<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/NCT03283098</url>
  </required_header>
  <id_info>
    <org_study_id>20140197</org_study_id>
    <nct_id>NCT03283098</nct_id>
  </id_info>
  <brief_title>A Phase 1 Study to Evaluate PK, Safety and Tolerability of AMG 416</brief_title>
  <official_title>A Phase 1, Multiple Dose, Randomized, Double-blind, Placebo-controlled Study to Evaluate Pharmacokinetics, Safety and Tolerability of AMG 416 Administered Intravenously to Chinese Subjects With Chronic Kidney Disease on Hemodialysis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Amgen</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Amgen</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>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This was a multiple-dose, double-blind, randomized, placebo-controlled study. Chinese&#xD;
      subjects residing in Mainland China with chronic kidney disease (CKD) receiving hemodialysis&#xD;
      were randomized in a 3:1 ratio to receive 5 mg intravenous (IV) of etelcalcetide or placebo 3&#xD;
      times a week (TIW) for approximately 4 weeks, with a subsequent follow up period of&#xD;
      approximately 4 weeks.&#xD;
&#xD;
      Doses were given at the end of each scheduled hemodialysis session on study days 1 through&#xD;
      day 27 and subject participation was complete after day 55 end-of-study (EOS) procedures were&#xD;
      performed. Doses were administered TIW for 4 weeks, for a total of 12 doses.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 1, 2018</start_date>
  <completion_date type="Actual">February 4, 2019</completion_date>
  <primary_completion_date type="Actual">February 4, 2019</primary_completion_date>
  <phase>Phase 1</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>
    <intervention_model_description>This is a multiple dose, double-blind, randomized, placebo-controlled clinical study conducted in Chinese subjects residing in Mainland China with chronic kidney disease receiving hemodialysis. The treatment duration will be approximately 4 weeks with a post treatment followup of 4 weeks. A dose will be given at each scheduled hemodialysis session (Dose administered three times a week for 4 weeks, for a total of 12 doses).</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pharmacokinetic (PK) Parameter: Time to Maximum Drug Concentration (Tmax) of Plasma Etelcalcetide on Days 1 and 27</measure>
    <time_frame>Days 1 and 27; PK blood sampling predialysis, and at 10, 30, 60, 90 min postdose, as well as on Day 2 and 28 between 18 and 30 hours after study drug administration</time_frame>
    <description>Tmax is the time to maximum drug concentration of plasma etelcalcetide after dosing on Days 1 and 27.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>PK: Maximum Observed Drug Concentration (Cmax) of Plasma Etelcalcetide on Days 1 and 27</measure>
    <time_frame>Days 1 and 27; PK blood sampling predialysis, and at 10, 30, 60, 90 min postdose, as well as on Day 2 and 28 between 18 and 30 hours after study drug administration</time_frame>
    <description>Cmax was defined as the maximum observed plasma drug concentration measured between the time of drug administration to the beginning of the next dialysis session.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetic (PK) Parameter: Area Under the Curve From Time Zero to the Beginning of the Subsequent Hemodialysis Treatment (AUClast) of Plasma Etelcalcetide on Days 1 and 27</measure>
    <time_frame>Days 1 and 27; PK blood sampling predialysis, and up to 44-50 hour postdose.at 10, 30, 60, 90 min postdose: Day 2 and 28 between 18 and 30 hours after study drug administration; Day 3 (predialysis) + Day 29</time_frame>
    <description>AUClast was specifically defined in this study as the area under the concentration time curve measured from the time of drug administration to the beginning of the next dialysis session, following the first and last dose.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetic (PK) Parameter: Accumulation Ratio Comparing Days 1 and 27</measure>
    <time_frame>Days 1 and 27; PK blood sampling predialysis, and up to 44-50 hour postdose.at 10, 30, 60, 90 min postdose: Day 2 and 28 between 18 and 30 hours after study drug administration; Day 3 (predialysis) + Day 29</time_frame>
    <description>Accumulation ratio, calculated as AUClast day 27/AUClast day 1.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Participants With Treatment-Emergent Adverse Events (TEAEs)</measure>
    <time_frame>Day 1 up to Day 55 (end of study)</time_frame>
    <description>The severity of each adverse event was assessed using the NCI-CTCAE Version 4.0 according to the following:&#xD;
Grade 1 - Mild: Asymptomatic or mild symptoms; intervention not indicated&#xD;
Grade 2 - Moderate: Minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL)&#xD;
Grade 3 - Severe: Medically significant but not life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL&#xD;
Grade 4 - Life-threatening&#xD;
Grade 5 - Fatal.&#xD;
A serious AE is an AE that met one or more of the following criteria:&#xD;
Death&#xD;
Life-threatening&#xD;
Required inpatient hospitalization or prolongation of an existing hospitalization&#xD;
Resulted in persistent or significant disability/incapacity&#xD;
A congenital anomaly/birth defect&#xD;
Important medical events that required medical or surgical intervention to prevent one of the outcomes above.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Participants With Treatment-Emergent Adverse Events (TEAEs) of Interest</measure>
    <time_frame>Day 1 up to Day 55 (end of study)</time_frame>
    <description>Terms were coded with Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. Narrow search criteria used for both standardized MedDRA queries (SMQ) and events of interest (EOI). One preferred term (PT) could match multiple EOIs. Infusion Reaction EOI counts included only those events which had onset day coinciding with study medication infusion and resolved on the same day or the day after onset.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Participants With Clinically-Significant Changes in Electrocardiograms (ECGs) From Baseline to End of Study</measure>
    <time_frame>Baseline is Day -2; End of Study is Day 55</time_frame>
    <description>Count of participants who exhibited a clinically significant change in the results of their 12-lead electrocardiograms (ECG) when comparing baseline to end of study ECGs.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to End of Study in Weight</measure>
    <time_frame>Day 1 up to Day 55</time_frame>
    <description>Change from baseline in weight measured at visit.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to End of Study in Systolic and Diastolic Blood Pressures</measure>
    <time_frame>Baseline Day 1 prior to dialysis; End of Study is Day 55</time_frame>
    <description>Participants remained seated for at least 10 minutes prior to measurement of predialysis heart rate and blood pressure.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Baseline and Change From Baseline to End of Study in Heart Rate</measure>
    <time_frame>Baseline Day 1 prior to dialysis; End of Study is Day 55</time_frame>
    <description>Participants remained seated for at least 10 minutes prior to measurement of predialysis heart rate and blood pressure.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to End of Study in Calcium</measure>
    <time_frame>Baseline is Day 1 prior to dialysis; End of Study is Day 55</time_frame>
    <description>Calcium was tested at a central laboratory.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to End of Study in Corrected Calcium (cCa)</measure>
    <time_frame>Baseline is the average of Day -2 and Day 1 prior to dialysis; End of Study is Day 55</time_frame>
    <description>Total serum calcium was corrected if the serum albumin was &lt; 4 g/dL or 40 g/L, otherwise cCa equals total serum calcium.&#xD;
The correction formula was:&#xD;
Corrected calcium (mg/dL) = Total calcium (mg/dL) + (4 - albumin [g/dL]) * 0.8</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Participants With Low Corrected Calcium (cCA) By Category</measure>
