<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/NCT02204579</url>
  </required_header>
  <id_info>
    <org_study_id>CAL-C13-001</org_study_id>
    <nct_id>NCT02204579</nct_id>
  </id_info>
  <brief_title>A Study to Determine the Effects of NPSP795 on the Calcium-sensing Receptor in Subjects With Autosomal Dominant Hypocalcemia as Measured by PTH Levels and Blood Calcium Concentrations</brief_title>
  <official_title>Open-label Dose Escalation Study Evaluating the Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of Intravenous NPSP795 in Autosomal Dominant Hypocalcemia Due to Mutations in the Calcium-sensing Receptor Gene: A Drug Repurposing Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shire</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institutes of Health (NIH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Takeda</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is an open-label study looking at the effects of NPSP795 (a selective calcium receptor&#xD;
      antagonist) on activating mutations of the Calcium-sensing receptor in patients with&#xD;
      Autosomal Dominant Hypocalcemia. Patients with ADH have low blood calcium levels and an&#xD;
      inappropriately increased renal calcium excretion, decreased renal phosphate excretion, and&#xD;
      hyperphosphatemia. PTH and blood calcium levels will be tested during and after the IV&#xD;
      infusion of NPSP795. Concentrations of NPSP795 and length of time of IV infusion will vary&#xD;
      depending on measured levels of ionized calcium.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 18, 2014</start_date>
  <completion_date type="Actual">May 4, 2015</completion_date>
  <primary_completion_date type="Actual">May 4, 2015</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)</measure>
    <time_frame>From Day 1 up to safety follow-up assessment (upto Day 17 after discharge)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With Clinically Significant Vital Signs and Electrocardiogram (ECG) Abnormalities</measure>
    <time_frame>From Day 1 up to safety follow-up assessment (upto Day 17 after discharge)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With Potentially Clinically Important Laboratory Abnormalities</measure>
    <time_frame>From Day 1 up to safety follow-up assessment (upto Day 17 after discharge)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With Clinically Significant Abnormalities Related to Physical Examination</measure>
    <time_frame>From Day 1 up to safety follow-up assessment (upto Day 17 after discharge)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline in Ionised Calcium</measure>
    <time_frame>10 Minute (min) Infusion Time: within 5 min pre-dose; &amp; post-dose 15, 30, 45, 60, 75, 90, 105 min, and 2, 2.5, 3, 3.5, &amp; 4 hour (hr) 3.5 hr Infusion Time: within 5 min pre-dose; &amp; post-dose 15, 30, 45, 60, 75, 90, 105 min, &amp; 2, 2.5, 3, 3.5, 4, 5, and 8 hr</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline in Serum Calcium</measure>
    <time_frame>10 Minutes (min) Infusion Time: within 5 min pre-dose; &amp; post-dose 1, 2, 3, 4, 8 12 hours (hr). 3.5 hr Infusion Time: within 5 min pre-dose; &amp; post-dose 1, 2, 3, 4, 8 12 hr.</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline in Urinary Calcium</measure>
    <time_frame>10 Minutes (min) Infusion Time: within 5 min pre-dose; &amp; post-dose 1, 2, 3, 4, 8 12 hours (hr). 3.5 hr Infusion Time: within 5 min pre-dose; &amp; post-dose 1, 2, 3, 4, 8 12 hr.</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline in Serum Parathyroid Hormone (PTH)</measure>
    <time_frame>10 Minutes (min) Infusion Time: within 5 min pre-dose; &amp; post-dose 5, 10, 15, 30 min, &amp; 1, 1.5, 2, 2.5, 3, 3.5, 4, 8 hours (hr). 3.5 hr Infusion Time: within 5 min pre-dose; &amp; post-dose 15, 30 min, &amp; 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 5.5 hr</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Area Under the Plasma Concentration Versus Time Curve (AUC[0-t]) of NPSP795</measure>
    <time_frame>10 Minutes (min) Infusion Time: within 5 min pre-dose; &amp; post-dose 5, 10, 15, 30 min, &amp; 1, 1.5, 2, 2.5, 3, 3.5, 4, 8 hours (hr). 3.5 hr Infusion Time: within 5 min pre-dose; &amp; post-dose 15, 30 min, &amp; 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 5.5 hr</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Concentration Time Curve Extrapolated to Infinity (AUC0-infinity) of NPSP795</measure>
    <time_frame>10 Minutes (min) Infusion Time: within 5 min pre-dose; &amp; post-dose 5, 10, 15, 30 min, &amp; 1, 1.5, 2, 2.5, 3, 3.5, 4, 8 hours (hr). 3.5 hr Infusion Time: within 5 min pre-dose; &amp; post-dose 15, 30 min, &amp; 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 5.5 hr</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Observed Drug Concentration (Cmax) of NPSP795 in Plasma</measure>
    <time_frame>10 Minutes (min) Infusion Time: within 5 min pre-dose; &amp; post-dose 5, 10, 15, 30 min, &amp; 1, 1.5, 2, 2.5, 3, 3.5, 4, 8 hours (hr). 3.5 hr Infusion Time: within 5 min pre-dose; &amp; post-dose 15, 30 min, &amp; 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 5.5 hr</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Elimination Half-life (t1/2) of NPSP795 in Plasma</measure>
    <time_frame>10 Minutes (min) Infusion Time: within 5 min pre-dose; &amp; post-dose 5, 10, 15, 30 min, &amp; 1, 1.5, 2, 2.5, 3, 3.5, 4, 8 hours (hr). 3.5 hr Infusion Time: within 5 min pre-dose; &amp; post-dose 15, 30 min, &amp; 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 5.5 hr</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Fractional Excretion of Calcium (FECa)</measure>
    <time_frame>10 Minutes (min) Infusion Time: within 5 min pre-dose; &amp; post-dose 1, 2, 3, 4, 8, 12 hours (hr). 3.5 hr Infusion Time: within 5 min pre-dose; &amp; post-dose 1, 2, 3, 4, 8, 12 hr.</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">7</enrollment>
  <condition>Autosomal Dominant Hypocalcemia (ADH)</condition>
  <arm_group>
    <arm_group_label>NPSP795</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>intravenous</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>NPSP795</intervention_name>
