Years</title>
            <description>Pediatric patients aged 7-11 years undergoing CNS contrast-enhanced MRI&#xD;
P03277: A dose of 0.05 mmol/kg body weight (0.1 mL/kg body weight) of P03277 will be administered to each patient in a single intravenous injection.</description>
          </group>
          <group group_id="O3">
            <title>CNS Cohort 12-17 Years</title>
            <description>Pediatric patients aged 12-17 years undergoing CNS contrast-enhanced MRI&#xD;
P03277: A dose of 0.05 mmol/kg body weight (0.1 mL/kg body weight) of P03277 will be administered to each patient in a single intravenous injection.</description>
          </group>
        </group_list>
        <measure>
          <title>Simulated Concentrations 10 Minutes Post-injection</title>
          <description>P03277 pharmacokinetic parameters in plasma were determined from the population PK model.&#xD;
This outcome was assessed only for the CNS cohort.</description>
          <population>All patients of the CNS cohort who received gadopiclenol administration except one patient, whose PK blood samples were assessed out of stability period</population>
          <units>mg/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="20"/>
                <count group_id="O3" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="302.11" spread="44.68"/>
                    <measurement group_id="O2" value="327.20" spread="47.95"/>
                    <measurement group_id="O3" value="349.15" spread="52.59"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Simulated Concentrations 20 Minutes Post-injection</title>
        <description>P03277 pharmacokinetic parameters in plasma were determined from the population PK model.&#xD;
This outcome was assessed only for the CNS cohort.</description>
        <time_frame>20 minutes post-injection</time_frame>
        <population>All patients of the CNS cohort who received gadopiclenol administration except one patient, whose PK blood samples were assessed out of stability period</population>
        <group_list>
          <group group_id="O1">
            <title>CNS Cohort 2-6 Years</title>
            <description>Pediatric patients aged 2-6 years undergoing CNS contrast-enhanced MRI&#xD;
P03277: A dose of 0.05 mmol/kg body weight (0.1 mL/kg body weight) of P03277 will be administered to each patient in a single intravenous injection.</description>
          </group>
          <group group_id="O2">
            <title>CNS Cohort 7-11 Years</title>
            <description>Pediatric patients aged 7-11 years undergoing CNS contrast-enhanced MRI&#xD;
P03277: A dose of 0.05 mmol/kg body weight (0.1 mL/kg body weight) of P03277 will be administered to each patient in a single intravenous injection.</description>
          </group>
          <group group_id="O3">
            <title>CNS Cohort 12-17 Years</title>
            <description>Pediatric patients aged 12-17 years undergoing CNS contrast-enhanced MRI&#xD;
P03277: A dose of 0.05 mmol/kg body weight (0.1 mL/kg body weight) of P03277 will be administered to each patient in a single intravenous injection.</description>
          </group>
        </group_list>
        <measure>
          <title>Simulated Concentrations 20 Minutes Post-injection</title>
          <description>P03277 pharmacokinetic parameters in plasma were determined from the population PK model.&#xD;
This outcome was assessed only for the CNS cohort.</description>
          <population>All patients of the CNS cohort who received gadopiclenol administration except one patient, whose PK blood samples were assessed out of stability period</population>
          <units>mg/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="20"/>
                <count group_id="O3" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="234.88" spread="30.18"/>
                    <measurement group_id="O2" value="259.67" spread="32.02"/>
                    <measurement group_id="O3" value="285.16" spread="35.35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Simulated Concentrations 30 Minutes Post-injection</title>
        <description>P03277 pharmacokinetic parameters in plasma were determined from the population PK model.&#xD;
This outcome was assessed only for the CNS cohort.</description>
        <time_frame>30 minutes post-injection</time_frame>
        <population>All patients of the CNS cohort who received gadopiclenol administration except one patient, whose PK blood samples were assessed out of stability period</population>
        <group_list>
          <group group_id="O1">
            <title>CNS Cohort 2-6 Years</title>
            <description>Pediatric patients aged 2-6 years undergoing CNS contrast-enhanced MRI&#xD;
P03277: A dose of 0.05 mmol/kg body weight (0.1 mL/kg body weight) of P03277 will be administered to each patient in a single intravenous injection.</description>
          </group>
          <group group_id="O2">
            <title>CNS Cohort 7-11 Years</title>
            <description>Pediatric patients aged 7-11 years undergoing CNS contrast-enhanced MRI&#xD;
P03277: A dose of 0.05 mmol/kg body weight (0.1 mL/kg body weight) of P03277 will be administered to each patient in a single intravenous injection.</description>
          </group>
          <group group_id="O3">
            <title>CNS Cohort 12-17 Years</title>
            <description>Pediatric patients aged 12-17 years undergoing CNS contrast-enhanced MRI&#xD;
P03277: A dose of 0.05 mmol/kg body weight (0.1 mL/kg body weight) of P03277 will be administered to each patient in a single intravenous injection.</description>
          </group>
        </group_list>
        <measure>
          <title>Simulated Concentrations 30 Minutes Post-injection</title>
          <description>P03277 pharmacokinetic parameters in plasma were determined from the population PK model.&#xD;
This outcome was assessed only for the CNS cohort.</description>