    <time_frame>Timeframes: Days 8, 15, 22, 27, 29, 34, 41, 55</time_frame>
    <description>The lowest cCA value for each participant is reported.&#xD;
Total serum calcium was corrected if the serum albumin was &lt; 4 g/dL or 40 g/L, otherwise cCa equals total serum calcium.&#xD;
The correction formula was:&#xD;
Corrected calcium (mg/dL) = Total calcium (mg/dL) + (4 - albumin [g/dL]) * 0.8</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Baseline and Change From Baseline to End of Study in Serum Albumin</measure>
    <time_frame>Baseline is the average of Day -2 and Day 1 prior to dialysis; End of Study is Day 55</time_frame>
    <description>Serum albumin was tested at a central laboratory.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to End of Study in Serum Phosphorus</measure>
    <time_frame>Baseline is Day 1 prior to dialysis; End of Study is Day 55</time_frame>
    <description>Serum phosphorus was tested at a central laboratory.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Participants With Anti-etelcalcetide Antibody at Baseline and Postbaseline</measure>
    <time_frame>Baseline: Day 1 prior to dialysis. Postbaseline: Days 29 and 55 prior to dialysis</time_frame>
    <description>Participants with positive titers for antibodies to etelcalcetide could be asked to return to the clinical research unit to provide additional serum samples.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">33</enrollment>
  <condition>Secondary Hyperparathyroidism</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Intravenous (IV) administration of placebo three times a week (TIW) for 4 weeks for a total of 12 doses. Participants were followed for an additional 4 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Etelcalcetide</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>5 mg intravenous (IV) dose of etelcalcetide three times a week (TIW) for 4 weeks for a total of 12 doses. Participants were followed for an additional 4 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Etelcalcetide</intervention_name>
    <description>Etelcalcetide was supplied as a sterile, preservative-free, aqueous solution in a single-use 3 mL glass vial.</description>
    <arm_group_label>Etelcalcetide</arm_group_label>
    <other_name>AMG 416</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo supplied to match active intervention.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subject has provided informed consent prior to initiation of any study-specific&#xD;
             activities/procedures&#xD;
&#xD;
          -  Resident in Mainland China and of Chinese ancestry&#xD;
&#xD;
          -  Male or female subject ≥ 18 and ≤ 70 years of age at the time of screening, with end&#xD;
             stage renal disease receiving hemodialysis&#xD;
&#xD;
          -  Subject must be receiving hemodialysis 3 times weekly for at least 3 months through a&#xD;
             functioning permanent dialysis access prior to Day -2 and have adequate hemodialysis&#xD;
             with a delivered Kt/V ≥ 1.2 or urea reduction ratio (URR) ≥ 65% within 4 weeks to&#xD;
             screening. The subject's routine hemodialysis session must be of 3-4.5 hours in&#xD;
             duration, inclusive&#xD;
&#xD;
          -  Subject has stable dialysis prescription and this prescription is not anticipated to&#xD;
             significantly change during the course of the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Corrected calcium (calculated) level is &lt; 2.07 mmol/L (8.3 mg/dL), and/or intact PTH&#xD;
             level is outside the range of 31.8 - 127.3 pmol/L (300 - 1200 pg/mL)&#xD;
&#xD;
          -  Female subjects who are pregnant, lactating/breastfeeding, or who plan to conceive, or&#xD;
             breastfeed while on study through 3 months after receiving the dose of study drug&#xD;
&#xD;
          -  Female subject of reproductive potential not willing to use a(n) acceptable method(s)&#xD;
             of effective birth control during treatment with AMG 416, and for an additional 3&#xD;
             months after the end of treatment with AMG 416. Female subjects who have had a&#xD;
             hysterectomy, bilateral salpingectomy, bilateral oophorectomy, bilateral tubal&#xD;
             ligation, or who are postmenopausal are not required to use contraception.&#xD;
             Postmenopausal is defined as:&#xD;
&#xD;
               -  Age &gt; 55 years with cessation of menses for 12 months or more&#xD;
&#xD;
               -  Age &lt; 55 but no spontaneous menses for at least 2 years&#xD;
&#xD;
               -  Age &lt; 55 years and spontaneous menses within the past 1 years, but currently&#xD;
                  amenorrheic, AND with postmenopausal gonadrotropin levels (luteinizing hormone&#xD;
                  and follicle-stimulating hormone levels &gt; 40 IU/L) or postmenopausal estradiol&#xD;
                  levels (&lt;5.3 pmol/L or 5 ng/dL) or according to the definition of &quot;postmenopausal&#xD;
                  range&quot; for the laboratory involved&#xD;
&#xD;
               -  Underwent a bilateral oophorectomy&#xD;
&#xD;
          -  Females of reproductive potential with a positive pregnancy test, unless medical&#xD;
             follow-up confirms the subject is not pregnant&#xD;
&#xD;
          -  Previous administration of AMG 416&#xD;
&#xD;
          -  Subject has received cinacalcet within the 30 days prior to informed consent&#xD;
             (treatment with cinacalcet is prohibited during the study)&#xD;
&#xD;
          -  Subject has lost 500 mL or more of blood or plasma within 8 weeks of study drug&#xD;
             administration or during the study period&#xD;
&#xD;
          -  Anticipated or scheduled to have major surgical procedures during the study period&#xD;
             such as kidney transplant or parathyroidectomy&#xD;
&#xD;
          -  History of malignancy within 5 years before Day -2 (except non melanoma skin cancers,&#xD;
             or cervical carcinoma in situ)&#xD;
&#xD;
          -  Subject's 12-lead electrocardiogram (ECG) at screening suggests unstable arrhythmia or&#xD;
             other cardiac abnormality that could place the subject at increased risk, based upon&#xD;
             the Investigator's opinion&#xD;
&#xD;
          -  Subject has current or history of cardiovascular conditions such as uncontrolled&#xD;
             hypertension, symptomatic ventricular dysrhythmias, Torsades de Pointes, angina&#xD;
             pectoris congestive heart failure (New York Heart Association Classification III or&#xD;
             IV), myocardial infarction, coronary angioplasty, or coronary arterial bypass grafting&#xD;
             within the past 6 months prior to screening&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>MD</last_name>
    <role>Study Director</role>
    <affiliation>Amgen</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100044</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Nanjing</city>
        <state>Jiangsu</state>
        <zip>210029</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200032</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200040</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200127</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <link>
    <url>http://www.amgentrials.com</url>
    <description>AmgenTrials clinical trials website</description>
  </link>
  <verification_date>January 2020</verification_date>
  <study_first_submitted>August 31, 2017</study_first_submitted>
  <study_first_submitted_qc>September 13, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 14, 2017</study_first_posted>
  <results_first_submitted>January 29, 2020</results_first_submitted>
  <results_first_submitted_qc>January 29, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">February 10, 2020</results_first_posted>
  <last_update_submitted>January 29, 2020</last_update_submitted>
  <last_update_submitted_qc>January 29, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">February 10, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Secondary hyperparathyroidism</keyword>
  <keyword>Chronic kidney disease CKD</keyword>
  <keyword>Intact parathyroid hormone iPTH</keyword>
  <keyword>Hemodialysis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hyperparathyroidism</mesh_term>