    <arm_group_label>NPSP795</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects with a heterozygous activating mutation of the CaSR gene (ADH); if not&#xD;
             previously confirmed, genetic testing will be performed at the screening visit&#xD;
&#xD;
          -  At least 18 years of age&#xD;
&#xD;
          -  Body mass index (BMI) ≥ 18.5 to &lt; 39 kg/m2&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Diseases or conditions that might compromise any major body system or interfere with&#xD;
             the pharmacokinetics of NPSP795&#xD;
&#xD;
          -  History of treatment with PTH 1-84 or 1-34 within the previous 6 months&#xD;
&#xD;
          -  History of hypocalcemia requiring frequent IV calcium infusions&#xD;
&#xD;
          -  History of hypocalcemic seizure within the past 3 months&#xD;
&#xD;
          -  Blood 25-hydroxy vitamin D level &lt; 25 ng/mL. If subjects have a blood 25-hydroxy&#xD;
             vitamin D level &lt; 25 ng/mL at the outpatient screening visit, they will be prescribed&#xD;
             vitamin D replacement. Once the 25-hydroxy vitamin D level is &gt; 25 ng/mL, the subject&#xD;
             will be eligible to continue on to the treatment phase of the study&#xD;
&#xD;
          -  Estimated glomerular filtration rate (GFR) &lt; 25 mL/minute, and/or abnormal hepatic,&#xD;
             hematologic, and/or clotting function&#xD;
&#xD;
          -  12 lead resting electrocardiogram (ECG) with clinically significant abnormalities&#xD;
&#xD;
          -  Concomitant medications with the potential to interfere with NPSP795 metabolism&#xD;
&#xD;
          -  History of thyroid or parathyroid surgery&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Study Director</last_name>
    <role>Study Director</role>
    <affiliation>Takeda</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>National Institute of Health (NIH)</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20892-1103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2021</verification_date>
  <study_first_submitted>July 28, 2014</study_first_submitted>
  <study_first_submitted_qc>July 29, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 30, 2014</study_first_posted>
  <results_first_submitted>October 27, 2016</results_first_submitted>
  <results_first_submitted_qc>October 27, 2016</results_first_submitted_qc>
  <results_first_posted type="Estimate">December 21, 2016</results_first_posted>
  <disposition_first_submitted>March 7, 2016</disposition_first_submitted>
  <disposition_first_submitted_qc>June 17, 2016</disposition_first_submitted_qc>
  <disposition_first_posted type="Estimate">June 21, 2016</disposition_first_posted>
  <last_update_submitted>August 5, 2021</last_update_submitted>
  <last_update_submitted_qc>August 5, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">August 9, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Autosomal Dominant Hypocalcemia</keyword>
  <keyword>Hypocalcemia</keyword>
  <keyword>ADH</keyword>
  <keyword>Hypoparathyroidism</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Arthrogryposis</mesh_term>
    <mesh_term>Hypocalcemia</mesh_term>
  </condition_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>NPSP795</title>
          <description>NPSP795 administered Intravenous (IV) infusion for 10 min on Day 1 if certain criteria for ionized calcium and/or blood parathyroid hormone (PTH) were met, an infusion was administered for either 10 min or 3.5 hours on Days 2 &amp; 3, according to a predefined dose escalation scheme. NPSP795 was administered as a 3.5-hour infusion on Day 4, or the participant underwent discharge procedures.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Participants Started in Pre-Amendment</title>
              <participants_list>
                <participants group_id="P1" count="2">Two participants completed treatment in pre-amendment and were re-enrolled in post-amendment.</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>Participants Started in Post-Amendment</title>
              <participants_list>
                <participants group_id="P1" count="5">Two participants from pre-amendment were re-enrolled with different identification numbers.</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>Treated</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Screen failures</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>NPSP795</title>
          <description>NPSP795 administered Intravenous (IV) infusion for 10 min on Day 1 if certain criteria for ionized calcium and/or blood parathyroid hormone (PTH) were met, an infusion was administered for either 10 min or 3.5 hours on Days 2 &amp; 3, according to a predefined dose escalation scheme. NPSP795 was administered as a 3.5-hour infusion on Day 4, or the participant underwent discharge procedures.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="5"/>
          </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="39.8" spread="15.2"/>
                  </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="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)</title>
        <time_frame>From Day 1 up to safety follow-up assessment (upto Day 17 after discharge)</time_frame>
        <population>Safety population included all participants who received at least 1 minute of study drug infusion (pre-amendment and post-amendment).</population>
        <group_list>
          <group group_id="O1">
            <title>NPSP795</title>
            <description>NPSP795 administered Intravenous (IV) infusion for 10 min on Day 1 if certain criteria for ionized calcium and/or blood parathyroid hormone (PTH) were met, an infusion was administered for either 10 min or 3.5 hours on Days 2 &amp; 3, according to a predefined dose escalation scheme. NPSP795 was administered as a 3.5-hour infusion on Day 4, or the participant underwent discharge procedures.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)</title>
          <population>Safety population included all participants who received at least 1 minute of study drug infusion (pre-amendment and post-amendment).</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Participants with TEAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participants with TESAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Clinically Significant Vital Signs and Electrocardiogram (ECG) Abnormalities</title>
