<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/NCT01689207</url>
  </required_header>
  <id_info>
    <org_study_id>D4910C00001</org_study_id>
    <nct_id>NCT01689207</nct_id>
  </id_info>
  <brief_title>To Investigate the Safety and Tolerability of Aztreonam-Avibactam (ATM-AVI)</brief_title>
  <official_title>A Phase I, Randomised, Double-blind, 3-Part Study in Healthy Young and Elderly Subjects to Assess the Safety and Tolerability, and Investigate the Pharmacokinetics of Aztreonam and Avibactam Given Alone and in Combination (ATM-AVI)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Pfizer</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Pfizer</source>
  <brief_summary>
    <textblock>
      This is a randomised, double-blind, 3-part study designed to investigate the safety and&#xD;
      tolerability of ATM-AVI. The study aims to characterise the pharmacokinetics of ATM-AVI, when&#xD;
      both drugs are administered alone (ATM or AVI) and in combination (ATM-AVI), following single&#xD;
      administration, and following multiple administrations of ATM-AVI in healthy male and female&#xD;
      (females of nonchildbearing potential) volunteers both young and elderly.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A Phase I, Randomised, Double-blind, 3-Part Study in Healthy Young and Elderly Subjects to&#xD;
      Assess the Safety and Tolerability, and Investigate the Pharmacokinetics of Aztreonam and&#xD;
      Avibactam given Alone and in Combination (ATM-AVI)&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">December 2014</completion_date>
  <primary_completion_date type="Actual">December 2014</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety Profile - Number of Subjects With at Least 1 AE</measure>
    <time_frame>Informed consent (up to 28 days before first dose) to follow up period (max of 22 days after first dose for Part A, a max of 28 days after first dose in Part B, max 17 days in Part C)</time_frame>
    <description>from screening visit (Day -28) to 3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>PK- Plasma Pharmacokinetic Parameter AUC (ug*h/mL) for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) in Parts A, B and C</measure>
    <time_frame>0 to 24 hours post-dose on Day 1 in Part A. 0 to 24 hours post-dose on Days 1, 2, 4 and 11 in Part B (varied intervals per cohort). 0 to 6 hours post-dose on Days 1, 4, 7 and 10 in Part C. Steady state measure on Day 11 in Part B or Day 10 in Part C</time_frame>
    <description>Area under the plasma concentration-time curve from zero extrapolated to infinity (AUC µg*h/mL) or AUC(0-last) in Part A on Day 1 after single infusion, area under the plasma concentration-time curve at steady state after multiple infusion (AUCss µg*h/mL).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK- Plasma Pharmacokinetic Parameter t1/2(h) for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) in Parts A, B and C</measure>
    <time_frame>0 to 24 hours post-dose on Day 1 in Part A. 0 to 24 hours post-dose on Days 1, 2, 4 and 11 in Part B (varied intervals per cohort). 0 to 6 hours post-dose on Days 1, 4, 7 and 10 in Part C. Steady state measure on Day 11 in Part B or Day 10 in Part C</time_frame>
    <description>Terminal half-life (t1/2), on Day 1 after single infusion and at steady state after multiple infusion.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK- Plasma Pharmacokinetic Parameter Tmax for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) on Day 1 in Parts A, B and C</measure>
    <time_frame>Day 1</time_frame>
    <description>Time to Cmax (tmax)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK- Plasma Pharmacokinetic Parameter Cmax for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) in Parts A, B and C</measure>
    <time_frame>0 to 24 hours post-dose on Day 1 in Part A. 0 to 24 hours post-dose on Days 1, 2, 4 and 11 in Part B (varied intervals per cohort). 0 to 6 hours post-dose on Days 1, 4, 7 and 10 in Part C. Steady state measure on Day 11 in Part B or Day 10 in Part C</time_frame>
    <description>Maximum plasma concentration (Cmax µg/mL) on Day 1 after single infusion , maximum plasma concentration at steady state (Css,max µg/mL) after multiple infusion.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK- Plasma Pharmacokinetic Parameters CL and CLr for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) in Parts A, B and C</measure>
    <time_frame>0 to 24 hours post-dose on Day 1 in Part A. 0 to 24 hours post-dose on Days 1, 2, 4 and 11 in Part B (varied intervals per cohort). 0 to 6 hours post-dose on Days 1, 4, 7 and 10 in Part C. Steady state measure on Day 11 in Part B or Day 10 in Part C</time_frame>
    <description>Systemic clearence (CL) and renal clearance (CLr) on Day 1 after single infusion and at steady state after multiple infusion.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK- Plasma Pharmacokinetic Parameter Vss for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) in Parts A, B and C</measure>
    <time_frame>0 to 24 hours post-dose on Day 1 in Part A. 0 to 24 hours post-dose on Days 1, 2, 4 and 11 in Part B (varied intervals per cohort). 0 to 6 hours post-dose on Days 1, 4, 7 and 10 in Part C. Steady state measure on Day 11 in Part B or Day 10 in Part C</time_frame>
    <description>Volume of distribution at steady state (Vss).</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">222</enrollment>
  <condition>Complicated Infection</condition>
  <condition>Bacterial Infections</condition>
  <arm_group>
    <arm_group_label>Drug: A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Avibactam (AVI)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Drug: B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Aztreonam (ATM)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Drug: C</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>combination of Aztreonam-Avibactam (ATM-AVI)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Drug: D</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Matching Placebo</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Avibactam (AVI)</intervention_name>
    <description>PART A: AVI IV infusion</description>
    <arm_group_label>Drug: A</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Aztreonam (ATM)</intervention_name>
    <description>PART A: ATM IV infusion</description>
    <arm_group_label>Drug: B</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>combination of Aztreonam - Avibactam (ATM-AVI)</intervention_name>
    <description>PART A: ATM-AVI IV infusion. PART B and C: ATM-AVI IV infusions.</description>
    <arm_group_label>Drug: C</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>PART A, PART B, PART C: matching placebo IV infusions</description>
    <arm_group_label>Drug: D</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Provision of signed and dated, written informed consent prior to any study specific&#xD;
             procedures&#xD;
&#xD;
          -  Healthy young male and female volunteers aged 18 to 45 years (inclusive) and healthy&#xD;
             elderly volunteers aged 65 or older (Part C) with suitable veins for cannulation or&#xD;
             repeated venipuncture&#xD;
&#xD;
          -  Have a body mass index (BMI) between 19 and 30 kg/m2&#xD;
&#xD;
          -  Be able to understand and willing to comply with study procedures, restrictions, and&#xD;
             requirements, as judged by the PI&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of any clinically significant disease or disorder which, in the opinion of the&#xD;
             PI, may either put the volunteer at risk because of participation in the study, or&#xD;
             influence the results or the volunteer's ability to participate in the study&#xD;
&#xD;
          -  History or presence of gastrointestinal, hepatic, or renal disease, or any other&#xD;
             condition known to interfere with absorption, distribution, metabolism, or excretion&#xD;
             of drugs&#xD;
&#xD;
          -  Known history of severe allergy to betalactam and/or L-arginine&#xD;
&#xD;
          -  History of severe allergy/hypersensitivity or ongoing clinically important&#xD;
             allergy/hypersensitivity, as judged by the PI or history of hypersensitivity to drugs&#xD;
             with a similar chemical structure or class to ATM or AVI&#xD;
&#xD;
          -  Any clinically significant illness, medical/surgical procedure, or trauma within 4&#xD;
             weeks prior to the first administration of IP&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>130 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Frans van den Berg, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hammersmith Medicines Research Cumberland Avenue Park Royal London NW10 7EW, England Telephone: +44 020 8961 4130 Fax: +44 020 8961 8665</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>September 12, 2012</study_first_submitted>
  <study_first_submitted_qc>September 20, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 21, 2012</study_first_posted>
  <results_first_submitted>December 14, 2015</results_first_submitted>
  <results_first_submitted_qc>September 6, 2016</results_first_submitted_qc>
  <results_first_posted type="Estimate">October 26, 2016</results_first_posted>
  <last_update_submitted>August 31, 2017</last_update_submitted>
  <last_update_submitted_qc>August 31, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">September 6, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Phase I, Safety, tolerability, healthy.</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infections</mesh_term>
    <mesh_term>Communicable Diseases</mesh_term>
    <mesh_term>Bacterial Infections</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aztreonam</mesh_term>
    <mesh_term>Avibactam</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>First subject enrolled 27 September 2012 and last subject last visit was 30 December 2014. Subjects were healthy male and female volunteers both young and elderly. Healthy volunteers were given full and adequate oral and written information about the nature, purpose, possible risk and benefit of the study and could discontinue at any time.</recruitment_details>
      <pre_assignment_details>A Screening visit was conducted within 28 days before admission to the study centre. 222 volunteers were screend, 92 volunteers were entered into the study. Healthy volunteers were admitted to the study centre on Day -1 of either Part A, Part B or Part C.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Part A: Placebo</title>
          <description>Placebo</description>
        </group>
        <group group_id="P2">
          <title>Part A: Drug</title>
          <description>Aztreonam (ATM) 2000mg, Avibactam (AVI) 600mg, ATM 2000mg +AVI 600mg (crossover)</description>
        </group>
        <group group_id="P3">
          <title>Part B: Placebo</title>
          <description>Placebo</description>
        </group>
        <group group_id="P4">
          <title>Part B: Cohort 1 Drug</title>
          <description>ATM (2000mg) + AVI (375mg)</description>
        </group>
        <group group_id="P5">
          <title>Part B: Cohort 2 Drug</title>
          <description>ATM (2000mg) + AVI (600mg)</description>
        </group>
        <group group_id="P6">
          <title>Part B: Cohort 3 Drug</title>
          <description>ATM (1500mg) + AVI (600mg)</description>
        </group>
        <group group_id="P7">
          <title>Part B: Cohort 4 Drug</title>
          <description>ATM (1500mg) + AVI (450mg)</description>
        </group>
        <group group_id="P8">
          <title>Part B: Cohort 5 Drug</title>
          <description>ATM (1500mg) + AVI (410mg)</description>
        </group>
        <group group_id="P9">
          <title>Part C: Placebo</title>