    <mesh_term>Hyperparathyroidism, Secondary</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.</ipd_time_frame>
    <ipd_access_criteria>Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.</ipd_access_criteria>
    <ipd_url>https://www.amgen.com/datasharing</ipd_url>
  </patient_data>
  <provided_document_section>
    <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>November 26, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/98/NCT03283098/SAP_000.pdf</document_url>
    </provided_document>
    <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>May 25, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/98/NCT03283098/Prot_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>This study was conducted at 5 centers in China.</recruitment_details>
      <pre_assignment_details>Of the 37 subjects screened, 33 participants were randomized in a 3:1 ratio to either etelcalcetide or placebo in a double-blind manner prior to the Day 1 activities.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Placebo</title>
          <description>Intravenous (IV) administration of placebo three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27) . Participants were followed for an additional 4 weeks.</description>
        </group>
        <group group_id="P2">
          <title>Etelcalcetide</title>
          <description>5 mg intravenous (IV) dose of etelcalcetide three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27). Participants were followed for an additional 4 weeks.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="25"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="24"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Safety analysis set consisting of all participants who received at least 1 dose of investigational product.</population>
      <group_list>
        <group group_id="B1">
          <title>Placebo</title>
          <description>Intravenous (IV) administration of placebo three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27) . Participants were followed for an additional 4 weeks.</description>
        </group>
        <group group_id="B2">
          <title>Etelcalcetide</title>
          <description>5 mg intravenous (IV) dose of etelcalcetide three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27). Participants were followed for an additional 4 weeks.</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="8"/>
            <count group_id="B2" value="25"/>
            <count group_id="B3" value="33"/>
          </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="49.8" spread="12.5"/>
                    <measurement group_id="B2" value="50.2" spread="11.4"/>
                    <measurement group_id="B3" value="50.1" spread="11.5"/>
                  </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="3"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="25"/>
                    <measurement group_id="B3" value="33"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Height</title>
          <units>cm</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="167.54" spread="8.17"/>
                    <measurement group_id="B2" value="164.48" spread="7.68"/>
                    <measurement group_id="B3" value="165.22" spread="7.79"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Weight</title>
          <units>kg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="65.74" spread="8.45"/>
                    <measurement group_id="B2" value="67.71" spread="13.53"/>
                    <measurement group_id="B3" value="67.24" spread="12.40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Body Mass Index (BMI)</title>
          <description>BMI equals a person's weight in kilograms divided by baseline height in meters squared (kg/m^2).</description>
          <units>kg/m^2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="23.64" spread="3.03"/>
                    <measurement group_id="B2" value="24.98" spread="4.03"/>
                    <measurement group_id="B3" value="24.65" spread="3.81"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Systolic Blood Pressure</title>
          <units>mmHg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="139.25" spread="27.37"/>
                    <measurement group_id="B2" value="141.24" spread="19.39"/>
                    <measurement group_id="B3" value="140.76" spread="21.13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Diastolic Blood Pressure</title>
          <units>mmHg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="80.38" spread="13.54"/>
                    <measurement group_id="B2" value="81.68" spread="13.00"/>
                    <measurement group_id="B3" value="81.36" spread="12.93"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Intact Parathyroid Hormone (iPTH)</title>
          <units>pmol/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="74.10" spread="35.08"/>
                    <measurement group_id="B2" value="63.03" spread="20.10"/>
                    <measurement group_id="B3" value="65.72" spread="24.40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Corrected Calcium</title>
          <units>mmol/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2.57" spread="0.12"/>
                    <measurement group_id="B2" value="2.46" spread="0.20"/>
                    <measurement group_id="B3" value="2.49" spread="0.19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Calcium</title>
          <units>mmol/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2.57" spread="0.14"/>
                    <measurement group_id="B2" value="2.44" spread="0.22"/>
                    <measurement group_id="B3" value="2.47" spread="0.21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Phosphorus</title>
          <units>mmol/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2.17" spread="0.49"/>
                    <measurement group_id="B2" value="2.11" spread="0.58"/>
                    <measurement group_id="B3" value="2.13" spread="0.55"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Potassium</title>
          <units>mmol/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4.67" spread="0.48"/>
                    <measurement group_id="B2" value="4.74" spread="0.80"/>
                    <measurement group_id="B3" value="4.72" spread="0.73"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Pharmacokinetic (PK) Parameter: Time to Maximum Drug Concentration (Tmax) of Plasma Etelcalcetide on Days 1 and 27</title>
        <description>Tmax is the time to maximum drug concentration of plasma etelcalcetide after dosing on Days 1 and 27.</description>
        <time_frame>Days 1 and 27; PK blood sampling predialysis, and at 10, 30, 60, 90 min postdose, as well as on Day 2 and 28 between 18 and 30 hours after study drug administration</time_frame>
        <population>Pharmacokinetic Concentration Analysis Set: all participants who received at least 1 dose of etelcalcetide and had at least 1 pharmacokinetic sample collected.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Intravenous (IV) administration of placebo three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27) . Participants were followed for an additional 4 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Etelcalcetide</title>
            <description>5 mg intravenous (IV) dose of etelcalcetide three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27). Participants were followed for an additional 4 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetic (PK) Parameter: Time to Maximum Drug Concentration (Tmax) of Plasma Etelcalcetide on Days 1 and 27</title>
          <description>Tmax is the time to maximum drug concentration of plasma etelcalcetide after dosing on Days 1 and 27.</description>
          <population>Pharmacokinetic Concentration Analysis Set: all participants who received at least 1 dose of etelcalcetide and had at least 1 pharmacokinetic sample collected.</population>
