<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/NCT03813407</url>
  </required_header>
  <id_info>
    <org_study_id>D9481C00001</org_study_id>
    <secondary_id>2018-001331-48</secondary_id>
    <nct_id>NCT03813407</nct_id>
  </id_info>
  <brief_title>An Open-label Study to Assess Safety and Efficacy of SZC in Paediatric Patients With Hyperkalaemia</brief_title>
  <acronym>PEDZ-K</acronym>
  <official_title>An Open-label Study to Assess Safety and Efficacy of SZC in Paediatric Patients With Hyperkalaemia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>AstraZeneca</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>
      Sodium zirconium cyclosilicate has been shown to be effective and safe in adults for the&#xD;
      treatment of hyperkalaemia, and therefore it is expected to be beneficial in children. This&#xD;
      study will evaluate the efficacy, safety and tolerability of sodium zirconium cyclosilicate&#xD;
      for the treatment of hyperkalaemia in children &lt;18 years of age. Approximately 140&#xD;
      participants will be enrolled at approximately 46 sites in locations including but not&#xD;
      limited to Europe and North America for this study. Treatment will include 3 phases: the CP,&#xD;
      MP, and LTMP. Enrolment will start in 2 cohorts, ages 6 to &lt; 12 years and 12 to &lt; 18 years.&#xD;
      After review of accumulated data, the independent Data Monitoring Committee (iDMC) will&#xD;
      determine whether to open enrolment in the ages 2 to &lt; 6 years cohort and later in the ages 0&#xD;
      to &lt; 2 years cohort. All eligible participants with hyperkalaemia will enter an open-label&#xD;
      Correction Phase (CP) receiving a fixed dose of SZC three times daily (TID) for up to 3 days&#xD;
      until normokalaemia is achieved. Within each age cohorts 2 to &lt; 18 years, initial&#xD;
      participants will be allocated to the dose level (DL) 5 g TID. After approval of higher DLs&#xD;
      by the iDMC, subsequent participants may be allocated in the CP to 10 g TID and then&#xD;
      potentially 15 g TID. All participants in the ages 0 to &lt; 2 years cohort will be assigned to&#xD;
      the same DL which will be decided based on data from older age cohorts. Participants who&#xD;
      successfully achieve normokalaemia in the CP will enter a 28-day open-label Maintenance Phase&#xD;
      (MP), which will be initiated with once daily administration of the dose received TID in the&#xD;
      CP. During MP, the Investigator is able to titrate the dose up or down in the range 2.5 g to&#xD;
      15 g body weight equivalent to maintain normokalaemia. For participants who, at the end of&#xD;
      MP, are normokalaemic or hyperkalaemic without being on maximum dose, the MP is followed by&#xD;
      the option to continue the study in an open-label long term maintenance phase (LTMP) where&#xD;
      the same titration regimen is used as in MP.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Protocol title: An open-label study to assess safety and efficacy of SZC in paediatric&#xD;
      patients with hyperkalaemia Rationale: Sodium zirconium cyclosilicate has been shown to be&#xD;
      effective and safe in adults for the treatment of hyperkalaemia, and therefore it is expected&#xD;
      to be beneficial in children. This study will evaluate the efficacy, safety and tolerability&#xD;
      of sodium zirconium cyclosilicate for the treatment of hyperkalaemia in children &lt;18 years of&#xD;
      age. Primary Objective: Correction phase (CP) primary objective: To evaluate the ability to&#xD;
      achieve normokalaemia during the CP when initiating treatment with SZC of different dose&#xD;
      levels (DLs) in children with hyperkalaemia 28-day Maintenance Phase (MP) primary objective:&#xD;
      To evaluate the ability to maintain normokalaemia during the MP when continuing SZC treatment&#xD;
      in children achieving normokalaemia Secondary Objectives: All phases secondary objective: To&#xD;
      evaluate the change in S-K+ in children treated with SZC MP secondary objectives: To evaluate&#xD;
      change in serum aldosterone levels in children treated with SZC during the MP To evaluate&#xD;
      change in serum electrolytes (including bicarbonate), spot urinary pH and urinary&#xD;
      electrolytes levels in children treated with SZC during the MP Long-term MP (LTMP) secondary&#xD;
      objectives: To evaluate the ability of maintaining normokalaemia in children treated with SZC&#xD;
      during the LTMP Safety Objective: Endpoint/Variable: To evaluate the safety and tolerability&#xD;
      of SZC in the 3 phases (CP, MP, and LTMP) Tertiary/Exploratory: To evaluate the acceptability&#xD;
      and palatability of SZC through the study Overall design: This is a Phase 3, international,&#xD;
      multi-centre, open-label study assessing different doses of SZC. The population to be studied&#xD;
      is hyperkalaemic children &lt; 18 years. Dosing will mirror the regimen approved for adults&#xD;
      using body weight equivalent doses. Enrolment will start in 2 cohorts, ages 6 to &lt; 12 years&#xD;
      and 12 to &lt; 18 years. After review of accumulated data, the independent Data Monitoring&#xD;
      Committee (iDMC) will determine whether to open enrolment in the ages 2 to &lt; 6 years cohort&#xD;
      and later in the ages 0 to &lt; 2 years cohort. The study will be conducted in approximately 8&#xD;
      countries and 46 sites. All eligible participants with hyperkalaemia will enter an open-label&#xD;
      Correction Phase (CP) receiving a fixed dose of SZC three times daily (TID) for up to 3 days&#xD;
      until normokalaemia is achieved. Within each age cohorts 2 to &lt; 18 years, initial&#xD;
      participants will be allocated to the dose level (DL) 5 g TID. After approval of higher DLs&#xD;
      by the iDMC, subsequent participants may be allocated in the CP to 10 g TID and then&#xD;
      potentially 15 g TID. All participants in the ages 0 to &lt; 2 years cohort will be assigned to&#xD;
      the same DL which will be decided based on data from older age cohorts. Participants who&#xD;
      successfully achieve normokalaemia in the CP will enter a 28-day open-label Maintenance Phase&#xD;
      (MP), which will be initiated with once daily administration of the dose received TID in the&#xD;
      CP. During MP, the Investigator is able to titrate the dose up or down in the range 2.5 g to&#xD;
      15 g body weight equivalent to maintain normokalaemia. The MP is followed by the option for&#xD;