          <description>Placebo</description>
        </group>
        <group group_id="P10">
          <title>Part C: Cohort 1 Drug</title>
          <description>Aged 18-45: ATM (500mg followed by 1500mg) + AVI (136.7mg followed by 410mg)</description>
        </group>
        <group group_id="P11">
          <title>Part C: Cohort 2 Drug</title>
          <description>Aged &gt;65: ATM (500mg followed by 1500mg) + AVI (136.7mg + 410mg)</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="4">Subjects randomised</participants>
                <participants group_id="P2" count="8">Subjects randomised</participants>
                <participants group_id="P3" count="16">Subjects randomised</participants>
                <participants group_id="P4" count="8">Subjects randomised</participants>
                <participants group_id="P5" count="4">Subjects randomised</participants>
                <participants group_id="P6" count="8">Subjects randomised</participants>
                <participants group_id="P7" count="10">Subjects randomised</participants>
                <participants group_id="P8" count="10">Subjects randomised</participants>
                <participants group_id="P9" count="6">Subjects randomised</participants>
                <participants group_id="P10" count="10">Subjects randomised</participants>
                <participants group_id="P11" count="8">Subjects randomised</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4">Subjects completed study</participants>
                <participants group_id="P2" count="7">Subjects completed study</participants>
                <participants group_id="P3" count="16">Subjects completed study</participants>
                <participants group_id="P4" count="8">Subjects completed study</participants>
                <participants group_id="P5" count="2">Subjects completed study</participants>
                <participants group_id="P6" count="7">Subjects completed study</participants>
                <participants group_id="P7" count="10">Subjects completed study</participants>
                <participants group_id="P8" count="10">Subjects completed study</participants>
                <participants group_id="P9" count="5">Subjects completed study</participants>
                <participants group_id="P10" count="10">Subjects completed study</participants>
                <participants group_id="P11" count="8">Subjects completed study</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="2"/>
                <participants group_id="P6" count="1"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="1"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="2"/>
                <participants group_id="P6" count="1"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="1"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>All randomised subjects</population>
      <group_list>
        <group group_id="B1">
          <title>Part A: Placebo</title>
          <description>Placebo</description>
        </group>
        <group group_id="B2">
          <title>Part A: Drug</title>
          <description>Aztreonam (ATM) 2000mg, Avibactam (AVI) 600mg, ATM 2000mg +AVI 600mg (crossover)</description>
        </group>
        <group group_id="B3">
          <title>Part B: Placebo</title>
          <description>Placebo</description>
        </group>
        <group group_id="B4">
          <title>Part B: Cohort 1 Drug</title>
          <description>ATM (2000mg) + AVI (375mg)</description>
        </group>
        <group group_id="B5">
          <title>Part B: Cohort 2 Drug</title>
          <description>ATM (2000mg) + AVI (600mg)</description>
        </group>
        <group group_id="B6">
          <title>Part B: Cohort 3 Drug</title>
          <description>ATM (1500mg) + AVI (600mg)</description>
        </group>
        <group group_id="B7">
          <title>Part B: Cohort 4 Drug</title>
          <description>ATM (1500mg) + AVI (450mg)</description>
        </group>
        <group group_id="B8">
          <title>Part B: Cohort 5 Drug</title>
          <description>ATM (1500mg) + AVI (410mg)</description>
        </group>
        <group group_id="B9">
          <title>Part C: Placebo</title>
          <description>Placebo</description>
        </group>
        <group group_id="B10">
          <title>Part C: Cohort 1 Drug</title>
          <description>Aged 18-45: ATM (500mg followed by 1500mg) + AVI (136.7mg followed by 410mg)</description>
        </group>
        <group group_id="B11">
          <title>Part C: Cohort 2 Drug</title>
          <description>Aged &gt;65: ATM (500mg followed by 1500mg) + AVI (136.7mg + 410mg)</description>
        </group>
        <group group_id="B12">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="4"/>
            <count group_id="B2" value="8"/>
            <count group_id="B3" value="16"/>
            <count group_id="B4" value="8"/>
            <count group_id="B5" value="4"/>
            <count group_id="B6" value="8"/>
            <count group_id="B7" value="10"/>
            <count group_id="B8" value="10"/>
            <count group_id="B9" value="6"/>
            <count group_id="B10" value="10"/>
            <count group_id="B11" value="8"/>
            <count group_id="B12" value="92"/>
          </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="33.8" spread="6.9"/>
                    <measurement group_id="B2" value="31.3" spread="7.1"/>
                    <measurement group_id="B3" value="27.4" spread="5.0"/>
                    <measurement group_id="B4" value="30.3" spread="4.9"/>
                    <measurement group_id="B5" value="27.8" spread="1.9"/>
                    <measurement group_id="B6" value="29.4" spread="9.9"/>
                    <measurement group_id="B7" value="29.7" spread="7.3"/>
                    <measurement group_id="B8" value="30.6" spread="6.3"/>
                    <measurement group_id="B9" value="51.3" spread="19.4"/>
                    <measurement group_id="B10" value="32.9" spread="8.4"/>
                    <measurement group_id="B11" value="68.5" spread="2.9"/>
                    <measurement group_id="B12" value="34.8" spread="14.0"/>
                  </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="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                    <measurement group_id="B8" value="0"/>
                    <measurement group_id="B9" value="1"/>
                    <measurement group_id="B10" value="0"/>
                    <measurement group_id="B11" value="2"/>
                    <measurement group_id="B12" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="16"/>
                    <measurement group_id="B4" value="8"/>
                    <measurement group_id="B5" value="4"/>
                    <measurement group_id="B6" value="8"/>
                    <measurement group_id="B7" value="10"/>
                    <measurement group_id="B8" value="10"/>
                    <measurement group_id="B9" value="5"/>
                    <measurement group_id="B10" value="10"/>
                    <measurement group_id="B11" value="6"/>
                    <measurement group_id="B12" value="89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Safety Profile - Number of Subjects With at Least 1 AE</title>
        <description>from screening visit (Day -28) to 3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.</description>
        <time_frame>Informed consent (up to 28 days before first dose) to follow up period (max of 22 days after first dose for Part A, a max of 28 days after first dose in Part B, max 17 days in Part C)</time_frame>
        <population>Safety population</population>
        <group_list>
          <group group_id="O1">
            <title>Part A: Placebo</title>
            <description>Placebo</description>
          </group>
          <group group_id="O2">
            <title>Part A: Drug</title>
            <description>Aztreonam (ATM) 2000mg, Avibactam (AVI) 600mg, ATM 2000mg +AVI 600mg (crossover)</description>
          </group>
          <group group_id="O3">
            <title>Part B: Placebo</title>
            <description>Placebo</description>
          </group>
          <group group_id="O4">
            <title>Part B: Cohort 1 Drug</title>
            <description>ATM (2000mg) + AVI (375mg)</description>
          </group>
          <group group_id="O5">
            <title>Part B: Cohort 2 Drug</title>
            <description>ATM (2000mg) + AVI (600mg)</description>
          </group>
          <group group_id="O6">
            <title>Part B: Cohort 3 Drug</title>
            <description>ATM (1500mg) + AVI (600mg)</description>
          </group>
          <group group_id="O7">
            <title>Part B: Cohort 4 Drug</title>
            <description>ATM (1500mg) + AVI (450mg)</description>
          </group>
          <group group_id="O8">
            <title>Part B: Cohort 5 Drug</title>
            <description>ATM (1500mg) + AVI (410mg)</description>
          </group>
          <group group_id="O9">
            <title>Part C: Placebo</title>
            <description>Placebo</description>
          </group>
          <group group_id="O10">
            <title>Part C: Cohort 1 Drug</title>
            <description>Aged 18-45: ATM (500mg followed by 1500mg) + AVI (136.7mg followed by 410mg)</description>
          </group>
          <group group_id="O11">
            <title>Part C: Cohort 2 Drug</title>
            <description>Aged &gt;65: ATM (500mg followed by 1500mg) + AVI (136.7mg + 410mg)</description>
          </group>
          <group group_id="O12">
            <title>Part A: Aztreonam (ATM) 2000mg</title>
            <description>Crossover period ATm 2000mg</description>
          </group>
          <group group_id="O13">
            <title>Part A: Avibactam (AVI) 600mg</title>
            <description>Crossover period AVI 600mg</description>
          </group>
          <group group_id="O14">
            <title>Part A: ATM 2000mg + AVI 600mg</title>
            <description>Crossover period ATM 2000mg + AVI 600mg</description>
          </group>
        </group_list>
        <measure>
          <title>Safety Profile - Number of Subjects With at Least 1 AE</title>
          <description>from screening visit (Day -28) to 3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.</description>
          <population>Safety population</population>
          <units>Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="8"/>
                <count group_id="O3" value="16"/>
                <count group_id="O4" value="8"/>
                <count group_id="O5" value="4"/>
                <count group_id="O6" value="8"/>
                <count group_id="O7" value="10"/>
                <count group_id="O8" value="10"/>
                <count group_id="O9" value="6"/>
                <count group_id="O10" value="10"/>
                <count group_id="O11" value="8"/>
                <count group_id="O12" value="7"/>
                <count group_id="O13" value="8"/>
                <count group_id="O14" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Number of subjects with at least 1 AE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="3"/>
                    <measurement group_id="O4" value="4"/>
                    <measurement group_id="O5" value="2"/>
                    <measurement group_id="O6" value="6"/>
                    <measurement group_id="O7" value="8"/>
                    <measurement group_id="O8" value="3"/>
                    <measurement group_id="O9" value="3"/>
                    <measurement group_id="O10" value="5"/>
                    <measurement group_id="O11" value="7"/>
                    <measurement group_id="O12" value="0"/>
                    <measurement group_id="O13" value="2"/>
