<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/NCT04486625</url>
  </required_header>
  <id_info>
    <org_study_id>C3601006</org_study_id>
    <nct_id>NCT04486625</nct_id>
  </id_info>
  <brief_title>Pharmacokinetic Study of Aztreonam-Avibactam in Severe Renal Impairment</brief_title>
  <official_title>AN OPEN-LABEL, PARALLEL-GROUP, PHARMACOKINETIC STUDY OF MULTIPLE INTRAVENOUS DOSES OF AZTREONAM AND AVIBACTAM IN SUBJECTS WITH SEVERE RENAL IMPAIRMENT AND NORMAL RENAL FUNCTION</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Pfizer</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Pfizer</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This Phase 1 study is being conducted to evaluate the effect of severe renal impairment on&#xD;
      the PK, safety and tolerability of Aztreonam-Avibactam. Results from this study along with&#xD;
      previous renal impairment data from each of the Aztreonam-Avibactam components will be used&#xD;
      to confirm the proposed dosing adjustment in severe renal impairment which was based on&#xD;
      modelling/simulation.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 10, 2020</start_date>
  <completion_date type="Actual">October 18, 2021</completion_date>
  <primary_completion_date type="Actual">September 20, 2021</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Total Daily Area Under the Plasma Concentration-time Profile From Time 0 to 24 Hours at Steady-state (AUC0-24,ss) of Aztreonam (ATM)</measure>
    <time_frame>Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.</time_frame>
    <description>AUC0-24,ss of ATM in Cohort 1 was calculated by 4*AUC0-tau (tau = 6 hours), where AUC0-tau was area under the concentration-time profile from time 0 to time tau (the dosing interval). AUC0-24,ss of ATM in Cohort 2 was calculated by 3*AUC0-tau (tau = 8 hours), where AUC0-tau was area under the plasma concentration-time profile from time 0 to time tau (the dosing interval).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum Plasma Concentration (Cmax) of ATM</measure>
    <time_frame>Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.</time_frame>
    <description>The Cmax of ATM was observed directly from data.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>AUC0-24,ss of Avibactam (AVI)</measure>
    <time_frame>Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.</time_frame>
    <description>AUC0-24,ss of AVI in Cohort 1 was calculated by 4*AUC0-tau (tau = 6 hours), where AUC0-tau was area under the concentration-time profile from time 0 to time tau (the dosing interval). AUC0-24,ss of AVI in Cohort 2 was calculated by 3*AUC0-tau (tau = 8 hours), where AUC0-tau was area under the plasma concentration-time profile from time 0 to time tau (the dosing interval).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cmax of AVI</measure>
    <time_frame>Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.</time_frame>
    <description>The Cmax of AVI was observed directly from data.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Area Under the Plasma Concentration-time Profile From Time 0 to Time Tau (The Dosing Interval)(AUC0-tau) of ATM</measure>
    <time_frame>Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.</time_frame>
    <description>The AUC0-tau was calculated by linear/log trapezoidal method. The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time for Cmax (Tmax) of ATM</measure>
    <time_frame>Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.</time_frame>
    <description>The Tmax was observed directly from data as time of first occurrence.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Observed Plasma Concentration at the End of the Dosing Interval (Tau) (Ctau) of ATM</measure>
    <time_frame>Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.</time_frame>
    <description>The Ctau was observed directly from data. The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal Elimination Half-life (t1/2) of ATM</measure>
    <time_frame>Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.</time_frame>
    <description>The t1/2 was calculated by loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log linear concentration time curve. Only those data points judged to describe the terminal log linear decline were used in the regression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clearance (CL) of ATM</measure>
    <time_frame>Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.</time_frame>
    <description>The CL was calculated by dose/AUC0-tau, where AUC0-tau was area under the concentration-time profile from time 0 to time tau (the dosing interval). The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Renal Clearance (CLr) of ATM</measure>
    <time_frame>In Cohort 1, at predose on Day 3, during 0-2, 2-4, and 4-6 hours after the start of a maintenance dose infusion. In Cohort 2, at predose on Day 3, during 0-2, 2-4, 4-6, and 6-8 hours after the start of a maintenance dose infusion.</time_frame>
    <description>The CLr was calculated by Ae0-tau/AUC0-tau, where Ae0-tau was cumulative amount of drug recovered unchanged in urine up to time tau and AUC0-tau was area under the plasma concentration time profile from time 0 to time tau (the dosing interval). The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent Volume of Distribution (Vz) of ATM</measure>
    <time_frame>Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.</time_frame>
    <description>The Vz was calculated by dose/(AUC0-tau*kel), where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve and AUC0-tau was area under the concentration-time profile from time 0 to time tau (the dosing interval). The dosing interval (tau) was 6 hours for the normal renal function group (Cohort 1) and 8 hours for the severe renal impairment group (Cohort 2).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent Volume of Distribution at Steady-state (Vss) of ATM</measure>
    <time_frame>Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.</time_frame>
    <description>Vss was calculated by CL*MRT, where CL was clearance and MRT was mean residence time.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulative Amount of Drug Recovered Unchanged in Urine up to Time Tau (Ae0-tau) of ATM</measure>
    <time_frame>In Cohort 1, at predose on Day 3, during 0-2, 2-4, and 4-6 hours after the start of a maintenance dose infusion. In Cohort 2, at predose on Day 3, during 0-2, 2-4, 4-6, and 6-8 hours after the start of a maintenance dose infusion.</time_frame>
    <description>The Ae0-tau was the sum of (urine concentration*sample volume). The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent of Dose Recovered Unchanged in Urine up to Time Tau (Ae0-tau%) of ATM</measure>
    <time_frame>In Cohort 1, at predose on Day 3, during 0-2, 2-4, and 4-6 hours after the start of a maintenance dose infusion. In Cohort 2, at predose on Day 3, during 0-2, 2-4, 4-6, and 6-8 hours after the start of a maintenance dose infusion.</time_frame>
    <description>The Ae0-tau was calculated by 100*Ae0-tau/dose, where Ae0-tau was cumulative amount of drug recovered unchanged in urine up to time tau. The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC0-tau of AVI</measure>
    <time_frame>Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.</time_frame>
    <description>The UC0-tau was calculated by linear/log trapezoidal method. The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).A</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tmax of AVI</measure>
    <time_frame>Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.</time_frame>
    <description>The Tmax was observed directly from data as time of first occurrence.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ctau of AVI</measure>
    <time_frame>Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.</time_frame>
    <description>The Ctau was observed directly from data. The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>t1/2 of AVI</measure>
    <time_frame>Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.</time_frame>
    <description>The t1/2 was calculated by loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log linear concentration time curve. Only those data points judged to describe the terminal log linear decline were used in the regression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CL of AVI</measure>
    <time_frame>Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.</time_frame>
    <description>The CL was calculated by dose/AUC0-tau, where AUC0-tau was area under the plasma concentration-time profile from time 0 to to time tau (the dosing interval). The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CLr of AVI</measure>
    <time_frame>In Cohort 1, at predose on Day 3, during 0-2, 2-4, and 4-6 hours after the start of a maintenance dose infusion. In Cohort 2, at predose on Day 3, during 0-2, 2-4, 4-6, and 6-8 hours after the start of a maintenance dose infusion.</time_frame>
    <description>The CLr was calculated by Ae0-tau/AUC0-tau, where Ae0-tau was cumulative amount of drug recovered unchanged in urine up to time tau and AUC0-tau was area under the plasma concentration time profile from time 0 to time tau (the dosing interval). The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vz of AVI</measure>
    <time_frame>Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.</time_frame>
    <description>The Vz was calculated by dose/(AUC0-tau*kel), where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve and AUC0-tau was area under the concentration-time profile from time 0 to time tau (the dosing interval). The dosing interval (tau) was 6 hours for the normal renal function group (Cohort 1) and 8 hours for the severe renal impairment group (Cohort 2).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vss of AVI</measure>
    <time_frame>Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.</time_frame>
    <description>Vss was calculated by CL*MRT, where CL was clearance and MRT was mean residence time.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ae0-tau of AVI</measure>