      participants to continue the study in an open-label long-term maintenance phase (LTMP) where&#xD;
      the same titration regimen is used as in MP, but with monthly visits. Study period: Estimated&#xD;
      date of first participant enrolled Q4 2018 Estimated date of last participant completed 29&#xD;
      December 2023 Number of participants: This study aims to enrol a total of approximately 140&#xD;
      participants with hyperkalaemia (defined as two screening serum potassium [S-K+] values &gt; 5.0&#xD;
      mmol/L [for the ages 2 to &lt; 18 years cohort] or &gt; 6.0 mmol/L [for the ages 0 to &lt; 2 years&#xD;
      cohort]). Of these, approximately 85 participants will have moderate to severe hyperkalaemia&#xD;
      (defined as baseline S-K+ &gt; 5.5 mmol/L). Enrolment will continue until at least 54&#xD;
      participants with moderate to severe hyperkalaemia have entered the MP and 45 participants&#xD;
      with moderate to severe hyperkalaemia have completed the MP. A maximum of 55 participants&#xD;
      with mild hyperkalaemia (defined as S-K+ between 5.0 and 5.5 mmol/L) will be enrolled. In&#xD;
      addition, there are minimum requirements for participants in each age cohort Duration: Study&#xD;
      duration is approximately 28 weeks including up to 3 days of correction treatment, followed&#xD;
      by maintenance treatment for 28 days, and a LTMP for up to 22 weeks. All participants will&#xD;
      also have a 1-week safety follow-up. Treatments and treatment duration: Treatment will&#xD;
      include 3 phases: the CP, MP, and LTMP. All age cohorts are eligible to participate in all&#xD;
      phases of the study. The 3 treatment phases are specified below: Correction phase (CP): All&#xD;
      eligible participants with hyperkalaemia will enter an open-label Correction Phase (CP)&#xD;
      receiving a fixed dose of SZC three times daily (TID) for up to 3 days until normokalaemia is&#xD;
      achieved. Within each age cohorts 2 to &lt; 18 years, initial participants will be allocated to&#xD;
      the dose level (DL) 5 g TID. After approval of higher DLs by the iDMC, subsequent&#xD;
      participants may be allocated in the CP to 10 g TID and then potentially 15 g TID. All&#xD;
      participants in the ages 0 to &lt; 2 years cohort will be assigned to the same DL which will be&#xD;
      decided based on data from older age cohorts. Maintenance phase (MP): Participants who&#xD;
      successfully achieve normokalaemia in the CP will enter a 28-day open-label Maintenance Phase&#xD;
      (MP), which will be initiated with once daily administration of the dose received TID in the&#xD;
      CP. During MP, the Investigator is able to titrate the dose up or down in the range 2.5 g to&#xD;
      15 g body weight equivalent to maintain normokalaemia. Long term Maintenance Phase (LTMP):&#xD;
      For participants who, at the end of MP, are normokalaemic or hyperkalaemic without being on&#xD;
      maximum dose, the MP is followed by the option to continue the study in an open-label long&#xD;
      term maintenance phase (LTMP) where the same titration regimen is used as in MP. Data&#xD;
      Monitoring Committee: The iDMC will decide on the opening of dose levels during the CP after&#xD;
      reviewing all available data. Additionally, iDMC will determine whether and when enrolment in&#xD;
      the ages 0 to &lt; 6 years cohorts will begin, and will also evaluate emerging safety data&#xD;
      during all phases of the study. Statistical methods Objectives will be evaluated based on&#xD;
      analysis populations corresponding to each study phase. Analysis sets are defined for each&#xD;
      phase as the set of all participants who transitioned from previous phase and who received at&#xD;
      least one dose of SZC during the phase. Primary assessments of the primary objectives, the&#xD;
      probability to achieve and maintain normokalaemia when treated with SZC, will be based on&#xD;
      point estimates together with 95% confidence intervals (CIs) from generalised linear models&#xD;
      (repeated measures model for the MP). The secondary objective of change in S-K+ over time&#xD;
      will be evaluated using a repeated measures linear model. Additional analyses, including&#xD;
      analyses for other secondary objectives, will be done descriptively. In general, data will be&#xD;
      analysed in the total analysis population, within each age cohort and, for the CP, within&#xD;
      adult body weight equivalent dose-level, as appropriate. An interim read-out may be conducted&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">April 2, 2019</start_date>
  <completion_date type="Anticipated">December 29, 2023</completion_date>
  <primary_completion_date type="Anticipated">December 29, 2023</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>Treatment includes 3 phases:CP,MP,LTMP.Eligible participants with hyperkalaemia will enter CP receiving fixed dose of SZC three times daily (TID) for up to 3 days until normokalaemia.Within each cohort 2 to &lt;18 years, initial participants will be allocated to dose level (DL) 5g TID. After higher DLs approval by iDMC,subsequent participants may be allocated in the CP to 10g TID and potentially 15g TID.Participants in 0 to &lt;2 years cohort will be assigned to the same DL decided based on data from older cohorts.Those who achieve normokalaemia in the CP will enter a 28-day MP,which starts with once daily administration of the dose received TID in the CP.During MP,the Investigator is able to titrate the dose up or down in the range 2.5g to 15g body weight equivalent to maintain normokalaemia.For participants who, at the end of MP,are normokalaemic/hyperkalaemic without being on maximum dose,the MP is followed by option to continue in an LTMP where the same titration regimen is used as in MP</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>All phases in the study are open-label</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Correction phase (CP) primary objective: To evaluate the ability to achieve normokalaemia during the CP when initiating treatment with SZC of different dose levels in children with hyperkalaemia</measure>
    <time_frame>3 days</time_frame>
    <description>Normokalaemia achieved in the CP within 3 days (yes/no)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>28-day Maintenance Phase (MP) primary objective: To evaluate the ability to maintain normokalaemia during the MP when continuing SZC treatment in children achieving normokalaemia</measure>
    <time_frame>last two scheduled visits in the MP</time_frame>