                    <measurement group_id="O14" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subjects with at least 1 AE with outcome of death</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                    <measurement group_id="O7" value="0"/>
                    <measurement group_id="O8" value="0"/>
                    <measurement group_id="O9" value="0"/>
                    <measurement group_id="O10" value="0"/>
                    <measurement group_id="O11" value="0"/>
                    <measurement group_id="O12" value="0"/>
                    <measurement group_id="O13" value="0"/>
                    <measurement group_id="O14" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At least 1 AE leading to discontinuation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="2"/>
                    <measurement group_id="O6" value="1"/>
                    <measurement group_id="O7" value="0"/>
                    <measurement group_id="O8" value="0"/>
                    <measurement group_id="O9" value="1"/>
                    <measurement group_id="O10" value="0"/>
                    <measurement group_id="O11" value="0"/>
                    <measurement group_id="O12" value="0"/>
                    <measurement group_id="O13" value="1"/>
                    <measurement group_id="O14" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>PK- Plasma Pharmacokinetic Parameter AUC (ug*h/mL) for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) in Parts A, B and C</title>
        <description>Area under the plasma concentration-time curve from zero extrapolated to infinity (AUC µg*h/mL) or AUC(0-last) in Part A on Day 1 after single infusion, area under the plasma concentration-time curve at steady state after multiple infusion (AUCss µg*h/mL).</description>
        <time_frame>0 to 24 hours post-dose on Day 1 in Part A. 0 to 24 hours post-dose on Days 1, 2, 4 and 11 in Part B (varied intervals per cohort). 0 to 6 hours post-dose on Days 1, 4, 7 and 10 in Part C. Steady state measure on Day 11 in Part B or Day 10 in Part C</time_frame>
        <population>Pharmacokinetic analysis set. Please note, PK parameters have not been calculated where data is available in &lt;3 subjects as this is considered to lack robustness.</population>
        <group_list>
          <group group_id="O1">
            <title>Part A: Placebo</title>
            <description>Placebo</description>
          </group>
          <group group_id="O2">
            <title>Part A: Drug</title>
            <description>Aztreonam (ATM) 2000mg, Avibactam (AVI) 600mg, ATM 2000mg +AVI 600mg (crossover)</description>
          </group>
          <group group_id="O3">
            <title>Part B: Placebo</title>
            <description>Placebo</description>
          </group>
          <group group_id="O4">
            <title>Part B: Cohort 1 Drug</title>
            <description>ATM (2000mg) + AVI (375mg)</description>
          </group>
          <group group_id="O5">
            <title>Part B: Cohort 2 Drug</title>
            <description>ATM (2000mg) + AVI (600mg)</description>
          </group>
          <group group_id="O6">
            <title>Part B: Cohort 3 Drug</title>
            <description>ATM (1500mg) + AVI (600mg)</description>
          </group>
          <group group_id="O7">
            <title>Part B: Cohort 4 Drug</title>
            <description>ATM (1500mg) + AVI (450mg)</description>
          </group>
          <group group_id="O8">
            <title>Part B: Cohort 5 Drug</title>
            <description>ATM (1500mg) + AVI (410mg)</description>
          </group>
          <group group_id="O9">
            <title>Part C: Placebo</title>
            <description>Placebo</description>
          </group>
          <group group_id="O10">
            <title>Part C: Cohort 1 Drug</title>
            <description>Aged 18-45: ATM (500mg followed by 1500mg) + AVI (136.7mg followed by 410mg)</description>
          </group>
          <group group_id="O11">
            <title>Part C: Cohort 2 Drug</title>
            <description>Aged &gt;65: ATM (500mg followed by 1500mg) + AVI (136.7mg + 410mg)</description>
          </group>
        </group_list>
        <measure>
          <title>PK- Plasma Pharmacokinetic Parameter AUC (ug*h/mL) for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) in Parts A, B and C</title>
          <description>Area under the plasma concentration-time curve from zero extrapolated to infinity (AUC µg*h/mL) or AUC(0-last) in Part A on Day 1 after single infusion, area under the plasma concentration-time curve at steady state after multiple infusion (AUCss µg*h/mL).</description>
          <population>Pharmacokinetic analysis set. Please note, PK parameters have not been calculated where data is available in &lt;3 subjects as this is considered to lack robustness.</population>
          <units>ug*h/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="8"/>
                <count group_id="O3" value="16"/>
                <count group_id="O4" value="8"/>
                <count group_id="O5" value="4"/>
                <count group_id="O6" value="8"/>
                <count group_id="O7" value="10"/>
                <count group_id="O8" value="10"/>
                <count group_id="O9" value="6"/>
                <count group_id="O10" value="10"/>
                <count group_id="O11" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>AUC (ug*h/mL) - Aztreonam (ATM) alone</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O2" value="372" spread="15.2"/>
                    <measurement group_id="O3" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O4" value="NA" spread="NA">ATM not administered alone</measurement>
                    <measurement group_id="O5" value="NA" spread="NA">ATM not administered alone</measurement>
                    <measurement group_id="O6" value="NA" spread="NA">ATM not administered alone</measurement>
                    <measurement group_id="O7" value="NA" spread="NA">ATM not administered alone</measurement>
                    <measurement group_id="O8" value="NA" spread="NA">ATM not administered alone</measurement>
                    <measurement group_id="O9" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O10" value="NA" spread="NA">ATM not administered alone</measurement>
                    <measurement group_id="O11" value="NA" spread="NA">ATM not administered alone</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AUC (ug*h/mL) - Avibactam (AVI)alone</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O2" value="52.6" spread="22.5"/>
                    <measurement group_id="O3" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O4" value="NA" spread="NA">AVI not administered alone</measurement>
                    <measurement group_id="O5" value="NA" spread="NA">AVI not administered alone</measurement>
                    <measurement group_id="O6" value="NA" spread="NA">AVI not administered alone</measurement>
                    <measurement group_id="O7" value="NA" spread="NA">AVI not administered alone</measurement>
                    <measurement group_id="O8" value="NA" spread="NA">AVI not administered alone</measurement>
                    <measurement group_id="O9" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O10" value="NA" spread="NA">AVI not administered alone</measurement>
                    <measurement group_id="O11" value="NA" spread="NA">AVI not administered alone</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AUC (ug*h/mL) - ATM in combination (Day 1)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O2" value="375" spread="12.8"/>
                    <measurement group_id="O3" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O4" value="345" spread="16.3"/>
                    <measurement group_id="O5" value="326" spread="5.5"/>
                    <measurement group_id="O6" value="283" spread="17.7"/>
                    <measurement group_id="O7" value="270" spread="9.8"/>
                    <measurement group_id="O8" value="250" spread="13.3"/>
                    <measurement group_id="O9" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O10" value="276" spread="13.5"/>
                    <measurement group_id="O11" value="308" spread="12.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AUCss (ug*h/mL) - ATM in combination</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O2" value="NA" spread="NA">No multiple dosing</measurement>
                    <measurement group_id="O3" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O4" value="275" spread="14.0"/>
                    <measurement group_id="O5" value="NA" spread="NA">Not determined as only 2 subjects</measurement>
                    <measurement group_id="O6" value="231" spread="15.9"/>
                    <measurement group_id="O7" value="223" spread="7.9"/>
                    <measurement group_id="O8" value="203" spread="11.1"/>
                    <measurement group_id="O9" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O10" value="211" spread="15.7"/>
                    <measurement group_id="O11" value="259" spread="12.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AUC (ug*h/mL) - AVI in combination (Day 1)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O2" value="58.3" spread="17.7"/>
                    <measurement group_id="O3" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O4" value="31.8" spread="12.5"/>
                    <measurement group_id="O5" value="47.8" spread="12.5"/>
                    <measurement group_id="O6" value="53.1" spread="12.9"/>
                    <measurement group_id="O7" value="35.7" spread="11.8"/>
                    <measurement group_id="O8" value="31.4" spread="14.7"/>
                    <measurement group_id="O9" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O10" value="41.9" spread="17.1"/>
                    <measurement group_id="O11" value="52.3" spread="11.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AUCss (ug*h/mL) - AVI in combination</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O2" value="NA" spread="NA">No multiple dosing in Part A</measurement>
                    <measurement group_id="O3" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O4" value="26.1" spread="13.0"/>
                    <measurement group_id="O5" value="NA" spread="NA">Not determined as only 2 subjects</measurement>
                    <measurement group_id="O6" value="43.3" spread="11.7"/>
                    <measurement group_id="O7" value="29.0" spread="10.2"/>
                    <measurement group_id="O8" value="26.7" spread="12.6"/>
                    <measurement group_id="O9" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O10" value="29.3" spread="19.6"/>
                    <measurement group_id="O11" value="38.8" spread="14.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>PK- Plasma Pharmacokinetic Parameter t1/2(h) for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) in Parts A, B and C</title>
        <description>Terminal half-life (t1/2), on Day 1 after single infusion and at steady state after multiple infusion.</description>
        <time_frame>0 to 24 hours post-dose on Day 1 in Part A. 0 to 24 hours post-dose on Days 1, 2, 4 and 11 in Part B (varied intervals per cohort). 0 to 6 hours post-dose on Days 1, 4, 7 and 10 in Part C. Steady state measure on Day 11 in Part B or Day 10 in Part C</time_frame>
        <population>Pharmacokinetic analysis set. Please note, PK parameters have not been calculated where data is available in &lt;3 subjects as this is considered to lack robustness. Placebo arms are not evaluated. Values shown where analysed (eg. not applicable for ATM alone in combination cohorts)</population>
        <group_list>
          <group group_id="O1">
            <title>Part A: Placebo</title>
            <description>Placebo</description>
