<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/NCT03002506</url>
  </required_header>
  <id_info>
    <org_study_id>070619</org_study_id>
    <nct_id>NCT03002506</nct_id>
  </id_info>
  <brief_title>Pharmacokinetics of Ceftolozane/Tazobactam in Patients With Burns</brief_title>
  <official_title>Pharmacokinetics of Ceftolozane/Tazobactam in Patients With Burns</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Texas Tech University Health Sciences Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Merck Sharp &amp; Dohme LLC</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Texas Tech University Health Sciences Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will help provide information about how patients with burn handle two antibiotics&#xD;
      (ceftolozane and tazobactam) and use that information to guide dosing recommendations for&#xD;
      these patients. The 12 patients who complete the study will receive a single dose of 3 grams&#xD;
      ceftolozane/tazobactam intravenously. We will collect blood and urine samples to determine&#xD;
      how much of each antibiotic is in the body and urine at various times over a 24 hour period.&#xD;
      This information will be used with previously published information from microbiology&#xD;
      laboratories to perform simulations that will provide recommendations on optimal dosing&#xD;
      recommendations of these antibiotics in patients with burns.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A single dose pharmacokinetic study of ceftolozane and tazobactam will be conducted in&#xD;
      patients with burns at the Burn Center at University Medical Center. A total of 12 adults&#xD;
      aged 18 to 80 years with &gt;/= 20% percent total body surface area burned will be required to&#xD;
      complete the study. A single intravenous dose of ceftolozane and tazobactam of 2 grams/1 gram&#xD;
      will be administered over 60 minutes and whole blood will be obtained predose and at 0.5, 1,&#xD;
      1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, and 24 hours following the start of infusion. Urine samples&#xD;
      (5 ml) will be collected from a urine collection bag (if the patient has urinated) at the&#xD;
      following timepoints: 0-0.5, 0.5-1, 1-2, 2-4, 4-8, 8-12, and 12-24 hours for analysis of&#xD;
      ceftolozane and tazobactam content. Urine for collected during each time period will be&#xD;
      measured to determine urine volume for urine clearance calculations. The volume of urine in&#xD;
      the urine over the entire 24 hour period and an aliquot sent for analysis of urine creatinine&#xD;
      content to determine the patient's 24 hour creatinine clearance.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Much slower recruitment than anticipated&#xD;
  </why_stopped>
  <start_date type="Actual">August 21, 2017</start_date>
  <completion_date type="Actual">June 30, 2020</completion_date>
  <primary_completion_date type="Actual">June 1, 2020</primary_completion_date>
  <phase>Phase 4</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>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Ceftolozane Clearnace</measure>
    <time_frame>24 hours</time_frame>
    <description>Liters/hour (continuous values)</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">6</enrollment>
  <condition>Burns</condition>
  <condition>Pharmacokinetics</condition>
  <arm_group>
    <arm_group_label>ceftolozane/tazobactam</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>One dose of 3 grams ceftolozane/tazobactam will be administered to each study participant.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ceftolozane/tazobactam</intervention_name>
    <description>Single dose of 2 grams/1 gram intravenously administered over 60 minutes.</description>
    <arm_group_label>ceftolozane/tazobactam</arm_group_label>
    <other_name>Zerbaxa</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male and female subjects, ages 18-80 years, of all racial and ethnic origins.&#xD;
&#xD;
          2. Non-English Spanish speakers will be included in the study.&#xD;
&#xD;
          3. We are recruiting 12 patients with thermal burn injuries (percent total body surface&#xD;
             area burned &gt;/= 20%). Patients will be at least five days from the date of the burn&#xD;
             injury.&#xD;
&#xD;
          4. Patients will have central venous or arterial line access.&#xD;
&#xD;
          5. Patients will be already be receiving standard of care antimicrobial therapy for a&#xD;
             suspected infection.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Pregnant or nursing or unwilling to use a reliable contraception method during the&#xD;
             study. The effects of ceftolozane and tazobactam on pregnancy are unknown. In&#xD;
             addition, the metabolic changes that accompany pregnancy may alter the&#xD;
             concentration-time profile of ceftolozane and tazobactam, so that the pregnancy and&#xD;
             post-partum state would be a confounding variable.&#xD;
&#xD;
          2. Abnormal liver function tests: transaminases &gt;10 times upper limit of normal, Alkaline&#xD;
             phosphatase &gt;5 times upper limit of normal, total bilirubin &gt;5 times upper limit of&#xD;
             normal.&#xD;
&#xD;
          3. History of allergies to beta-lactam antibiotics.&#xD;
&#xD;
          4. Patients unwilling to comply with study procedures.&#xD;
&#xD;
          5. Current or previous participation within 28 days of enrollment in another research&#xD;
             study that involves the use of medication, contrast, or any other compound that may&#xD;
             alter blood count and/or blood chemistry (liver function, kidney function or&#xD;
             electrolyte balance), unless waved by principal investigator (PI).&#xD;
&#xD;
          6. Donation of 450mL (one unit) of blood or more within 8 weeks (56 days) prior to study&#xD;
             enrollment, unless waved by PI.&#xD;
&#xD;
          7. Creatinine clearance &lt; 30 ml/min as estimated by the Cockcroft-Gault equation.&#xD;
&#xD;
          8. Patients who are receiving piperazillin/tazobactam or have received&#xD;
             piperacillin/tazobactam within the past 48 hours.&#xD;
&#xD;
          9. Patients who are receiving vasopressors.&#xD;
&#xD;
         10. Patients with a total body weight &lt; 60 kg or &gt; 130 kg.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ronald G Hall, PharmD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Texas Tech University HSC</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Medical Center</name>
      <address>
        <city>Lubbock</city>
        <state>Texas</state>
        <zip>79415</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2021</verification_date>
  <study_first_submitted>December 21, 2016</study_first_submitted>
  <study_first_submitted_qc>December 21, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 23, 2016</study_first_posted>