    <description>28-day MP primary endpoint: Serum potassium (S-K+) value within normokalaemia range (yes/no) at each of the last two scheduled visits in the MP</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>All phases secondary objective: To evaluate the change in S-K+ in children treated with SZC</measure>
    <time_frame>at each scheduled visit</time_frame>
    <description>All phases secondary endpoint: S-K+ level at each scheduled visit</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MP secondary objectives: To evaluate change in serum aldosterone levels in children treated with SZC during the MP</measure>
    <time_frame>from baseline to Week 3 of the IMP</time_frame>
    <description>MP secondary endpoints: Change in serum aldosterone levels from baseline to Week 3 of the MP</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MP Secondary objective: To evaluate change in serum electrolytes (including bicarbonate), spot urinary pH and urinary electrolytes levels in children treated with SZC during the MP</measure>
    <time_frame>from baseline to week 3 of the MP</time_frame>
    <description>Change in serum electrolytes (including bicarbonate), and spot urinary pH and urinary electrolytes from baseline to week 3 of the MP</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Long-term MP (LTMP) secondary objectives: To evaluate the ability of maintaining normokalaemia in children treated with SZC during the LTMP</measure>
    <time_frame>at each scheduled visit</time_frame>
    <description>LTMP secondary endpoints: S-K+ value within normokalaemia range (yes/no) at each scheduled visit in the LTMP</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Safety objective: To evaluate the safety and tolerability of SZC in the 3 phases (CP, MP and LTMP)</measure>
    <time_frame>Throughout the study, 27 weeks</time_frame>
    <description>Adverse events/serious adverse events, Vital signs, Electrocardiogram, Clinical laboratory variables</description>
  </other_outcome>
  <other_outcome>
    <measure>Tertiary/Exploratory objective: To evaluate the acceptability and palatability of SZC through the study</measure>
    <time_frame>At certain timepoints throughout the study</time_frame>
    <description>Response categories in Study Medication Palatability Assessment questionnaires</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">90</enrollment>
  <condition>Hyperkalaemia</condition>
  <arm_group>
    <arm_group_label>Active Arm ( Sodium Zirconium Cyclosilicate SZC)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dosage formulation: 5 g sachets 2.5 g sachets 0.25 g sprinkle capsules 0.125 g sprinkle capsules (can be manufactured to support participants &lt;2 years of age) Route of administration: Oral Dosing instructions: SZC is provided as a powder. At the time of dosing SZC is mixed with a quantity of water or sprinkled onto semi-solid food (eg, milk, baby food, yogurt, or ice cream) within an hour of drug administration. Packaging and labelling: Study treatment will be provided in sachets packed in cartons or sprinkle capsules in high density polyethylene bottles, as appropriate for the dose. Each carton of sachets, individual sachets, and bottle of capsules will be labelled in accordance with Good Manufacturing Practice Annex 13 and per country regulatory requirement. Participant-specific dosing cards (diary) will be provided.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sodium Zirconium Cyclosilicate (SZC) Reduced Dose Level</intervention_name>
    <description>Sodium Zirconium Cyclosilicate (SZC) Dose: Paediatric dose based on body weight equivalent to an adult 2.5 g</description>
    <arm_group_label>Active Arm ( Sodium Zirconium Cyclosilicate SZC)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sodium Zirconium Cyclosilicate (SZC) Dose Level 1 (DL1)</intervention_name>
    <description>Sodium Zirconium Cyclosilicate (SZC)Paediatric dose based on body weight equivalent to an adult 5 g</description>
    <arm_group_label>Active Arm ( Sodium Zirconium Cyclosilicate SZC)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sodium Zirconium Cyclosilicate (SZC) Dose Level 2 (DL2)</intervention_name>
    <description>Sodium Zirconium Cyclosilicate (SZC) Paediatric dose based on body weight equivalent to an adult 10 g</description>
    <arm_group_label>Active Arm ( Sodium Zirconium Cyclosilicate SZC)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sodium Zirconium Cyclosilicate (SZC) Dose Level 3 (DL3)</intervention_name>
    <description>Sodium Zirconium Cyclosilicate (SZC) Paediatric dose based on body weight equivalent to an adult 15 g</description>
    <arm_group_label>Active Arm ( Sodium Zirconium Cyclosilicate SZC)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sodium Zirconium Cyclosilicate (SZC) Dose During 28 Day Maintenance Phase</intervention_name>
    <description>A 28-day period during which SZC is administered orally once daily (QD) to maintain normokalaemia. A dose titration regimen starting with QD administration of the dose of SZC the participants received TID in the CP will be studied in the MP and continued in the LTMP. The maximum dose that can be used is the calculated body weight equivalent to the 15 g adult dose</description>
    <arm_group_label>Active Arm ( Sodium Zirconium Cyclosilicate SZC)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Provision of written informed consent of the participant or legal representative, and&#xD;
             informed assent from the participant (as appropriate)&#xD;
&#xD;
          2. Female or male from birth to &lt; 18 years of age.&#xD;
&#xD;
          3. Participants (including those receiving a stable peritoneal dialysis regimen)&#xD;
             requiring long-term treatment of hyperkalaemia (chronic hyperkalaemia) in the age&#xD;
             cohort ≥ 2 years, and participants requiring either short- or long-term treatment for&#xD;
             hyperkalaemia (acute and chronic hyperkalaemia) in the age cohort &lt; 2 years.&#xD;
&#xD;
          4. Participants must meet the following criteria for hyperkalaemia: For participants aged&#xD;
             ≥ 2 years, Local Laboratory S-K+ level &gt; 5.0 mmol/L and for participants aged 0 to &lt; 2&#xD;
             years, Local Laboratory S-K+ level &gt;6.0 mmol/L at Screening, measured 3 to 14 days&#xD;
             prior to first dose of SZC on CP Study Day 1. This should also be confirmed prior to&#xD;
             dosing on Day 1.&#xD;
&#xD;
          5. Using digital ECG, QT interval corrected by Bazett's method (QTcB) must meet the&#xD;