        <time_frame>From Day 1 up to safety follow-up assessment (upto Day 17 after discharge)</time_frame>
        <population>Safety population included all participants who received at least 1 minute of study drug infusion (both pre-amendment and post-amendment participants).</population>
        <group_list>
          <group group_id="O1">
            <title>NPSP795</title>
            <description>NPSP795 administered Intravenous (IV) infusion for 10 min on Day 1 if certain criteria for ionized calcium and/or blood parathyroid hormone (PTH) were met, an infusion was administered for either 10 min or 3.5 hours on Days 2 &amp; 3, according to a predefined dose escalation scheme. NPSP795 was administered as a 3.5-hour infusion on Day 4, or the participant underwent discharge procedures.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Clinically Significant Vital Signs and Electrocardiogram (ECG) Abnormalities</title>
          <population>Safety population included all participants who received at least 1 minute of study drug infusion (both pre-amendment and post-amendment participants).</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Potentially Clinically Important Laboratory Abnormalities</title>
        <time_frame>From Day 1 up to safety follow-up assessment (upto Day 17 after discharge)</time_frame>
        <population>Safety population included all participants who received at least 1 minute of study drug infusion (pre-amendment and post-amendment).</population>
        <group_list>
          <group group_id="O1">
            <title>NPSP795</title>
            <description>NPSP795 administered Intravenous (IV) infusion for 10 min on Day 1 if certain criteria for ionized calcium and/or blood parathyroid hormone (PTH) were met, an infusion was administered for either 10 min or 3.5 hours on Days 2 &amp; 3, according to a predefined dose escalation scheme. NPSP795 was administered as a 3.5-hour infusion on Day 4, or the participant underwent discharge procedures.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Potentially Clinically Important Laboratory Abnormalities</title>
          <population>Safety population included all participants who received at least 1 minute of study drug infusion (pre-amendment and post-amendment).</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Clinically Significant Abnormalities Related to Physical Examination</title>
        <time_frame>From Day 1 up to safety follow-up assessment (upto Day 17 after discharge)</time_frame>
        <population>Safety population included all participants who received at least 1 minute of study drug infusion (both pre-amendment and post-amendment participants).</population>
        <group_list>
          <group group_id="O1">
            <title>NPSP795</title>
            <description>NPSP795 administered Intravenous (IV) infusion for 10 min on Day 1 if certain criteria for ionized calcium and/or blood parathyroid hormone (PTH) were met, an infusion was administered for either 10 min or 3.5 hours on Days 2 &amp; 3, according to a predefined dose escalation scheme. NPSP795 was administered as a 3.5-hour infusion on Day 4, or the participant underwent discharge procedures.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Clinically Significant Abnormalities Related to Physical Examination</title>
          <population>Safety population included all participants who received at least 1 minute of study drug infusion (both pre-amendment and post-amendment participants).</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Ionised Calcium</title>
        <time_frame>10 Minute (min) Infusion Time: within 5 min pre-dose; &amp; post-dose 15, 30, 45, 60, 75, 90, 105 min, and 2, 2.5, 3, 3.5, &amp; 4 hour (hr) 3.5 hr Infusion Time: within 5 min pre-dose; &amp; post-dose 15, 30, 45, 60, 75, 90, 105 min, &amp; 2, 2.5, 3, 3.5, 4, 5, and 8 hr</time_frame>
        <population>Post-amendment pharmacodynamic (PD) analysis population included all participants who received at least 5 minutes of the study drug infusion and had at least one PD measurement on at least 1 day of infusion. Here, n=number of participants analysed for specified category at the specified time points in each arm respectively.</population>
        <group_list>
          <group group_id="O1">
            <title>NPSP795 on Day 1 (5 mg/10 Minutes)</title>
          </group>
          <group group_id="O2">
            <title>NPSP795 on Day 2 (15 mg/3.5 Hours)</title>
          </group>
          <group group_id="O3">
            <title>NPSP795 on Day 3 (30 mg/3.5 Hours)</title>
          </group>
          <group group_id="O4">
            <title>NPSP795 on Day 4 (30 mg/3.5 Hours)</title>
          </group>
          <group group_id="O5">
            <title>NPSP795 on Day 4 (50 mg/3.5 Hours)</title>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Ionised Calcium</title>
          <population>Post-amendment pharmacodynamic (PD) analysis population included all participants who received at least 5 minutes of the study drug infusion and had at least one PD measurement on at least 1 day of infusion. Here, n=number of participants analysed for specified category at the specified time points in each arm respectively.</population>
          <units>millimole/liter (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="5"/>
                <count group_id="O2" value="5"/>
                <count group_id="O3" value="5"/>
                <count group_id="O4" value="5"/>
                <count group_id="O5" value="5"/>
              </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="5"/>
                    <count group_id="O2" value="5"/>
                    <count group_id="O3" value="5"/>
                    <count group_id="O4" value="3"/>
                    <count group_id="O5" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.972" spread="0.058"/>
                    <measurement group_id="O2" value="0.950" spread="0.054"/>
                    <measurement group_id="O3" value="0.986" spread="0.045"/>