          <units>hour</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="25"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="0.22" lower_limit="0.17" upper_limit="0.27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 27</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="24"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="0.22" lower_limit="0.17" upper_limit="0.25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>PK: Maximum Observed Drug Concentration (Cmax) of Plasma Etelcalcetide on Days 1 and 27</title>
        <description>Cmax was defined as the maximum observed plasma drug concentration measured between the time of drug administration to the beginning of the next dialysis session.</description>
        <time_frame>Days 1 and 27; PK blood sampling predialysis, and at 10, 30, 60, 90 min postdose, as well as on Day 2 and 28 between 18 and 30 hours after study drug administration</time_frame>
        <population>Pharmacokinetic concentration analysis set</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Intravenous (IV) administration of placebo three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27) . Participants were followed for an additional 4 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Etelcalcetide</title>
            <description>5 mg intravenous (IV) dose of etelcalcetide three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27). Participants were followed for an additional 4 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>PK: Maximum Observed Drug Concentration (Cmax) of Plasma Etelcalcetide on Days 1 and 27</title>
          <description>Cmax was defined as the maximum observed plasma drug concentration measured between the time of drug administration to the beginning of the next dialysis session.</description>
          <population>Pharmacokinetic concentration analysis set</population>
          <units>ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="25"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="216" spread="157"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 27</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="24"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="236" spread="53.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Pharmacokinetic (PK) Parameter: Area Under the Curve From Time Zero to the Beginning of the Subsequent Hemodialysis Treatment (AUClast) of Plasma Etelcalcetide on Days 1 and 27</title>
        <description>AUClast was specifically defined in this study as the area under the concentration time curve measured from the time of drug administration to the beginning of the next dialysis session, following the first and last dose.</description>
        <time_frame>Days 1 and 27; PK blood sampling predialysis, and up to 44-50 hour postdose.at 10, 30, 60, 90 min postdose: Day 2 and 28 between 18 and 30 hours after study drug administration; Day 3 (predialysis) + Day 29</time_frame>
        <population>Pharmacokinetic concentration analysis set</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Intravenous (IV) administration of placebo three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27) . Participants were followed for an additional 4 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Etelcalcetide</title>
            <description>5 mg intravenous (IV) dose of etelcalcetide three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27). Participants were followed for an additional 4 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetic (PK) Parameter: Area Under the Curve From Time Zero to the Beginning of the Subsequent Hemodialysis Treatment (AUClast) of Plasma Etelcalcetide on Days 1 and 27</title>
          <description>AUClast was specifically defined in this study as the area under the concentration time curve measured from the time of drug administration to the beginning of the next dialysis session, following the first and last dose.</description>
          <population>Pharmacokinetic concentration analysis set</population>
          <units>hour*ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="25"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="1110" spread="311"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 27</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="24"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="3310" spread="893"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Pharmacokinetic (PK) Parameter: Accumulation Ratio Comparing Days 1 and 27</title>
        <description>Accumulation ratio, calculated as AUClast day 27/AUClast day 1.</description>
        <time_frame>Days 1 and 27; PK blood sampling predialysis, and up to 44-50 hour postdose.at 10, 30, 60, 90 min postdose: Day 2 and 28 between 18 and 30 hours after study drug administration; Day 3 (predialysis) + Day 29</time_frame>
        <population>Pharmacokinetic concentration analysis set</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Intravenous (IV) administration of placebo three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27) . Participants were followed for an additional 4 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Etelcalcetide</title>
            <description>5 mg intravenous (IV) dose of etelcalcetide three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27). Participants were followed for an additional 4 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetic (PK) Parameter: Accumulation Ratio Comparing Days 1 and 27</title>
          <description>Accumulation ratio, calculated as AUClast day 27/AUClast day 1.</description>
          <population>Pharmacokinetic concentration analysis set</population>
          <units>ratio</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="3.02" spread="0.607"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Participants With Treatment-Emergent Adverse Events (TEAEs)</title>
        <description>The severity of each adverse event was assessed using the NCI-CTCAE Version 4.0 according to the following:&#xD;
Grade 1 - Mild: Asymptomatic or mild symptoms; intervention not indicated&#xD;
Grade 2 - Moderate: Minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL)&#xD;
Grade 3 - Severe: Medically significant but not life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL&#xD;
Grade 4 - Life-threatening&#xD;
Grade 5 - Fatal.&#xD;
A serious AE is an AE that met one or more of the following criteria:&#xD;
Death&#xD;
Life-threatening&#xD;
Required inpatient hospitalization or prolongation of an existing hospitalization&#xD;
Resulted in persistent or significant disability/incapacity&#xD;
A congenital anomaly/birth defect&#xD;
Important medical events that required medical or surgical intervention to prevent one of the outcomes above.</description>
        <time_frame>Day 1 up to Day 55 (end of study)</time_frame>
        <population>Safety Analysis set containing all participants who received at least 1 dose of investigational product (IP)</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Intravenous (IV) administration of placebo three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27) . Participants were followed for an additional 4 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Etelcalcetide</title>
            <description>5 mg intravenous (IV) dose of etelcalcetide three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27). Participants were followed for an additional 4 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Participants With Treatment-Emergent Adverse Events (TEAEs)</title>
          <description>The severity of each adverse event was assessed using the NCI-CTCAE Version 4.0 according to the following:&#xD;
Grade 1 - Mild: Asymptomatic or mild symptoms; intervention not indicated&#xD;
Grade 2 - Moderate: Minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL)&#xD;
Grade 3 - Severe: Medically significant but not life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL&#xD;
Grade 4 - Life-threatening&#xD;
Grade 5 - Fatal.&#xD;
A serious AE is an AE that met one or more of the following criteria:&#xD;
Death&#xD;
Life-threatening&#xD;
Required inpatient hospitalization or prolongation of an existing hospitalization&#xD;
Resulted in persistent or significant disability/incapacity&#xD;
A congenital anomaly/birth defect&#xD;
Important medical events that required medical or surgical intervention to prevent one of the outcomes above.</description>