          </group>
          <group group_id="O2">
            <title>Part A: Drug</title>
            <description>Aztreonam (ATM) 2000mg, Avibactam (AVI) 600mg, ATM 2000mg +AVI 600mg (crossover)</description>
          </group>
          <group group_id="O3">
            <title>Part B: Placebo</title>
            <description>Placebo</description>
          </group>
          <group group_id="O4">
            <title>Part B: Cohort 1 Drug</title>
            <description>ATM (2000mg) + AVI (375mg)</description>
          </group>
          <group group_id="O5">
            <title>Part B: Cohort 2 Drug</title>
            <description>ATM (2000mg) + AVI (600mg)</description>
          </group>
          <group group_id="O6">
            <title>Part B: Cohort 3 Drug</title>
            <description>ATM (1500mg) + AVI (600mg)</description>
          </group>
          <group group_id="O7">
            <title>Part B: Cohort 4 Drug</title>
            <description>ATM (1500mg) + AVI (450mg)</description>
          </group>
          <group group_id="O8">
            <title>Part B: Cohort 5 Drug</title>
            <description>ATM (1500mg) + AVI (410mg)</description>
          </group>
          <group group_id="O9">
            <title>Part C: Placebo</title>
            <description>Placebo</description>
          </group>
          <group group_id="O10">
            <title>Part C: Cohort 1 Drug</title>
            <description>Aged 18-45: ATM (500mg followed by 1500mg) + AVI (136.7mg followed by 410mg)</description>
          </group>
          <group group_id="O11">
            <title>Part C: Cohort 2 Drug</title>
            <description>Aged &gt;65: ATM (500mg followed by 1500mg) + AVI (136.7mg + 410mg)</description>
          </group>
        </group_list>
        <measure>
          <title>PK- Plasma Pharmacokinetic Parameter t1/2(h) for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) in Parts A, B and C</title>
          <description>Terminal half-life (t1/2), on Day 1 after single infusion and at steady state after multiple infusion.</description>
          <population>Pharmacokinetic analysis set. Please note, PK parameters have not been calculated where data is available in &lt;3 subjects as this is considered to lack robustness. Placebo arms are not evaluated. Values shown where analysed (eg. not applicable for ATM alone in combination cohorts)</population>
          <units>h</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="8"/>
                <count group_id="O3" value="16"/>
                <count group_id="O4" value="8"/>
                <count group_id="O5" value="4"/>
                <count group_id="O6" value="8"/>
                <count group_id="O7" value="10"/>
                <count group_id="O8" value="10"/>
                <count group_id="O9" value="6"/>
                <count group_id="O10" value="10"/>
                <count group_id="O11" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>t1/2 (h) - Aztreonam (ATM) alone</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O2" value="1.98" spread="18.9"/>
                    <measurement group_id="O3" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O4" value="NA" spread="NA">ATM not dosed alone</measurement>
                    <measurement group_id="O5" value="NA" spread="NA">ATM not dosed alone</measurement>
                    <measurement group_id="O6" value="NA" spread="NA">ATM not dosed alone</measurement>
                    <measurement group_id="O7" value="NA" spread="NA">ATM not dosed alone</measurement>
                    <measurement group_id="O8" value="NA" spread="NA">ATM not dosed alone</measurement>
                    <measurement group_id="O9" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O10" value="NA" spread="NA">ATM not dosed alone</measurement>
                    <measurement group_id="O11" value="NA" spread="NA">ATM not dosed alone</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>t1/2 (h) - Avibactam (AVI)alone</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O2" value="2.22" spread="26.3"/>
                    <measurement group_id="O3" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O4" value="NA" spread="NA">AVI not dosed alone</measurement>
                    <measurement group_id="O5" value="NA" spread="NA">AVI not dosed alone</measurement>
                    <measurement group_id="O6" value="NA" spread="NA">AVI not dosed alone</measurement>
                    <measurement group_id="O7" value="NA" spread="NA">AVI not dosed alone</measurement>
                    <measurement group_id="O8" value="NA" spread="NA">AVI not dosed alone</measurement>
                    <measurement group_id="O9" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O10" value="NA" spread="NA">AVI not dosed alone</measurement>
                    <measurement group_id="O11" value="NA" spread="NA">AVI not dosed alone</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>t1/2 (h) - ATM in combination</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O2" value="2.09" spread="14.0"/>
                    <measurement group_id="O3" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O4" value="2.24" spread="16.6"/>
                    <measurement group_id="O5" value="1.98" spread="3.3"/>
                    <measurement group_id="O6" value="1.90" spread="16.2"/>
                    <measurement group_id="O7" value="2.14" spread="21.2"/>
                    <measurement group_id="O8" value="2.28" spread="25.9"/>
                    <measurement group_id="O9" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O10" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O11" value="NA" spread="NA">Not evaluated</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>t1/2 (h) - AVI in combination</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O2" value="2.35" spread="25.4"/>
                    <measurement group_id="O3" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O4" value="2.17" spread="30.9"/>
                    <measurement group_id="O5" value="2.82" spread="41.1"/>
                    <measurement group_id="O6" value="2.61" spread="10.1"/>
                    <measurement group_id="O7" value="2.26" spread="30.1"/>
                    <measurement group_id="O8" value="1.85" spread="27.4"/>
                    <measurement group_id="O9" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O10" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O11" value="NA" spread="NA">Not evaluated</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>PK- Plasma Pharmacokinetic Parameter Tmax for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) on Day 1 in Parts A, B and C</title>
        <description>Time to Cmax (tmax)</description>
        <time_frame>Day 1</time_frame>
        <population>Pharmacokinetic analysis set. Please note, PK parameters have not been calculated where data is available in &lt;3 subjects as this is considered to lack robustness. Placebo arms are not evaluated. Values shown where analysed (eg. not applicable for ATM alone in combination cohorts)</population>
        <group_list>
          <group group_id="O1">
            <title>Part A: Placebo</title>
            <description>Placebo</description>
          </group>
          <group group_id="O2">
            <title>Part A: Drug</title>
            <description>Aztreonam (ATM) 2000mg, Avibactam (AVI) 600mg, ATM 2000mg +AVI 600mg (crossover)</description>
          </group>
          <group group_id="O3">
            <title>Part B: Placebo</title>
            <description>Placebo</description>
          </group>
          <group group_id="O4">
            <title>Part B: Cohort 1 Drug</title>
            <description>ATM (2000mg) + AVI (375mg)</description>
          </group>
          <group group_id="O5">
            <title>Part B: Cohort 2 Drug</title>
            <description>ATM (2000mg) + AVI (600mg)</description>
          </group>
          <group group_id="O6">
            <title>Part B: Cohort 3 Drug</title>
            <description>ATM (1500mg) + AVI (600mg)</description>
          </group>
          <group group_id="O7">
            <title>Part B: Cohort 4 Drug</title>
            <description>ATM (1500mg) + AVI (450mg)</description>
          </group>
          <group group_id="O8">
            <title>Part B: Cohort 5 Drug</title>
            <description>ATM (1500mg) + AVI (410mg)</description>
          </group>
          <group group_id="O9">
            <title>Part C: Placebo</title>
            <description>Placebo</description>
          </group>
          <group group_id="O10">
            <title>Part C: Cohort 1 Drug</title>
            <description>Aged 18-45: ATM (500mg followed by 1500mg) + AVI (136.7mg followed by 410mg)</description>
          </group>
          <group group_id="O11">
            <title>Part C: Cohort 2 Drug</title>
            <description>Aged &gt;65: ATM (500mg followed by 1500mg) + AVI (136.7mg + 410mg)</description>
          </group>
        </group_list>
        <measure>
          <title>PK- Plasma Pharmacokinetic Parameter Tmax for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) on Day 1 in Parts A, B and C</title>
          <description>Time to Cmax (tmax)</description>
          <population>Pharmacokinetic analysis set. Please note, PK parameters have not been calculated where data is available in &lt;3 subjects as this is considered to lack robustness. Placebo arms are not evaluated. Values shown where analysed (eg. not applicable for ATM alone in combination cohorts)</population>
          <units>(h)</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="8"/>
                <count group_id="O3" value="16"/>
                <count group_id="O4" value="8"/>
                <count group_id="O5" value="4"/>
                <count group_id="O6" value="8"/>
                <count group_id="O7" value="10"/>
                <count group_id="O8" value="10"/>
                <count group_id="O9" value="6"/>
                <count group_id="O10" value="10"/>
                <count group_id="O11" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>tmax (h) - ATM alone</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" lower_limit="NA" upper_limit="NA">Not evaluated</measurement>
                    <measurement group_id="O2" value="0.98" lower_limit="0.98" upper_limit="0.98"/>
                    <measurement group_id="O3" value="NA" lower_limit="NA" upper_limit="NA">Not evaluated</measurement>
                    <measurement group_id="O4" value="NA" lower_limit="NA" upper_limit="NA">ATM not dosed alone</measurement>
                    <measurement group_id="O5" value="NA" lower_limit="NA" upper_limit="NA">ATM not dosed alone</measurement>
                    <measurement group_id="O6" value="NA" lower_limit="NA" upper_limit="NA">ATM not dosed alone</measurement>
                    <measurement group_id="O7" value="NA" lower_limit="NA" upper_limit="NA">ATM not dosed alone</measurement>
                    <measurement group_id="O8" value="NA" lower_limit="NA" upper_limit="NA">ATM not dosed alone</measurement>
                    <measurement group_id="O9" value="NA" lower_limit="NA" upper_limit="NA">Not evaluated</measurement>
                    <measurement group_id="O10" value="NA" lower_limit="NA" upper_limit="NA">ATM not dosed alone</measurement>
                    <measurement group_id="O11" value="NA" lower_limit="NA" upper_limit="NA">ATM not dosed alone</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>tmax (h) - AVI alone</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" lower_limit="NA" upper_limit="NA">Not evaluated</measurement>
                    <measurement group_id="O2" value="0.98" lower_limit="0.98" upper_limit="1.12"/>
                    <measurement group_id="O3" value="NA" lower_limit="NA" upper_limit="NA">Not evaluated</measurement>