                    <measurement group_id="O4" value="0.933" spread="0.055"/>
                    <measurement group_id="O5" value="1.025" spread="0.078"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at 4 Hours Post dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                    <count group_id="O2" value="5"/>
                    <count group_id="O3" value="5"/>
                    <count group_id="O4" value="3"/>
                    <count group_id="O5" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.016" spread="0.027"/>
                    <measurement group_id="O2" value="0.010" spread="0.026"/>
                    <measurement group_id="O3" value="-0.014" spread="0.023"/>
                    <measurement group_id="O4" value="-0.030" spread="0.046"/>
                    <measurement group_id="O5" value="-0.015" spread="0.035"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at 8 Hours Post dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                    <count group_id="O2" value="5"/>
                    <count group_id="O3" value="5"/>
                    <count group_id="O4" value="3"/>
                    <count group_id="O5" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" spread="NA">Data was calculated for 5 mg/10 minutes infusion until hour 4 only.</measurement>
                    <measurement group_id="O2" value="-0.034" spread="0.044"/>
                    <measurement group_id="O3" value="-0.040" spread="0.060"/>
                    <measurement group_id="O4" value="-0.033" spread="0.046"/>
                    <measurement group_id="O5" value="-0.060" spread="0.028"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Serum Calcium</title>
        <time_frame>10 Minutes (min) Infusion Time: within 5 min pre-dose; &amp; post-dose 1, 2, 3, 4, 8 12 hours (hr). 3.5 hr Infusion Time: within 5 min pre-dose; &amp; post-dose 1, 2, 3, 4, 8 12 hr.</time_frame>
        <population>Post-amendment PD analysis population included all participants who received at least 5 minutes of the study drug infusion and had at least one PD measurement on at least 1 day of infusion. Here, n=number of participants analysed for specified category at the specified time points in each arm respectively.</population>
        <group_list>
          <group group_id="O1">
            <title>NPSP795 on Day 1 (5 mg/10 Minutes)</title>
          </group>
          <group group_id="O2">
            <title>NPSP795 on Day 2 (15 mg/3.5 Hours)</title>
          </group>
          <group group_id="O3">
            <title>NPSP795 on Day 3 (30 mg/3.5 Hours)</title>
          </group>
          <group group_id="O4">
            <title>NPSP795 on Day 4 (30 mg/3.5 Hours)</title>
          </group>
          <group group_id="O5">
            <title>NPSP795 on Day 4 (50 mg/3.5 Hours)</title>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Serum Calcium</title>
          <population>Post-amendment PD analysis population included all participants who received at least 5 minutes of the study drug infusion and had at least one PD measurement on at least 1 day of infusion. Here, n=number of participants analysed for specified category at the specified time points in each arm respectively.</population>
          <units>millimole/liter (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="5"/>
                <count group_id="O2" value="5"/>
                <count group_id="O3" value="5"/>
                <count group_id="O4" value="5"/>
                <count group_id="O5" value="5"/>
              </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="5"/>
                    <count group_id="O2" value="5"/>
                    <count group_id="O3" value="5"/>
                    <count group_id="O4" value="3"/>
                    <count group_id="O5" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.914" spread="0.157"/>
                    <measurement group_id="O2" value="1.790" spread="0.125"/>
                    <measurement group_id="O3" value="1.852" spread="0.132"/>
                    <measurement group_id="O4" value="1.677" spread="0.135"/>
                    <measurement group_id="O5" value="1.980" spread="0.184"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at 12 Hours Postdose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                    <count group_id="O2" value="5"/>
                    <count group_id="O3" value="5"/>
                    <count group_id="O4" value="3"/>
                    <count group_id="O5" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.114" spread="0.141"/>
                    <measurement group_id="O2" value="-0.042" spread="0.054"/>
                    <measurement group_id="O3" value="-0.106" spread="0.079"/>
                    <measurement group_id="O4" value="-0.040" spread="0.053"/>
                    <measurement group_id="O5" value="-0.270" spread="0.057"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Urinary Calcium</title>
        <time_frame>10 Minutes (min) Infusion Time: within 5 min pre-dose; &amp; post-dose 1, 2, 3, 4, 8 12 hours (hr). 3.5 hr Infusion Time: within 5 min pre-dose; &amp; post-dose 1, 2, 3, 4, 8 12 hr.</time_frame>
        <population>PD analysis population included all participants who received at least 5 minutes of the study drug infusion and had at least one PD measurement on at least 1 day of infusion. Here, n=number of participants analysed for specified category at the specified time points in each arm respectively.</population>
        <group_list>
          <group group_id="O1">
            <title>NPSP795 on Day 1 (5 mg/10 Minutes)</title>
          </group>
          <group group_id="O2">
            <title>NPSP795 on Day 2 (15 mg/3.5 Hours)</title>
          </group>
          <group group_id="O3">
            <title>NPSP795 on Day 3 (30 mg/3.5 Hours)</title>
          </group>
          <group group_id="O4">
            <title>NPSP795 on Day 4 (30 mg/3.5 Hours)</title>
          </group>
          <group group_id="O5">
            <title>NPSP795 on Day 4 (50 mg/3.5 Hours)</title>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Urinary Calcium</title>