          <population>Safety Analysis set containing all participants who received at least 1 dose of investigational product (IP)</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>All TEAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEAEs Grade &gt;= 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEAEs Grade &gt;= 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Serious TEAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEAEs leading to study treatment discontinuation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Fatal TEAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Treatment-related TEAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Treatment-related TEAEs Grade &gt;= 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Treatment-related TEAEs Grade &gt;= 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Treatment-related serious TEAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Trt-related TEAEs leading to study trt discon</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Treatment-related Fatal TEAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Participants With Treatment-Emergent Adverse Events (TEAEs) of Interest</title>
        <description>Terms were coded with Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. Narrow search criteria used for both standardized MedDRA queries (SMQ) and events of interest (EOI). One preferred term (PT) could match multiple EOIs. Infusion Reaction EOI counts included only those events which had onset day coinciding with study medication infusion and resolved on the same day or the day after onset.</description>
        <time_frame>Day 1 up to Day 55 (end of study)</time_frame>
        <population>Safety Analysis Set</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Intravenous (IV) administration of placebo three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27) . Participants were followed for an additional 4 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Etelcalcetide</title>
            <description>5 mg intravenous (IV) dose of etelcalcetide three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27). Participants were followed for an additional 4 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Participants With Treatment-Emergent Adverse Events (TEAEs) of Interest</title>
          <description>Terms were coded with Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. Narrow search criteria used for both standardized MedDRA queries (SMQ) and events of interest (EOI). One preferred term (PT) could match multiple EOIs. Infusion Reaction EOI counts included only those events which had onset day coinciding with study medication infusion and resolved on the same day or the day after onset.</description>
          <population>Safety Analysis Set</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Adynamic bone (EOI)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cardiac Failure (EOI)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Convulsions (SMQ)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Fractures (EOI)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypersensitivity (SMQ)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dermatitis allergic (PT)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Rash (PT)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dermatitis (PT)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypocalcemia (EOI)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Blood calcium decreased (PT)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypocalcaemia (PT)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypophosphatemia (EOI)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Infusion reaction (EOI)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypotension (PT)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Torsade de pointes-QT prolongation (SMQ)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ventricular tachyarrhythmias (SMQ)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Participants With Clinically-Significant Changes in Electrocardiograms (ECGs) From Baseline to End of Study</title>
        <description>Count of participants who exhibited a clinically significant change in the results of their 12-lead electrocardiograms (ECG) when comparing baseline to end of study ECGs.</description>
        <time_frame>Baseline is Day -2; End of Study is Day 55</time_frame>
        <population>Safety Analysis set of participants with both a baseline and end of study ECG.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Intravenous (IV) administration of placebo three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27) . Participants were followed for an additional 4 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Etelcalcetide</title>
            <description>5 mg intravenous (IV) dose of etelcalcetide three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27). Participants were followed for an additional 4 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Participants With Clinically-Significant Changes in Electrocardiograms (ECGs) From Baseline to End of Study</title>
          <description>Count of participants who exhibited a clinically significant change in the results of their 12-lead electrocardiograms (ECG) when comparing baseline to end of study ECGs.</description>
          <population>Safety Analysis set of participants with both a baseline and end of study ECG.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Normal Baseline / Abnormal End of Study</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Abnormal Baseline / Normal End of Study</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No Change in Baseline to End of Study</title>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                    <measurement group_id="O2" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to End of Study in Weight</title>
        <description>Change from baseline in weight measured at visit.</description>
        <time_frame>Day 1 up to Day 55</time_frame>
        <population>Safety Analysis set</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Intravenous (IV) administration of placebo three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27) . Participants were followed for an additional 4 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Etelcalcetide</title>
            <description>5 mg intravenous (IV) dose of etelcalcetide three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27). Participants were followed for an additional 4 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to End of Study in Weight</title>
          <description>Change from baseline in weight measured at visit.</description>
          <population>Safety Analysis set</population>
          <units>kg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.32" spread="0.79"/>
                    <measurement group_id="O2" value="0.76" spread="1.39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to End of Study in Systolic and Diastolic Blood Pressures</title>
        <description>Participants remained seated for at least 10 minutes prior to measurement of predialysis heart rate and blood pressure.</description>
        <time_frame>Baseline Day 1 prior to dialysis; End of Study is Day 55</time_frame>
        <population>Safety Analysis set</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Intravenous (IV) administration of placebo three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27) . Participants were followed for an additional 4 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Etelcalcetide</title>
            <description>5 mg intravenous (IV) dose of etelcalcetide three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27). Participants were followed for an additional 4 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to End of Study in Systolic and Diastolic Blood Pressures</title>
          <description>Participants remained seated for at least 10 minutes prior to measurement of predialysis heart rate and blood pressure.</description>
          <population>Safety Analysis set</population>
          <units>mmHg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Systolic Blood Pressure</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="24"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.1" spread="15.5"/>