    <time_frame>In Cohort 1, at predose on Day 3, during 0-2, 2-4, and 4-6 hours after the start of a maintenance dose infusion. In Cohort 2, at predose on Day 3, during 0-2, 2-4, 4-6, and 6-8 hours after the start of a maintenance dose infusion.</time_frame>
    <description>The Ae0-tau was the sum of (urine concentration*sample volume). The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ae0-tau% of AVI</measure>
    <time_frame>In Cohort 1, at predose on Day 3, during 0-2, 2-4, and 4-6 hours after the start of a maintenance dose infusion. In Cohort 2, at predose on Day 3, during 0-2, 2-4, 4-6, and 6-8 hours after the start of a maintenance dose infusion.</time_frame>
    <description>The Ae0-tau was calculated by 100*Ae0-tau/dose, where Ae0-tau was cumulative amount of drug recovered unchanged in urine up to time tau. The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Treatment Emergent Adverse Events (TEAEs) (All-causality)</measure>
    <time_frame>Day 1 up to at least 28 days after last dose of study medication (maximum of 33 days).</time_frame>
    <description>An adverse event (AE) is any untoward medical occurrence in a study participant administered a product; the event need not necessarily have a causal relationship with the treatment or usage. A serious adverse event is any untoward medical occurrence at any dose that: (1) results in death; (2) is life threatening (immediate risk of death); (3) requires inpatient hospitalization or prolongation of existing hospitalization; (4) results in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); (5) results in congenital anomaly/birth defect; or that is considered to be an important medical event. Treatment-emergent are events between first dose of study medication and up to at least 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. A severe AE is defined as a event interferes significantly with participant's usual function.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With TEAEs (Treatment-related)</measure>
    <time_frame>Day 1 up to at least 28 days after last dose of study medication (maximum of 33 days).</time_frame>
    <description>An adverse event (AE) is any untoward medical occurrence in a study participant administered a product; the event attributed to the study medication. A serious AE is any untoward medical occurrence at any dose that: (1) results in death; (2) is life threatening (immediate risk of death); (3) requires inpatient hospitalization or prolongation of existing hospitalization; (4) results in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); (5) results in congenital anomaly/birth defect; or that is considered to be an important medical event. Treatment-emergent are events between first dose of study medication and up to at least 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. A severe AE is defined as a event interferes significantly with participant's usual function.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Categorical Post-Baseline Vital Signs Data</measure>
    <time_frame>Days 1 to 3</time_frame>
    <description>Categorical post-baseline vital signs included: (1) pulse rate: value less than (&lt;) 40 beats per minute (bpm), lager than (&gt;) 120 bpm; (2) supine diastolic blood pressure (DBP): value &lt;50 mmHg, change of more than or equal to (&gt;=) 20 mmHg increase, change of &gt;=20 mmHg decrease; (3) supine systolic blood pressure (SBP): value &lt;90 mmHg, change of &gt;=30 mmHg increase, change of &gt;=30 mmHg decrease.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Abnormal Electrocardiogram (ECG)</measure>
    <time_frame>Days 1 to 3</time_frame>
    <description>Criteria for ECG abnormalities: maximum QT interval &gt;500 milliseconds (msec); maximum QTc interval of &gt;=450 msec to less than or equal to (&lt;=) 480 msec, &gt;480 msec, and &gt;500 msec and a maximum change of &lt;30 change&lt;=60 or &gt;60 msec from baseline; maximum QTcF (Fridericia's Correction) interval of &gt;=450 msec to &lt;=480 msec, &gt;480 msec, and &gt;500 msec and a maximum change of &lt;30 change&lt;=60 or &gt;60 msec from baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)</measure>
    <time_frame>Days 1 to 3</time_frame>
    <description>Following laboratory parameters were abnormal (without regard to baseline abnormality): hemoglobin, hematocrit, erythrocytes, lymphocytes, neutrophils, activated partial thromboplastin time, protein, urea nitrogen, creatinine, urate, urine glucose, and urine protein.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">11</enrollment>
  <condition>Renal Insufficiency</condition>
  <arm_group>
    <arm_group_label>Cohort 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Normal renal function</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Severe renal impairment (not on dialysis)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Aztreonam-Avibactam</intervention_name>
    <description>500/167 mg ATM/AVI loading infusion, followed by 1500/500 mg ATM/AVI extended loading infusion, then 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours</description>
    <arm_group_label>Cohort 1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Aztreonam-Avibactam</intervention_name>
    <description>675/225 mg ATM/AVI loading infusion, followed by 675/225 mg ATM/AVI extended loading infusion, then 675/225 mg ATM/AVI maintenance dose infusion every 8 hours</description>
    <arm_group_label>Cohort 2</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy female subjects and/or male subjects between the ages of 18 and 75 years,&#xD;
             inclusive. Male and female subjects of childbearing potential must agree to use highly&#xD;
             effective method(s) of contraception&#xD;
&#xD;
          -  Body mass index (BMI) of 17.5 to 40.5 kg/m2; and a total body weight &gt;50 kg (110 lb)&#xD;
&#xD;
          -  Stable renal function defined as &lt;/=25% difference between 2 measurements of eGFR&#xD;
             obtained on 2 separate occasions during the screening period that are at least 72&#xD;
             hours but no more than 14 days apart Specific Requirements for Healthy Subjects with&#xD;
             Normal Renal Function&#xD;
&#xD;
          -  Normal renal function (eGFR&gt;/= 80 mL/min) at Screening based on the Day -2 value,&#xD;
             using the MDRD formula adjusting for BSA&#xD;
&#xD;
          -  Demographically comparable to the group of subjects with severe impaired renal&#xD;
             function Specific Requirements for Subjects with Severe Renal Impairment&#xD;
&#xD;
          -  Good general health commensurate with the population with chronic kidney disease.&#xD;
&#xD;
          -  Documented severe renal impairment indicated by eGFR &gt;15 -&lt;/=30 mL/min but not&#xD;
             requiring hemodialysis, using the MDRD formula adjusting for BSA&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Positive urine drug test&#xD;
&#xD;
          -  History of regular alcohol use (within 6 months) exceeding 7 drinks/week for female or&#xD;
             14 drinks/week for male subjects&#xD;
&#xD;
          -  Treatment with an investigational product within 30 days or 5 half-lives preceding the&#xD;
             first dose of investigational product (whichever is longer)&#xD;
&#xD;
          -  Subjects with abnormalities in clinical laboratory tests (AST, ALT, Total bilirubin,&#xD;
             aPTT, PT, INR) at Screening&#xD;
&#xD;
          -  Pregnant females; breastfeeding females; fertile male subjects and female subjects of&#xD;
             childbearing potential who are unwilling or unable to use a highly effective method of&#xD;
             contraception&#xD;
&#xD;
          -  Use of prescription or nonprescription drugs and dietary supplements within 7 days or&#xD;
             5 half-lives (whichever is longer) prior to the first dose of investigational product.&#xD;
             For subjects with severe renal impairment, concomitant medications may be given if&#xD;
             considered necessary for the subject welfare (eg, standard therapy for underlying&#xD;
             diseases), are not contraindicated with the study drug, and are unlikely to interfere&#xD;
             with the PK/PD response of the study drug. Use of oral anticoagulants and potent&#xD;
             inhibitors of OAT1 and/or OAT3 (eg, probenecid) are prohibited in all subjects.&#xD;
&#xD;
          -  Blood donation (excluding plasma donations) of approximately 1 pint or more within 60&#xD;
             days prior to dosing&#xD;
&#xD;
          -  History of sensitivity to heparin or heparin-induced thrombocytopenia&#xD;
&#xD;
          -  History of serious allergy, hypersensitivity or any serious reaction to aztreonam,&#xD;
             carbapenem, monobactam or other beta-lactam antibiotics, avibactam, or any of the&#xD;
             excipients of the respective (investigational) medicinal products&#xD;
&#xD;
          -  History of human immunodeficiency virus (HIV), hepatitis B, or hepatitis C&#xD;
&#xD;
          -  Other acute or chronic medical or psychiatric condition&#xD;
&#xD;
          -  Past or current history of epilepsy or seizure disorders excluding febrile seizures of&#xD;
             childhood Exclusion criteria: Subjects with Severe Renal Impairment&#xD;
&#xD;
          -  Any significant hepatic, cardiac, or pulmonary disease&#xD;
&#xD;
          -  Renal allograft recipients or subjects who are clinically nephrotic&#xD;
&#xD;
          -  Subjects requiring dialysis&#xD;
&#xD;
          -  Screening supine 12-lead ECG demonstrating QT interval corrected by Fridericia's&#xD;
             formula (QTcF) &gt;470 msec or a QRS interval &gt;120 msec&#xD;
&#xD;
          -  Screening supine BP &gt;/=180 millimeters of mercury (mm Hg) (systolic) or &gt;/=110 mm Hg&#xD;
             (diastolic), on a single measurement (confirmed by a single repeat, if necessary)&#xD;
             following at least 5 minutes of rest Exclusion criteria: Subjects with Normal Renal&#xD;
             Function&#xD;
&#xD;
          -  Evidence or history of clinically significant hematological, renal, endocrine,&#xD;
             pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or&#xD;
