<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/NCT03303144</url>
  </required_header>
  <id_info>
    <org_study_id>RMFPC-20</org_study_id>
    <nct_id>NCT03303144</nct_id>
  </id_info>
  <brief_title>Equivalence of Triferic® (Ferric Pyrophosphate Citrate) Administered Via Hemodialysate and Intravenously to Adult CKD-5HD Patients</brief_title>
  <official_title>Equivalence of Triferic® (Ferric Pyrophosphate Citrate) Administered Via Hemodialysate and Intravenously to Adult CKD-5HD Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Rockwell Medical Technologies, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Rockwell Medical Technologies, Inc.</source>
  <oversight_info>
    <has_dmc>No</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 main purpose is to establish the equivalence of Triferic iron administered via dialysate&#xD;
      into the arterial blood line and into the venous blood line&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      An open-label, four period, randomized, crossover study of Triferic iron administered via&#xD;
      hemodialysis compared to Triferic administered intravenously pre- and post- hemodialyzer.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 1, 2017</start_date>
  <completion_date type="Actual">December 28, 2017</completion_date>
  <primary_completion_date type="Actual">December 28, 2017</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pharmacokinetics (PK) of Triferic Iron Administered Via Hemodialysate in Adult CKD-5HD Patients: Cmax.</measure>
    <time_frame>1, 2, 3, 3.5, 4, 4.5, 5, 6, 8, 10, and 12 hours</time_frame>
    <description>The PK will be done by assessing the mean Cmax of total serum iron from Triferic administered via hemodialysate, compared to Triferic administered at a fixed IV dose of 6.6 mg iron/kg during a single dialysis session.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetics (PK) of Triferic Iron Administered IV in Adult CKD-5HD Patients:Cmax</measure>
    <time_frame>1, 2, 3, 3.5, 4, 4.5, 5, 6, 8, 10, and 12 hours</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetics (PK) of Triferic Iron Administered IV in Adult CKD-5HD Patients: AUC(0-end).</measure>
    <time_frame>1, 2, 3, 3.5, 4, 4.5, 5, 6, 8, 10, and 12 hours</time_frame>
    <description>The PK will be done by assessing the mean AUC(0-end) of total serum iron from Triferic administered via hemodialysate, compared to Triferic administered at a fixed IV dose of 6.5 mg iron/kg during a single dialysis session.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Safety Endpoint: Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs) Incidence of Treatment Emergent Serious Adverse Events</measure>
    <time_frame>From the start of the HD #1 through the end of study participation or 7 days after the last dose of Triferic, whichever is later, assessed up to 2 months</time_frame>
    <description>Safety will be documented by recording the incidence of treatment-emergent serious adverse events (TESAEs).The number of patients that experienced treatment emergent serious adverse events will be quantified. Please see the adverse event table for specifics.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">27</enrollment>
  <condition>End Stage Renal Disease</condition>
  <arm_group>
    <arm_group_label>Triferic via Hemodialysate</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Triferic will be mixed with the liquid bicarbonate concentrate used in the preparation of the hemodialysate solution. This will result in a final Triferic iron concentration in the dialysate of 2 µM (110 µg/L). The patients will receive Triferic over 4 hrs at one hemodialysis session.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Triferic via IV infusion( pre-dialyzer)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will receive a single 6.5-mg dose of Triferic iron administered IV over 3 hrs during hemodialysis via arterial blood line (pre-dialyzer)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Triferic via IV infusion (post-dialyzer)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will receive a single 6.5-mg dose of Triferic iron administered IV over 3 hrs during hemodialysis via venous blood line (post-dialyzer)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Triferic</intervention_name>
    <description>ferric pyrophosphate citrate</description>
    <arm_group_label>Triferic via Hemodialysate</arm_group_label>
    <arm_group_label>Triferic via IV infusion (post-dialyzer)</arm_group_label>
    <arm_group_label>Triferic via IV infusion( pre-dialyzer)</arm_group_label>
    <other_name>ferric pyrophosphate citrate</other_name>
    <other_name>FPC</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. The patient must be able to provide informed consent and have personally signed and&#xD;
             dated the written informed consent document before completing any study-related&#xD;
             procedures.&#xD;
&#xD;
          2. The patient must be 18-80 years of age inclusive at the time of consent.&#xD;
&#xD;
          3. The patient must have been undergoing chronic hemodialysis for chronic kidney disease&#xD;
             for at least 3 months, and be expected to remain on hemodialysis and be able to&#xD;
             complete the study.&#xD;
&#xD;