                    <measurement group_id="O2" value="6.1" spread="18.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Diastolic Blood Pressure</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="24"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.4" spread="9.2"/>
                    <measurement group_id="O2" value="1.5" spread="11.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Baseline and Change From Baseline to End of Study in Heart Rate</title>
        <description>Participants remained seated for at least 10 minutes prior to measurement of predialysis heart rate and blood pressure.</description>
        <time_frame>Baseline Day 1 prior to dialysis; End of Study is Day 55</time_frame>
        <population>Safety Analysis set</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Intravenous (IV) administration of placebo three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27) . Participants were followed for an additional 4 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Etelcalcetide</title>
            <description>5 mg intravenous (IV) dose of etelcalcetide three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27). Participants were followed for an additional 4 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Baseline and Change From Baseline to End of Study in Heart Rate</title>
          <description>Participants remained seated for at least 10 minutes prior to measurement of predialysis heart rate and blood pressure.</description>
          <population>Safety Analysis set</population>
          <units>beats/minute</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="25"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="79.5" spread="8.3"/>
                    <measurement group_id="O2" value="82.8" spread="13.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline to End of Study</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="24"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.9" spread="6.5"/>
                    <measurement group_id="O2" value="-1.4" spread="8.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to End of Study in Calcium</title>
        <description>Calcium was tested at a central laboratory.</description>
        <time_frame>Baseline is Day 1 prior to dialysis; End of Study is Day 55</time_frame>
        <population>Safety Analysis set</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Intravenous (IV) administration of placebo three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27) . Participants were followed for an additional 4 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Etelcalcetide</title>
            <description>5 mg intravenous (IV) dose of etelcalcetide three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27). Participants were followed for an additional 4 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to End of Study in Calcium</title>
          <description>Calcium was tested at a central laboratory.</description>
          <population>Safety Analysis set</population>
          <units>mmol/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.10" spread="0.11"/>
                    <measurement group_id="O2" value="-0.07" spread="0.12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to End of Study in Corrected Calcium (cCa)</title>
        <description>Total serum calcium was corrected if the serum albumin was &lt; 4 g/dL or 40 g/L, otherwise cCa equals total serum calcium.&#xD;
The correction formula was:&#xD;
Corrected calcium (mg/dL) = Total calcium (mg/dL) + (4 - albumin [g/dL]) * 0.8</description>
        <time_frame>Baseline is the average of Day -2 and Day 1 prior to dialysis; End of Study is Day 55</time_frame>
        <population>Safety Analysis set</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Intravenous (IV) administration of placebo three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27) . Participants were followed for an additional 4 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Etelcalcetide</title>
            <description>5 mg intravenous (IV) dose of etelcalcetide three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27). Participants were followed for an additional 4 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to End of Study in Corrected Calcium (cCa)</title>
          <description>Total serum calcium was corrected if the serum albumin was &lt; 4 g/dL or 40 g/L, otherwise cCa equals total serum calcium.&#xD;
The correction formula was:&#xD;
Corrected calcium (mg/dL) = Total calcium (mg/dL) + (4 - albumin [g/dL]) * 0.8</description>
          <population>Safety Analysis set</population>
          <units>mmol/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.08" spread="0.10"/>
                    <measurement group_id="O2" value="-0.05" spread="0.10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Participants With Low Corrected Calcium (cCA) By Category</title>
        <description>The lowest cCA value for each participant is reported.&#xD;
Total serum calcium was corrected if the serum albumin was &lt; 4 g/dL or 40 g/L, otherwise cCa equals total serum calcium.&#xD;
The correction formula was:&#xD;
Corrected calcium (mg/dL) = Total calcium (mg/dL) + (4 - albumin [g/dL]) * 0.8</description>
        <time_frame>Timeframes: Days 8, 15, 22, 27, 29, 34, 41, 55</time_frame>
        <population>Safety Analysis set</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Intravenous (IV) administration of placebo three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27) . Participants were followed for an additional 4 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Etelcalcetide</title>
            <description>5 mg intravenous (IV) dose of etelcalcetide three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27). Participants were followed for an additional 4 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Participants With Low Corrected Calcium (cCA) By Category</title>
          <description>The lowest cCA value for each participant is reported.&#xD;
Total serum calcium was corrected if the serum albumin was &lt; 4 g/dL or 40 g/L, otherwise cCa equals total serum calcium.&#xD;
The correction formula was:&#xD;
Corrected calcium (mg/dL) = Total calcium (mg/dL) + (4 - albumin [g/dL]) * 0.8</description>
          <population>Safety Analysis set</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Participants with cCA &lt; 1.75 mmol/L</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participants with cCA 1.75 to &lt; 1.87 mmol/L</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participants with cCA 1.87 to &lt; 2.07 mmol/L</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Baseline and Change From Baseline to End of Study in Serum Albumin</title>
        <description>Serum albumin was tested at a central laboratory.</description>
        <time_frame>Baseline is the average of Day -2 and Day 1 prior to dialysis; End of Study is Day 55</time_frame>
        <population>Safety Analysis set</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Intravenous (IV) administration of placebo three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27) . Participants were followed for an additional 4 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Etelcalcetide</title>
            <description>5 mg intravenous (IV) dose of etelcalcetide three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27). Participants were followed for an additional 4 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Baseline and Change From Baseline to End of Study in Serum Albumin</title>
          <description>Serum albumin was tested at a central laboratory.</description>
          <population>Safety Analysis set</population>
          <units>g/dL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="25"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="41.20" spread="2.37"/>
                    <measurement group_id="O2" value="39.37" spread="2.79"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline to End of Study</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="24"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.06" spread="1.81"/>