                    <measurement group_id="O4" value="NA" lower_limit="NA" upper_limit="NA">AVI not dosed alone</measurement>
                    <measurement group_id="O5" value="NA" lower_limit="NA" upper_limit="NA">AVI not dosed alone</measurement>
                    <measurement group_id="O6" value="NA" lower_limit="NA" upper_limit="NA">AVI not dosed alone</measurement>
                    <measurement group_id="O7" value="NA" lower_limit="NA" upper_limit="NA">AVI not dosed alone</measurement>
                    <measurement group_id="O8" value="NA" lower_limit="NA" upper_limit="NA">AVI not dosed alone</measurement>
                    <measurement group_id="O9" value="NA" lower_limit="NA" upper_limit="NA">Not evaluated</measurement>
                    <measurement group_id="O10" value="NA" lower_limit="NA" upper_limit="NA">AVI not dosed alone</measurement>
                    <measurement group_id="O11" value="NA" lower_limit="NA" upper_limit="NA">AVI not dosed alone</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>tmax (h) - ATM in combination (Day 1)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" lower_limit="NA" upper_limit="NA">Not evaluated</measurement>
                    <measurement group_id="O2" value="0.98" lower_limit="0.98" upper_limit="0.98"/>
                    <measurement group_id="O3" value="NA" lower_limit="NA" upper_limit="NA">Not evaluated</measurement>
                    <measurement group_id="O4" value="0.98" lower_limit="0.98" upper_limit="1.25"/>
                    <measurement group_id="O5" value="0.98" lower_limit="0.98" upper_limit="1.00"/>
                    <measurement group_id="O6" value="1.98" lower_limit="1.50" upper_limit="1.98"/>
                    <measurement group_id="O7" value="2.98" lower_limit="2.00" upper_limit="3.00"/>
                    <measurement group_id="O8" value="2.98" lower_limit="2.50" upper_limit="3.03"/>
                    <measurement group_id="O9" value="NA" lower_limit="NA" upper_limit="NA">Not evaluated</measurement>
                    <measurement group_id="O10" value="2.98" lower_limit="2.98" upper_limit="3.00"/>
                    <measurement group_id="O11" value="2.98" lower_limit="2.68" upper_limit="3.03"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>tmax (h) - AVI in combination (Day 1)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" lower_limit="NA" upper_limit="NA">Not evaluated</measurement>
                    <measurement group_id="O2" value="0.98" lower_limit="0.98" upper_limit="0.98"/>
                    <measurement group_id="O3" value="NA" lower_limit="NA" upper_limit="NA">Not evaluated</measurement>
                    <measurement group_id="O4" value="0.98" lower_limit="0.98" upper_limit="0.98"/>
                    <measurement group_id="O5" value="0.98" lower_limit="0.98" upper_limit="1.00"/>
                    <measurement group_id="O6" value="1.98" lower_limit="1.50" upper_limit="1.98"/>
                    <measurement group_id="O7" value="2.98" lower_limit="2.00" upper_limit="3.00"/>
                    <measurement group_id="O8" value="2.50" lower_limit="2.50" upper_limit="3.05"/>
                    <measurement group_id="O9" value="NA" lower_limit="NA" upper_limit="NA">Not evaluated</measurement>
                    <measurement group_id="O10" value="2.98" lower_limit="2.00" upper_limit="3.00"/>
                    <measurement group_id="O11" value="2.98" lower_limit="2.50" upper_limit="3.03"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>PK- Plasma Pharmacokinetic Parameter Cmax for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) in Parts A, B and C</title>
        <description>Maximum plasma concentration (Cmax µg/mL) on Day 1 after single infusion , maximum plasma concentration at steady state (Css,max µg/mL) after multiple infusion.</description>
        <time_frame>0 to 24 hours post-dose on Day 1 in Part A. 0 to 24 hours post-dose on Days 1, 2, 4 and 11 in Part B (varied intervals per cohort). 0 to 6 hours post-dose on Days 1, 4, 7 and 10 in Part C. Steady state measure on Day 11 in Part B or Day 10 in Part C</time_frame>
        <population>Pharmacokinetic analysis set. Please note, PK parameters have not been calculated where data is available in &lt;3 subjects as this is considered to lack robustness. Placebo arms are not evaluated. Values shown where analysed (eg. not applicable for ATM alone in combination cohorts)</population>
        <group_list>
          <group group_id="O1">
            <title>Part A: Placebo</title>
            <description>Placebo</description>
          </group>
          <group group_id="O2">
            <title>Part A: Drug</title>
            <description>Aztreonam (ATM) 2000mg, Avibactam (AVI) 600mg, ATM 2000mg +AVI 600mg (crossover)</description>
          </group>
          <group group_id="O3">
            <title>Part B: Placebo</title>
            <description>Placebo</description>
          </group>
          <group group_id="O4">
            <title>Part B: Cohort 1 Drug</title>
            <description>ATM (2000mg) + AVI (375mg)</description>
          </group>
          <group group_id="O5">
            <title>Part B: Cohort 2 Drug</title>
            <description>ATM (2000mg) + AVI (600mg)</description>
          </group>
          <group group_id="O6">
            <title>Part B: Cohort 3 Drug</title>
            <description>ATM (1500mg) + AVI (600mg)</description>
          </group>
          <group group_id="O7">
            <title>Part B: Cohort 4 Drug</title>
            <description>ATM (1500mg) + AVI (450mg)</description>
          </group>
          <group group_id="O8">
            <title>Part B: Cohort 5 Drug</title>
            <description>ATM (1500mg) + AVI (410mg)</description>
          </group>
          <group group_id="O9">
            <title>Part C: Placebo</title>
            <description>Placebo</description>
          </group>
          <group group_id="O10">
            <title>Part C: Cohort 1 Drug</title>
            <description>Aged 18-45: ATM (500mg followed by 1500mg) + AVI (136.7mg followed by 410mg)</description>
          </group>
          <group group_id="O11">
            <title>Part C: Cohort 2 Drug</title>
            <description>Aged &gt;65: ATM (500mg followed by 1500mg) + AVI (136.7mg + 410mg)</description>
          </group>
        </group_list>
        <measure>
          <title>PK- Plasma Pharmacokinetic Parameter Cmax for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) in Parts A, B and C</title>
          <description>Maximum plasma concentration (Cmax µg/mL) on Day 1 after single infusion , maximum plasma concentration at steady state (Css,max µg/mL) after multiple infusion.</description>
          <population>Pharmacokinetic analysis set. Please note, PK parameters have not been calculated where data is available in &lt;3 subjects as this is considered to lack robustness. Placebo arms are not evaluated. Values shown where analysed (eg. not applicable for ATM alone in combination cohorts)</population>
          <units>ug/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="8"/>
                <count group_id="O3" value="16"/>
                <count group_id="O4" value="8"/>
                <count group_id="O5" value="4"/>
                <count group_id="O6" value="8"/>
                <count group_id="O7" value="10"/>
                <count group_id="O8" value="10"/>
                <count group_id="O9" value="6"/>
                <count group_id="O10" value="10"/>
                <count group_id="O11" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cmax (ug/mL) - ATM alone</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O2" value="143" spread="14.0"/>
                    <measurement group_id="O3" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O4" value="NA" spread="NA">ATM not administered alone</measurement>
                    <measurement group_id="O5" value="NA" spread="NA">ATM not administered alone</measurement>
                    <measurement group_id="O6" value="NA" spread="NA">ATM not administered alone</measurement>
                    <measurement group_id="O7" value="NA" spread="NA">ATM not administered alone</measurement>
                    <measurement group_id="O8" value="NA" spread="NA">ATM not administered alone</measurement>
                    <measurement group_id="O9" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O10" value="NA" spread="NA">ATM not administered alone</measurement>
                    <measurement group_id="O11" value="NA" spread="NA">ATM not administered alone</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cmax (ug/mL) - AVI alone</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O2" value="26.8" spread="14.2"/>
                    <measurement group_id="O3" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O4" value="NA" spread="NA">AVI not administered alone</measurement>
                    <measurement group_id="O5" value="NA" spread="NA">AVI not administered alone</measurement>
                    <measurement group_id="O6" value="NA" spread="NA">AVI not administered alone</measurement>
                    <measurement group_id="O7" value="NA" spread="NA">AVI not administered alone</measurement>
                    <measurement group_id="O8" value="NA" spread="NA">AVI not administered alone</measurement>
                    <measurement group_id="O9" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O10" value="NA" spread="NA">AVI not administered alone</measurement>
                    <measurement group_id="O11" value="NA" spread="NA">AVI not administered alone</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cmax (ug/mL) - ATM in combination (Day1)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O2" value="137" spread="11.3"/>
                    <measurement group_id="O3" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O4" value="123" spread="16.7"/>
                    <measurement group_id="O5" value="123" spread="6.2"/>
                    <measurement group_id="O6" value="82.4" spread="16.0"/>
                    <measurement group_id="O7" value="63.2" spread="9.4"/>
                    <measurement group_id="O8" value="59.2" spread="13.1"/>
                    <measurement group_id="O9" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O10" value="75.6" spread="13.8"/>
                    <measurement group_id="O11" value="81.6" spread="11.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Css, max (ug/mL) - ATM in combination</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O2" value="NA" spread="NA">No multiple dosing in Part A</measurement>
                    <measurement group_id="O3" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O4" value="124" spread="9.0"/>
                    <measurement group_id="O5" value="NA" spread="NA">Not determined as only 2 subjects</measurement>
                    <measurement group_id="O6" value="80.9" spread="12.9"/>
                    <measurement group_id="O7" value="62.6" spread="9.1"/>
                    <measurement group_id="O8" value="55.7" spread="9.0"/>
                    <measurement group_id="O9" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O10" value="57.2" spread="14.9"/>
                    <measurement group_id="O11" value="66.2" spread="13.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cmax (ug/mL) - AVI in combination (Day1)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O2" value="137" spread="11.3"/>
                    <measurement group_id="O3" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O4" value="16.0" spread="10.1"/>
                    <measurement group_id="O5" value="25.1" spread="5.8"/>
                    <measurement group_id="O6" value="19.3" spread="16.4"/>
                    <measurement group_id="O7" value="9.99" spread="11.2"/>