             age-appropriate parameters at Screening: a. For participants aged 0 to ≤ 3 days after&#xD;
             birth: &lt; 450 ms b. For participants aged &gt;3 days to &lt; 12 years: &lt; 440 ms c. For&#xD;
             participants aged ≥ 12 to &lt; 18 years: &lt; 450 ms (male), &lt; 460 ms (female) All QTcB&#xD;
             values outside the reference values specified in the protocol should be manually&#xD;
             re-measured and re-calculated, and if there is a difference in measurement between the&#xD;
             automatic and manual ECG, the manual measurement should always be considered correct.&#xD;
&#xD;
          6. Ability to have repeated blood draws or effective venous catheterisation.&#xD;
&#xD;
          7. Females of childbearing potential must have a negative pregnancy test within one day&#xD;
             prior to the first dose of SZC on CP Study Day 1 and sexually active females of&#xD;
             childbearing potential must be using 2 forms of medically acceptable contraception&#xD;
             with at least one being a barrier method&#xD;
&#xD;
          8. Optional open-label, LTMP only:&#xD;
&#xD;
               1. Provision of written informed consent of the participant or legal representative,&#xD;
                  and informed assent from the participant (as appropriate) to take part in the&#xD;
                  LTMP.&#xD;
&#xD;
               2. Participants who are normokalaemic at the end of MP or hyperkalaemic and not on&#xD;
                  maximum dose.&#xD;
&#xD;
               3. Participants who would benefit from long-term treatment for their hyperkalaemia,&#xD;
                  as judged by the Investigator.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Neonates with a gestational age &lt; 37 weeks at birth or a birth weight &lt; 2500 g.&#xD;
&#xD;
          2. Term and preterm neonates with suspected conditions predisposing them to intestinal&#xD;
             ischaemia (eg, perinatal hypoxia or sepsis).&#xD;
&#xD;
          3. Participants with pseudohyperkalaemia caused by excessive fist clenching to enable&#xD;
             venepuncture, by haemolysed blood specimens, or by severe leukocytosis or&#xD;
             thrombocytosis.&#xD;
&#xD;
          4. Participants with hyperkalaemia due to soft-tissue damage from crush injury or burns.&#xD;
             5. Participants with hyperkalaemia due to a secondary cause, such as dehydration,&#xD;
             excessive use of K+ supplements, or drug use (eg, beta-adrenergic antagonists) and&#xD;
             that would be more appropriately treated with other interventions (eg, fluid&#xD;
             resuscitation, dose adjustments of medications).&#xD;
&#xD;
        6. Participants with transient iatrogenic hyperkalaemia (eg, due to treatment with&#xD;
        tacrolimus or cyclosporine).&#xD;
&#xD;
        7. Participants treated with lactulose, rifaximin (XIFAXAN™), or other nonabsorbed&#xD;
        antibiotics for hyperammonaemia within the last 7 days.&#xD;
&#xD;
        8. Participants treated with CPS, sodium polystyrene sulfonate (eg, KAYEXALATE™), or&#xD;
        patiromer within the last 4 days prior to first dose of study treatment.&#xD;
&#xD;
        9. Participants with a life expectancy of less than 3 months. 10. Participants who are&#xD;
        known to have tested Human Immunodeficiency Virus (HIV) positive.&#xD;
&#xD;
        11. Presence of any condition which, in the opinion of the Investigator, places the&#xD;
        participant at undue risk or potentially jeopardises the quality of the data to be&#xD;
        generated. 12. Known hypersensitivity or previous anaphylaxis to SZC or to components&#xD;
        thereof.&#xD;
&#xD;
        13. Participants with cardiac arrhythmias that require immediate treatment. 14.&#xD;
        Participants with a family history of long QT syndrome. 15. Participants on haemodialysis.&#xD;
        16. Participants with a history of bowel obstruction. 17. Participants with severe&#xD;
        gastrointestinal disorder or major gastrointestinal surgery (eg, large bowel resection).&#xD;
&#xD;
        18. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca&#xD;
        staff and/or staff at the study site).&#xD;
&#xD;
        19. Previous treatment with SZC. 20. Treatment with a drug or device within the last 30&#xD;
        days prior to first dose of study treatment that has not received regulatory approval at&#xD;
        the time of study entry.&#xD;
&#xD;
        21. Previous enrolment in the present study. 22. Females who are pregnant, breastfeeding,&#xD;
        or planning to become pregnant. 23. Judgement by the Investigator that the participant&#xD;
        should not participate in the study if the participant is unlikely to comply with study&#xD;
        procedures, restrictions, and requirements. 24. If the participant has evidence of&#xD;
        Coronavirus disease 2019 (COVID-19) within 2 weeks prior to enrolment (a positive COVID-19&#xD;
        test or suspicion of COVID-19 infection) the participant cannot be enrolled in the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>0 Years</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>AstraZeneca Clinical Study Information Center</last_name>
    <phone>1-877-240-9479</phone>
    <email>information.center@astrazeneca.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35233</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Suspended</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21287</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63104</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Hackensack</city>
        <state>New Jersey</state>
        <zip>07601</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Suspended</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Stony Brook</city>
        <state>New York</state>
        <zip>11794</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <zip>28207</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Winston-Salem</city>
        <state>North Carolina</state>
        <zip>27157</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Akron</city>
        <state>Ohio</state>
        <zip>44308</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Morgantown</city>
        <state>West Virginia</state>
        <zip>26506-7900</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Calgary</city>
        <state>Alberta</state>
        <zip>T3B 6A8</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Edmonton</city>
        <state>Alberta</state>