                    <measurement group_id="O2" value="-0.59" spread="2.13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to End of Study in Serum Phosphorus</title>
        <description>Serum phosphorus was tested at a central laboratory.</description>
        <time_frame>Baseline is Day 1 prior to dialysis; End of Study is Day 55</time_frame>
        <population>Safety Analysis set</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Intravenous (IV) administration of placebo three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27) . Participants were followed for an additional 4 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Etelcalcetide</title>
            <description>5 mg intravenous (IV) dose of etelcalcetide three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27). Participants were followed for an additional 4 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to End of Study in Serum Phosphorus</title>
          <description>Serum phosphorus was tested at a central laboratory.</description>
          <population>Safety Analysis set</population>
          <units>mmol/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.03" spread="0.53"/>
                    <measurement group_id="O2" value="-0.06" spread="0.56"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Participants With Anti-etelcalcetide Antibody at Baseline and Postbaseline</title>
        <description>Participants with positive titers for antibodies to etelcalcetide could be asked to return to the clinical research unit to provide additional serum samples.</description>
        <time_frame>Baseline: Day 1 prior to dialysis. Postbaseline: Days 29 and 55 prior to dialysis</time_frame>
        <population>Safety Analysis set</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Intravenous (IV) administration of placebo three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27) . Participants were followed for an additional 4 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Etelcalcetide</title>
            <description>5 mg intravenous (IV) dose of etelcalcetide three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27). Participants were followed for an additional 4 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Participants With Anti-etelcalcetide Antibody at Baseline and Postbaseline</title>
          <description>Participants with positive titers for antibodies to etelcalcetide could be asked to return to the clinical research unit to provide additional serum samples.</description>
          <population>Safety Analysis set</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Binding antibody positive at or before baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Positive postbaseline/negative baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Transient, i.e. negative at last timepoint tested</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Day 1 up to Day 55 (end of study)</time_frame>
      <desc>Treatment-emergent adverse events - any adverse events started on or after the first dose of investigational product (IP) up to the end of study date (Day 55).</desc>
      <group_list>
        <group group_id="E1">
          <title>Placebo</title>
          <description>Intravenous (IV) administration of placebo three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27) . Participants were followed for an additional 4 weeks.</description>
        </group>
        <group group_id="E2">
          <title>Etelcalcetide</title>
          <description>5 mg intravenous (IV) dose of etelcalcetide three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27). Participants were followed for an additional 4 weeks.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 21.1</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="8"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hypocalcaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Intervertebral disc protrusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 21.1</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="8"/>
                <counts group_id="E2" subjects_affected="22" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Arrhythmia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Atrioventricular block first degree</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Eye disorder</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Limb injury</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood alkaline phosphatase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Blood calcium decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperphosphataemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Hypertriglyceridaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Hypoalbuminaemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Hypoproteinaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Muscle spasticity</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Dermatitis allergic</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Blood pressure inadequately controlled</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="25"/>
              </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 Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Study Director</name_or_title>
      <organization>Amgen Inc.</organization>
      <phone>866-572-6436</phone>
      <email>medinfo@amgen.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/NCT03283098
org study id: 20140197
nct id: NCT03283098
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
This was a multiple-dose, double-blind, randomized, placebo-controlled study. Chinese
      subjects residing in Mainland China with chronic kidney disease (CKD) receiving hemodialysis
      were randomized in a 3:1 ratio to receive 5 mg intravenous (IV) of etelcalcetide or placebo 3
      times a week (TIW) for approximately 4 weeks, with a subsequent follow up period of
      approximately 4 weeks.

      Doses were given at the end of each scheduled hemodialysis session on study days 1 through
      day 27 and subject participation was complete after day 55 end-of-study (EOS) procedures were
      performed. Doses were administered TIW for 4 weeks, for a total of 12 doses.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: This is a multiple dose, double-blind, randomized, placebo-controlled clinical study conducted in Chinese subjects residing in Mainland China with chronic kidney disease receiving hemodialysis. The treatment duration will be approximately 4 weeks with a post treatment followup of 4 weeks. A dose will be given at each scheduled hemodialysis session (Dose administered three times a week for 4 weeks, for a total of 12 doses).
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Pharmacokinetic (PK) Parameter: Time to Maximum Drug Concentration (Tmax) of Plasma Etelcalcetide on Days 1 and 27
time frame: Days 1 and 27; PK blood sampling predialysis, and at 10, 30, 60, 90 min postdose, as well as on Day 2 and 28 between 18 and 30 hours after study drug administration
description: Tmax is the time to maximum drug concentration of plasma etelcalcetide after dosing on Days 1 and 27.
measure: PK: Maximum Observed Drug Concentration (Cmax) of Plasma Etelcalcetide on Days 1 and 27
time frame: Days 1 and 27; PK blood sampling predialysis, and at 10, 30, 60, 90 min postdose, as well as on Day 2 and 28 between 18 and 30 hours after study drug administration
description: Cmax was defined as the maximum observed plasma drug concentration measured between the time of drug administration to the beginning of the next dialysis session.
measure: Pharmacokinetic (PK) Parameter: Area Under the Curve From Time Zero to the Beginning of the Subsequent Hemodialysis Treatment (AUClast) of Plasma Etelcalcetide on Days 1 and 27
time frame: Days 1 and 27; PK blood sampling predialysis, and up to 44-50 hour postdose.at 10, 30, 60, 90 min postdose: Day 2 and 28 between 18 and 30 hours after study drug administration; Day 3 (predialysis) + Day 29
description: AUClast was specifically defined in this study as the area under the concentration time curve measured from the time of drug administration to the beginning of the next dialysis session, following the first and last dose.
