<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/NCT03303521</url>
  </required_header>
  <id_info>
    <org_study_id>D9480C00006</org_study_id>
    <secondary_id>2017-003029-14</secondary_id>
    <nct_id>NCT03303521</nct_id>
  </id_info>
  <brief_title>A Study to Test Whether ZS (Sodium Zirconium Cyclosilicate) Can Reduce the Incidence of Increased Blood Potassium Levels Among Dialized Patients.</brief_title>
  <acronym>DIALIZE</acronym>
  <official_title>A Phase 3b, Multicenter, Prospective, Randomized, Double Blind, Placebocontrolled Study to Reduce Incidence of Pre-dialysis Hyperkalemia With Sodium Zirconium Cyclosilicate (DIALIZE)</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>
      The purpose of this study is to evaluate the efficacy of ZS in the treatment of hyperkalemia&#xD;
      in patients on hemodialysis.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 14, 2017</start_date>
  <completion_date type="Actual">November 7, 2018</completion_date>
  <primary_completion_date type="Actual">November 7, 2018</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of Responders</measure>
    <time_frame>Evaluation period runs over the last 4 weeks of the treatment period up to 8 weeks, starting after visit 11 and ending on visit 15, thus it comprises post-long inter-dialytic interval visits 12, 13, 14 and 15.</time_frame>
    <description>A subject was considered to be a responder if, during the evaluation period, they maintained a pre-dialysis serum potassium (S-K) between 4.0 and 5.0 mmol/L on at least 3 out of 4 dialysis treatments following the long inter-dialytic interval and did not receive rescue therapy. The S-K levels used for this analysis were based on the measurements obtained by the central laboratory.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of Responders When Accounting for Missing Central Laboratory Serum Potassium Data</measure>
    <time_frame>Evaluation period runs over the last 4 weeks of the treatment period up to 8 weeks, starting after visit 11 and ending on visit 15, thus it comprises post-long inter-dialytic interval visits 12, 13, 14 and 15.</time_frame>
    <description>The sensitivity analysis assessed the impact of subjects classified as non-responders due to missing serum potassium (S-K) data. Missing central lab (c-lab) pre-dialysis values were imputed using corresponding pre-dialysis i-STAT (a portable blood analyser) measurements. In addition, a &quot;last observation carried forward&quot; (LOCF) approach was utilized to further impute missing values of pre-dialysis S-K during the evaluation period. This technique will replace missing c-lab S-K values with the last available non-missing pre-dialysis LIDI observation recorded for that patient (and this could be a c-lab value or an imputed c-lab value). The Primary endpoint analysis was repeated on the imputed data.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Patients Needing Rescue Therapy</measure>
    <time_frame>An 8 week overall treatment period (a 4 week adjustment phase plus a 4 week evaluation phase) and a 2 week follow up period.</time_frame>
    <description>Patients requiring any urgent intervention consistent with local practice patterns to reduce serum potassium (S-K) including insulin/glucose, beta-adrenergic agonists, sodium bicarbonate, K binders or any form of renal replacement therapy.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">196</enrollment>
  <condition>Hyperkalemia</condition>
  <arm_group>
    <arm_group_label>Sodium Zirconium Cyclosilicate (ZS)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Suspension administered orally for a treatment period of eight weeks (4 weeks of dose adjustment, 4 weeks in stable dose) Single dose contains from 1 to 3 sachets of ZS 5g depending on dose level assigned to a patient per non-dialysis days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Suspension administered orally for a treatment period of eight weeks (4 weeks of dose adjustment, 4 weeks in stable dose) Single dose contains from 1 to 3 sachets of Placebo depending on dose level assigned to a patient per non-dialysis days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Suspension administered orally for a treatment period of eight weeks (4 weeks of dose adjustment, 4 weeks in stable dose) .&#xD;
Single dose contains from 1 to 3 sachets of Placebo depending on dose level assigned to a patient per non-dialysis days.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sodium Zirconium Cyclosilicate (ZS)</intervention_name>
    <description>Suspension administered orally for a treatment period of eight weeks (4 weeks of dose adjustment, 4 weeks in stable dose) .&#xD;
Single dose contains from 1 to 3 sachets of ZS 5g depending on dose level assigned to a patient per non-dialysis days.</description>
    <arm_group_label>Sodium Zirconium Cyclosilicate (ZS)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Provision of informed consent prior to any study specific procedures&#xD;
&#xD;
          2. Female or male aged ≥ 18 years at screening Visit 1. For patients aged &lt;20 years and&#xD;
             enrolled in Japan, a written informed consent should be obtained from the patient and&#xD;
             his or her legally acceptable representative.&#xD;
&#xD;
          3. Receiving hemodialysis (or hemodiafiltration) 3 times a week for treatment of endstage&#xD;
             renal disease (ESRD) for at least 3 months before randomization.&#xD;
&#xD;
          4. Patients must have hemodialysis access consisting of an arteriovenous fistula, AV&#xD;