        <zip>T6G 1C9</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Beijing</city>
        <zip>100034</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Beijing</city>
        <zip>100045</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Changsha</city>
        <zip>410007</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Chengdu</city>
        <zip>610000</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Chengdu</city>
        <zip>610041</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Chongqing</city>
        <zip>400014</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Hangzhou</city>
        <zip>310052</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Hefei</city>
        <zip>230001</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Shanghai</city>
        <zip>200062</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Shanghai</city>
        <zip>201102</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Bunkyo-ku</city>
        <zip>113-8431</zip>
        <country>Japan</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Fuchu-shi</city>
        <zip>183-8561</zip>
        <country>Japan</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kawasaki-shi</city>
        <zip>211-0063</zip>
        <country>Japan</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Matsumoto-shi</city>
        <zip>390-8621</zip>
        <country>Japan</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Nakagami-gun</city>
        <zip>903-0215</zip>
        <country>Japan</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Saitama-Shi</city>
        <zip>330-8777</zip>
        <country>Japan</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sendai-Shi</city>
        <zip>989-3126</zip>
        <country>Japan</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Shizuoka-Shi</city>
        <zip>420-8660</zip>
        <country>Japan</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Białystok</city>
        <zip>15-274</zip>
        <country>Poland</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Krakow</city>
        <zip>30-663</zip>
        <country>Poland</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Warszawa</city>
        <zip>02-097</zip>
        <country>Poland</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Łódź</city>
        <zip>93-338</zip>
        <country>Poland</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Bucuresti</city>
        <zip>077120</zip>
        <country>Romania</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Bucuresti</city>
        <zip>22328</zip>
        <country>Romania</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Cluj-Napoca</city>
        <zip>400177</zip>
        <country>Romania</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Targu Mures</city>
        <zip>540136</zip>
        <country>Romania</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Samara</city>
        <zip>443095</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Dnipropetrovsk</city>
        <zip>49100</zip>
        <country>Ukraine</country>
      </address>
    </facility>
    <status>Suspended</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kharkiv Region</city>
        <zip>61075</zip>
        <country>Ukraine</country>
      </address>
    </facility>
    <status>Suspended</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kyiv</city>
        <zip>04050</zip>
        <country>Ukraine</country>
      </address>
    </facility>
    <status>Suspended</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Odesa</city>
        <zip>65038</zip>
        <country>Ukraine</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sumy</city>
        <zip>40031</zip>
        <country>Ukraine</country>
      </address>
    </facility>
    <status>Suspended</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Zaporizhzhia</city>
        <zip>69063</zip>
        <country>Ukraine</country>
      </address>
    </facility>
    <status>Terminated</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Glasgow</city>
        <zip>G51 4TF</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Manchester</city>
        <zip>M13 9WL</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Nottingham</city>
        <zip>NG7 2UH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>China</country>
    <country>Japan</country>
    <country>Poland</country>
    <country>Romania</country>
    <country>Russian Federation</country>
    <country>Ukraine</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Italy</country>
  </removed_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>November 22, 2018</study_first_submitted>
  <study_first_submitted_qc>January 18, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 23, 2019</study_first_posted>
  <last_update_submitted>May 11, 2023</last_update_submitted>
  <last_update_submitted_qc>May 11, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 15, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>sodium zirconium cyclosilicate</keyword>
  <keyword>Hyperkalaemia in children</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hyperkalemia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment:&#xD;
https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.&#xD;
Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_time_frame>AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please refer to our disclosure commitment at&#xD;
https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.</ipd_time_frame>
    <ipd_access_criteria>When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at&#xD;
https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.</ipd_access_criteria>
    <ipd_url>https://astrazenecagroup-dt.pharmacm.com/DT/Home</ipd_url>
  </patient_data>
  <!-- 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/NCT03813407
org study id: D9481C00001
secondary id: 2018-001331-48
nct id: NCT03813407
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Sodium zirconium cyclosilicate has been shown to be effective and safe in adults for the
      treatment of hyperkalaemia, and therefore it is expected to be beneficial in children. This
      study will evaluate the efficacy, safety and tolerability of sodium zirconium cyclosilicate
      for the treatment of hyperkalaemia in children <18 years of age. Approximately 140
      participants will be enrolled at approximately 46 sites in locations including but not
      limited to Europe and North America for this study. Treatment will include 3 phases: the CP,
      MP, and LTMP. Enrolment will start in 2 cohorts, ages 6 to < 12 years and 12 to < 18 years.