             allergic disease (including clinically relevant and significant drug allergies, but&#xD;
             excluding untreated, asymptomatic, seasonal allergies at time of dosing)&#xD;
&#xD;
          -  Screening supine 12-lead ECG demonstrating QTcF &gt;450 msec or a QRS interval &gt;120 msec&#xD;
&#xD;
          -  Screening supine BP &gt;/=140 mm Hg (systolic) or &gt;/=90 mm Hg (diastolic), following at&#xD;
             least 5 minutes of supine rest&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Pfizer CT.gov Call Center</last_name>
    <role>Study Director</role>
    <affiliation>Pfizer</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Prism Research LLC dba Nucleus Network</name>
      <address>
        <city>Saint Paul</city>
        <state>Minnesota</state>
        <zip>55114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://pmiform.com/clinical-trial-info-request?StudyID=C3601006</url>
    <description>To obtain contact information for a study center near you, click here.</description>
  </link>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>July 22, 2020</study_first_submitted>
  <study_first_submitted_qc>July 22, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 24, 2020</study_first_posted>
  <results_first_submitted>September 9, 2022</results_first_submitted>
  <results_first_submitted_qc>September 9, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">July 28, 2023</results_first_posted>
  <last_update_submitted>September 9, 2022</last_update_submitted>
  <last_update_submitted_qc>September 9, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">July 28, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Infection</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Renal Insufficiency</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>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.</ipd_description>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>July 14, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/25/NCT04486625/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>August 27, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/25/NCT04486625/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>This was a Phase 1, open-label, parallel-group study where an intravenous (IV) loading dose (30-minute infusion) followed by multiple IV doses (3-hour infusion) of aztreonam-avibactam (ATM-AVI) were administered to participants with severe renal impairment (not on dialysis) (Cohort 1) and to healthy participants with normal renal function (Cohort 2).</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Cohort 1: Normal Renal Function</title>
          <description>Participants with normal renal function received 30-minute IV loading dose infusion (500/167 mg aztreonam [ATM]/avibactam [AVI]), followed by 3-hour IV extended loading infusion (1500/500 mg ATM/AVI), then 3-hour 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours on Days 1 to 3.</description>
        </group>
        <group group_id="P2">
          <title>Cohort 2: Severe Renal Impairment</title>
          <description>Participants with severe renal impairment (not on dialysis) received 30-minute IV loading dose infusion (675/255 mg aztreonam [ATM]/avibactam [AVI]), followed by 3-hour IV extended loading infusion (675/255 mg ATM/AVI), then 3-hour 675/255 mg ATM/AVI maintenance dose infusion every 8 hours on Days 1 to 3.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The baseline analysis population included all participants who received at least 1 dose of study medication.</population>
      <group_list>
        <group group_id="B1">
          <title>Cohort 1: Normal Renal Function</title>
          <description>Participants with normal renal function received 30-minute IV loading dose infusion (500/167 mg aztreonam [ATM]/avibactam [AVI]), followed by 3-hour IV extended loading infusion (1500/500 mg ATM/AVI), then 3-hour 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours on Days 1 to 3.</description>
        </group>
        <group group_id="B2">
          <title>Cohort 2: Severe Renal Impairment</title>
          <description>Participants with severe renal impairment (not on dialysis) received 30-minute IV loading dose infusion (675/255 mg aztreonam [ATM]/avibactam [AVI]), followed by 3-hour IV extended loading infusion (675/255 mg ATM/AVI), then 3-hour 675/255 mg ATM/AVI maintenance dose infusion every 8 hours on Days 1 to 3.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="6"/>
            <count group_id="B2" value="5"/>
            <count group_id="B3" value="11"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <title>Mean</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="61.0" spread="1.67"/>
                    <measurement group_id="B2" value="67.8" spread="8.56"/>
                    <measurement group_id="B3" value="64.1" spread="6.58"/>
                  </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_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Race</title>
              <category_list>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Ethnicity</title>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Body Weight</title>
          <units>kilogram (kg)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="98.65" spread="6.354"/>
                    <measurement group_id="B2" value="101.06" spread="13.068"/>
                    <measurement group_id="B3" value="99.75" spread="9.491"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Total Daily Area Under the Plasma Concentration-time Profile From Time 0 to 24 Hours at Steady-state (AUC0-24,ss) of Aztreonam (ATM)</title>
        <description>AUC0-24,ss of ATM in Cohort 1 was calculated by 4*AUC0-tau (tau = 6 hours), where AUC0-tau was area under the concentration-time profile from time 0 to time tau (the dosing interval). AUC0-24,ss of ATM in Cohort 2 was calculated by 3*AUC0-tau (tau = 8 hours), where AUC0-tau was area under the plasma concentration-time profile from time 0 to time tau (the dosing interval).</description>
        <time_frame>Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.</time_frame>
        <population>The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: Normal Renal Function</title>
            <description>Participants with normal renal function received 30-minute IV loading dose infusion (500/167 mg aztreonam [ATM]/avibactam [AVI]), followed by 3-hour IV extended loading infusion (1500/500 mg ATM/AVI), then 3-hour 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours on Days 1 to 3.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2: Severe Renal Impairment</title>
            <description>Participants with severe renal impairment (not on dialysis) received 30-minute IV loading dose infusion (675/255 mg aztreonam [ATM]/avibactam [AVI]), followed by 3-hour IV extended loading infusion (675/255 mg ATM/AVI), then 3-hour 675/255 mg ATM/AVI maintenance dose infusion every 8 hours on Days 1 to 3.</description>
          </group>
        </group_list>
        <measure>
          <title>Total Daily Area Under the Plasma Concentration-time Profile From Time 0 to 24 Hours at Steady-state (AUC0-24,ss) of Aztreonam (ATM)</title>
          <description>AUC0-24,ss of ATM in Cohort 1 was calculated by 4*AUC0-tau (tau = 6 hours), where AUC0-tau was area under the concentration-time profile from time 0 to time tau (the dosing interval). AUC0-24,ss of ATM in Cohort 2 was calculated by 3*AUC0-tau (tau = 8 hours), where AUC0-tau was area under the plasma concentration-time profile from time 0 to time tau (the dosing interval).</description>
          <population>The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.</population>
          <units>Microgram*hour per milliliter (ug*hr/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="6"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="922.9" spread="16"/>
                    <measurement group_id="O2" value="733.5" spread="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Analysis of variance (ANOVA) was used to compare the natural log transformed AUC0-24,ss between the normal renal function group (Reference) and the severe renal impairment group (Test). The geometric least squares mean point estimate and the associated 90% confidence intervals (CIs) for the difference of each comparison was estimated.</non_inferiority_desc>
            <param_type>Ratio (%) of adjusted geometric means</param_type>
            <param_value>79.48</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>66.52</ci_lower_limit>
            <ci_upper_limit>94.96</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Maximum Plasma Concentration (Cmax) of ATM</title>
        <description>The Cmax of ATM was observed directly from data.</description>
        <time_frame>Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.</time_frame>
        <population>The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: Normal Renal Function</title>
            <description>Participants with normal renal function received 30-minute IV loading dose infusion (500/167 mg aztreonam [ATM]/avibactam [AVI]), followed by 3-hour IV extended loading infusion (1500/500 mg ATM/AVI), then 3-hour 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours on Days 1 to 3.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2: Severe Renal Impairment</title>
            <description>Participants with severe renal impairment (not on dialysis) received 30-minute IV loading dose infusion (675/255 mg aztreonam [ATM]/avibactam [AVI]), followed by 3-hour IV extended loading infusion (675/255 mg ATM/AVI), then 3-hour 675/255 mg ATM/AVI maintenance dose infusion every 8 hours on Days 1 to 3.</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Plasma Concentration (Cmax) of ATM</title>
          <description>The Cmax of ATM was observed directly from data.</description>
          <population>The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.</population>
          <units>Microgram per milliliter (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="6"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="57.34" spread="13"/>