             graft, or tunneled (permanent) catheter which is expected to remain in place for the&#xD;
             entire duration of the study.&#xD;
&#xD;
          5. Pre-dialysis serum K &gt;5.4 mmol/L after long inter-dialytic interval and &gt;5.0 mmol/L&#xD;
             after one short inter-dialytic interval during screening (as assessed by central lab).&#xD;
&#xD;
          6. Prescribed dialysate K concentration ≤ 3 mmol/L during screening&#xD;
&#xD;
          7. Sustained Qb ≥200 ml/min and spKt/V ≥1.2 (or URR ≥ 63) on stable&#xD;
             hemodialysis/hemodiafltration prescription during screening with prescription (time,&#xD;
             dialyzer, blood flow [Qb], dialysate flow rate [Qd] and bicarbonate concentration)&#xD;
             expected to remain unchanged during study&#xD;
&#xD;
          8. Heparin dose (if used) must be stable during screening and expected to be stable&#xD;
             during the study&#xD;
&#xD;
          9. Subjects must be receiving dietary counseling appropriate for ESRD patients treated&#xD;
             with hemodialysis/hemodiafiltration as per local guidelines, which includes dietary&#xD;
             potassium restriction.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca,&#xD;
             including ZS Pharma staff and/or staff at the study site)&#xD;
&#xD;
          2. Hemoglobin &lt;9 g/dL on screening (as assessed on Visit 1)&#xD;
&#xD;
          3. Lack of compliance with hemodialysis prescription (both number and duration of&#xD;
             treatments) during the two-week period preceding screening (100% compliance required)&#xD;
&#xD;
          4. Patients treated with sodium polystyrene sulfonate (SPS, Kayexalate, Resonium),&#xD;
             calcium polystyrene sulfonate (CPS, Resonium calcium) or patiromer (Veltassa) within 7&#xD;
             days before screening or anticipated in requiring any of these agents during the study&#xD;
&#xD;
          5. Myocardial infarction, acute coronary syndrome, stroke, seizure or a&#xD;
             thrombotic/thromboembolic event (e.g., deep vein thrombosis or pulmonary embolism, but&#xD;
             excluding vascular access thrombosis) within 12 weeks prior to randomization&#xD;
&#xD;
          6. Laboratory diagnosis of hypokalemia (K &lt; 3.5 mmol/L), hypocalcemia (Ca &lt; 8.2 mg/dL;&#xD;
             for Japan hypocalcemia is defined as albumin-corrected Ca &lt; 8.0 mg/dL), hypomagnesemia&#xD;
             (Mg &lt; 1.7 mg/dL) or severe acidosis (serum bicarbonate 16 mEq/L or less) in the 4&#xD;
             weeks preceding randomization&#xD;
&#xD;
          7. Pseudohyperkalemia secondary to hemolyzed blood specimen (this situation is not&#xD;
             considered screening failure, sampling or full screening can be postponed to a later&#xD;
             time as applicable).&#xD;
&#xD;
          8. Severe leukocytosis (&gt;20× 10^9/L) or thrombocytosis (≥450 × 10^9/L) during screening&#xD;
&#xD;
          9. Polycythemia (Hb &gt;14 g/dL) during screening&#xD;
&#xD;
         10. Diagnosis of rhabdomyolysis during the 4 weeks preceding randomization&#xD;
&#xD;
         11. Patients treated with lactulose, xifaxan (rifaximin) or other non-absorbed antibiotics&#xD;
             for hyperammonemia within 7 days prior to the first dose of study drug&#xD;
&#xD;
         12. Patients unable to take oral ZS drug mix&#xD;
&#xD;
         13. Scheduled date for living donor kidney transplant&#xD;
&#xD;
         14. Patients with a life expectancy of less than 6 months&#xD;
&#xD;
         15. Female patients who are pregnant or breastfeeding&#xD;
&#xD;
         16. Females of childbearing potential, unless using contraception as detailed in the&#xD;
             protocol or sexual abstinence.&#xD;
&#xD;
         17. Known hypersensitivity or previous anaphylaxis to ZS or to components thereof&#xD;
&#xD;
         18. Participation in another clinical study with an investigational product during the&#xD;
             last 1 month before screening&#xD;
&#xD;
         19. Any medical condition, including active, clinically significant infection, that in the&#xD;
             opinion of the investigator or Sponsor may pose a safety risk to a patient in this&#xD;
             study, which may confound safety or efficacy assessment and jeopardize the quality of&#xD;
             the data, or may interfere with study participation&#xD;
&#xD;
         20. Presence of cardiac arrhythmias or conduction defects that require immediate treatment&#xD;
&#xD;
         21. History of alcohol or drug abuse within 2 years prior to randomization&#xD;
&#xD;
         22. Previous randomization in the present study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>130 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Steven Fishbane, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>NSUH,Dept of Medicine,300 Community Drive,Manhasset,NY11030</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90022</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90025</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Ontario</city>
        <state>California</state>
        <zip>91762</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>San Dimas</city>
        <state>California</state>
        <zip>91773</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Whittier</city>
        <state>California</state>
        <zip>90606</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kansas City</city>
        <state>Missouri</state>