          <population>PD analysis population included all participants who received at least 5 minutes of the study drug infusion and had at least one PD measurement on at least 1 day of infusion. Here, n=number of participants analysed for specified category at the specified time points in each arm respectively.</population>
          <units>millimole/liter (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="5"/>
                <count group_id="O2" value="5"/>
                <count group_id="O3" value="5"/>
                <count group_id="O4" value="5"/>
                <count group_id="O5" value="5"/>
              </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="5"/>
                    <count group_id="O2" value="5"/>
                    <count group_id="O3" value="5"/>
                    <count group_id="O4" value="3"/>
                    <count group_id="O5" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.302" spread="2.283"/>
                    <measurement group_id="O2" value="3.912" spread="3.299"/>
                    <measurement group_id="O3" value="2.936" spread="1.750"/>
                    <measurement group_id="O4" value="2.537" spread="1.968"/>
                    <measurement group_id="O5" value="2.065" spread="1.916"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at 12 Hours Postdose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                    <count group_id="O2" value="5"/>
                    <count group_id="O3" value="5"/>
                    <count group_id="O4" value="3"/>
                    <count group_id="O5" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.590" spread="0.861"/>
                    <measurement group_id="O2" value="-2.162" spread="2.027"/>
                    <measurement group_id="O3" value="-1.188" spread="1.634"/>
                    <measurement group_id="O4" value="-1.190" spread="1.460"/>
                    <measurement group_id="O5" value="-0.755" spread="1.082"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Serum Parathyroid Hormone (PTH)</title>
        <time_frame>10 Minutes (min) Infusion Time: within 5 min pre-dose; &amp; post-dose 5, 10, 15, 30 min, &amp; 1, 1.5, 2, 2.5, 3, 3.5, 4, 8 hours (hr). 3.5 hr Infusion Time: within 5 min pre-dose; &amp; post-dose 15, 30 min, &amp; 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 5.5 hr</time_frame>
        <population>Post amendment PD analysis population included all participants who received at least 5 minutes of the study drug infusion and had at least one PD measurement on at least 1 day of infusion. Here, n=number of participants analysed for specified category at the specified time points in each arm respectively.</population>
        <group_list>
          <group group_id="O1">
            <title>NPSP795 on Day 1 (5 mg/10 Minutes)</title>
          </group>
          <group group_id="O2">
            <title>NPSP795 on Day 2 (15 mg/3.5 Hours)</title>
          </group>
          <group group_id="O3">
            <title>NPSP795 on Day 3 (30 mg/3.5 Hours)</title>
          </group>
          <group group_id="O4">
            <title>NPSP795 on Day 4 (30 mg/3.5 Hours)</title>
          </group>
          <group group_id="O5">
            <title>NPSP795 on Day 4 (50 mg/3.5 Hours)</title>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Serum Parathyroid Hormone (PTH)</title>
          <population>Post amendment PD analysis population included all participants who received at least 5 minutes of the study drug infusion and had at least one PD measurement on at least 1 day of infusion. Here, n=number of participants analysed for specified category at the specified time points in each arm respectively.</population>
          <units>nanogram/liter (ng/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="5"/>
                <count group_id="O2" value="5"/>
                <count group_id="O3" value="5"/>
                <count group_id="O4" value="5"/>
                <count group_id="O5" value="5"/>
              </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="5"/>
                    <count group_id="O2" value="5"/>
                    <count group_id="O3" value="5"/>
                    <count group_id="O4" value="3"/>
                    <count group_id="O5" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.32" spread="2.93"/>
                    <measurement group_id="O2" value="9.14" spread="3.29"/>
                    <measurement group_id="O3" value="9.58" spread="5.32"/>
                    <measurement group_id="O4" value="12.80" spread="8.68"/>
                    <measurement group_id="O5" value="7.40" spread="3.54"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at 5.5 Hours Postdose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                    <count group_id="O2" value="5"/>
                    <count group_id="O3" value="5"/>
                    <count group_id="O4" value="3"/>
                    <count group_id="O5" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" spread="NA">Data for 10 minutes infusion was not calculated at 5.5-hours.</measurement>
                    <measurement group_id="O2" value="0.84" spread="0.86"/>
                    <measurement group_id="O3" value="1.92" spread="1.53"/>
                    <measurement group_id="O4" value="0.13" spread="1.50"/>
                    <measurement group_id="O5" value="1.75" spread="0.64"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at 8 Hours Postdose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                    <count group_id="O2" value="5"/>
                    <count group_id="O3" value="5"/>
                    <count group_id="O4" value="3"/>
                    <count group_id="O5" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.60" spread="1.56"/>
                    <measurement group_id="O2" value="NA" spread="NA">Data for 3.5-hours infusions was calculated until hour 5.5 only.</measurement>
                    <measurement group_id="O3" value="NA" spread="NA">Data for 3.5-hours infusions was calculated until hour 5.5 only.</measurement>
                    <measurement group_id="O4" value="NA" spread="NA">Data for 3.5-hours infusions was calculated until hour 5.5 only.</measurement>