                    <measurement group_id="O2" value="43.34" spread="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>ANOVA was used to compare the natural log transformed Cmax between the normal renal function group (Reference) and the severe renal impairment group (Test). The geometric least squares mean point estimate and the associated 90% CIs for the difference of each comparison was estimated.</non_inferiority_desc>
            <param_type>Ratio (%) of adjusted geometric means</param_type>
            <param_value>75.58</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>66.10</ci_lower_limit>
            <ci_upper_limit>86.43</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>AUC0-24,ss of Avibactam (AVI)</title>
        <description>AUC0-24,ss of AVI in Cohort 1 was calculated by 4*AUC0-tau (tau = 6 hours), where AUC0-tau was area under the concentration-time profile from time 0 to time tau (the dosing interval). AUC0-24,ss of AVI in Cohort 2 was calculated by 3*AUC0-tau (tau = 8 hours), where AUC0-tau was area under the plasma concentration-time profile from time 0 to time tau (the dosing interval).</description>
        <time_frame>Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.</time_frame>
        <population>The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: Normal Renal Function</title>
            <description>Participants with normal renal function received 30-minute IV loading dose infusion (500/167 mg aztreonam [ATM]/avibactam [AVI]), followed by 3-hour IV extended loading infusion (1500/500 mg ATM/AVI), then 3-hour 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours on Days 1 to 3.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2: Severe Renal Impairment</title>
            <description>Participants with severe renal impairment (not on dialysis) received 30-minute IV loading dose infusion (675/255 mg aztreonam [ATM]/avibactam [AVI]), followed by 3-hour IV extended loading infusion (675/255 mg ATM/AVI), then 3-hour 675/255 mg ATM/AVI maintenance dose infusion every 8 hours on Days 1 to 3.</description>
          </group>
        </group_list>
        <measure>
          <title>AUC0-24,ss of Avibactam (AVI)</title>
          <description>AUC0-24,ss of AVI in Cohort 1 was calculated by 4*AUC0-tau (tau = 6 hours), where AUC0-tau was area under the concentration-time profile from time 0 to time tau (the dosing interval). AUC0-24,ss of AVI in Cohort 2 was calculated by 3*AUC0-tau (tau = 8 hours), where AUC0-tau was area under the plasma concentration-time profile from time 0 to time tau (the dosing interval).</description>
          <population>The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.</population>
          <units>ug*hr/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="6"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="164.8" spread="18"/>
                    <measurement group_id="O2" value="204.6" spread="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>ANOVA was used to compare the natural log transformed AUC0-24,ss between the normal renal function group (Reference) and the severe renal impairment group (Test). The geometric least squares mean point estimate and the associated 90% CIs for the difference of each comparison was estimated.</non_inferiority_desc>
            <param_type>Ratio (%) of of adjusted geometric means</param_type>
            <param_value>124.19</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>100.18</ci_lower_limit>
            <ci_upper_limit>153.97</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Cmax of AVI</title>
        <description>The Cmax of AVI was observed directly from data.</description>
        <time_frame>Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.</time_frame>
        <population>The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: Normal Renal Function</title>
            <description>Participants with normal renal function received 30-minute IV loading dose infusion (500/167 mg aztreonam [ATM]/avibactam [AVI]), followed by 3-hour IV extended loading infusion (1500/500 mg ATM/AVI), then 3-hour 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours on Days 1 to 3.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2: Severe Renal Impairment</title>
            <description>Participants with severe renal impairment (not on dialysis) received 30-minute IV loading dose infusion (675/255 mg aztreonam [ATM]/avibactam [AVI]), followed by 3-hour IV extended loading infusion (675/255 mg ATM/AVI), then 3-hour 675/255 mg ATM/AVI maintenance dose infusion every 8 hours on Days 1 to 3.</description>
          </group>
        </group_list>
        <measure>
          <title>Cmax of AVI</title>
          <description>The Cmax of AVI was observed directly from data.</description>
          <population>The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.</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="6"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.08" spread="14"/>
                    <measurement group_id="O2" value="11.35" spread="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>ANOVA was used to compare the natural log transformed Cmax between the normal renal function group (Reference) and the severe renal impairment group (Test). The geometric least squares mean point estimate and the associated 90% CIs for the difference of each comparison was estimated.</non_inferiority_desc>
            <param_type>Ratio (%) of adjusted geometric means</param_type>
            <param_value>102.42</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>87.55</ci_lower_limit>
            <ci_upper_limit>119.83</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Area Under the Plasma Concentration-time Profile From Time 0 to Time Tau (The Dosing Interval)(AUC0-tau) of ATM</title>
        <description>The AUC0-tau was calculated by linear/log trapezoidal method. The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).</description>
        <time_frame>Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.</time_frame>
        <population>The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: Normal Renal Function</title>
            <description>Participants with normal renal function received 30-minute IV loading dose infusion (500/167 mg aztreonam [ATM]/avibactam [AVI]), followed by 3-hour IV extended loading infusion (1500/500 mg ATM/AVI), then 3-hour 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours on Days 1 to 3.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2: Severe Renal Impairment</title>
            <description>Participants with severe renal impairment (not on dialysis) received 30-minute IV loading dose infusion (675/255 mg aztreonam [ATM]/avibactam [AVI]), followed by 3-hour IV extended loading infusion (675/255 mg ATM/AVI), then 3-hour 675/255 mg ATM/AVI maintenance dose infusion every 8 hours on Days 1 to 3.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration-time Profile From Time 0 to Time Tau (The Dosing Interval)(AUC0-tau) of ATM</title>
          <description>The AUC0-tau was calculated by linear/log trapezoidal method. The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).</description>
          <population>The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.</population>
          <units>ug*hr/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="6"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="230.8" spread="16"/>
                    <measurement group_id="O2" value="244.3" spread="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time for Cmax (Tmax) of ATM</title>
        <description>The Tmax was observed directly from data as time of first occurrence.</description>
        <time_frame>Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.</time_frame>
        <population>The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: Normal Renal Function</title>
            <description>Participants with normal renal function received 30-minute IV loading dose infusion (500/167 mg aztreonam [ATM]/avibactam [AVI]), followed by 3-hour IV extended loading infusion (1500/500 mg ATM/AVI), then 3-hour 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours on Days 1 to 3.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2: Severe Renal Impairment</title>
            <description>Participants with severe renal impairment (not on dialysis) received 30-minute IV loading dose infusion (675/255 mg aztreonam [ATM]/avibactam [AVI]), followed by 3-hour IV extended loading infusion (675/255 mg ATM/AVI), then 3-hour 675/255 mg ATM/AVI maintenance dose infusion every 8 hours on Days 1 to 3.</description>
          </group>
        </group_list>
        <measure>
          <title>Time for Cmax (Tmax) of ATM</title>
          <description>The Tmax was observed directly from data as time of first occurrence.</description>
          <population>The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.</population>
          <units>Hours</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.92" lower_limit="2" upper_limit="2.92"/>
                    <measurement group_id="O2" value="2.92" lower_limit="2.92" upper_limit="3.75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Observed Plasma Concentration at the End of the Dosing Interval (Tau) (Ctau) of ATM</title>
        <description>The Ctau was observed directly from data. The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).</description>
        <time_frame>Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.</time_frame>
        <population>The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: Normal Renal Function</title>
            <description>Participants with normal renal function received 30-minute IV loading dose infusion (500/167 mg aztreonam [ATM]/avibactam [AVI]), followed by 3-hour IV extended loading infusion (1500/500 mg ATM/AVI), then 3-hour 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours on Days 1 to 3.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2: Severe Renal Impairment</title>