        <zip>64108</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Paterson</city>
        <state>New Jersey</state>
        <zip>07504</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Bronx</city>
        <state>New York</state>
        <zip>10461</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Fresh Meadows</city>
        <state>New York</state>
        <zip>11365</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Great Neck</city>
        <state>New York</state>
        <zip>11021</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Ridgewood</city>
        <state>New York</state>
        <zip>11385</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>East Providence</city>
        <state>Rhode Island</state>
        <zip>02914</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>El Paso</city>
        <state>Texas</state>
        <zip>79924</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77004</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Hamamatsu-shi</city>
        <zip>432-8036</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kumamoto-shi</city>
        <zip>860-4112</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Miyagi-gun</city>
        <zip>981-0112</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Nagano-shi</city>
        <zip>388-8004</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Niigata-shi</city>
        <zip>950-2087</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Ora-gun</city>
        <zip>370-0615</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Osaka-shi</city>
        <zip>543-0052</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sakai-shi</city>
        <zip>599-8272</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sashima-gun</city>
        <zip>306-0433</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sendai-shi</city>
        <zip>980-0801</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Shinjuku-ku</city>
        <zip>169-0075</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Toride-shi</city>
        <zip>302-0022</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Tsukuba-shi</city>
        <zip>305-0861</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Wakayama-shi</city>
        <zip>640-8335</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Yachiyo-shi</city>
        <zip>276-0031</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Yokosuka-shi</city>
        <zip>238-0004</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kemerovo</city>
        <zip>650066</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kolomna</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Moscow</city>
        <zip>141007</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Novosibirsk</city>
        <zip>630087</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Omsk</city>
        <zip>644111</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Penza</city>
        <zip>440034</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Podolsk</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Rostov-on-Don</city>
        <zip>344029</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Saint-Petersburg</city>
        <zip>191104</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Saint-Petersburg</city>
        <zip>198205</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>St-Petersburg</city>
        <zip>196247</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Yaroslavl</city>
        <zip>150062</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Yekaterinburg</city>
        <zip>620102</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Cardiff</city>
        <zip>CF14 4XW</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Hull</city>
        <zip>HU3 2JZ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Leicester</city>
        <zip>LE5 4PW</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>London</city>
        <zip>EC1A 7BE</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>London</city>
        <zip>SE5 9RS</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>London</city>
        <zip>SM5 1AA</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>London</city>
        <zip>SW17 0QT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Swansea</city>
        <zip>SA6 6NL</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>York</city>
        <zip>YO31 8HE</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Japan</country>
    <country>Russian Federation</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&amp;amp;parentIdentifier=D9480C00006&amp;amp;attachmentIdentifier=c9e82fef-889a-4fa8-a7a4-d2f8c17e1653&amp;amp;fileName=D9480C00006_CSP_redacted.pdf&amp;amp;versionIdentifier=</url>
    <description>CSP redacted</description>
  </link>
  <link>
    <url>https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&amp;amp;parentIdentifier=D9480C00006&amp;amp;attachmentIdentifier=bd3feeb6-4e7a-49da-8b34-b2ef1e35c582&amp;amp;fileName=D9480C00006_SAP_redacted.pdf&amp;amp;versionIdentifier=</url>
    <description>D9480C00006 SAP redacted</description>
  </link>
  <verification_date>February 2020</verification_date>
  <study_first_submitted>September 26, 2017</study_first_submitted>
  <study_first_submitted_qc>October 2, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 6, 2017</study_first_posted>
  <results_first_submitted>November 5, 2019</results_first_submitted>
  <results_first_submitted_qc>February 10, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">February 20, 2020</results_first_posted>