      After review of accumulated data, the independent Data Monitoring Committee (iDMC) will
      determine whether to open enrolment in the ages 2 to < 6 years cohort and later in the ages 0
      to < 2 years cohort. All eligible participants with hyperkalaemia will enter an open-label
      Correction Phase (CP) receiving a fixed dose of SZC three times daily (TID) for up to 3 days
      until normokalaemia is achieved. Within each age cohorts 2 to < 18 years, initial
      participants will be allocated to the dose level (DL) 5 g TID. After approval of higher DLs
      by the iDMC, subsequent participants may be allocated in the CP to 10 g TID and then
      potentially 15 g TID. All participants in the ages 0 to < 2 years cohort will be assigned to
      the same DL which will be decided based on data from older age cohorts. Participants who
      successfully achieve normokalaemia in the CP will enter a 28-day open-label Maintenance Phase
      (MP), which will be initiated with once daily administration of the dose received TID in the
      CP. During MP, the Investigator is able to titrate the dose up or down in the range 2.5 g to
      15 g body weight equivalent to maintain normokalaemia. For participants who, at the end of
      MP, are normokalaemic or hyperkalaemic without being on maximum dose, the MP is followed by
      the option to continue the study in an open-label long term maintenance phase (LTMP) where
      the same titration regimen is used as in MP.
Protocol title: An open-label study to assess safety and efficacy of SZC in paediatric
      patients with hyperkalaemia Rationale: Sodium zirconium cyclosilicate has been shown to be
      effective and safe in adults for the treatment of hyperkalaemia, and therefore it is expected
      to be beneficial in children. This study will evaluate the efficacy, safety and tolerability
      of sodium zirconium cyclosilicate for the treatment of hyperkalaemia in children <18 years of
      age. Primary Objective: Correction phase (CP) primary objective: To evaluate the ability to
      achieve normokalaemia during the CP when initiating treatment with SZC of different dose
      levels (DLs) in children with hyperkalaemia 28-day Maintenance Phase (MP) primary objective:
      To evaluate the ability to maintain normokalaemia during the MP when continuing SZC treatment
      in children achieving normokalaemia Secondary Objectives: All phases secondary objective: To
      evaluate the change in S-K+ in children treated with SZC MP secondary objectives: To evaluate
      change in serum aldosterone levels in children treated with SZC during the MP To evaluate
      change in serum electrolytes (including bicarbonate), spot urinary pH and urinary
      electrolytes levels in children treated with SZC during the MP Long-term MP (LTMP) secondary
      objectives: To evaluate the ability of maintaining normokalaemia in children treated with SZC
      during the LTMP Safety Objective: Endpoint/Variable: To evaluate the safety and tolerability
      of SZC in the 3 phases (CP, MP, and LTMP) Tertiary/Exploratory: To evaluate the acceptability
      and palatability of SZC through the study Overall design: This is a Phase 3, international,
      multi-centre, open-label study assessing different doses of SZC. The population to be studied
      is hyperkalaemic children < 18 years. Dosing will mirror the regimen approved for adults
      using body weight equivalent doses. Enrolment will start in 2 cohorts, ages 6 to < 12 years
      and 12 to < 18 years. After review of accumulated data, the independent Data Monitoring
      Committee (iDMC) will determine whether to open enrolment in the ages 2 to < 6 years cohort
      and later in the ages 0 to < 2 years cohort. The study will be conducted in approximately 8
      countries and 46 sites. All eligible participants with hyperkalaemia will enter an open-label
      Correction Phase (CP) receiving a fixed dose of SZC three times daily (TID) for up to 3 days
      until normokalaemia is achieved. Within each age cohorts 2 to < 18 years, initial
      participants will be allocated to the dose level (DL) 5 g TID. After approval of higher DLs
      by the iDMC, subsequent participants may be allocated in the CP to 10 g TID and then
      potentially 15 g TID. All participants in the ages 0 to < 2 years cohort will be assigned to
      the same DL which will be decided based on data from older age cohorts. Participants who
      successfully achieve normokalaemia in the CP will enter a 28-day open-label Maintenance Phase
      (MP), which will be initiated with once daily administration of the dose received TID in the
      CP. During MP, the Investigator is able to titrate the dose up or down in the range 2.5 g to
      15 g body weight equivalent to maintain normokalaemia. The MP is followed by the option for
      participants to continue the study in an open-label long-term maintenance phase (LTMP) where
      the same titration regimen is used as in MP, but with monthly visits. Study period: Estimated
      date of first participant enrolled Q4 2018 Estimated date of last participant completed 29
      December 2023 Number of participants: This study aims to enrol a total of approximately 140
      participants with hyperkalaemia (defined as two screening serum potassium [S-K+] values > 5.0
      mmol/L [for the ages 2 to < 18 years cohort] or > 6.0 mmol/L [for the ages 0 to < 2 years
      cohort]). Of these, approximately 85 participants will have moderate to severe hyperkalaemia
      (defined as baseline S-K+ > 5.5 mmol/L). Enrolment will continue until at least 54
      participants with moderate to severe hyperkalaemia have entered the MP and 45 participants