            <description>Participants with severe renal impairment (not on dialysis) received 30-minute IV loading dose infusion (675/255 mg aztreonam [ATM]/avibactam [AVI]), followed by 3-hour IV extended loading infusion (675/255 mg ATM/AVI), then 3-hour 675/255 mg ATM/AVI maintenance dose infusion every 8 hours on Days 1 to 3.</description>
          </group>
        </group_list>
        <measure>
          <title>Observed Plasma Concentration at the End of the Dosing Interval (Tau) (Ctau) of ATM</title>
          <description>The Ctau was observed directly from data. The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).</description>
          <population>The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.</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="6"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="21.43" spread="19"/>
                    <measurement group_id="O2" value="18.55" spread="24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Terminal Elimination Half-life (t1/2) of ATM</title>
        <description>The t1/2 was calculated by loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log linear concentration time curve. Only those data points judged to describe the terminal log linear decline were used in the regression.</description>
        <time_frame>Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.</time_frame>
        <population>The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: Normal Renal Function</title>
            <description>Participants with normal renal function received 30-minute IV loading dose infusion (500/167 mg aztreonam [ATM]/avibactam [AVI]), followed by 3-hour IV extended loading infusion (1500/500 mg ATM/AVI), then 3-hour 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours on Days 1 to 3.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2: Severe Renal Impairment</title>
            <description>Participants with severe renal impairment (not on dialysis) received 30-minute IV loading dose infusion (675/255 mg aztreonam [ATM]/avibactam [AVI]), followed by 3-hour IV extended loading infusion (675/255 mg ATM/AVI), then 3-hour 675/255 mg ATM/AVI maintenance dose infusion every 8 hours on Days 1 to 3.</description>
          </group>
        </group_list>
        <measure>
          <title>Terminal Elimination Half-life (t1/2) of ATM</title>
          <description>The t1/2 was calculated by loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log linear concentration time curve. Only those data points judged to describe the terminal log linear decline were used in the regression.</description>
          <population>The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.</population>
          <units>Hours</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.605" spread="0.34944"/>
                    <measurement group_id="O2" value="4.902" spread="1.4286"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Clearance (CL) of ATM</title>
        <description>The CL was calculated by dose/AUC0-tau, where AUC0-tau was area under the concentration-time profile from time 0 to time tau (the dosing interval). The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).</description>
        <time_frame>Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.</time_frame>
        <population>The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: Normal Renal Function</title>
            <description>Participants with normal renal function received 30-minute IV loading dose infusion (500/167 mg aztreonam [ATM]/avibactam [AVI]), followed by 3-hour IV extended loading infusion (1500/500 mg ATM/AVI), then 3-hour 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours on Days 1 to 3.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2: Severe Renal Impairment</title>
            <description>Participants with severe renal impairment (not on dialysis) received 30-minute IV loading dose infusion (675/255 mg aztreonam [ATM]/avibactam [AVI]), followed by 3-hour IV extended loading infusion (675/255 mg ATM/AVI), then 3-hour 675/255 mg ATM/AVI maintenance dose infusion every 8 hours on Days 1 to 3.</description>
          </group>
        </group_list>
        <measure>
          <title>Clearance (CL) of ATM</title>
          <description>The CL was calculated by dose/AUC0-tau, where AUC0-tau was area under the concentration-time profile from time 0 to time tau (the dosing interval). The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).</description>
          <population>The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.</population>
          <units>Liters per hour (L/hr)</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="6"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.499" spread="16"/>
                    <measurement group_id="O2" value="2.761" spread="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Renal Clearance (CLr) of ATM</title>
        <description>The CLr was calculated by Ae0-tau/AUC0-tau, where Ae0-tau was cumulative amount of drug recovered unchanged in urine up to time tau and AUC0-tau was area under the plasma concentration time profile from time 0 to time tau (the dosing interval). The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).</description>
        <time_frame>In Cohort 1, at predose on Day 3, during 0-2, 2-4, and 4-6 hours after the start of a maintenance dose infusion. In Cohort 2, at predose on Day 3, during 0-2, 2-4, 4-6, and 6-8 hours after the start of a maintenance dose infusion.</time_frame>
        <population>The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: Normal Renal Function</title>
            <description>Participants with normal renal function received 30-minute IV loading dose infusion (500/167 mg aztreonam [ATM]/avibactam [AVI]), followed by 3-hour IV extended loading infusion (1500/500 mg ATM/AVI), then 3-hour 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours on Days 1 to 3.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2: Severe Renal Impairment</title>
            <description>Participants with severe renal impairment (not on dialysis) received 30-minute IV loading dose infusion (675/255 mg aztreonam [ATM]/avibactam [AVI]), followed by 3-hour IV extended loading infusion (675/255 mg ATM/AVI), then 3-hour 675/255 mg ATM/AVI maintenance dose infusion every 8 hours on Days 1 to 3.</description>
          </group>
        </group_list>
        <measure>
          <title>Renal Clearance (CLr) of ATM</title>
          <description>The CLr was calculated by Ae0-tau/AUC0-tau, where Ae0-tau was cumulative amount of drug recovered unchanged in urine up to time tau and AUC0-tau was area under the plasma concentration time profile from time 0 to time tau (the dosing interval). The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).</description>
          <population>The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.</population>
          <units>L/hr</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="6"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.527" spread="18"/>
                    <measurement group_id="O2" value="1.477" spread="23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Apparent Volume of Distribution (Vz) of ATM</title>
        <description>The Vz was calculated by dose/(AUC0-tau*kel), where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve and AUC0-tau was area under the concentration-time profile from time 0 to time tau (the dosing interval). The dosing interval (tau) was 6 hours for the normal renal function group (Cohort 1) and 8 hours for the severe renal impairment group (Cohort 2).</description>
        <time_frame>Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.</time_frame>
        <population>The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: Normal Renal Function</title>
            <description>Participants with normal renal function received 30-minute IV loading dose infusion (500/167 mg aztreonam [ATM]/avibactam [AVI]), followed by 3-hour IV extended loading infusion (1500/500 mg ATM/AVI), then 3-hour 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours on Days 1 to 3.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2: Severe Renal Impairment</title>
            <description>Participants with severe renal impairment (not on dialysis) received 30-minute IV loading dose infusion (675/255 mg aztreonam [ATM]/avibactam [AVI]), followed by 3-hour IV extended loading infusion (675/255 mg ATM/AVI), then 3-hour 675/255 mg ATM/AVI maintenance dose infusion every 8 hours on Days 1 to 3.</description>
          </group>
        </group_list>
        <measure>
          <title>Apparent Volume of Distribution (Vz) of ATM</title>
          <description>The Vz was calculated by dose/(AUC0-tau*kel), where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve and AUC0-tau was area under the concentration-time profile from time 0 to time tau (the dosing interval). The dosing interval (tau) was 6 hours for the normal renal function group (Cohort 1) and 8 hours for the severe renal impairment group (Cohort 2).</description>
          <population>The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.</population>
          <units>Liters (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="6"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="24.25" spread="23"/>
                    <measurement group_id="O2" value="18.79" spread="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Apparent Volume of Distribution at Steady-state (Vss) of ATM</title>
        <description>Vss was calculated by CL*MRT, where CL was clearance and MRT was mean residence time.</description>
        <time_frame>Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.</time_frame>
        <population>The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: Normal Renal Function</title>
            <description>Participants with normal renal function received 30-minute IV loading dose infusion (500/167 mg aztreonam [ATM]/avibactam [AVI]), followed by 3-hour IV extended loading infusion (1500/500 mg ATM/AVI), then 3-hour 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours on Days 1 to 3.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2: Severe Renal Impairment</title>