                    <measurement group_id="O8" value="8.68" spread="14.0"/>
                    <measurement group_id="O9" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O10" value="12.1" spread="18.4"/>
                    <measurement group_id="O11" value="15.2" spread="13.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Css, max (ug/mL) - AVI in combination</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O2" value="NA" spread="NA">No multiple dosing in Part A</measurement>
                    <measurement group_id="O3" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O4" value="14.5" spread="15.9"/>
                    <measurement group_id="O5" value="NA" spread="NA">Not determined as only 2 subjects</measurement>
                    <measurement group_id="O6" value="17.6" spread="12.2"/>
                    <measurement group_id="O7" value="8.69" spread="9.9"/>
                    <measurement group_id="O8" value="8.36" spread="16.5"/>
                    <measurement group_id="O9" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O10" value="8.88" spread="19.9"/>
                    <measurement group_id="O11" value="11.6" spread="15.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>PK- Plasma Pharmacokinetic Parameters CL and CLr for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) in Parts A, B and C</title>
        <description>Systemic clearence (CL) and renal clearance (CLr) on Day 1 after single infusion and at steady state after multiple infusion.</description>
        <time_frame>0 to 24 hours post-dose on Day 1 in Part A. 0 to 24 hours post-dose on Days 1, 2, 4 and 11 in Part B (varied intervals per cohort). 0 to 6 hours post-dose on Days 1, 4, 7 and 10 in Part C. Steady state measure on Day 11 in Part B or Day 10 in Part C</time_frame>
        <population>Pharmacokinetic analysis set. Please note, PK parameters have not been calculated where data is available in &lt;3 subjects as this is considered to lack robustness. Placebo arms are not evaluated. Values shown where analysed (eg. not applicable for ATM alone in combination cohorts)</population>
        <group_list>
          <group group_id="O1">
            <title>Part A: Placebo</title>
            <description>Placebo</description>
          </group>
          <group group_id="O2">
            <title>Part A: Drug</title>
            <description>Aztreonam (ATM) 2000mg, Avibactam (AVI) 600mg, ATM 2000mg +AVI 600mg (crossover)</description>
          </group>
          <group group_id="O3">
            <title>Part B: Placebo</title>
            <description>Placebo</description>
          </group>
          <group group_id="O4">
            <title>Part B: Cohort 1 Drug</title>
            <description>ATM (2000mg) + AVI (375mg)</description>
          </group>
          <group group_id="O5">
            <title>Part B: Cohort 2 Drug</title>
            <description>ATM (2000mg) + AVI (600mg)</description>
          </group>
          <group group_id="O6">
            <title>Part B: Cohort 3 Drug</title>
            <description>ATM (1500mg) + AVI (600mg)</description>
          </group>
          <group group_id="O7">
            <title>Part B: Cohort 4 Drug</title>
            <description>ATM (1500mg) + AVI (450mg)</description>
          </group>
          <group group_id="O8">
            <title>Part B: Cohort 5 Drug</title>
            <description>ATM (1500mg) + AVI (410mg)</description>
          </group>
          <group group_id="O9">
            <title>Part C: Placebo</title>
            <description>Placebo</description>
          </group>
          <group group_id="O10">
            <title>Part C: Cohort 1 Drug</title>
            <description>Aged 18-45: ATM (500mg followed by 1500mg) + AVI (136.7mg followed by 410mg)</description>
          </group>
          <group group_id="O11">
            <title>Part C: Cohort 2 Drug</title>
            <description>Aged &gt;65: ATM (500mg followed by 1500mg) + AVI (136.7mg + 410mg)</description>
          </group>
        </group_list>
        <measure>
          <title>PK- Plasma Pharmacokinetic Parameters CL and CLr for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) in Parts A, B and C</title>
          <description>Systemic clearence (CL) and renal clearance (CLr) on Day 1 after single infusion and at steady state after multiple infusion.</description>
          <population>Pharmacokinetic analysis set. Please note, PK parameters have not been calculated where data is available in &lt;3 subjects as this is considered to lack robustness. Placebo arms are not evaluated. Values shown where analysed (eg. not applicable for ATM alone in combination cohorts)</population>
          <units>L/h</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="8"/>
                <count group_id="O3" value="16"/>
                <count group_id="O4" value="8"/>
                <count group_id="O5" value="4"/>
                <count group_id="O6" value="8"/>
                <count group_id="O7" value="10"/>
                <count group_id="O8" value="10"/>
                <count group_id="O9" value="6"/>
                <count group_id="O10" value="10"/>
                <count group_id="O11" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>CL (L/h) - ATM alone</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O2" value="5.37" spread="15.2"/>
                    <measurement group_id="O3" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O4" value="NA" spread="NA">ATM not dosed alone</measurement>
                    <measurement group_id="O5" value="NA" spread="NA">ATM not dosed alone</measurement>
                    <measurement group_id="O6" value="NA" spread="NA">ATM not dosed alone</measurement>
                    <measurement group_id="O7" value="NA" spread="NA">ATM not dosed alone</measurement>
                    <measurement group_id="O8" value="NA" spread="NA">ATM not dosed alone</measurement>
                    <measurement group_id="O9" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O10" value="NA" spread="NA">ATM not dosed alone</measurement>
                    <measurement group_id="O11" value="NA" spread="NA">ATM not dosed alone</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>CL(L/h) - AVI alone</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O2" value="11.4" spread="22.4"/>
                    <measurement group_id="O3" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O4" value="NA" spread="NA">AVI not dosed alone</measurement>
                    <measurement group_id="O5" value="NA" spread="NA">AVI not dosed alone</measurement>
                    <measurement group_id="O6" value="NA" spread="NA">AVI not dosed alone</measurement>
                    <measurement group_id="O7" value="NA" spread="NA">AVI not dosed alone</measurement>
                    <measurement group_id="O8" value="NA" spread="NA">AVI not dosed alone</measurement>
                    <measurement group_id="O9" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O10" value="NA" spread="NA">AVI not dosed alone</measurement>
                    <measurement group_id="O11" value="NA" spread="NA">AVI not dosed alone</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>CLr (L/h) - ATM alone</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O2" value="3.93" spread="19.0"/>
                    <measurement group_id="O3" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O4" value="NA" spread="NA">ATM not dosed alone</measurement>
                    <measurement group_id="O5" value="NA" spread="NA">ATM not dosed alone</measurement>
                    <measurement group_id="O6" value="NA" spread="NA">ATM not dosed alone</measurement>
                    <measurement group_id="O7" value="NA" spread="NA">ATM not dosed alone</measurement>
                    <measurement group_id="O8" value="NA" spread="NA">ATM not dosed alone</measurement>
                    <measurement group_id="O9" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O10" value="NA" spread="NA">ATM not dosed alone</measurement>
                    <measurement group_id="O11" value="NA" spread="NA">ATM not dosed alone</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>CLr (L/h) - AVI alone</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O2" value="9.77" spread="21.6"/>
                    <measurement group_id="O3" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O4" value="NA" spread="NA">AVI not dosed alone</measurement>
                    <measurement group_id="O5" value="NA" spread="NA">AVI not dosed alone</measurement>
                    <measurement group_id="O6" value="NA" spread="NA">AVI not dosed alone</measurement>
                    <measurement group_id="O7" value="NA" spread="NA">AVI not dosed alone</measurement>
                    <measurement group_id="O8" value="NA" spread="NA">AVI not dosed alone</measurement>
                    <measurement group_id="O9" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O10" value="NA" spread="NA">AVI not dosed alone</measurement>
                    <measurement group_id="O11" value="NA" spread="NA">AVI not dosed alone</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>CL(L/h) - ATM in combination (Day 1)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O2" value="5.33" spread="12.9"/>
                    <measurement group_id="O3" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O4" value="5.79" spread="16.3"/>
                    <measurement group_id="O5" value="6.15" spread="5.5"/>
                    <measurement group_id="O6" value="5.29" spread="17.8"/>
                    <measurement group_id="O7" value="5.56" spread="9.9"/>
                    <measurement group_id="O8" value="5.99" spread="13.4"/>
                    <measurement group_id="O9" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O10" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O11" value="NA" spread="NA">Not evaluated</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>CLr (L/h) - ATM in comination (Day 1)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O2" value="3.78" spread="17.6"/>
                    <measurement group_id="O3" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O4" value="4.04" spread="14.4"/>
                    <measurement group_id="O5" value="4.10" spread="7.4"/>
                    <measurement group_id="O6" value="4.18" spread="14.0"/>
                    <measurement group_id="O7" value="4.09" spread="21.5"/>
                    <measurement group_id="O8" value="4.43" spread="11.8"/>
                    <measurement group_id="O9" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O10" value="4.22" spread="17.2"/>
                    <measurement group_id="O11" value="3.41" spread="16.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>CL(L/h) - AVI in combination (Day 1)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O2" value="10.3" spread="17.7"/>
                    <measurement group_id="O3" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O4" value="11.8" spread="12.4"/>
                    <measurement group_id="O5" value="12.5" spread="12.7"/>
                    <measurement group_id="O6" value="11.3" spread="12.8"/>
                    <measurement group_id="O7" value="12.6" spread="11.9"/>
                    <measurement group_id="O8" value="13.1" spread="14.8"/>
                    <measurement group_id="O9" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O10" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O11" value="NA" spread="NA">Not evaluated</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>CLr (L/h) - AVI in comination (Day 1)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O2" value="8.71" spread="17.1"/>
                    <measurement group_id="O3" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O4" value="10.6" spread="19.3"/>
