<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/NCT03235375</url>
  </required_header>
  <id_info>
    <org_study_id>D5670C00008</org_study_id>
    <nct_id>NCT03235375</nct_id>
  </id_info>
  <brief_title>A Study to Evaluate Pharmacokinetics, Safety and Tolerability of MEDI0382 in Renal Impairment Subjects</brief_title>
  <official_title>A Phase 1, Open-Label, Single Dose, Parallel-Group Study to Evaluate the Pharmacokinetics, Safety and Tolerability of MEDI0382 in Subjects With Renal Impairment</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>MedImmune LLC</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>MedImmune LLC</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      A phase 1 open-label, single-dose study to evaluate the pharmacokinetics (PK), safety,&#xD;
      tolerability and immunogenicity of MEDI0382 in subjects with renal impairment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is an open-label, single-dose, parallel group study to evaluate the PK, safety,&#xD;
      tolerability, and immunogenicity of MEDI0382 in subjects with renal impairment. Enrollment of&#xD;
      approximately 40 subjects across multiple sites is planned. Subjects will be divided into 4&#xD;
      groups based on renal function.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 27, 2017</start_date>
  <completion_date type="Actual">April 24, 2018</completion_date>
  <primary_completion_date type="Actual">April 24, 2018</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum Observed Concentration of MEDI0382 (Cmax)</measure>
    <time_frame>0-48 hours</time_frame>
    <description>The first occurrence of the maximum observed plasma concentration determined directly from the raw concentration-time data</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area under the Concentration Time Curve (AUC) of MEDI0382</measure>
    <time_frame>0-48 hours</time_frame>
    <description>The area under the plasma concentration-time curve to 48 hours concentration determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to maximum observed concentration (Tmax)</measure>
    <time_frame>0-48 hours</time_frame>
    <description>Time to maximum observed concentration.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>apparent clearance (Cl/F)</measure>
    <time_frame>0-48 hours</time_frame>
    <description>The apparent clearance will be calculated as CL/F=Dose/AUC(0-inf)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUCinf</measure>
    <time_frame>0-48 hours</time_frame>
    <description>The AUC extrapolated to infinity will be calculated, where data permit, as the sum of AUC((0-t) and Ct/z, where Ct is the observed plasma concentration obtained from the log-linear regression analysis of the last quantifiable time-point and z is the terminal phase rate constant.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Half-life (T1/2)</measure>
    <time_frame>0-48 hours</time_frame>
    <description>The apparent terminal elimination half-life (t1/2) obtained as the ratio of ln2/z, where z is the terminal phase rate constant estimated by linear regression analysis of the log transformed concentration-time data</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anti-drug Antibody (ADA) titer</measure>
    <time_frame>Day -1 to day 28</time_frame>
    <description>ADA titer through to day 28</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with Adverse Events</measure>
    <time_frame>Study onset till 28 days post dosing</time_frame>
    <description>Treatment emergent adverse events (TEAEs) and serious adverse events (TESAEs)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with Adverse Events</measure>
    <time_frame>Study onset till 28 days post dosing</time_frame>
    <description>Vital Signs (systolic and diastolic blood pressure, pulse rate, temperature and respiratory rates)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with Adverse Events</measure>
    <time_frame>Study onset till 28 days post dosing</time_frame>
    <description>Clinical laboratory assessments (serum chemistry, hematology, and urinalysis)</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">37</enrollment>
  <condition>Renal Insufficiency</condition>
  <arm_group>
    <arm_group_label>Group 1: End Stage Renal Disease (ESRD)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects with CrCl &lt;20ml/min will receive MEDI0382 administered subcutaneously</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2: Severe and ESRD Subjects</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects with CrCl &gt;20 and &lt; 30 ml/min will receive MEDI0382 administered subcutaneously</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 3: Healthy Subjects</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subjects with CrCl &gt;90 ml/min will receive MEDI0382 administered subcutaneously</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 4: Moderate Renal Disease</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects with CrCl &gt; or equal to 30 and &lt; 60 mL/min will receive MEDI0382 administered subcutaneously</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>MEDI0382</intervention_name>
    <description>MEDI0382 administered subcutaneously</description>
    <arm_group_label>Group 1: End Stage Renal Disease (ESRD)</arm_group_label>
    <arm_group_label>Group 2: Severe and ESRD Subjects</arm_group_label>
    <arm_group_label>Group 3: Healthy Subjects</arm_group_label>
    <arm_group_label>Group 4: Moderate Renal Disease</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Must provide written informed consent&#xD;
&#xD;