          <population>All patients of the CNS cohort who received gadopiclenol administration except one patient, whose PK blood samples were assessed out of stability period</population>
          <units>mg/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="20"/>
                <count group_id="O3" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="188.26" spread="25.10"/>
                    <measurement group_id="O2" value="211.20" spread="25.82"/>
                    <measurement group_id="O3" value="237.25" spread="26.97"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were recorded from informed consent signature untill the end of the study (up to 120 days after gadopiclenol administration).</time_frame>
      <desc>The Safety Set included all patients who had received at least one injection of gadopiclenol.</desc>
      <group_list>
        <group group_id="E1">
          <title>CNS &amp; Body Cohorts 2-6 Years</title>
          <description>Pediatric patients aged 2-6 years undergoing CNS or Body contrast-enhanced MRI&#xD;
P03277: A dose of 0.05 mmol/kg body weight (0.1 mL/kg body weight) of P03277 will be administered to each patient in a single intravenous injection.</description>
        </group>
        <group group_id="E2">
          <title>CNS &amp; Body Cohorts 7-11 Years</title>
          <description>Pediatric patients aged 7-11 years undergoing CNS or Body contrast-enhanced MRI&#xD;
P03277: A dose of 0.05 mmol/kg body weight (0.1 mL/kg body weight) of P03277 will be administered to each patient in a single intravenous injection.</description>
        </group>
        <group group_id="E3">
          <title>CNS &amp; Body Cohorts 12-17 Years</title>
          <description>Pediatric patients aged 12-17 years undergoing CNS or Body contrast-enhanced MRI&#xD;
P03277: A dose of 0.05 mmol/kg body weight (0.1 mL/kg body weight) of P03277 will be administered to each patient in a single intravenous injection.</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="26"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="31"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Condition aggravated</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Tonsillitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Head injury</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Epilepsy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="31"/>
              </event>
              <event>
                <sub_title>Coma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Hydronephrosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</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="4" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="23"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Long QT syndrome</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Glaucoma</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="31"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="31"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Condition aggravated</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="31"/>
              </event>
              <event>
                <sub_title>Application site erythema</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Herpes virus infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="31"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="31"/>
              </event>
              <event>
                <sub_title>Pharyngitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="31"/>
              </event>
              <event>
                <sub_title>Respiratory tract infection viral</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="31"/>
              </event>
              <event>
                <sub_title>Tracheobronchitis mycoplasmal</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="31"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="31"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Procedural Anxiety</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood pressure increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="31"/>
              </event>
              <event>
                <sub_title>Electrocardiogram QT prolonged</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="31"/>
              </event>
              <event>
                <sub_title>Eosinophil count increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="31"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Epilepsy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="31"/>
              </event>
              <event>
                <sub_title>Rhinorrhoea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="31"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="31"/>
              </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>There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Global Head of Medical Affairs &amp; Clinical Development</name_or_title>
      <organization>Guerbet</organization>
      <phone>+33 (0) 1 45 91 50 00</phone>
      <email>jing.hao@guerbet.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/NCT03749252
org study id: GDX-44-007
secondary id: 2018-001516-30
nct id: NCT03749252
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a pharmacokinetics (PK), open-label, uncontrolled, multicenter phase II trial with
      age-staggered approach.

      The primary objective is to evaluate the PK profile of gadopiclenol in plasma following
      single IV injection of 0.05 mmol/kg body weight (BW) in pediatric population aged from 2 to
      17 years undergoing CNS contrast-enhanced MRI (CNS cohort).
A population PK approach and an age-down staggered approach will be used. Patients will be
      recruited into 3 predefined age groups: 12-17, 7-11 and 2-6 years. The inclusions will start
      with the older group (Adolescents, 12-17 years), followed by Preadolescents (7-11 years) and
      finally Young Children (2-6 years of age).