measure: Pharmacokinetic (PK) Parameter: Accumulation Ratio Comparing Days 1 and 27
time frame: Days 1 and 27; PK blood sampling predialysis, and up to 44-50 hour postdose.at 10, 30, 60, 90 min postdose: Day 2 and 28 between 18 and 30 hours after study drug administration; Day 3 (predialysis) + Day 29
description: Accumulation ratio, calculated as AUClast day 27/AUClast day 1.
measure: Participants With Treatment-Emergent Adverse Events (TEAEs)
time frame: Day 1 up to Day 55 (end of study)
description: The severity of each adverse event was assessed using the NCI-CTCAE Version 4.0 according to the following:
Grade 1 - Mild: Asymptomatic or mild symptoms; intervention not indicated
Grade 2 - Moderate: Minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL)
Grade 3 - Severe: Medically significant but not life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL
Grade 4 - Life-threatening
Grade 5 - Fatal.
A serious AE is an AE that met one or more of the following criteria:
Death
Life-threatening
Required inpatient hospitalization or prolongation of an existing hospitalization
Resulted in persistent or significant disability/incapacity
A congenital anomaly/birth defect
Important medical events that required medical or surgical intervention to prevent one of the outcomes above.
measure: Participants With Treatment-Emergent Adverse Events (TEAEs) of Interest
time frame: Day 1 up to Day 55 (end of study)
description: Terms were coded with Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. Narrow search criteria used for both standardized MedDRA queries (SMQ) and events of interest (EOI). One preferred term (PT) could match multiple EOIs. Infusion Reaction EOI counts included only those events which had onset day coinciding with study medication infusion and resolved on the same day or the day after onset.
measure: Participants With Clinically-Significant Changes in Electrocardiograms (ECGs) From Baseline to End of Study
time frame: Baseline is Day -2; End of Study is Day 55
description: Count of participants who exhibited a clinically significant change in the results of their 12-lead electrocardiograms (ECG) when comparing baseline to end of study ECGs.
measure: Change From Baseline to End of Study in Weight
time frame: Day 1 up to Day 55
description: Change from baseline in weight measured at visit.
measure: Change From Baseline to End of Study in Systolic and Diastolic Blood Pressures
time frame: Baseline Day 1 prior to dialysis; End of Study is Day 55
description: Participants remained seated for at least 10 minutes prior to measurement of predialysis heart rate and blood pressure.
measure: Baseline and Change From Baseline to End of Study in Heart Rate
time frame: Baseline Day 1 prior to dialysis; End of Study is Day 55
description: Participants remained seated for at least 10 minutes prior to measurement of predialysis heart rate and blood pressure.
measure: Change From Baseline to End of Study in Calcium
time frame: Baseline is Day 1 prior to dialysis; End of Study is Day 55
description: Calcium was tested at a central laboratory.
measure: Change From Baseline to End of Study in Corrected Calcium (cCa)
time frame: Baseline is the average of Day -2 and Day 1 prior to dialysis; End of Study is Day 55
description: Total serum calcium was corrected if the serum albumin was < 4 g/dL or 40 g/L, otherwise cCa equals total serum calcium.
The correction formula was:
Corrected calcium (mg/dL) = Total calcium (mg/dL) + (4 - albumin [g/dL]) * 0.8
measure: Participants With Low Corrected Calcium (cCA) By Category
time frame: Timeframes: Days 8, 15, 22, 27, 29, 34, 41, 55
description: The lowest cCA value for each participant is reported.
Total serum calcium was corrected if the serum albumin was < 4 g/dL or 40 g/L, otherwise cCa equals total serum calcium.
The correction formula was:
Corrected calcium (mg/dL) = Total calcium (mg/dL) + (4 - albumin [g/dL]) * 0.8
measure: Baseline and Change From Baseline to End of Study in Serum Albumin
time frame: Baseline is the average of Day -2 and Day 1 prior to dialysis; End of Study is Day 55
description: Serum albumin was tested at a central laboratory.
measure: Change From Baseline to End of Study in Serum Phosphorus
time frame: Baseline is Day 1 prior to dialysis; End of Study is Day 55
description: Serum phosphorus was tested at a central laboratory.
measure: Participants With Anti-etelcalcetide Antibody at Baseline and Postbaseline
time frame: Baseline: Day 1 prior to dialysis. Postbaseline: Days 29 and 55 prior to dialysis
description: Participants with positive titers for antibodies to etelcalcetide could be asked to return to the clinical research unit to provide additional serum samples.
arm group label: Placebo
arm group type: Placebo Comparator
description: Intravenous (IV) administration of placebo three times a week (TIW) for 4 weeks for a total of 12 doses. Participants were followed for an additional 4 weeks.
arm group label: Etelcalcetide
arm group type: Experimental
description: 5 mg intravenous (IV) dose of etelcalcetide three times a week (TIW) for 4 weeks for a total of 12 doses. Participants were followed for an additional 4 weeks.
intervention type: Drug
intervention name: Etelcalcetide
description: Etelcalcetide was supplied as a sterile, preservative-free, aqueous solution in a single-use 3 mL glass vial.
arm group label: Etelcalcetide
other name: AMG 416
intervention type: Drug
intervention name: Placebo
description: Placebo supplied to match active intervention.
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: MD
role: Study Director
affiliation: Amgen
facility: 
facility: 
facility: 
facility: 
facility: 
country: China
url: http://www.amgentrials.com
description: AmgenTrials clinical trials website
responsible party type: Sponsor
mesh term: Hyperparathyroidism
mesh term: Hyperparathyroidism, Secondary
sharing ipd: Yes
ipd description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd time frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
ipd access criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
ipd url: https://www.amgen.com/datasharing
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 