  <results_first_submitted>October 19, 2020</results_first_submitted>
  <results_first_submitted_qc>March 1, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">March 2, 2021</results_first_posted>
  <last_update_submitted>March 1, 2021</last_update_submitted>
  <last_update_submitted_qc>March 1, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 2, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>ceftolozane</keyword>
  <keyword>tazobactam</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Burns</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tazobactam</mesh_term>
    <mesh_term>Ceftolozane</mesh_term>
    <mesh_term>Ceftolozane, tazobactam drug combination</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>December 19, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/06/NCT03002506/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Ceftolozane/Tazobactam</title>
          <description>One dose of 3 grams ceftolozane/tazobactam will be administered to each study participant.&#xD;
Ceftolozane/tazobactam: Single dose of 2 grams/1 gram intravenously administered over 60 minutes.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>All participants who provided informed consent and received ceftolozane/tazobactam.</population>
      <group_list>
        <group group_id="B1">
          <title>Ceftolozane/Tazobactam</title>
          <description>One dose of 3 grams ceftolozane/tazobactam will be administered to each study participant.&#xD;
Ceftolozane/tazobactam: Single dose of 2 grams/1 gram intravenously administered over 60 minutes.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="6"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <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="42.67" spread="13.91"/>
                  </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="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Ceftolozane Clearnace</title>
        <description>Liters/hour (continuous values)</description>
        <time_frame>24 hours</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Ceftolozane/Tazobactam</title>
            <description>One dose of 3 grams ceftolozane/tazobactam will be administered to each study participant.&#xD;
Ceftolozane/tazobactam: Single dose of 2 grams/1 gram intravenously administered over 60 minutes.</description>
          </group>
        </group_list>
        <measure>
          <title>Ceftolozane Clearnace</title>
          <description>Liters/hour (continuous values)</description>
          <units>Liters per 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="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.79" spread="2.30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>24 hours</time_frame>
      <desc>Adverse events were to be reported if reported by the participant, healthcare team member, research team member, or lab documented.</desc>
      <group_list>
        <group group_id="E1">
          <title>Ceftolozane/Tazobactam</title>
          <description>One dose of 3 grams ceftolozane/tazobactam will be administered to each study participant.&#xD;
Ceftolozane/tazobactam: Single dose of 2 grams/1 gram intravenously administered over 60 minutes.</description>
        </group>
      </group_list>
      <serious_events>
        <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="6"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>Single-dose pharmacokinetic study. No clinical outcomes to evaluate efficacy. No safety data provided by this study beyond a single dose in this population.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Ronald Hall, PharmD, MSCS</name_or_title>
      <organization>Texas Tech UHSC</organization>
      <phone>214-358-9009</phone>
      <email>ronald.hall@ttuhsc.edu</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/NCT03002506
org study id: 070619
nct id: NCT03002506
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
This study will help provide information about how patients with burn handle two antibiotics
      (ceftolozane and tazobactam) and use that information to guide dosing recommendations for
      these patients. The 12 patients who complete the study will receive a single dose of 3 grams
      ceftolozane/tazobactam intravenously. We will collect blood and urine samples to determine
      how much of each antibiotic is in the body and urine at various times over a 24 hour period.
      This information will be used with previously published information from microbiology
      laboratories to perform simulations that will provide recommendations on optimal dosing
      recommendations of these antibiotics in patients with burns.
A single dose pharmacokinetic study of ceftolozane and tazobactam will be conducted in
      patients with burns at the Burn Center at University Medical Center. A total of 12 adults
      aged 18 to 80 years with >/= 20% percent total body surface area burned will be required to
      complete the study. A single intravenous dose of ceftolozane and tazobactam of 2 grams/1 gram
      will be administered over 60 minutes and whole blood will be obtained predose and at 0.5, 1,
      1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, and 24 hours following the start of infusion. Urine samples
      (5 ml) will be collected from a urine collection bag (if the patient has urinated) at the
      following timepoints: 0-0.5, 0.5-1, 1-2, 2-4, 4-8, 8-12, and 12-24 hours for analysis of
      ceftolozane and tazobactam content. Urine for collected during each time period will be
      measured to determine urine volume for urine clearance calculations. The volume of urine in
      the urine over the entire 24 hour period and an aliquot sent for analysis of urine creatinine
      content to determine the patient's 24 hour creatinine clearance.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Other
masking: None (Open Label)
measure: Ceftolozane Clearnace
time frame: 24 hours
description: Liters/hour (continuous values)
arm group label: ceftolozane/tazobactam
arm group type: Experimental
description: One dose of 3 grams ceftolozane/tazobactam will be administered to each study participant.
intervention type: Drug
intervention name: Ceftolozane/tazobactam
description: Single dose of 2 grams/1 gram intravenously administered over 60 minutes.
arm group label: ceftolozane/tazobactam
other name: Zerbaxa
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Ronald G Hall, PharmD
role: Principal Investigator
affiliation: Texas Tech University HSC
facility: 
country: United States
responsible party type: Sponsor
mesh term: Burns
mesh term: Tazobactam
mesh term: Ceftolozane
mesh term: Ceftolozane, tazobactam drug combination
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Single-dose pharmacokinetic study. No clinical outcomes to evaluate efficacy. No safety data provided by this study beyond a single dose in this population.
point of contact: 