          -  BMI greater than or equal to 17 and less than or equal to 40 kg/m2&#xD;
&#xD;
          -  Creatinine clearance rate greater than or equal to 90 (healthy); or renally impaired&#xD;
             (less than 60 mL/min)&#xD;
&#xD;
          -  Females of childbearing potential must use a highly effective form of contraception.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any history of or concurrent condition that in the opinion of the investigator would&#xD;
             compromise the subjects safety.&#xD;
&#xD;
          -  Subjects on dialysis&#xD;
&#xD;
          -  Subjects with pancreatitis&#xD;
&#xD;
          -  Renal transplant subjects&#xD;
&#xD;
          -  Females pregnant or lactating&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kiel</city>
        <zip>24105</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>München</city>
        <zip>81241</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Auckland</city>
        <zip>1010</zip>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Christchurch</city>
        <zip>8011</zip>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
    <country>New Zealand</country>
  </location_countries>
  <verification_date>April 2018</verification_date>
  <study_first_submitted>July 27, 2017</study_first_submitted>
  <study_first_submitted_qc>July 27, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 1, 2017</study_first_posted>
  <last_update_submitted>April 30, 2018</last_update_submitted>
  <last_update_submitted_qc>April 30, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">May 1, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Kidney Failure, Kidney Insufficiency, Renal Failure, Renal Insufficiency, MEDI0382</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Renal Insufficiency</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03235375
org study id: D5670C00008
nct id: NCT03235375
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
A phase 1 open-label, single-dose study to evaluate the pharmacokinetics (PK), safety,
      tolerability and immunogenicity of MEDI0382 in subjects with renal impairment.
This is an open-label, single-dose, parallel group study to evaluate the PK, safety,
      tolerability, and immunogenicity of MEDI0382 in subjects with renal impairment. Enrollment of
      approximately 40 subjects across multiple sites is planned. Subjects will be divided into 4
      groups based on renal function.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Maximum Observed Concentration of MEDI0382 (Cmax)
time frame: 0-48 hours
description: The first occurrence of the maximum observed plasma concentration determined directly from the raw concentration-time data
measure: Area under the Concentration Time Curve (AUC) of MEDI0382
time frame: 0-48 hours
description: The area under the plasma concentration-time curve to 48 hours concentration determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations
measure: Time to maximum observed concentration (Tmax)
time frame: 0-48 hours
description: Time to maximum observed concentration.
measure: apparent clearance (Cl/F)
time frame: 0-48 hours
description: The apparent clearance will be calculated as CL/F=Dose/AUC(0-inf)
measure: AUCinf
time frame: 0-48 hours
description: The AUC extrapolated to infinity will be calculated, where data permit, as the sum of AUC((0-t) and Ct/z, where Ct is the observed plasma concentration obtained from the log-linear regression analysis of the last quantifiable time-point and z is the terminal phase rate constant.
measure: Half-life (T1/2)
time frame: 0-48 hours
description: The apparent terminal elimination half-life (t1/2) obtained as the ratio of ln2/z, where z is the terminal phase rate constant estimated by linear regression analysis of the log transformed concentration-time data
measure: Anti-drug Antibody (ADA) titer
time frame: Day -1 to day 28
description: ADA titer through to day 28
measure: Number of subjects with Adverse Events
time frame: Study onset till 28 days post dosing
description: Treatment emergent adverse events (TEAEs) and serious adverse events (TESAEs)
measure: Number of subjects with Adverse Events
time frame: Study onset till 28 days post dosing
description: Vital Signs (systolic and diastolic blood pressure, pulse rate, temperature and respiratory rates)
measure: Number of subjects with Adverse Events
time frame: Study onset till 28 days post dosing
description: Clinical laboratory assessments (serum chemistry, hematology, and urinalysis)
arm group label: Group 1: End Stage Renal Disease (ESRD)
arm group type: Experimental
description: Subjects with CrCl <20ml/min will receive MEDI0382 administered subcutaneously
arm group label: Group 2: Severe and ESRD Subjects
arm group type: Experimental
description: Subjects with CrCl >20 and < 30 ml/min will receive MEDI0382 administered subcutaneously
arm group label: Group 3: Healthy Subjects
arm group type: Active Comparator
description: Subjects with CrCl >90 ml/min will receive MEDI0382 administered subcutaneously
arm group label: Group 4: Moderate Renal Disease
arm group type: Experimental
description: Subjects with CrCl > or equal to 30 and < 60 mL/min will receive MEDI0382 administered subcutaneously
intervention type: Drug
intervention name: MEDI0382
description: MEDI0382 administered subcutaneously
arm group label: Group 1: End Stage Renal Disease (ESRD)
arm group label: Group 2: Severe and ESRD Subjects
arm group label: Group 3: Healthy Subjects
arm group label: Group 4: Moderate Renal Disease
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
country: Germany
country: New Zealand
responsible party type: Sponsor
mesh term: Renal Insufficiency