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Elimination Half-life
time frame: 4 blood samples per patient were taken post-injection for PK analysis, one within each window: 1 min to 20 min, 30 min to 45 min, 2 to 3 hours and 7 to 8 hours
description: P03277 pharmacokinetic parameters in plasma were determined from the population PK model.
This outcome was assessed only for the CNS cohort.
measure: Total Clearance
time frame: 4 blood samples per patient were taken post-injection for PK analysis, one within each window: 1 min to 20 min, 30 min to 45 min, 2 to 3 hours and 7 to 8 hours
description: P03277 pharmacokinetic parameters in plasma were determined from the population PK model.
This outcome was assessed only for the CNS cohort.
measure: Central Volume of Distribution
time frame: 4 blood samples per patient were taken post-injection for PK analysis, one within each window: 1 min to 20 min, 30 min to 45 min, 2 to 3 hours and 7 to 8 hours
description: P03277 pharmacokinetic parameters in plasma were determined from the population PK model.
This outcome was assessed only for the CNS cohort.
measure: Peripheral Volume of Distribution
time frame: 4 blood samples per patient were taken post-injection for PK analysis, one within each window: 1 min to 20 min, 30 min to 45 min, 2 to 3 hours and 7 to 8 hours
description: P03277 pharmacokinetic parameters in plasma were determined from the population PK model.
This outcome was assessed only for the CNS cohort.
measure: Area Under the Curve
time frame: 4 blood samples per patient were taken post-injection for PK analysis, one within each window: 1 min to 20 min, 30 min to 45 min, 2 to 3 hours and 7 to 8 hours
description: P03277 pharmacokinetic parameters in plasma were determined from the population PK model.
This outcome was assessed only for the CNS cohort.
measure: Simulated Concentrations 10 Minutes Post-injection
time frame: 10 minutes post-injection
description: P03277 pharmacokinetic parameters in plasma were determined from the population PK model.
This outcome was assessed only for the CNS cohort.
measure: Simulated Concentrations 20 Minutes Post-injection
time frame: 20 minutes post-injection
description: P03277 pharmacokinetic parameters in plasma were determined from the population PK model.
This outcome was assessed only for the CNS cohort.
measure: Simulated Concentrations 30 Minutes Post-injection
time frame: 30 minutes post-injection
description: P03277 pharmacokinetic parameters in plasma were determined from the population PK model.
This outcome was assessed only for the CNS cohort.
arm group label: CNS Cohort 2-6 years
arm group type: Experimental
description: Pediatric patients aged 2-6 years undergoing CNS contrast-enhanced MRI
arm group label: CNS Cohort 7-11 years
arm group type: Experimental
description: Pediatric patients aged 7-11 years undergoing CNS contrast-enhanced MRI
arm group label: CNS Cohort 12-17 years
arm group type: Experimental
description: Pediatric patients aged 12-17 years undergoing CNS contrast-enhanced MRI
arm group label: Body Cohort 2-6 years
arm group type: Experimental
description: Pediatric patients aged 2-6 years undergoing contrast-enhanced MRI of other body organs (head and neck, thorax, abdomen, pelvis or musculoskeletal system)
arm group label: Body Cohort 7-11 years
arm group type: Experimental
description: Pediatric patients aged 7-11 years undergoing contrast-enhanced MRI of other body organs (head and neck, thorax, abdomen, pelvis or musculoskeletal system)
arm group label: Body Cohort 12-17 years
arm group type: Experimental
description: Pediatric patients aged 12-17 years undergoing contrast-enhanced MRI of other body organs (head and neck, thorax, abdomen, pelvis or musculoskeletal system)
intervention type: Drug
intervention name: P03277
description: A dose of 0.05 mmol/kg body weight (0.1 mL/kg body weight) of P03277 will be administered to each patient in a single intravenous injection.
arm group label: Body Cohort 12-17 years
arm group label: Body Cohort 2-6 years
arm group label: Body Cohort 7-11 years
arm group label: CNS Cohort 12-17 years
arm group label: CNS Cohort 2-6 years
arm group label: CNS Cohort 7-11 years
other name: gadopiclenol
criteria: 
gender: All
minimum age: 2 Years
maximum age: 17 Years
healthy volunteers: No
last name: Elżbieta Jurkiewicz, MD
role: Principal Investigator
affiliation: Instytut Pomnik
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Bulgaria
country: Hungary
country: Poland
country: Slovakia
country: Ukraine
responsible party type: Sponsor
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 