      with moderate to severe hyperkalaemia have completed the MP. A maximum of 55 participants
      with mild hyperkalaemia (defined as S-K+ between 5.0 and 5.5 mmol/L) will be enrolled. In
      addition, there are minimum requirements for participants in each age cohort Duration: Study
      duration is approximately 28 weeks including up to 3 days of correction treatment, followed
      by maintenance treatment for 28 days, and a LTMP for up to 22 weeks. All participants will
      also have a 1-week safety follow-up. Treatments and treatment duration: Treatment will
      include 3 phases: the CP, MP, and LTMP. All age cohorts are eligible to participate in all
      phases of the study. The 3 treatment phases are specified below: Correction phase (CP): All
      eligible participants with hyperkalaemia will enter an open-label Correction Phase (CP)
      receiving a fixed dose of SZC three times daily (TID) for up to 3 days until normokalaemia is
      achieved. Within each age cohorts 2 to < 18 years, initial participants will be allocated to
      the dose level (DL) 5 g TID. After approval of higher DLs by the iDMC, subsequent
      participants may be allocated in the CP to 10 g TID and then potentially 15 g TID. All
      participants in the ages 0 to < 2 years cohort will be assigned to the same DL which will be
      decided based on data from older age cohorts. Maintenance phase (MP): Participants who
      successfully achieve normokalaemia in the CP will enter a 28-day open-label Maintenance Phase
      (MP), which will be initiated with once daily administration of the dose received TID in the
      CP. During MP, the Investigator is able to titrate the dose up or down in the range 2.5 g to
      15 g body weight equivalent to maintain normokalaemia. Long term Maintenance Phase (LTMP):
      For participants who, at the end of MP, are normokalaemic or hyperkalaemic without being on
      maximum dose, the MP is followed by the option to continue the study in an open-label long
      term maintenance phase (LTMP) where the same titration regimen is used as in MP. Data
      Monitoring Committee: The iDMC will decide on the opening of dose levels during the CP after
      reviewing all available data. Additionally, iDMC will determine whether and when enrolment in
      the ages 0 to < 6 years cohorts will begin, and will also evaluate emerging safety data
      during all phases of the study. Statistical methods Objectives will be evaluated based on
      analysis populations corresponding to each study phase. Analysis sets are defined for each
      phase as the set of all participants who transitioned from previous phase and who received at
      least one dose of SZC during the phase. Primary assessments of the primary objectives, the
      probability to achieve and maintain normokalaemia when treated with SZC, will be based on
      point estimates together with 95% confidence intervals (CIs) from generalised linear models
      (repeated measures model for the MP). The secondary objective of change in S-K+ over time
      will be evaluated using a repeated measures linear model. Additional analyses, including
      analyses for other secondary objectives, will be done descriptively. In general, data will be
      analysed in the total analysis population, within each age cohort and, for the CP, within
      adult body weight equivalent dose-level, as appropriate. An interim read-out may be conducted
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Treatment includes 3 phases:CP,MP,LTMP.Eligible participants with hyperkalaemia will enter CP receiving fixed dose of SZC three times daily (TID) for up to 3 days until normokalaemia.Within each cohort 2 to <18 years, initial participants will be allocated to dose level (DL) 5g TID. After higher DLs approval by iDMC,subsequent participants may be allocated in the CP to 10g TID and potentially 15g TID.Participants in 0 to <2 years cohort will be assigned to the same DL decided based on data from older cohorts.Those who achieve normokalaemia in the CP will enter a 28-day MP,which starts with once daily administration of the dose received TID in the CP.During MP,the Investigator is able to titrate the dose up or down in the range 2.5g to 15g body weight equivalent to maintain normokalaemia.For participants who, at the end of MP,are normokalaemic/hyperkalaemic without being on maximum dose,the MP is followed by option to continue in an LTMP where the same titration regimen is used as in MP
primary purpose: Treatment
masking: None (Open Label)
masking description: All phases in the study are open-label
measure: Correction phase (CP) primary objective: To evaluate the ability to achieve normokalaemia during the CP when initiating treatment with SZC of different dose levels in children with hyperkalaemia
time frame: 3 days
description: Normokalaemia achieved in the CP within 3 days (yes/no)
measure: 28-day Maintenance Phase (MP) primary objective: To evaluate the ability to maintain normokalaemia during the MP when continuing SZC treatment in children achieving normokalaemia
time frame: last two scheduled visits in the MP
description: 28-day MP primary endpoint: Serum potassium (S-K+) value within normokalaemia range (yes/no) at each of the last two scheduled visits in the MP
measure: All phases secondary objective: To evaluate the change in S-K+ in children treated with SZC
time frame: at each scheduled visit
description: All phases secondary endpoint: S-K+ level at each scheduled visit
measure: MP secondary objectives: To evaluate change in serum aldosterone levels in children treated with SZC during the MP
time frame: from baseline to Week 3 of the IMP