                    <measurement group_id="O5" value="NA" spread="NA">Data for 3.5-hours infusions was calculated until hour 5.5 only.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Area Under the Plasma Concentration Versus Time Curve (AUC[0-t]) of NPSP795</title>
        <time_frame>10 Minutes (min) Infusion Time: within 5 min pre-dose; &amp; post-dose 5, 10, 15, 30 min, &amp; 1, 1.5, 2, 2.5, 3, 3.5, 4, 8 hours (hr). 3.5 hr Infusion Time: within 5 min pre-dose; &amp; post-dose 15, 30 min, &amp; 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 5.5 hr</time_frame>
        <population>Post amendment pharmacokinetic (PK) analysis population included all participants who received at least 5 minutes of the study drug infusion and had at least one PK measurement on at least 1 day of infusion.</population>
        <group_list>
          <group group_id="O1">
            <title>NPSP795 on Day 1 (5 mg/10 Minutes)</title>
          </group>
          <group group_id="O2">
            <title>NPSP795 on Day 2 (15 mg/3.5 Hours)</title>
          </group>
          <group group_id="O3">
            <title>NPSP795 on Day 3 (30 mg/3.5 Hours)</title>
          </group>
          <group group_id="O4">
            <title>NPSP795 on Day 4 (30 mg/3.5 Hours)</title>
          </group>
          <group group_id="O5">
            <title>NPSP795 on Day 4 (50 mg/3.5 Hours)</title>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration Versus Time Curve (AUC[0-t]) of NPSP795</title>
          <population>Post amendment pharmacokinetic (PK) analysis population included all participants who received at least 5 minutes of the study drug infusion and had at least one PK measurement on at least 1 day of infusion.</population>
          <units>nanogram*hour per millilitre (ng·h/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="5"/>
                <count group_id="O2" value="5"/>
                <count group_id="O3" value="5"/>
                <count group_id="O4" value="3"/>
                <count group_id="O5" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="309.512" spread="122.601"/>
                    <measurement group_id="O2" value="795.766" spread="294.345"/>
                    <measurement group_id="O3" value="1561.746" spread="546.479"/>
                    <measurement group_id="O4" value="1657.057" spread="650.156"/>
                    <measurement group_id="O5" value="2251.818" spread="568.782"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Area Under the Concentration Time Curve Extrapolated to Infinity (AUC0-infinity) of NPSP795</title>
        <time_frame>10 Minutes (min) Infusion Time: within 5 min pre-dose; &amp; post-dose 5, 10, 15, 30 min, &amp; 1, 1.5, 2, 2.5, 3, 3.5, 4, 8 hours (hr). 3.5 hr Infusion Time: within 5 min pre-dose; &amp; post-dose 15, 30 min, &amp; 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 5.5 hr</time_frame>
        <population>Post amendment PK analysis population included all participants who received at least 5 minutes of the study drug infusion and had at least one PK measurement on at least 1 day of infusion.</population>
        <group_list>
          <group group_id="O1">
            <title>NPSP795 on Day 1 (5 mg/10 Minutes)</title>
          </group>
          <group group_id="O2">
            <title>NPSP795 on Day 2 (15 mg/3.5 Hours)</title>
          </group>
          <group group_id="O3">
            <title>NPSP795 on Day 3 (30 mg/3.5 Hours)</title>
          </group>
          <group group_id="O4">
            <title>NPSP795 on Day 4 (30 mg/3.5 Hours)</title>
          </group>
          <group group_id="O5">
            <title>NPSP795 on Day 4 (50 mg/3.5 Hours)</title>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Concentration Time Curve Extrapolated to Infinity (AUC0-infinity) of NPSP795</title>
          <population>Post amendment PK analysis population included all participants who received at least 5 minutes of the study drug infusion and had at least one PK measurement on at least 1 day of infusion.</population>
          <units>nanogram*hour per milliliter(ng·h/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="5"/>
                <count group_id="O2" value="5"/>
                <count group_id="O3" value="5"/>
                <count group_id="O4" value="3"/>
                <count group_id="O5" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.672" spread="1.775"/>
                    <measurement group_id="O2" value="5.572" spread="2.724"/>
                    <measurement group_id="O3" value="5.437" spread="2.587"/>
                    <measurement group_id="O4" value="7.648" spread="3.607"/>
                    <measurement group_id="O5" value="4.521" spread="2.991"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Maximum Observed Drug Concentration (Cmax) of NPSP795 in Plasma</title>
        <time_frame>10 Minutes (min) Infusion Time: within 5 min pre-dose; &amp; post-dose 5, 10, 15, 30 min, &amp; 1, 1.5, 2, 2.5, 3, 3.5, 4, 8 hours (hr). 3.5 hr Infusion Time: within 5 min pre-dose; &amp; post-dose 15, 30 min, &amp; 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 5.5 hr</time_frame>
        <population>Post amendment PK analysis population included all randomized participants who received at least 5 minutes of the study drug infusion and had at least one PK measurement on at least one day of infusion.</population>
        <group_list>
          <group group_id="O1">
            <title>NPSP795 on Day 1 (5 mg/10 Minutes)</title>
          </group>
          <group group_id="O2">
            <title>NPSP795 on Day 2 (15 mg/3.5 Hours)</title>
          </group>
          <group group_id="O3">
            <title>NPSP795 on Day 3 (30 mg/3.5 Hours)</title>
          </group>
          <group group_id="O4">
            <title>NPSP795 on Day 4 (30 mg/3.5 Hours)</title>
          </group>
          <group group_id="O5">
            <title>NPSP795 on Day 4 (50 mg/3.5 Hours)</title>
          </group>
        </group_list>
        <measure>
          <title>Maximum Observed Drug Concentration (Cmax) of NPSP795 in Plasma</title>
          <population>Post amendment PK analysis population included all randomized participants who received at least 5 minutes of the study drug infusion and had at least one PK measurement on at least one day of infusion.</population>