            <description>Participants with severe renal impairment (not on dialysis) received 30-minute IV loading dose infusion (675/255 mg aztreonam [ATM]/avibactam [AVI]), followed by 3-hour IV extended loading infusion (675/255 mg ATM/AVI), then 3-hour 675/255 mg ATM/AVI maintenance dose infusion every 8 hours on Days 1 to 3.</description>
          </group>
        </group_list>
        <measure>
          <title>Apparent Volume of Distribution at Steady-state (Vss) of ATM</title>
          <description>Vss was calculated by CL*MRT, where CL was clearance and MRT was mean residence time.</description>
          <population>The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.</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="6"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23.70" spread="29"/>
                    <measurement group_id="O2" value="18.46" spread="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cumulative Amount of Drug Recovered Unchanged in Urine up to Time Tau (Ae0-tau) of ATM</title>
        <description>The Ae0-tau was the sum of (urine concentration*sample volume). The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).</description>
        <time_frame>In Cohort 1, at predose on Day 3, during 0-2, 2-4, and 4-6 hours after the start of a maintenance dose infusion. In Cohort 2, at predose on Day 3, during 0-2, 2-4, 4-6, and 6-8 hours after the start of a maintenance dose infusion.</time_frame>
        <population>The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: Normal Renal Function</title>
            <description>Participants with normal renal function received 30-minute IV loading dose infusion (500/167 mg aztreonam [ATM]/avibactam [AVI]), followed by 3-hour IV extended loading infusion (1500/500 mg ATM/AVI), then 3-hour 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours on Days 1 to 3.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2: Severe Renal Impairment</title>
            <description>Participants with severe renal impairment (not on dialysis) received 30-minute IV loading dose infusion (675/255 mg aztreonam [ATM]/avibactam [AVI]), followed by 3-hour IV extended loading infusion (675/255 mg ATM/AVI), then 3-hour 675/255 mg ATM/AVI maintenance dose infusion every 8 hours on Days 1 to 3.</description>
          </group>
        </group_list>
        <measure>
          <title>Cumulative Amount of Drug Recovered Unchanged in Urine up to Time Tau (Ae0-tau) of ATM</title>
          <description>The Ae0-tau was the sum of (urine concentration*sample volume). The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).</description>
          <population>The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.</population>
          <units>Milligram (mg)</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="6"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1047" spread="11"/>
                    <measurement group_id="O2" value="361.2" spread="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent of Dose Recovered Unchanged in Urine up to Time Tau (Ae0-tau%) of ATM</title>
        <description>The Ae0-tau was calculated by 100*Ae0-tau/dose, where Ae0-tau was cumulative amount of drug recovered unchanged in urine up to time tau. The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).</description>
        <time_frame>In Cohort 1, at predose on Day 3, during 0-2, 2-4, and 4-6 hours after the start of a maintenance dose infusion. In Cohort 2, at predose on Day 3, during 0-2, 2-4, 4-6, and 6-8 hours after the start of a maintenance dose infusion.</time_frame>
        <population>The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: Normal Renal Function</title>
            <description>Participants with normal renal function received 30-minute IV loading dose infusion (500/167 mg aztreonam [ATM]/avibactam [AVI]), followed by 3-hour IV extended loading infusion (1500/500 mg ATM/AVI), then 3-hour 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours on Days 1 to 3.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2: Severe Renal Impairment</title>
            <description>Participants with severe renal impairment (not on dialysis) received 30-minute IV loading dose infusion (675/255 mg aztreonam [ATM]/avibactam [AVI]), followed by 3-hour IV extended loading infusion (675/255 mg ATM/AVI), then 3-hour 675/255 mg ATM/AVI maintenance dose infusion every 8 hours on Days 1 to 3.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent of Dose Recovered Unchanged in Urine up to Time Tau (Ae0-tau%) of ATM</title>
          <description>The Ae0-tau was calculated by 100*Ae0-tau/dose, where Ae0-tau was cumulative amount of drug recovered unchanged in urine up to time tau. The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).</description>
          <population>The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.</population>
          <units>Percent of dose</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="6"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="69.68" spread="11"/>
                    <measurement group_id="O2" value="53.51" spread="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>AUC0-tau of AVI</title>
        <description>The UC0-tau was calculated by linear/log trapezoidal method. The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).A</description>
        <time_frame>Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.</time_frame>
        <population>The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: Normal Renal Function</title>
            <description>Participants with normal renal function received 30-minute IV loading dose infusion (500/167 mg aztreonam [ATM]/avibactam [AVI]), followed by 3-hour IV extended loading infusion (1500/500 mg ATM/AVI), then 3-hour 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours on Days 1 to 3.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2: Severe Renal Impairment</title>
            <description>Participants with severe renal impairment (not on dialysis) received 30-minute IV loading dose infusion (675/255 mg aztreonam [ATM]/avibactam [AVI]), followed by 3-hour IV extended loading infusion (675/255 mg ATM/AVI), then 3-hour 675/255 mg ATM/AVI maintenance dose infusion every 8 hours on Days 1 to 3.</description>
          </group>
        </group_list>
        <measure>
          <title>AUC0-tau of AVI</title>
          <description>The UC0-tau was calculated by linear/log trapezoidal method. The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).A</description>
          <population>The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.</population>
          <units>ug*hr/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="6"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="41.19" spread="18"/>
                    <measurement group_id="O2" value="68.31" spread="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Tmax of AVI</title>
        <description>The Tmax was observed directly from data as time of first occurrence.</description>
        <time_frame>Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.</time_frame>
        <population>The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: Normal Renal Function</title>
            <description>Participants with normal renal function received 30-minute IV loading dose infusion (500/167 mg aztreonam [ATM]/avibactam [AVI]), followed by 3-hour IV extended loading infusion (1500/500 mg ATM/AVI), then 3-hour 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours on Days 1 to 3.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2: Severe Renal Impairment</title>
            <description>Participants with severe renal impairment (not on dialysis) received 30-minute IV loading dose infusion (675/255 mg aztreonam [ATM]/avibactam [AVI]), followed by 3-hour IV extended loading infusion (675/255 mg ATM/AVI), then 3-hour 675/255 mg ATM/AVI maintenance dose infusion every 8 hours on Days 1 to 3.</description>
          </group>
        </group_list>
        <measure>
          <title>Tmax of AVI</title>
          <description>The Tmax was observed directly from data as time of first occurrence.</description>
          <population>The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.</population>
          <units>Hours</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.46" lower_limit="2" upper_limit="2.92"/>
                    <measurement group_id="O2" value="2.92" lower_limit="2" upper_limit="3.25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Ctau of AVI</title>
        <description>The Ctau was observed directly from data. The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).</description>
        <time_frame>Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.</time_frame>
        <population>The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: Normal Renal Function</title>
            <description>Participants with normal renal function received 30-minute IV loading dose infusion (500/167 mg aztreonam [ATM]/avibactam [AVI]), followed by 3-hour IV extended loading infusion (1500/500 mg ATM/AVI), then 3-hour 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours on Days 1 to 3.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2: Severe Renal Impairment</title>
            <description>Participants with severe renal impairment (not on dialysis) received 30-minute IV loading dose infusion (675/255 mg aztreonam [ATM]/avibactam [AVI]), followed by 3-hour IV extended loading infusion (675/255 mg ATM/AVI), then 3-hour 675/255 mg ATM/AVI maintenance dose infusion every 8 hours on Days 1 to 3.</description>
          </group>
        </group_list>
        <measure>
          <title>Ctau of AVI</title>
          <description>The Ctau was observed directly from data. The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).</description>
          <population>The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.</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="6"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.100" spread="24"/>
                    <measurement group_id="O2" value="5.597" spread="39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>t1/2 of AVI</title>