          4. The patient must have a Screening ferritin level of ≥100µg/L.&#xD;
&#xD;
          5. The patient must have a Screening transferrin saturation (TSAT) of 15-45%, inclusive.&#xD;
&#xD;
          6. The patient must have a Screening hemoglobin (Hgb) concentration ≥9.0 g/dL.&#xD;
&#xD;
          7. The patient must be undergoing hemodialysis at least 3x/week.&#xD;
&#xD;
          8. The patient must have at least a minimally adequate measured dialysis dose defined as&#xD;
             single-pool Kt/V (dialyzer clearance of urea multiplied by dialysis time, divided by&#xD;
             patient's total body water) ≥1.2, or KIDt/V (online dialyzer clearance measured using&#xD;
             ionic dialysance multiplied by dialysis time, divided by patient's total body water)&#xD;
             ≥1.2 measured within the 90 days prior to HD #1.&#xD;
&#xD;
          9. Patient is receiving, or can receive anticoagulation for dialysis by a single dose of&#xD;
             unfractionated heparin or low molecular weight heparin pre-dialysis; or by&#xD;
             intermittent IV heparin bolus.&#xD;
&#xD;
         10. The patient's vascular access for dialysis that will be used during the study must&#xD;
             have stable function in the judgment of the Investigator.&#xD;
&#xD;
         11. The patient must agree to discontinue all iron preparations (oral and IV) for 14 days&#xD;
             prior to the start of HD#1 and throughout the study.&#xD;
&#xD;
         12. Female patients must not be pregnant or breastfeeding. They must have been amenorrheic&#xD;
             for the past year or be surgically sterile or agree to not become pregnant by&#xD;
             continuous use of an effective birth control method acceptable to the Investigator for&#xD;
             the duration of their participation in the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. The patient has had an RBC or whole blood transfusion within 4 weeks prior to&#xD;
             Screening.&#xD;
&#xD;
          2. The patient requires a continuous infusion of heparin during standard hemodialysis.&#xD;
&#xD;
          3. The patient has had administration of IV or oral iron supplements (including&#xD;
             multivitamins with iron or iron based phosphate binders) within 14 days prior to the&#xD;
             start of HD #1. (The patient may subsequently become eligible if additional time&#xD;
             elapses and all other eligibility criteria are met.).&#xD;
&#xD;
          4. The patient has known active bleeding from any site other than AV fistula or graft&#xD;
             (e.g., gastrointestinal, hemorrhoidal, nasal, pulmonary, etc.).&#xD;
&#xD;
          5. The patient has a living kidney donor identified or living-donor kidney transplant&#xD;
             scheduled to occur during study participation. (Note: Patients awaiting deceased-donor&#xD;
             transplant need not be excluded.)&#xD;
&#xD;
          6. The patient is scheduled to have a surgical procedure during the study.&#xD;
&#xD;
          7. The patient has had a hospitalization within the 4 weeks prior to Screening (except&#xD;
             for vascular access surgery) that, in the opinion of the Investigator, confers a&#xD;
             significant risk of hospitalization during the course of the study.&#xD;
&#xD;
          8. The patient has a history of noncompliance with the dialysis regimen in the opinion of&#xD;
             the Investigator.&#xD;
&#xD;
          9. The patient has a known ongoing active inflammatory disorder (other than CKD), such as&#xD;
             systemic lupus erythematosus, rheumatoid arthritis, or other collagen-vascular&#xD;
             disease, that currently requires systemic anti-inflammatory or immunomodulatory&#xD;
             therapy.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Thomas Marbury</last_name>
    <role>Principal Investigator</role>
    <affiliation>Orlando Clinical Research Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Orlando Clinical Research Center</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32809</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>September 28, 2017</study_first_submitted>
  <study_first_submitted_qc>October 2, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 5, 2017</study_first_posted>
  <results_first_submitted>August 14, 2020</results_first_submitted>
  <results_first_submitted_qc>October 21, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">November 16, 2020</results_first_posted>
  <last_update_submitted>October 21, 2020</last_update_submitted>
  <last_update_submitted_qc>October 21, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">November 16, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Pharmacokinetics</keyword>
  <keyword>Equivalence</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Kidney Failure, Chronic</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>September 18, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/44/NCT03303144/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>All 27 participants in the study were randomly assigned to cross-over between the three treatments on Day 3, Day 8 and Day 10.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Triferic Via Hemodialysate (Day 3)</title>