  <last_update_submitted>February 10, 2020</last_update_submitted>
  <last_update_submitted_qc>February 10, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">February 20, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hyperkalemia</mesh_term>
  </condition_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>February 5, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/21/NCT03303521/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 8, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/21/NCT03303521/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Sodium Zirconium Cyclosilicate (SZC)</title>
          <description>Suspension administered orally for a treatment period of eight weeks (4 weeks of dose adjustment, 4 weeks in stable dose).&#xD;
Single dose contains 1 to 3 sachets that should be suspended in 45 mL of water by patient and administered on non-dialysis days.</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Suspension administered orally for a treatment period of eight weeks (4 weeks of dose adjustment, 4 weeks in stable dose).&#xD;
Single dose contains 1 to 3 sachets that should be suspended in 45 mL of water by patient and administered on non-dialysis days.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="97"/>
                <participants group_id="P2" count="99"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="92"/>
                <participants group_id="P2" count="96"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Kidney transplantation</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Investigational product discontinuation</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Transferred to non-study dialysis center</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Non-comliance to study protocol</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Sodium Zirconium Cyclosilicate (SZC)</title>
          <description>Suspension administered orally for a treatment period of eight weeks (4 weeks of dose adjustment, 4 weeks in stable dose).&#xD;
Single dose contains 1 to 3 sachets that should be suspended in 45 mL of water by patient and administered on non-dialysis days.</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Suspension administered orally for a treatment period of eight weeks (4 weeks of dose adjustment, 4 weeks in stable dose).&#xD;
Single dose contains 1 to 3 sachets that should be suspended in 45 mL of water by patient and administered on non-dialysis days.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="97"/>
            <count group_id="B2" value="99"/>
            <count group_id="B3" value="196"/>
          </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="55.7" spread="13.84"/>
                    <measurement group_id="B2" value="60.4" spread="13.2"/>
                    <measurement group_id="B3" value="58.1" spread="13.69"/>
                  </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="40"/>
                    <measurement group_id="B2" value="41"/>
                    <measurement group_id="B3" value="81"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="57"/>
                    <measurement group_id="B2" value="58"/>
                    <measurement group_id="B3" value="115"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="50"/>
                    <measurement group_id="B2" value="52"/>
                    <measurement group_id="B3" value="102"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black Or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="19"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="33"/>
                    <measurement group_id="B2" value="33"/>
                    <measurement group_id="B3" value="66"/>
                  </measurement_list>
                </category>
                <category>
                  <title>American Indian Or Alasa Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Other</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Responders</title>
        <description>A subject was considered to be a responder if, during the evaluation period, they maintained a pre-dialysis serum potassium (S-K) between 4.0 and 5.0 mmol/L on at least 3 out of 4 dialysis treatments following the long inter-dialytic interval and did not receive rescue therapy. The S-K levels used for this analysis were based on the measurements obtained by the central laboratory.</description>
        <time_frame>Evaluation period runs over the last 4 weeks of the treatment period up to 8 weeks, starting after visit 11 and ending on visit 15, thus it comprises post-long inter-dialytic interval visits 12, 13, 14 and 15.</time_frame>
        <population>Full Analysis Set (all randomized patients)</population>
        <group_list>
          <group group_id="O1">
            <title>Sodium Zirconium Cyclosilicate (SZC)</title>
            <description>Suspension administered orally for a treatment period of eight weeks (4 weeks of dose adjustment, 4 weeks in stable dose).&#xD;
Single dose contains 1 to 3 sachets that should be suspended in 45 mL of water by patient and administered on non-dialysis days.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Suspension administered orally for a treatment period of eight weeks (4 weeks of dose adjustment, 4 weeks in stable dose).&#xD;
Single dose contains 1 to 3 sachets that should be suspended in 45 mL of water by patient and administered on non-dialysis days.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Responders</title>