                    <measurement group_id="O5" value="10.9" spread="12.5"/>
                    <measurement group_id="O6" value="11.1" spread="11.7"/>
                    <measurement group_id="O7" value="11.9" spread="24.6"/>
                    <measurement group_id="O8" value="12.5" spread="15.6"/>
                    <measurement group_id="O9" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O10" value="10.8" spread="16.3"/>
                    <measurement group_id="O11" value="7.78" spread="27.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>CL(L/h) - ATM in combination (Steady state)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O2" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O3" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O4" value="7.27" spread="14.0"/>
                    <measurement group_id="O5" value="NA" spread="NA">Not calculated as &lt;3 patients</measurement>
                    <measurement group_id="O6" value="6.49" spread="15.9"/>
                    <measurement group_id="O7" value="6.72" spread="7.9"/>
                    <measurement group_id="O8" value="7.39" spread="11.1"/>
                    <measurement group_id="O9" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O10" value="7.10" spread="15.8"/>
                    <measurement group_id="O11" value="5.79" spread="12.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>CLr (L/h) - ATM in comination (Steady state)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O2" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O3" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O4" value="4.66" spread="18.9"/>
                    <measurement group_id="O5" value="NA" spread="NA">Not calculated as &lt;3 patients</measurement>
                    <measurement group_id="O6" value="4.93" spread="15.2"/>
                    <measurement group_id="O7" value="5.07" spread="27.8"/>
                    <measurement group_id="O8" value="5.25" spread="13.5"/>
                    <measurement group_id="O9" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O10" value="4.97" spread="19.0"/>
                    <measurement group_id="O11" value="3.99" spread="21.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>CL(L/h) - AVI in combination (Steady state)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O2" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O3" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O4" value="14.3" spread="13.1"/>
                    <measurement group_id="O5" value="NA" spread="NA">Not calculated as &lt;3 patients</measurement>
                    <measurement group_id="O6" value="13.8" spread="11.7"/>
                    <measurement group_id="O7" value="15.5" spread="10.4"/>
                    <measurement group_id="O8" value="15.4" spread="12.7"/>
                    <measurement group_id="O9" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O10" value="14.0" spread="19.7"/>
                    <measurement group_id="O11" value="10.6" spread="14.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>CLr (L/h) - AVI in comination (Steady state)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O2" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O3" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O4" value="12.4" spread="24.8"/>
                    <measurement group_id="O5" value="NA" spread="NA">Not calculated as &lt;3 patients</measurement>
                    <measurement group_id="O6" value="13.9" spread="11.5"/>
                    <measurement group_id="O7" value="14.7" spread="24.6"/>
                    <measurement group_id="O8" value="14.5" spread="14.6"/>
                    <measurement group_id="O9" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O10" value="13.0" spread="22.0"/>
                    <measurement group_id="O11" value="9.49" spread="18.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>PK- Plasma Pharmacokinetic Parameter Vss for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) in Parts A, B and C</title>
        <description>Volume of distribution at steady state (Vss).</description>
        <time_frame>0 to 24 hours post-dose on Day 1 in Part A. 0 to 24 hours post-dose on Days 1, 2, 4 and 11 in Part B (varied intervals per cohort). 0 to 6 hours post-dose on Days 1, 4, 7 and 10 in Part C. Steady state measure on Day 11 in Part B or Day 10 in Part C</time_frame>
        <population>Pharmacokinetic analysis set. Please note, PK parameters have not been calculated where data is available in &lt;3 subjects as this is considered to lack robustness. Placebo arms are not evaluated. Values shown where analysed (eg. not applicable for ATM alone in combination cohorts)</population>
        <group_list>
          <group group_id="O1">
            <title>Part A: Placebo</title>
            <description>Placebo</description>
          </group>
          <group group_id="O2">
            <title>Part A: Drug</title>
            <description>Aztreonam (ATM) 2000mg, Avibactam (AVI) 600mg, ATM 2000mg +AVI 600mg (crossover)</description>
          </group>
          <group group_id="O3">
            <title>Part B: Placebo</title>
            <description>Placebo</description>
          </group>
          <group group_id="O4">
            <title>Part B: Cohort 1 Drug</title>
            <description>ATM (2000mg) + AVI (375mg)</description>
          </group>
          <group group_id="O5">
            <title>Part B: Cohort 2 Drug</title>
            <description>ATM (2000mg) + AVI (600mg)</description>
          </group>
          <group group_id="O6">
            <title>Part B: Cohort 3 Drug</title>
            <description>ATM (1500mg) + AVI (600mg)</description>
          </group>
          <group group_id="O7">
            <title>Part B: Cohort 4 Drug</title>
            <description>ATM (1500mg) + AVI (450mg)</description>
          </group>
          <group group_id="O8">
            <title>Part B: Cohort 5 Drug</title>
            <description>ATM (1500mg) + AVI (410mg)</description>
          </group>
          <group group_id="O9">
            <title>Part C: Placebo</title>
            <description>Placebo</description>
          </group>
          <group group_id="O10">
            <title>Part C: Cohort 1 Drug</title>
            <description>Aged 18-45: ATM (500mg followed by 1500mg) + AVI (136.7mg followed by 410mg)</description>
          </group>
          <group group_id="O11">
            <title>Part C: Cohort 2 Drug</title>
            <description>Aged &gt;65: ATM (500mg followed by 1500mg) + AVI (136.7mg + 410mg)</description>
          </group>
        </group_list>
        <measure>
          <title>PK- Plasma Pharmacokinetic Parameter Vss for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) in Parts A, B and C</title>
          <description>Volume of distribution at steady state (Vss).</description>
          <population>Pharmacokinetic analysis set. Please note, PK parameters have not been calculated where data is available in &lt;3 subjects as this is considered to lack robustness. Placebo arms are not evaluated. Values shown where analysed (eg. not applicable for ATM alone in combination cohorts)</population>
          <units>L</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="8"/>
                <count group_id="O3" value="16"/>
                <count group_id="O4" value="8"/>
                <count group_id="O5" value="4"/>
                <count group_id="O6" value="8"/>
                <count group_id="O7" value="10"/>
                <count group_id="O8" value="10"/>
                <count group_id="O9" value="6"/>
                <count group_id="O10" value="10"/>
                <count group_id="O11" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Vss (L) - ATM alone</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O2" value="13.4" spread="16.3"/>
                    <measurement group_id="O3" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O4" value="NA" spread="NA">ATM not dosed alone</measurement>
                    <measurement group_id="O5" value="NA" spread="NA">ATM not dosed alone</measurement>
                    <measurement group_id="O6" value="NA" spread="NA">ATM not dosed alone</measurement>
                    <measurement group_id="O7" value="NA" spread="NA">ATM not dosed alone</measurement>
                    <measurement group_id="O8" value="NA" spread="NA">ATM not dosed alone</measurement>
                    <measurement group_id="O9" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O10" value="NA" spread="NA">ATM not dosed alone</measurement>
                    <measurement group_id="O11" value="NA" spread="NA">ATM not dosed alone</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Vss (L) - AVI alone</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O2" value="20.1" spread="10.0"/>
                    <measurement group_id="O3" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O4" value="NA" spread="NA">AVI not dosed alone</measurement>
                    <measurement group_id="O5" value="NA" spread="NA">AVI not dosed alone</measurement>
                    <measurement group_id="O6" value="NA" spread="NA">AVI not dosed alone</measurement>
                    <measurement group_id="O7" value="NA" spread="NA">AVI not dosed alone</measurement>
                    <measurement group_id="O8" value="NA" spread="NA">AVI not dosed alone</measurement>
                    <measurement group_id="O9" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O10" value="NA" spread="NA">AVI not dosed alone</measurement>
                    <measurement group_id="O11" value="NA" spread="NA">AVI not dosed alone</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Vss (L) - ATM in comination</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O2" value="13.8" spread="10.4"/>
                    <measurement group_id="O3" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O4" value="15.4" spread="13.3"/>
                    <measurement group_id="O5" value="15.1" spread="5.2"/>
                    <measurement group_id="O6" value="12.5" spread="14.9"/>
                    <measurement group_id="O7" value="13.7" spread="11.9"/>
                    <measurement group_id="O8" value="15.6" spread="18.9"/>
                    <measurement group_id="O9" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O10" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O11" value="NA" spread="NA">Not evaluated</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Vss (L) - AVI in comination</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O2" value="19.0" spread="15.3"/>
                    <measurement group_id="O3" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O4" value="22.8" spread="15.6"/>
                    <measurement group_id="O5" value="22.2" spread="10.6"/>
                    <measurement group_id="O6" value="20.0" spread="18.9"/>
                    <measurement group_id="O7" value="23.5" spread="15.5"/>
                    <measurement group_id="O8" value="25.2" spread="26.0"/>
                    <measurement group_id="O9" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O10" value="NA" spread="NA">Not evaluated</measurement>
                    <measurement group_id="O11" value="NA" spread="NA">Not evaluated</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>from screening visit (Day -28) to follow up visit (FUP).</time_frame>
      <desc>FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.</desc>
      <group_list>
        <group group_id="E1">
          <title>Part A: Placebo</title>
          <description>Placebo</description>
        </group>
        <group group_id="E2">
          <title>Part A: Drug</title>
          <description>Aztreonam (ATM) 2000mg, Avibactam (AVI) 600mg, ATM 2000mg +AVI 600mg (crossover)</description>
        </group>