          <description>Triferic will be mixed with the liquid bicarbonate concentrate used in the preparation of the hemodialysate solution. This will result in a final Triferic iron concentration in the dialysate of 2 µM (110 µg/L). The patients will receive Triferic over 4 hrs at one hemodialysis session.</description>
        </group>
        <group group_id="P2">
          <title>Triferic Via IV Infusion( Pre-dialyzer) (Day 8)</title>
          <description>Patients will receive a single 6.5-mg dose of Triferic iron administered IV over 3 hrs during hemodialysis via arterial blood line (pre-dialyzer)</description>
        </group>
        <group group_id="P3">
          <title>Triferic Via IV Infusion (Post-dialyzer) (Day 10)</title>
          <description>Patients will receive a single 6.5-mg dose of Triferic iron administered IV over 3 hrs during hemodialysis via venous blood line (post-dialyzer)</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Triferic Via Hemodialysate (Day 3)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="26"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="26"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Triferic Via IV Infusion (Day 8)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="26"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="25"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Triferic Via IV Infusion (Day 10)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="26"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="25"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Safety Population</title>
          <description>All patients in study</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="27"/>
          </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="53.9" spread="8.11"/>
                  </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="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="25"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="23"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Pharmacokinetics (PK) of Triferic Iron Administered Via Hemodialysate in Adult CKD-5HD Patients: Cmax.</title>
        <description>The PK will be done by assessing the mean Cmax of total serum iron from Triferic administered via hemodialysate, compared to Triferic administered at a fixed IV dose of 6.6 mg iron/kg during a single dialysis session.</description>
        <time_frame>1, 2, 3, 3.5, 4, 4.5, 5, 6, 8, 10, and 12 hours</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Triferic Via Hemodialysate</title>
            <description>Triferic will be mixed with the liquid bicarbonate concentrate used in the preparation of the hemodialysate solution. This will result in a final Triferic iron concentration in the dialysate of 2 µM (110 µg/L). The patients will receive Triferic over 4 hrs at one hemodialysis session.&#xD;
Triferic: ferric pyrophosphate citrate</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetics (PK) of Triferic Iron Administered Via Hemodialysate in Adult CKD-5HD Patients: Cmax.</title>
          <description>The PK will be done by assessing the mean Cmax of total serum iron from Triferic administered via hemodialysate, compared to Triferic administered at a fixed IV dose of 6.6 mg iron/kg during a single dialysis session.</description>
          <units>h*ug/dL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="207" spread="30.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Pharmacokinetics (PK) of Triferic Iron Administered IV in Adult CKD-5HD Patients:Cmax</title>
        <time_frame>1, 2, 3, 3.5, 4, 4.5, 5, 6, 8, 10, and 12 hours</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Triferic Via IV Infusion( Pre-dialyzer)</title>
            <description>Patients will receive a single 6.5-mg dose of Triferic iron administered IV over 3 hrs during hemodialysis via arterial blood line (pre-dialyzer)&#xD;
Triferic: ferric pyrophosphate citrate</description>
          </group>
          <group group_id="O2">
            <title>Triferic Via IV Infusion (Post-dialyzer)</title>
            <description>Patients will receive a single 6.5-mg dose of Triferic iron administered IV over 3 hrs during hemodialysis via venous blood line (post-dialyzer)&#xD;
Triferic: ferric pyrophosphate citrate</description>
          </group>
          <group group_id="O3">
            <title>Triferic Via Hemodialysate</title>
            <description>Triferic will be mixed with the liquid bicarbonate concentrate used in the preparation of the hemodialysate solution. This will result in a final Triferic iron concentration in the dialysate of 2 µM (110 µg/L). The patients will receive Triferic over 4 hrs at one hemodialysis session.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetics (PK) of Triferic Iron Administered IV in Adult CKD-5HD Patients:Cmax</title>
          <units>h*ug/dL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="25"/>
                <count group_id="O3" value="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="215" spread="21.6"/>
                    <measurement group_id="O2" value="195" spread="25.6"/>
                    <measurement group_id="O3" value="207" spread="30.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Pharmacokinetics (PK) of Triferic Iron Administered IV in Adult CKD-5HD Patients: AUC(0-end).</title>