          <description>A subject was considered to be a responder if, during the evaluation period, they maintained a pre-dialysis serum potassium (S-K) between 4.0 and 5.0 mmol/L on at least 3 out of 4 dialysis treatments following the long inter-dialytic interval and did not receive rescue therapy. The S-K levels used for this analysis were based on the measurements obtained by the central laboratory.</description>
          <population>Full Analysis Set (all randomized patients)</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="97"/>
                <count group_id="O2" value="99"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="41.2"/>
                    <measurement group_id="O2" value="1.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>Fisher Exact</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>68.77</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>10.85</ci_lower_limit>
            <ci_upper_limit>2810.85</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Patients Needing Rescue Therapy</title>
        <description>Patients requiring any urgent intervention consistent with local practice patterns to reduce serum potassium (S-K) including insulin/glucose, beta-adrenergic agonists, sodium bicarbonate, K binders or any form of renal replacement therapy.</description>
        <time_frame>An 8 week overall treatment period (a 4 week adjustment phase plus a 4 week evaluation phase) and a 2 week follow up period.</time_frame>
        <population>Full Analysis Set (all randomized patients)</population>
        <group_list>
          <group group_id="O1">
            <title>Sodium Zirconium Cyclosilicate (SZC)</title>
            <description>Suspension administered orally for a treatment period of eight weeks (4 weeks of dose adjustment, 4 weeks in stable dose).&#xD;
Single dose contains 1 to 3 sachets that should be suspended in 45 mL of water by patient and administered on non-dialysis days.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Suspension administered orally for a treatment period of eight weeks (4 weeks of dose adjustment, 4 weeks in stable dose).&#xD;
Single dose contains 1 to 3 sachets that should be suspended in 45 mL of water by patient and administered on non-dialysis days.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Patients Needing Rescue Therapy</title>
          <description>Patients requiring any urgent intervention consistent with local practice patterns to reduce serum potassium (S-K) including insulin/glucose, beta-adrenergic agonists, sodium bicarbonate, K binders or any form of renal replacement therapy.</description>
          <population>Full Analysis Set (all randomized patients)</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="97"/>
                <count group_id="O2" value="99"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.1"/>
                    <measurement group_id="O2" value="5.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Responders When Accounting for Missing Central Laboratory Serum Potassium Data</title>
        <description>The sensitivity analysis assessed the impact of subjects classified as non-responders due to missing serum potassium (S-K) data. Missing central lab (c-lab) pre-dialysis values were imputed using corresponding pre-dialysis i-STAT (a portable blood analyser) measurements. In addition, a &quot;last observation carried forward&quot; (LOCF) approach was utilized to further impute missing values of pre-dialysis S-K during the evaluation period. This technique will replace missing c-lab S-K values with the last available non-missing pre-dialysis LIDI observation recorded for that patient (and this could be a c-lab value or an imputed c-lab value). The Primary endpoint analysis was repeated on the imputed data.</description>
        <time_frame>Evaluation period runs over the last 4 weeks of the treatment period up to 8 weeks, starting after visit 11 and ending on visit 15, thus it comprises post-long inter-dialytic interval visits 12, 13, 14 and 15.</time_frame>
        <population>Full Analysis Set (all randomized patients)</population>
        <group_list>
          <group group_id="O1">
            <title>Sodium Zirconium Cyclosilicate (SZC)</title>
            <description>Suspension administered orally for a treatment period of eight weeks (4 weeks of dose adjustment, 4 weeks in stable dose).&#xD;
Single dose contains 1 to 3 sachets that should be suspended in 45 mL of water by patient and administered on non-dialysis days.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Suspension administered orally for a treatment period of eight weeks (4 weeks of dose adjustment, 4 weeks in stable dose).&#xD;
Single dose contains 1 to 3 sachets that should be suspended in 45 mL of water by patient and administered on non-dialysis days.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Responders When Accounting for Missing Central Laboratory Serum Potassium Data</title>
          <description>The sensitivity analysis assessed the impact of subjects classified as non-responders due to missing serum potassium (S-K) data. Missing central lab (c-lab) pre-dialysis values were imputed using corresponding pre-dialysis i-STAT (a portable blood analyser) measurements. In addition, a &quot;last observation carried forward&quot; (LOCF) approach was utilized to further impute missing values of pre-dialysis S-K during the evaluation period. This technique will replace missing c-lab S-K values with the last available non-missing pre-dialysis LIDI observation recorded for that patient (and this could be a c-lab value or an imputed c-lab value). The Primary endpoint analysis was repeated on the imputed data.</description>