        <group group_id="E3">
          <title>Part B: Placebo</title>
          <description>Placebo</description>
        </group>
        <group group_id="E4">
          <title>Part B: Cohort 1 Drug</title>
          <description>ATM (2000mg) + AVI (375mg)</description>
        </group>
        <group group_id="E5">
          <title>Part B: Cohort 2 Drug</title>
          <description>ATM (2000mg) + AVI (600mg)</description>
        </group>
        <group group_id="E6">
          <title>Part B: Cohort 3 Drug</title>
          <description>ATM (1500mg) + AVI (600mg)</description>
        </group>
        <group group_id="E7">
          <title>Part B: Cohort 4 Drug</title>
          <description>ATM (1500mg) + AVI (450mg)</description>
        </group>
        <group group_id="E8">
          <title>Part B: Cohort 5 Drug</title>
          <description>ATM (1500mg) + AVI (410mg)</description>
        </group>
        <group group_id="E9">
          <title>Part C: Placebo</title>
          <description>Placebo</description>
        </group>
        <group group_id="E10">
          <title>Part C: Cohort 1 Drug</title>
          <description>Aged 18-45: ATM (500mg followed by 1500mg) + AVI (136.7mg followed by 410mg)</description>
        </group>
        <group group_id="E11">
          <title>Part C: Cohort 2 Drug</title>
          <description>Aged &gt;65: ATM (500mg followed by 1500mg) + AVI (136.7mg + 410mg)</description>
        </group>
        <group group_id="E12">
          <title>Part A: Aztreonam (ATM) 2000mg</title>
          <description>Crossover period ATM 2000mg</description>
        </group>
        <group group_id="E13">
          <title>Part A: Avibactam (AVI) 600mg</title>
          <description>Crossover period AVI 600mg</description>
        </group>
        <group group_id="E14">
          <title>Part A: ATM 2000mg + AVI 600mg</title>
          <description>Crossover period ATM 2000mg + AVI 600mg</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA version 15.1</default_vocab>
        <default_assessment>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="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA version 15.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="4"/>
                <counts group_id="E6" subjects_affected="6" subjects_at_risk="8"/>
                <counts group_id="E7" subjects_affected="8" subjects_at_risk="10"/>
                <counts group_id="E8" subjects_affected="3" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="5" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="7" subjects_at_risk="8"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E13" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E7" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="4" subjects_at_risk="8"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Abdominal discomfort</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E8" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Frequent bowel movements</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Oral pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Catheter site pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E8" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Infusion site reaction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E8" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Catheter site erythema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Catheter site haematoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Catheter site oedema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Infusion site pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Seasonal allergy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Candidiasis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Otitis externa</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Rhinitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Liver function test abnormal</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="4"/>
                <counts group_id="E6" subjects_affected="3" subjects_at_risk="8"/>
                <counts group_id="E7" subjects_affected="3" subjects_at_risk="10"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Transaminases increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperamylasaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E13" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E7" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E8" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E8" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E13" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Paraesthesia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Pollakiuria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Skin irritation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E7" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Blister</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Phlebitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Hot flush</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="7"/>
              </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>Confidentiality clauses are in place through a Master Services agreement, which limits the discloser of confidential information to what's expressed in 33.2 and 33.3: disclosure to third party only after written consent, or disclosure of confidential information only to the extent necessary to comply with reporting obligations from AZ, CRO or applicable laws.</restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>No formal statistical hypothesis testing was performed. The analyses of safety, tolerability, and pharmacokinetic data were summarised descriptively including tables, listings, and graphs, as appropriate.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Paul Newell, Medical Science Director</name_or_title>
      <organization>AstraZeneca</organization>
      <phone>+44 1625 515727</phone>
      <email>paul.newell@astrazeneca.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/NCT01689207
org study id: D4910C00001
nct id: NCT01689207
lead sponsor: 
This is a randomised, double-blind, 3-part study designed to investigate the safety and
      tolerability of ATM-AVI. The study aims to characterise the pharmacokinetics of ATM-AVI, when
      both drugs are administered alone (ATM or AVI) and in combination (ATM-AVI), following single
      administration, and following multiple administrations of ATM-AVI in healthy male and female
      (females of nonchildbearing potential) volunteers both young and elderly.
A Phase I, Randomised, Double-blind, 3-Part Study in Healthy Young and Elderly Subjects to
      Assess the Safety and Tolerability, and Investigate the Pharmacokinetics of Aztreonam and
      Avibactam given Alone and in Combination (ATM-AVI)
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: Double (Participant, Investigator)
measure: Safety Profile - Number of Subjects With at Least 1 AE
time frame: Informed consent (up to 28 days before first dose) to follow up period (max of 22 days after first dose for Part A, a max of 28 days after first dose in Part B, max 17 days in Part C)
description: from screening visit (Day -28) to 3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.
measure: PK- Plasma Pharmacokinetic Parameter AUC (ug*h/mL) for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) in Parts A, B and C
time frame: 0 to 24 hours post-dose on Day 1 in Part A. 0 to 24 hours post-dose on Days 1, 2, 4 and 11 in Part B (varied intervals per cohort). 0 to 6 hours post-dose on Days 1, 4, 7 and 10 in Part C. Steady state measure on Day 11 in Part B or Day 10 in Part C
description: Area under the plasma concentration-time curve from zero extrapolated to infinity (AUC µg*h/mL) or AUC(0-last) in Part A on Day 1 after single infusion, area under the plasma concentration-time curve at steady state after multiple infusion (AUCss µg*h/mL).
measure: PK- Plasma Pharmacokinetic Parameter t1/2(h) for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) in Parts A, B and C
time frame: 0 to 24 hours post-dose on Day 1 in Part A. 0 to 24 hours post-dose on Days 1, 2, 4 and 11 in Part B (varied intervals per cohort). 0 to 6 hours post-dose on Days 1, 4, 7 and 10 in Part C. Steady state measure on Day 11 in Part B or Day 10 in Part C
description: Terminal half-life (t1/2), on Day 1 after single infusion and at steady state after multiple infusion.
measure: PK- Plasma Pharmacokinetic Parameter Tmax for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) on Day 1 in Parts A, B and C
time frame: Day 1
description: Time to Cmax (tmax)
measure: PK- Plasma Pharmacokinetic Parameter Cmax for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) in Parts A, B and C
time frame: 0 to 24 hours post-dose on Day 1 in Part A. 0 to 24 hours post-dose on Days 1, 2, 4 and 11 in Part B (varied intervals per cohort). 0 to 6 hours post-dose on Days 1, 4, 7 and 10 in Part C. Steady state measure on Day 11 in Part B or Day 10 in Part C
description: Maximum plasma concentration (Cmax µg/mL) on Day 1 after single infusion , maximum plasma concentration at steady state (Css,max µg/mL) after multiple infusion.
measure: PK- Plasma Pharmacokinetic Parameters CL and CLr for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) in Parts A, B and C
time frame: 0 to 24 hours post-dose on Day 1 in Part A. 0 to 24 hours post-dose on Days 1, 2, 4 and 11 in Part B (varied intervals per cohort). 0 to 6 hours post-dose on Days 1, 4, 7 and 10 in Part C. Steady state measure on Day 11 in Part B or Day 10 in Part C
description: Systemic clearence (CL) and renal clearance (CLr) on Day 1 after single infusion and at steady state after multiple infusion.
measure: PK- Plasma Pharmacokinetic Parameter Vss for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) in Parts A, B and C
time frame: 0 to 24 hours post-dose on Day 1 in Part A. 0 to 24 hours post-dose on Days 1, 2, 4 and 11 in Part B (varied intervals per cohort). 0 to 6 hours post-dose on Days 1, 4, 7 and 10 in Part C. Steady state measure on Day 11 in Part B or Day 10 in Part C
description: Volume of distribution at steady state (Vss).
arm group label: Drug: A
arm group type: Experimental
description: Avibactam (AVI)
arm group label: Drug: B
arm group type: Experimental
description: Aztreonam (ATM)
arm group label: Drug: C
arm group type: Experimental
description: combination of Aztreonam-Avibactam (ATM-AVI)
arm group label: Drug: D
arm group type: Placebo Comparator
description: Matching Placebo
intervention type: Drug
intervention name: Avibactam (AVI)
description: PART A: AVI IV infusion
arm group label: Drug: A
intervention type: Drug
intervention name: Aztreonam (ATM)
description: PART A: ATM IV infusion
arm group label: Drug: B
intervention type: Drug
intervention name: combination of Aztreonam - Avibactam (ATM-AVI)
description: PART A: ATM-AVI IV infusion. PART B and C: ATM-AVI IV infusions.
arm group label: Drug: C
intervention type: Drug
intervention name: Placebo
description: PART A, PART B, PART C: matching placebo IV infusions
arm group label: Drug: D
criteria: 
gender: All
minimum age: 18 Years
maximum age: 130 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Frans van den Berg, MD
role: Principal Investigator
affiliation: Hammersmith Medicines Research Cumberland Avenue Park Royal London NW10 7EW, England Telephone: +44 020 8961 4130 Fax: +44 020 8961 8665
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Infections
mesh term: Communicable Diseases
mesh term: Bacterial Infections
mesh term: Aztreonam
mesh term: Avibactam
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: No formal statistical hypothesis testing was performed. The analyses of safety, tolerability, and pharmacokinetic data were summarised descriptively including tables, listings, and graphs, as appropriate.
point of contact: 