          <units>nanogram/milliliter (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="5"/>
                <count group_id="O2" value="5"/>
                <count group_id="O3" value="5"/>
                <count group_id="O4" value="3"/>
                <count group_id="O5" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="301.900" spread="120.664"/>
                    <measurement group_id="O2" value="745.335" spread="254.205"/>
                    <measurement group_id="O3" value="1467.102" spread="475.343"/>
                    <measurement group_id="O4" value="1515.086" spread="548.056"/>
                    <measurement group_id="O5" value="2141.500" spread="475.706"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Elimination Half-life (t1/2) of NPSP795 in Plasma</title>
        <time_frame>10 Minutes (min) Infusion Time: within 5 min pre-dose; &amp; post-dose 5, 10, 15, 30 min, &amp; 1, 1.5, 2, 2.5, 3, 3.5, 4, 8 hours (hr). 3.5 hr Infusion Time: within 5 min pre-dose; &amp; post-dose 15, 30 min, &amp; 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 5.5 hr</time_frame>
        <population>Post amendment PK analysis population included all participants who received at least 5 minutes of the study drug infusion and had at least one PK measurement on at least 1 day of infusion.</population>
        <group_list>
          <group group_id="O1">
            <title>NPSP795 on Day 1 (5 mg/10 Minutes)</title>
          </group>
          <group group_id="O2">
            <title>NPSP795 on Day 2 (15 mg/3.5 Hours)</title>
          </group>
          <group group_id="O3">
            <title>NPSP795 on Day 3 (30 mg/3.5 Hours)</title>
          </group>
          <group group_id="O4">
            <title>NPSP795 on Day 4 (30 mg/3.5 Hours)</title>
          </group>
          <group group_id="O5">
            <title>NPSP795 on Day 4 (50 mg/3.5 Hours)</title>
          </group>
        </group_list>
        <measure>
          <title>Elimination Half-life (t1/2) of NPSP795 in Plasma</title>
          <population>Post amendment PK analysis population included all participants who received at least 5 minutes of the study drug infusion and had at least one PK measurement on at least 1 day of infusion.</population>
          <units>hour</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="5"/>
                <count group_id="O3" value="5"/>
                <count group_id="O4" value="3"/>
                <count group_id="O5" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.013" spread="0.612"/>
                    <measurement group_id="O2" value="3.913" spread="0.222"/>
                    <measurement group_id="O3" value="4.213" spread="0.449"/>
                    <measurement group_id="O4" value="3.839" spread="0.294"/>
                    <measurement group_id="O5" value="4.000" spread="0.000"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Fractional Excretion of Calcium (FECa)</title>
        <time_frame>10 Minutes (min) Infusion Time: within 5 min pre-dose; &amp; post-dose 1, 2, 3, 4, 8, 12 hours (hr). 3.5 hr Infusion Time: within 5 min pre-dose; &amp; post-dose 1, 2, 3, 4, 8, 12 hr.</time_frame>
        <population>Post-amendment PD analysis population included all participants who received at least 5 minutes of the study drug infusion and had at least one PD measurement on at least 1 day of infusion. Here n=number of participants analysed for specified category at the specified time points in each arm respectively.</population>
        <group_list>
          <group group_id="O1">
            <title>NPSP795 on Day 1 (5 mg/10 Minutes)</title>
          </group>
          <group group_id="O2">
            <title>NPSP795 on Day 2 (15 mg/3.5 Hours)</title>
          </group>
          <group group_id="O3">
            <title>NPSP795 on Day 3 (30 mg/3.5 Hours)</title>
          </group>
          <group group_id="O4">
            <title>NPSP795 on Day 4 (30 mg/3.5 Hours)</title>
          </group>
          <group group_id="O5">
            <title>NPSP795 on Day 4 (50 mg/3.5 Hours)</title>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Fractional Excretion of Calcium (FECa)</title>
          <population>Post-amendment PD analysis population included all participants who received at least 5 minutes of the study drug infusion and had at least one PD measurement on at least 1 day of infusion. Here n=number of participants analysed for specified category at the specified time points in each arm respectively.</population>
          <units>Fraction of excretion</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="5"/>
                <count group_id="O3" value="5"/>
                <count group_id="O4" value="5"/>
                <count group_id="O5" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>FECa: Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                    <count group_id="O2" value="5"/>
                    <count group_id="O3" value="5"/>
                    <count group_id="O4" value="3"/>
                    <count group_id="O5" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.030" spread="0.023"/>
                    <measurement group_id="O2" value="0.031" spread="0.017"/>
                    <measurement group_id="O3" value="0.027" spread="0.014"/>
                    <measurement group_id="O4" value="0.030" spread="0.011"/>
                    <measurement group_id="O5" value="0.026" spread="0.032"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FECa: Change at 12 Hours Postdose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                    <count group_id="O2" value="5"/>
                    <count group_id="O3" value="5"/>
                    <count group_id="O4" value="3"/>
                    <count group_id="O5" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.002" spread="0.005"/>
                    <measurement group_id="O2" value="0.002" spread="0.012"/>
                    <measurement group_id="O3" value="0.001" spread="0.011"/>
                    <measurement group_id="O4" value="-0.009" spread="0.018"/>