          <population>Full Analysis Set (all randomized patients)</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="97"/>
                <count group_id="O2" value="99"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="42.3"/>
                    <measurement group_id="O2" value="2.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>Fisher Exact</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>35.51</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>8.53</ci_lower_limit>
            <ci_upper_limit>309.48</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse Events will be collected from time of randomization throughout the treatment period and including the follow-up period (until Visit 16 or the last patient visit in the study), up to 10 weeks (Day 71 +/- 3 days). SAEs will be recorded from the time of informed consent.</time_frame>
      <desc>Safety Analysis Set (All randomized subjects who received at least 1 dose of investigational product, SZC or placebo. N=96 for SZC, N=99 for Placebo). Subjects excluded from the Safety Analysis Set (n=1 for SZC, n=0 Placebo) did not receive treatment.</desc>
      <group_list>
        <group group_id="E1">
          <title>Sodium Zirconium Cyclosilicate (SZC)</title>
          <description>Suspension administered orally for a treatment period of eight weeks (4 weeks of dose adjustment, 4 weeks in stable dose).&#xD;
Single dose contains 1 to 3 sachets that should be suspended in 45 mL of water by patient and administered on non-dialysis days.</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Suspension administered orally for a treatment period of eight weeks (4 weeks of dose adjustment, 4 weeks in stable dose).&#xD;
Single dose contains 1 to 3 sachets that should be suspended in 45 mL of water by patient and administered on non-dialysis days.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 21.0</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="1" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="99"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="99"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Angina pectoris</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="96"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="99"/>
              </event>
              <event>
                <sub_title>Cardiac failure congestive</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="99"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Gastrointestinal haemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="99"/>
              </event>
              <event>
                <sub_title>Small intestinal obstruction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="99"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bacteraemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="99"/>
              </event>
              <event>
                <sub_title>Gangrene</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="99"/>
              </event>
              <event>
                <sub_title>Gastroenteritis viral</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="99"/>
              </event>
              <event>
                <sub_title>Vascular device infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="99"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Arteriovenous fistula occlusion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="99"/>
              </event>
              <event>
                <sub_title>Arteriovenous fistula site complication</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="99"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="99"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Fluid overload</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="99"/>
              </event>
              <event>
                <sub_title>Hyperkalaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="99"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Peripheral arterial occlusive disease</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="99"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 21.0</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="7" subjects_at_risk="96"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="99"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="96"/>
                <counts group_id="E2" events="6" subjects_affected="6" subjects_at_risk="99"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="96"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="99"/>
              </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 NOT 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>AstraZeneca Clinical</name_or_title>
      <organization>AstraZeneca</organization>
      <phone>1-877-240-9479</phone>
      <email>information.center@astrazeneca.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/NCT03303521
org study id: D9480C00006
secondary id: 2017-003029-14
nct id: NCT03303521
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to evaluate the efficacy of ZS in the treatment of hyperkalemia
      in patients on hemodialysis.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Percentage of Responders
time frame: Evaluation period runs over the last 4 weeks of the treatment period up to 8 weeks, starting after visit 11 and ending on visit 15, thus it comprises post-long inter-dialytic interval visits 12, 13, 14 and 15.