        <description>The PK will be done by assessing the mean AUC(0-end) of total serum iron from Triferic administered via hemodialysate, compared to Triferic administered at a fixed IV dose of 6.5 mg iron/kg during a single dialysis session.</description>
        <time_frame>1, 2, 3, 3.5, 4, 4.5, 5, 6, 8, 10, and 12 hours</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Triferic Via IV Infusion( Pre-dialyzer)</title>
            <description>Patients will receive a single 6.5-mg dose of Triferic iron administered IV over 3 hrs during hemodialysis via arterial blood line (pre-dialyzer)&#xD;
Triferic: ferric pyrophosphate citrate</description>
          </group>
          <group group_id="O2">
            <title>Triferic Via IV Infusion (Post-dialyzer)</title>
            <description>Patients will receive a single 6.5-mg dose of Triferic iron administered IV over 3 hrs during hemodialysis via venous blood line (post-dialyzer)&#xD;
Triferic: ferric pyrophosphate citrate</description>
          </group>
          <group group_id="O3">
            <title>Triferic Via Hemodialysate</title>
            <description>Triferic will be mixed with the liquid bicarbonate concentrate used in the preparation of the hemodialysate solution. This will result in a final Triferic iron concentration in the dialysate of 2 µM (110 µg/L). The patients will receive Triferic over 4 hrs at one hemodialysis session.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetics (PK) of Triferic Iron Administered IV in Adult CKD-5HD Patients: AUC(0-end).</title>
          <description>The PK will be done by assessing the mean AUC(0-end) of total serum iron from Triferic administered via hemodialysate, compared to Triferic administered at a fixed IV dose of 6.5 mg iron/kg during a single dialysis session.</description>
          <units>h*ug/dL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="25"/>
                <count group_id="O3" value="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1540" spread="28.5"/>
                    <measurement group_id="O2" value="1450" spread="31.4"/>
                    <measurement group_id="O3" value="1500" spread="31.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Safety Endpoint: Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs) Incidence of Treatment Emergent Serious Adverse Events</title>
        <description>Safety will be documented by recording the incidence of treatment-emergent serious adverse events (TESAEs).The number of patients that experienced treatment emergent serious adverse events will be quantified. Please see the adverse event table for specifics.</description>
        <time_frame>From the start of the HD #1 through the end of study participation or 7 days after the last dose of Triferic, whichever is later, assessed up to 2 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Triferic Via IV Infusion( Pre-dialyzer)</title>
            <description>Patients will receive a single 6.5-mg dose of Triferic iron administered IV over 3 hrs during hemodialysis via arterial blood line (pre-dialyzer)</description>
          </group>
          <group group_id="O2">
            <title>Triferic Via IV Infusion (Post-dialyzer)</title>
            <description>Patients will receive a single 6.5-mg dose of Triferic iron administered IV over 3 hrs during hemodialysis via venous blood line (post-dialyzer)</description>
          </group>
          <group group_id="O3">
            <title>Triferic Via Hemodialysate</title>
            <description>Triferic will be mixed with the liquid bicarbonate concentrate used in the preparation of the hemodialysate solution. This will result in a final Triferic iron concentration in the dialysate of 2 µM (110 µg/L). The patients will receive Triferic over 4 hrs at one hemodialysis session.</description>
          </group>
        </group_list>
        <measure>
          <title>Safety Endpoint: Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs) Incidence of Treatment Emergent Serious Adverse Events</title>
          <description>Safety will be documented by recording the incidence of treatment-emergent serious adverse events (TESAEs).The number of patients that experienced treatment emergent serious adverse events will be quantified. Please see the adverse event table for specifics.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="27"/>
                <count group_id="O2" value="27"/>
                <count group_id="O3" value="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events will be recorded on the AE CRF from the start of HD #1 (Day 1) through the end of study participation or 7 days after the last dose of Triferic (Day 10).</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Triferic Via Hemodialysate</title>
          <description>Triferic will be mixed with the liquid bicarbonate concentrate used in the preparation of the hemodialysate solution. This will result in a final Triferic iron concentration in the dialysate of 2 µM (110 µg/L). The patients will receive Triferic over 4 hrs at one hemodialysis session.&#xD;
Triferic: ferric pyrophosphate citrate</description>
        </group>
        <group group_id="E2">
          <title>Triferic Via IV Infusion( Pre-dialyzer)</title>
          <description>Patients will receive a single 6.5-mg dose of Triferic iron administered IV over 3 hrs during hemodialysis via arterial blood line (pre-dialyzer)&#xD;