                    <measurement group_id="O5" value="0.002" spread="0.007"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From the sign of informed consent form (Day -93) up to safety follow-up assessment (upto Day 17 after discharge)</time_frame>
      <group_list>
        <group group_id="E1">
          <title>NPSP795</title>
          <description>NPSP795 administered Intravenous (IV) infusion for 10 min on Day 1 if certain criteria for ionized calcium and/or blood parathyroid hormone (PTH) were met, an infusion was administered for either 10 min or 3.5 hours on Days 2 &amp; 3, according to a predefined dose escalation scheme. NPSP795 was administered as a 3.5-hour infusion on Day 4, or the participant underwent discharge procedures.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 17.1</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholelithiasis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 17.1</default_vocab>
        <default_assessment>Non-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="3" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholelithiasis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Hypersensitivity reaction</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Nipple pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </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>If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Study Director</name_or_title>
      <organization>Shire</organization>
      <phone>+1 866 842 5335</phone>
      <email>ClinicalTransparency@shire.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/NCT02204579
org study id: CAL-C13-001
nct id: NCT02204579
lead sponsor: 
collaborator: 
has dmc: Yes
This is an open-label study looking at the effects of NPSP795 (a selective calcium receptor
      antagonist) on activating mutations of the Calcium-sensing receptor in patients with
      Autosomal Dominant Hypocalcemia. Patients with ADH have low blood calcium levels and an
      inappropriately increased renal calcium excretion, decreased renal phosphate excretion, and
      hyperphosphatemia. PTH and blood calcium levels will be tested during and after the IV
      infusion of NPSP795. Concentrations of NPSP795 and length of time of IV infusion will vary
      depending on measured levels of ionized calcium.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
time frame: From Day 1 up to safety follow-up assessment (upto Day 17 after discharge)
measure: Number of Participants With Clinically Significant Vital Signs and Electrocardiogram (ECG) Abnormalities
time frame: From Day 1 up to safety follow-up assessment (upto Day 17 after discharge)
measure: Number of Participants With Potentially Clinically Important Laboratory Abnormalities
time frame: From Day 1 up to safety follow-up assessment (upto Day 17 after discharge)
measure: Number of Participants With Clinically Significant Abnormalities Related to Physical Examination
time frame: From Day 1 up to safety follow-up assessment (upto Day 17 after discharge)
measure: Change From Baseline in Ionised Calcium
time frame: 10 Minute (min) Infusion Time: within 5 min pre-dose; & post-dose 15, 30, 45, 60, 75, 90, 105 min, and 2, 2.5, 3, 3.5, & 4 hour (hr) 3.5 hr Infusion Time: within 5 min pre-dose; & post-dose 15, 30, 45, 60, 75, 90, 105 min, & 2, 2.5, 3, 3.5, 4, 5, and 8 hr
measure: Change From Baseline in Serum Calcium
time frame: 10 Minutes (min) Infusion Time: within 5 min pre-dose; & post-dose 1, 2, 3, 4, 8 12 hours (hr). 3.5 hr Infusion Time: within 5 min pre-dose; & post-dose 1, 2, 3, 4, 8 12 hr.
measure: Change From Baseline in Urinary Calcium
time frame: 10 Minutes (min) Infusion Time: within 5 min pre-dose; & post-dose 1, 2, 3, 4, 8 12 hours (hr). 3.5 hr Infusion Time: within 5 min pre-dose; & post-dose 1, 2, 3, 4, 8 12 hr.
measure: Change From Baseline in Serum Parathyroid Hormone (PTH)
time frame: 10 Minutes (min) Infusion Time: within 5 min pre-dose; & post-dose 5, 10, 15, 30 min, & 1, 1.5, 2, 2.5, 3, 3.5, 4, 8 hours (hr). 3.5 hr Infusion Time: within 5 min pre-dose; & post-dose 15, 30 min, & 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 5.5 hr
measure: Area Under the Plasma Concentration Versus Time Curve (AUC[0-t]) of NPSP795
time frame: 10 Minutes (min) Infusion Time: within 5 min pre-dose; & post-dose 5, 10, 15, 30 min, & 1, 1.5, 2, 2.5, 3, 3.5, 4, 8 hours (hr). 3.5 hr Infusion Time: within 5 min pre-dose; & post-dose 15, 30 min, & 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 5.5 hr
measure: Area Under the Concentration Time Curve Extrapolated to Infinity (AUC0-infinity) of NPSP795
time frame: 10 Minutes (min) Infusion Time: within 5 min pre-dose; & post-dose 5, 10, 15, 30 min, & 1, 1.5, 2, 2.5, 3, 3.5, 4, 8 hours (hr). 3.5 hr Infusion Time: within 5 min pre-dose; & post-dose 15, 30 min, & 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 5.5 hr
measure: Maximum Observed Drug Concentration (Cmax) of NPSP795 in Plasma
time frame: 10 Minutes (min) Infusion Time: within 5 min pre-dose; & post-dose 5, 10, 15, 30 min, & 1, 1.5, 2, 2.5, 3, 3.5, 4, 8 hours (hr). 3.5 hr Infusion Time: within 5 min pre-dose; & post-dose 15, 30 min, & 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 5.5 hr
measure: Elimination Half-life (t1/2) of NPSP795 in Plasma
time frame: 10 Minutes (min) Infusion Time: within 5 min pre-dose; & post-dose 5, 10, 15, 30 min, & 1, 1.5, 2, 2.5, 3, 3.5, 4, 8 hours (hr). 3.5 hr Infusion Time: within 5 min pre-dose; & post-dose 15, 30 min, & 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 5.5 hr
measure: Change From Baseline in Fractional Excretion of Calcium (FECa)
time frame: 10 Minutes (min) Infusion Time: within 5 min pre-dose; & post-dose 1, 2, 3, 4, 8, 12 hours (hr). 3.5 hr Infusion Time: within 5 min pre-dose; & post-dose 1, 2, 3, 4, 8, 12 hr.
arm group label: NPSP795
arm group type: Experimental
description: intravenous
intervention type: Drug
intervention name: NPSP795
arm group label: NPSP795
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Study Director
role: Study Director
affiliation: Takeda
facility: 
country: United States
responsible party type: Sponsor
mesh term: Arthrogryposis
mesh term: Hypocalcemia
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 