description: A subject was considered to be a responder if, during the evaluation period, they maintained a pre-dialysis serum potassium (S-K) between 4.0 and 5.0 mmol/L on at least 3 out of 4 dialysis treatments following the long inter-dialytic interval and did not receive rescue therapy. The S-K levels used for this analysis were based on the measurements obtained by the central laboratory.
measure: Percentage of Responders When Accounting for Missing Central Laboratory Serum Potassium Data
time frame: Evaluation period runs over the last 4 weeks of the treatment period up to 8 weeks, starting after visit 11 and ending on visit 15, thus it comprises post-long inter-dialytic interval visits 12, 13, 14 and 15.
description: The sensitivity analysis assessed the impact of subjects classified as non-responders due to missing serum potassium (S-K) data. Missing central lab (c-lab) pre-dialysis values were imputed using corresponding pre-dialysis i-STAT (a portable blood analyser) measurements. In addition, a "last observation carried forward" (LOCF) approach was utilized to further impute missing values of pre-dialysis S-K during the evaluation period. This technique will replace missing c-lab S-K values with the last available non-missing pre-dialysis LIDI observation recorded for that patient (and this could be a c-lab value or an imputed c-lab value). The Primary endpoint analysis was repeated on the imputed data.
measure: Percentage of Patients Needing Rescue Therapy
time frame: An 8 week overall treatment period (a 4 week adjustment phase plus a 4 week evaluation phase) and a 2 week follow up period.
description: Patients requiring any urgent intervention consistent with local practice patterns to reduce serum potassium (S-K) including insulin/glucose, beta-adrenergic agonists, sodium bicarbonate, K binders or any form of renal replacement therapy.
arm group label: Sodium Zirconium Cyclosilicate (ZS)
arm group type: Experimental
description: Suspension administered orally for a treatment period of eight weeks (4 weeks of dose adjustment, 4 weeks in stable dose) Single dose contains from 1 to 3 sachets of ZS 5g depending on dose level assigned to a patient per non-dialysis days.
arm group label: Placebo
arm group type: Placebo Comparator
description: Suspension administered orally for a treatment period of eight weeks (4 weeks of dose adjustment, 4 weeks in stable dose) Single dose contains from 1 to 3 sachets of Placebo depending on dose level assigned to a patient per non-dialysis days.
intervention type: Drug
intervention name: Placebo
description: Suspension administered orally for a treatment period of eight weeks (4 weeks of dose adjustment, 4 weeks in stable dose) .
Single dose contains from 1 to 3 sachets of Placebo depending on dose level assigned to a patient per non-dialysis days.
arm group label: Placebo
intervention type: Drug
intervention name: Sodium Zirconium Cyclosilicate (ZS)
description: Suspension administered orally for a treatment period of eight weeks (4 weeks of dose adjustment, 4 weeks in stable dose) .
Single dose contains from 1 to 3 sachets of ZS 5g depending on dose level assigned to a patient per non-dialysis days.
arm group label: Sodium Zirconium Cyclosilicate (ZS)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 130 Years
healthy volunteers: No
last name: Steven Fishbane, MD
role: Principal Investigator
affiliation: NSUH,Dept of Medicine,300 Community Drive,Manhasset,NY11030
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country: Japan
country: Russian Federation
country: United Kingdom
country: United States
url: https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&amp;parentIdentifier=D9480C00006&amp;attachmentIdentifier=c9e82fef-889a-4fa8-a7a4-d2f8c17e1653&amp;fileName=D9480C00006_CSP_redacted.pdf&amp;versionIdentifier=
description: CSP redacted
url: https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&amp;parentIdentifier=D9480C00006&amp;attachmentIdentifier=bd3feeb6-4e7a-49da-8b34-b2ef1e35c582&amp;fileName=D9480C00006_SAP_redacted.pdf&amp;versionIdentifier=
description: D9480C00006 SAP redacted
responsible party type: Sponsor
mesh term: Hyperkalemia
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