<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/NCT01724138</url>
  </required_header>
  <id_info>
    <org_study_id>CICL670ACN02</org_study_id>
    <nct_id>NCT01724138</nct_id>
  </id_info>
  <brief_title>An Open Label Study to Evaluate the Pharmacokinetics, Safety, Tolerability and Efficacy of Deferasirox Administered to Chinese Patients With β-thalassemia Major Aged From 2 to Less Than 6 Years Old</brief_title>
  <acronym>MACS2163</acronym>
  <official_title>An Open Label Study to Evaluate the Pharmacokinetics, Safety, Tolerability and Efficacy of Deferasirox Administered to Chinese Patients With β-thalassemia Major Aged From 2 to Less Than 6 Years Old</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Novartis Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Novartis</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      To characterize the PK of deferasirox in pediatric β-thalassemia major patients aged from 2&#xD;
      to less than 6 years old, when administrated with a fixed starting dose of 20 mg/kg/day.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <start_date>June 2013</start_date>
  <completion_date type="Anticipated">October 2014</completion_date>
  <primary_completion_date type="Anticipated">April 2014</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>the PK profile of deferasirox in pediatric β-thalassemia major patients aged from 2 to less than 6 years old.</measure>
    <time_frame>PK sampling times are 0.5, 2.5, 6, 10h in Day 1 postdose; Day 2, 3, 4 and 5 predose and 0.5, 2.5, 6, 10h post dose on Day 4, then pre-dose at each subsequent visit until Week 49. Day -1 PK sample will be treated as Day 1 predose sample.</time_frame>
    <description>Area under the plasma concentration-time curve from time zero to the end of the dosing interval.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>the PK profile of deferasirox in pediatric β-thalassemia major patients aged from 2 to less than 6 years old: Cmax</measure>
    <time_frame>PK sampling times are 0.5, 2.5, 6, 10h in Day 1 postdose; Day 2, 3, 4 and 5 predose and 0.5, 2.5, 6, 10h post dose on Day 4, then pre-dose at each subsequent visit until Week 49. Day -1 PK sample will be treated as Day 1 predose sample.</time_frame>
    <description>The maximum plasma concentration of study medication.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>the PK profile of deferasirox in pediatric β-thalassemia major patients aged from 2 to less than 6 years old: Tmax</measure>
    <time_frame>PK sampling times are 0.5, 2.5, 6, 10h in Day 1 postdose; Day 2, 3, 4 and 5 predose and 0.5, 2.5, 6, 10h post dose on Day 4, then pre-dose at each subsequent visit until Week 49. Day -1 PK sample will be treated as Day 1 predose sample.</time_frame>
    <description>Tmax was directly determined from the raw plasma concentration-time data.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The safety and tolerability of deferasirox following multiple dosing in pediatric β-thalassemia major patients.</measure>
    <time_frame>Baseline, every 4 weeks until 48 weeks after taking the drug</time_frame>
    <description>The adverse events and abnormal measurements of hematology, blood chemistry, urinalysis, urinary protein/creatinine ratio, physical examination, auditory and ocular examinations, ECG, ECHO, and growth development are collected for the measurement of safety and tolerability.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The efficacy of deferasirox in pediatric β-thalassemia patients as measured by change of serum ferritin.</measure>
    <time_frame>Baseline, every 4 weeks until 48 weeks after taking the drug</time_frame>
    <description>Changes in serum ferritin from baseline to every 4 weeks are collected for the measurement of efficacy.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>β-thalassemia Major</condition>
  <arm_group>
    <arm_group_label>Deferasirox</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The study will provide PK, safety, tolerability and efficacy data collected during 48 weeks of treatment with deferasirox in Chinese pediatric patients with transfusion dependent -thalassemia major, aged 2 to &lt;6 years at enrollment. The target patient pool consists of 20 patients with evidence of iron overload measured by serum ferritin level at the start of study. Patients will start their deferasirox treatment with a dose of 20 mg/kg/day. Serum ferritin will be monitored every month and the dose of deferasirox will be adjusted if necessary every 3 months based on the trends in serum ferritin. Other possible dose adjustments will be based on the patient's safety assessments.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Deferasirox</intervention_name>
    <description>Patients will start their deferasirox treatment with a dose of 20 mg/kg/day.</description>
    <arm_group_label>Deferasirox</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Pediatric patients aged from 2 to less than 6 years old.&#xD;
&#xD;
          -  Patients with transfusion dependent β-thalassemia major.&#xD;
&#xD;
          -  Serum ferritin values ≥ 1000 ng/ml at screening.&#xD;
&#xD;
          -  Written informed consent must be obtained from the patient's legal guardian in&#xD;
             accordance with local law and regulation prior to any screening procedures.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Non-transfusion-dependent thalassemia.&#xD;
&#xD;
          -  Systemic diseases which would prevent study treatment (e.g. uncontrolled hypertension,&#xD;
             cardiovascular, renal, hepatic, metabolic, etc.)&#xD;
&#xD;
          -  Serum creatinine &gt; age adjusted ULN.&#xD;
&#xD;
          -  Significant proteinuria as indicated by a urinary protein/creatinine ratio (UPCR) ≥&#xD;
             0.5mg/mg in a non-first void urine sample at screening. If UPCR is found to be ≥ 0.5&#xD;