        <description>The t1/2 was calculated by loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log linear concentration time curve. Only those data points judged to describe the terminal log linear decline were used in the regression.</description>
        <time_frame>Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.</time_frame>
        <population>The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: Normal Renal Function</title>
            <description>Participants with normal renal function received 30-minute IV loading dose infusion (500/167 mg aztreonam [ATM]/avibactam [AVI]), followed by 3-hour IV extended loading infusion (1500/500 mg ATM/AVI), then 3-hour 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours on Days 1 to 3.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2: Severe Renal Impairment</title>
            <description>Participants with severe renal impairment (not on dialysis) received 30-minute IV loading dose infusion (675/255 mg aztreonam [ATM]/avibactam [AVI]), followed by 3-hour IV extended loading infusion (675/255 mg ATM/AVI), then 3-hour 675/255 mg ATM/AVI maintenance dose infusion every 8 hours on Days 1 to 3.</description>
          </group>
        </group_list>
        <measure>
          <title>t1/2 of AVI</title>
          <description>The t1/2 was calculated by loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log linear concentration time curve. Only those data points judged to describe the terminal log linear decline were used in the regression.</description>
          <population>The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.</population>
          <units>Hours</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.188" spread="0.071391"/>
                    <measurement group_id="O2" value="6.524" spread="1.6469"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>CL of AVI</title>
        <description>The CL was calculated by dose/AUC0-tau, where AUC0-tau was area under the plasma concentration-time profile from time 0 to to time tau (the dosing interval). The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).</description>
        <time_frame>Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.</time_frame>
        <population>The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: Normal Renal Function</title>
            <description>Participants with normal renal function received 30-minute IV loading dose infusion (500/167 mg aztreonam [ATM]/avibactam [AVI]), followed by 3-hour IV extended loading infusion (1500/500 mg ATM/AVI), then 3-hour 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours on Days 1 to 3.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2: Severe Renal Impairment</title>
            <description>Participants with severe renal impairment (not on dialysis) received 30-minute IV loading dose infusion (675/255 mg aztreonam [ATM]/avibactam [AVI]), followed by 3-hour IV extended loading infusion (675/255 mg ATM/AVI), then 3-hour 675/255 mg ATM/AVI maintenance dose infusion every 8 hours on Days 1 to 3.</description>
          </group>
        </group_list>
        <measure>
          <title>CL of AVI</title>
          <description>The CL was calculated by dose/AUC0-tau, where AUC0-tau was area under the plasma concentration-time profile from time 0 to to time tau (the dosing interval). The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).</description>
          <population>The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.</population>
          <units>L/hr</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="6"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.16" spread="18"/>
                    <measurement group_id="O2" value="3.295" spread="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>CLr of AVI</title>
        <description>The CLr was calculated by Ae0-tau/AUC0-tau, where Ae0-tau was cumulative amount of drug recovered unchanged in urine up to time tau and AUC0-tau was area under the plasma concentration time profile from time 0 to time tau (the dosing interval). The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).</description>
        <time_frame>In Cohort 1, at predose on Day 3, during 0-2, 2-4, and 4-6 hours after the start of a maintenance dose infusion. In Cohort 2, at predose on Day 3, during 0-2, 2-4, 4-6, and 6-8 hours after the start of a maintenance dose infusion.</time_frame>
        <population>The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: Normal Renal Function</title>
            <description>Participants with normal renal function received 30-minute IV loading dose infusion (500/167 mg aztreonam [ATM]/avibactam [AVI]), followed by 3-hour IV extended loading infusion (1500/500 mg ATM/AVI), then 3-hour 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours on Days 1 to 3.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2: Severe Renal Impairment</title>
            <description>Participants with severe renal impairment (not on dialysis) received 30-minute IV loading dose infusion (675/255 mg aztreonam [ATM]/avibactam [AVI]), followed by 3-hour IV extended loading infusion (675/255 mg ATM/AVI), then 3-hour 675/255 mg ATM/AVI maintenance dose infusion every 8 hours on Days 1 to 3.</description>
          </group>
        </group_list>
        <measure>
          <title>CLr of AVI</title>
          <description>The CLr was calculated by Ae0-tau/AUC0-tau, where Ae0-tau was cumulative amount of drug recovered unchanged in urine up to time tau and AUC0-tau was area under the plasma concentration time profile from time 0 to time tau (the dosing interval). The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).</description>
          <population>The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.</population>
          <units>L/hr</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="6"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.30" spread="20"/>
                    <measurement group_id="O2" value="3.948" spread="36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Vz of AVI</title>
        <description>The Vz was calculated by dose/(AUC0-tau*kel), where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve and AUC0-tau was area under the concentration-time profile from time 0 to time tau (the dosing interval). The dosing interval (tau) was 6 hours for the normal renal function group (Cohort 1) and 8 hours for the severe renal impairment group (Cohort 2).</description>
        <time_frame>Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.</time_frame>
        <population>The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: Normal Renal Function</title>
            <description>Participants with normal renal function received 30-minute IV loading dose infusion (500/167 mg aztreonam [ATM]/avibactam [AVI]), followed by 3-hour IV extended loading infusion (1500/500 mg ATM/AVI), then 3-hour 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours on Days 1 to 3.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2: Severe Renal Impairment</title>
            <description>Participants with severe renal impairment (not on dialysis) received 30-minute IV loading dose infusion (675/255 mg aztreonam [ATM]/avibactam [AVI]), followed by 3-hour IV extended loading infusion (675/255 mg ATM/AVI), then 3-hour 675/255 mg ATM/AVI maintenance dose infusion every 8 hours on Days 1 to 3.</description>
          </group>
        </group_list>
        <measure>
          <title>Vz of AVI</title>
          <description>The Vz was calculated by dose/(AUC0-tau*kel), where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve and AUC0-tau was area under the concentration-time profile from time 0 to time tau (the dosing interval). The dosing interval (tau) was 6 hours for the normal renal function group (Cohort 1) and 8 hours for the severe renal impairment group (Cohort 2).</description>
          <population>The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.</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="6"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="55.83" spread="19"/>
                    <measurement group_id="O2" value="30.14" spread="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Vss of AVI</title>
        <description>Vss was calculated by CL*MRT, where CL was clearance and MRT was mean residence time.</description>
        <time_frame>Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.</time_frame>
        <population>The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: Normal Renal Function</title>
            <description>Participants with normal renal function received 30-minute IV loading dose infusion (500/167 mg aztreonam [ATM]/avibactam [AVI]), followed by 3-hour IV extended loading infusion (1500/500 mg ATM/AVI), then 3-hour 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours on Days 1 to 3.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2: Severe Renal Impairment</title>
            <description>Participants with severe renal impairment (not on dialysis) received 30-minute IV loading dose infusion (675/255 mg aztreonam [ATM]/avibactam [AVI]), followed by 3-hour IV extended loading infusion (675/255 mg ATM/AVI), then 3-hour 675/255 mg ATM/AVI maintenance dose infusion every 8 hours on Days 1 to 3.</description>
          </group>
        </group_list>
        <measure>
          <title>Vss of AVI</title>
          <description>Vss was calculated by CL*MRT, where CL was clearance and MRT was mean residence time.</description>
          <population>The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.</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="6"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="37.37" spread="30"/>
                    <measurement group_id="O2" value="27.78" spread="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Ae0-tau of AVI</title>
        <description>The Ae0-tau was the sum of (urine concentration*sample volume). The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).</description>
        <time_frame>In Cohort 1, at predose on Day 3, during 0-2, 2-4, and 4-6 hours after the start of a maintenance dose infusion. In Cohort 2, at predose on Day 3, during 0-2, 2-4, 4-6, and 6-8 hours after the start of a maintenance dose infusion.</time_frame>