Triferic: ferric pyrophosphate citrate</description>
        </group>
        <group group_id="E3">
          <title>Triferic Via IV Infusion (Post-dialyzer)</title>
          <description>Patients will receive a single 6.5-mg dose of Triferic iron administered IV over 3 hrs during hemodialysis via venous blood line (post-dialyzer)&#xD;
Triferic: ferric pyrophosphate citrate</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MEDDRA (20.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="27"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="27"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="27"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="27"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cardiac arrest</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="27"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="27"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="27"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="27"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Chronic obstructive pulmonary disease</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="27"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="27"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MEDDRA (20.0)</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="1" subjects_at_risk="27"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="27"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hypoglycaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="27"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="27"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr Ray Pratt</name_or_title>
      <organization>Rockwell Medical</organization>
      <phone>248 960-9009 ext 405</phone>
      <email>rpratt@rockwellmed.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/NCT03303144
org study id: RMFPC-20
nct id: NCT03303144
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The main purpose is to establish the equivalence of Triferic iron administered via dialysate
      into the arterial blood line and into the venous blood line
An open-label, four period, randomized, crossover study of Triferic iron administered via
      hemodialysis compared to Triferic administered intravenously pre- and post- hemodialyzer.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Pharmacokinetics (PK) of Triferic Iron Administered Via Hemodialysate in Adult CKD-5HD Patients: Cmax.
time frame: 1, 2, 3, 3.5, 4, 4.5, 5, 6, 8, 10, and 12 hours
description: The PK will be done by assessing the mean Cmax of total serum iron from Triferic administered via hemodialysate, compared to Triferic administered at a fixed IV dose of 6.6 mg iron/kg during a single dialysis session.
measure: Pharmacokinetics (PK) of Triferic Iron Administered IV in Adult CKD-5HD Patients:Cmax
time frame: 1, 2, 3, 3.5, 4, 4.5, 5, 6, 8, 10, and 12 hours
measure: Pharmacokinetics (PK) of Triferic Iron Administered IV in Adult CKD-5HD Patients: AUC(0-end).
time frame: 1, 2, 3, 3.5, 4, 4.5, 5, 6, 8, 10, and 12 hours
description: The PK will be done by assessing the mean AUC(0-end) of total serum iron from Triferic administered via hemodialysate, compared to Triferic administered at a fixed IV dose of 6.5 mg iron/kg during a single dialysis session.
measure: Safety Endpoint: Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs) Incidence of Treatment Emergent Serious Adverse Events
time frame: From the start of the HD #1 through the end of study participation or 7 days after the last dose of Triferic, whichever is later, assessed up to 2 months
description: Safety will be documented by recording the incidence of treatment-emergent serious adverse events (TESAEs).The number of patients that experienced treatment emergent serious adverse events will be quantified. Please see the adverse event table for specifics.
arm group label: Triferic via Hemodialysate
arm group type: Experimental
description: Triferic will be mixed with the liquid bicarbonate concentrate used in the preparation of the hemodialysate solution. This will result in a final Triferic iron concentration in the dialysate of 2 µM (110 µg/L). The patients will receive Triferic over 4 hrs at one hemodialysis session.
arm group label: Triferic via IV infusion( pre-dialyzer)
arm group type: Experimental
description: Patients will receive a single 6.5-mg dose of Triferic iron administered IV over 3 hrs during hemodialysis via arterial blood line (pre-dialyzer)
arm group label: Triferic via IV infusion (post-dialyzer)
arm group type: Experimental
description: Patients will receive a single 6.5-mg dose of Triferic iron administered IV over 3 hrs during hemodialysis via venous blood line (post-dialyzer)
intervention type: Drug
intervention name: Triferic
description: ferric pyrophosphate citrate
arm group label: Triferic via Hemodialysate
arm group label: Triferic via IV infusion (post-dialyzer)
arm group label: Triferic via IV infusion( pre-dialyzer)
other name: ferric pyrophosphate citrate
other name: FPC
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Thomas Marbury
role: Principal Investigator
affiliation: Orlando Clinical Research Center
facility: 
country: United States
responsible party type: Sponsor
mesh term: Kidney Failure, Chronic
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 