description: MP secondary endpoints: Change in serum aldosterone levels from baseline to Week 3 of the MP
measure: MP Secondary objective: To evaluate change in serum electrolytes (including bicarbonate), spot urinary pH and urinary electrolytes levels in children treated with SZC during the MP
time frame: from baseline to week 3 of the MP
description: Change in serum electrolytes (including bicarbonate), and spot urinary pH and urinary electrolytes from baseline to week 3 of the MP
measure: Long-term MP (LTMP) secondary objectives: To evaluate the ability of maintaining normokalaemia in children treated with SZC during the LTMP
time frame: at each scheduled visit
description: LTMP secondary endpoints: S-K+ value within normokalaemia range (yes/no) at each scheduled visit in the LTMP
measure: Safety objective: To evaluate the safety and tolerability of SZC in the 3 phases (CP, MP and LTMP)
time frame: Throughout the study, 27 weeks
description: Adverse events/serious adverse events, Vital signs, Electrocardiogram, Clinical laboratory variables
measure: Tertiary/Exploratory objective: To evaluate the acceptability and palatability of SZC through the study
time frame: At certain timepoints throughout the study
description: Response categories in Study Medication Palatability Assessment questionnaires
arm group label: Active Arm ( Sodium Zirconium Cyclosilicate SZC)
arm group type: Experimental
description: Dosage formulation: 5 g sachets 2.5 g sachets 0.25 g sprinkle capsules 0.125 g sprinkle capsules (can be manufactured to support participants <2 years of age) Route of administration: Oral Dosing instructions: SZC is provided as a powder. At the time of dosing SZC is mixed with a quantity of water or sprinkled onto semi-solid food (eg, milk, baby food, yogurt, or ice cream) within an hour of drug administration. Packaging and labelling: Study treatment will be provided in sachets packed in cartons or sprinkle capsules in high density polyethylene bottles, as appropriate for the dose. Each carton of sachets, individual sachets, and bottle of capsules will be labelled in accordance with Good Manufacturing Practice Annex 13 and per country regulatory requirement. Participant-specific dosing cards (diary) will be provided.
intervention type: Drug
intervention name: Sodium Zirconium Cyclosilicate (SZC) Reduced Dose Level
description: Sodium Zirconium Cyclosilicate (SZC) Dose: Paediatric dose based on body weight equivalent to an adult 2.5 g
arm group label: Active Arm ( Sodium Zirconium Cyclosilicate SZC)
intervention type: Drug
intervention name: Sodium Zirconium Cyclosilicate (SZC) Dose Level 1 (DL1)
description: Sodium Zirconium Cyclosilicate (SZC)Paediatric dose based on body weight equivalent to an adult 5 g
arm group label: Active Arm ( Sodium Zirconium Cyclosilicate SZC)
intervention type: Drug
intervention name: Sodium Zirconium Cyclosilicate (SZC) Dose Level 2 (DL2)
description: Sodium Zirconium Cyclosilicate (SZC) Paediatric dose based on body weight equivalent to an adult 10 g
arm group label: Active Arm ( Sodium Zirconium Cyclosilicate SZC)
intervention type: Drug
intervention name: Sodium Zirconium Cyclosilicate (SZC) Dose Level 3 (DL3)
description: Sodium Zirconium Cyclosilicate (SZC) Paediatric dose based on body weight equivalent to an adult 15 g
arm group label: Active Arm ( Sodium Zirconium Cyclosilicate SZC)
intervention type: Drug
intervention name: Sodium Zirconium Cyclosilicate (SZC) Dose During 28 Day Maintenance Phase
description: A 28-day period during which SZC is administered orally once daily (QD) to maintain normokalaemia. A dose titration regimen starting with QD administration of the dose of SZC the participants received TID in the CP will be studied in the MP and continued in the LTMP. The maximum dose that can be used is the calculated body weight equivalent to the 15 g adult dose
arm group label: Active Arm ( Sodium Zirconium Cyclosilicate SZC)
criteria: 
gender: All
minimum age: 0 Years
maximum age: 18 Years
healthy volunteers: No
last name: AstraZeneca Clinical Study Information Center
phone: 1-877-240-9479
email: information.center@astrazeneca.com
facility: 
status: Recruiting
facility: 
status: Suspended
facility: 
status: Recruiting
facility: 
status: Not yet recruiting
facility: 
status: Suspended
facility: 
status: Recruiting
facility: 
status: Withdrawn
facility: 
status: Withdrawn
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Withdrawn
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Not yet recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Withdrawn
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Withdrawn
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Withdrawn
facility: 
status: Suspended
facility: 
status: Suspended
facility: 
status: Suspended
facility: 
status: Withdrawn
facility: 
status: Suspended
facility: 
status: Terminated
facility: 
status: Recruiting
facility: 
status: Completed
facility: 
status: Recruiting
country: Canada
country: China
country: Japan
country: Poland
country: Romania
country: Russian Federation
country: Ukraine
country: United Kingdom
country: United States
country: Italy
responsible party type: Sponsor
mesh term: Hyperkalemia
sharing ipd: Yes
ipd description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment:
https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd time frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please refer to our disclosure commitment at
https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
ipd access criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at
https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
ipd url: https://astrazenecagroup-dt.pharmacm.com/DT/Home