             mg/mg the test can be repeated after 1 month.&#xD;
&#xD;
          -  ALT/AST &gt; 2.5xULN and total bilirubin &gt; 1×ULN.&#xD;
&#xD;
          -  Left ventricular ejection fraction &lt; 56% by echocardiography.&#xD;
&#xD;
          -  Patient has a known history of HIV seropositivity or history of active/treated&#xD;
             hepatitis B or C (a test for screening is not required).&#xD;
&#xD;
          -  A history of clinically relevant ocular and/or auditory toxicity related to iron&#xD;
             chelation therapy&#xD;
&#xD;
          -  Any surgical or medical conditions which will significantly alter the absorption,&#xD;
             distribution, metabolism or excretion of the drug(e.g. ulcerative disease,&#xD;
             uncontrolled nausea, vomiting, malabsorption syndrome, obstruction, or stomach and/or&#xD;
             small bowel resection).&#xD;
&#xD;
          -  Other conditions which investigator deems potential harm to patients if participate&#xD;
             the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>2 Years</minimum_age>
    <maximum_age>71 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Novartis Pharmaceuticals</last_name>
    <role>Study Director</role>
    <affiliation>Novartis Pharmaceuticals</affiliation>
  </overall_official>
  <removed_countries>
    <country>China</country>
  </removed_countries>
  <verification_date>August 2014</verification_date>
  <study_first_submitted>October 24, 2012</study_first_submitted>
  <study_first_submitted_qc>November 6, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 9, 2012</study_first_posted>
  <last_update_submitted>April 19, 2017</last_update_submitted>
  <last_update_submitted_qc>April 19, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">April 20, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>deferasirox</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Thalassemia</mesh_term>
    <mesh_term>beta-Thalassemia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Deferasirox</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT01724138
org study id: CICL670ACN02
nct id: NCT01724138
lead sponsor: 
has dmc: No
To characterize the PK of deferasirox in pediatric β-thalassemia major patients aged from 2
      to less than 6 years old, when administrated with a fixed starting dose of 20 mg/kg/day.
allocation: Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: the PK profile of deferasirox in pediatric β-thalassemia major patients aged from 2 to less than 6 years old.
time frame: PK sampling times are 0.5, 2.5, 6, 10h in Day 1 postdose; Day 2, 3, 4 and 5 predose and 0.5, 2.5, 6, 10h post dose on Day 4, then pre-dose at each subsequent visit until Week 49. Day -1 PK sample will be treated as Day 1 predose sample.
description: Area under the plasma concentration-time curve from time zero to the end of the dosing interval.
measure: the PK profile of deferasirox in pediatric β-thalassemia major patients aged from 2 to less than 6 years old: Cmax
time frame: PK sampling times are 0.5, 2.5, 6, 10h in Day 1 postdose; Day 2, 3, 4 and 5 predose and 0.5, 2.5, 6, 10h post dose on Day 4, then pre-dose at each subsequent visit until Week 49. Day -1 PK sample will be treated as Day 1 predose sample.
description: The maximum plasma concentration of study medication.
measure: the PK profile of deferasirox in pediatric β-thalassemia major patients aged from 2 to less than 6 years old: Tmax
time frame: PK sampling times are 0.5, 2.5, 6, 10h in Day 1 postdose; Day 2, 3, 4 and 5 predose and 0.5, 2.5, 6, 10h post dose on Day 4, then pre-dose at each subsequent visit until Week 49. Day -1 PK sample will be treated as Day 1 predose sample.
description: Tmax was directly determined from the raw plasma concentration-time data.
measure: The safety and tolerability of deferasirox following multiple dosing in pediatric β-thalassemia major patients.
time frame: Baseline, every 4 weeks until 48 weeks after taking the drug
description: The adverse events and abnormal measurements of hematology, blood chemistry, urinalysis, urinary protein/creatinine ratio, physical examination, auditory and ocular examinations, ECG, ECHO, and growth development are collected for the measurement of safety and tolerability.
measure: The efficacy of deferasirox in pediatric β-thalassemia patients as measured by change of serum ferritin.
time frame: Baseline, every 4 weeks until 48 weeks after taking the drug
description: Changes in serum ferritin from baseline to every 4 weeks are collected for the measurement of efficacy.
arm group label: Deferasirox
arm group type: Experimental
description: The study will provide PK, safety, tolerability and efficacy data collected during 48 weeks of treatment with deferasirox in Chinese pediatric patients with transfusion dependent -thalassemia major, aged 2 to <6 years at enrollment. The target patient pool consists of 20 patients with evidence of iron overload measured by serum ferritin level at the start of study. Patients will start their deferasirox treatment with a dose of 20 mg/kg/day. Serum ferritin will be monitored every month and the dose of deferasirox will be adjusted if necessary every 3 months based on the trends in serum ferritin. Other possible dose adjustments will be based on the patient's safety assessments.
intervention type: Drug
intervention name: Deferasirox
description: Patients will start their deferasirox treatment with a dose of 20 mg/kg/day.
arm group label: Deferasirox
criteria: 
gender: All
minimum age: 2 Years
maximum age: 71 Years
healthy volunteers: No
last name: Novartis Pharmaceuticals
role: Study Director
affiliation: Novartis Pharmaceuticals
country: China
responsible party type: Sponsor
mesh term: Thalassemia
mesh term: beta-Thalassemia
mesh term: Deferasirox