        <population>The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: Normal Renal Function</title>
            <description>Participants with normal renal function received 30-minute IV loading dose infusion (500/167 mg aztreonam [ATM]/avibactam [AVI]), followed by 3-hour IV extended loading infusion (1500/500 mg ATM/AVI), then 3-hour 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours on Days 1 to 3.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2: Severe Renal Impairment</title>
            <description>Participants with severe renal impairment (not on dialysis) received 30-minute IV loading dose infusion (675/255 mg aztreonam [ATM]/avibactam [AVI]), followed by 3-hour IV extended loading infusion (675/255 mg ATM/AVI), then 3-hour 675/255 mg ATM/AVI maintenance dose infusion every 8 hours on Days 1 to 3.</description>
          </group>
        </group_list>
        <measure>
          <title>Ae0-tau of AVI</title>
          <description>The Ae0-tau was the sum of (urine concentration*sample volume). The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).</description>
          <population>The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.</population>
          <units>mg</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="6"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="465.6" spread="11"/>
                    <measurement group_id="O2" value="270.0" spread="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Ae0-tau% of AVI</title>
        <description>The Ae0-tau was calculated by 100*Ae0-tau/dose, where Ae0-tau was cumulative amount of drug recovered unchanged in urine up to time tau. The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).</description>
        <time_frame>In Cohort 1, at predose on Day 3, during 0-2, 2-4, and 4-6 hours after the start of a maintenance dose infusion. In Cohort 2, at predose on Day 3, during 0-2, 2-4, 4-6, and 6-8 hours after the start of a maintenance dose infusion.</time_frame>
        <population>The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: Normal Renal Function</title>
            <description>Participants with normal renal function received 30-minute IV loading dose infusion (500/167 mg aztreonam [ATM]/avibactam [AVI]), followed by 3-hour IV extended loading infusion (1500/500 mg ATM/AVI), then 3-hour 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours on Days 1 to 3.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2: Severe Renal Impairment</title>
            <description>Participants with severe renal impairment (not on dialysis) received 30-minute IV loading dose infusion (675/255 mg aztreonam [ATM]/avibactam [AVI]), followed by 3-hour IV extended loading infusion (675/255 mg ATM/AVI), then 3-hour 675/255 mg ATM/AVI maintenance dose infusion every 8 hours on Days 1 to 3.</description>
          </group>
        </group_list>
        <measure>
          <title>Ae0-tau% of AVI</title>
          <description>The Ae0-tau was calculated by 100*Ae0-tau/dose, where Ae0-tau was cumulative amount of drug recovered unchanged in urine up to time tau. The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).</description>
          <population>The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.</population>
          <units>Percent of dose</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="6"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="93.19" spread="11"/>
                    <measurement group_id="O2" value="119.9" spread="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Treatment Emergent Adverse Events (TEAEs) (All-causality)</title>
        <description>An adverse event (AE) is any untoward medical occurrence in a study participant administered a product; the event need not necessarily have a causal relationship with the treatment or usage. A serious adverse event is any untoward medical occurrence at any dose that: (1) results in death; (2) is life threatening (immediate risk of death); (3) requires inpatient hospitalization or prolongation of existing hospitalization; (4) results in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); (5) results in congenital anomaly/birth defect; or that is considered to be an important medical event. Treatment-emergent are events between first dose of study medication and up to at least 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. A severe AE is defined as a event interferes significantly with participant's usual function.</description>
        <time_frame>Day 1 up to at least 28 days after last dose of study medication (maximum of 33 days).</time_frame>
        <population>The analysis population included all participants who received at least 1 dose of study medication.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: Normal Renal Function</title>
            <description>Participants with normal renal function received 30-minute IV loading dose infusion (500/167 mg aztreonam [ATM]/avibactam [AVI]), followed by 3-hour IV extended loading infusion (1500/500 mg ATM/AVI), then 3-hour 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours on Days 1 to 3.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2: Severe Renal Impairment</title>
            <description>Participants with severe renal impairment (not on dialysis) received 30-minute IV loading dose infusion (675/255 mg aztreonam [ATM]/avibactam [AVI]), followed by 3-hour IV extended loading infusion (675/255 mg ATM/AVI), then 3-hour 675/255 mg ATM/AVI maintenance dose infusion every 8 hours on Days 1 to 3.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Treatment Emergent Adverse Events (TEAEs) (All-causality)</title>
          <description>An adverse event (AE) is any untoward medical occurrence in a study participant administered a product; the event need not necessarily have a causal relationship with the treatment or usage. A serious adverse event is any untoward medical occurrence at any dose that: (1) results in death; (2) is life threatening (immediate risk of death); (3) requires inpatient hospitalization or prolongation of existing hospitalization; (4) results in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); (5) results in congenital anomaly/birth defect; or that is considered to be an important medical event. Treatment-emergent are events between first dose of study medication and up to at least 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. A severe AE is defined as a event interferes significantly with participant's usual function.</description>
          <population>The analysis population included all participants who received at least 1 dose of study medication.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Participants with AEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participants with serious AEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participants with severe AEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participants discontinued from study due to AEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participants discontinued study drug due to AEs and continue study</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participants with dose reduced or temporary discontinuation due to AEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With TEAEs (Treatment-related)</title>
        <description>An adverse event (AE) is any untoward medical occurrence in a study participant administered a product; the event attributed to the study medication. A serious AE is any untoward medical occurrence at any dose that: (1) results in death; (2) is life threatening (immediate risk of death); (3) requires inpatient hospitalization or prolongation of existing hospitalization; (4) results in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); (5) results in congenital anomaly/birth defect; or that is considered to be an important medical event. Treatment-emergent are events between first dose of study medication and up to at least 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. A severe AE is defined as a event interferes significantly with participant's usual function.</description>
        <time_frame>Day 1 up to at least 28 days after last dose of study medication (maximum of 33 days).</time_frame>
        <population>The analysis population included all participants who received at least 1 dose of study medication.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: Normal Renal Function</title>
            <description>Participants with normal renal function received 30-minute IV loading dose infusion (500/167 mg aztreonam [ATM]/avibactam [AVI]), followed by 3-hour IV extended loading infusion (1500/500 mg ATM/AVI), then 3-hour 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours on Days 1 to 3.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2: Severe Renal Impairment</title>
            <description>Participants with severe renal impairment (not on dialysis) received 30-minute IV loading dose infusion (675/255 mg aztreonam [ATM]/avibactam [AVI]), followed by 3-hour IV extended loading infusion (675/255 mg ATM/AVI), then 3-hour 675/255 mg ATM/AVI maintenance dose infusion every 8 hours on Days 1 to 3.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With TEAEs (Treatment-related)</title>
          <description>An adverse event (AE) is any untoward medical occurrence in a study participant administered a product; the event attributed to the study medication. A serious AE is any untoward medical occurrence at any dose that: (1) results in death; (2) is life threatening (immediate risk of death); (3) requires inpatient hospitalization or prolongation of existing hospitalization; (4) results in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); (5) results in congenital anomaly/birth defect; or that is considered to be an important medical event. Treatment-emergent are events between first dose of study medication and up to at least 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. A severe AE is defined as a event interferes significantly with participant's usual function.</description>
          <population>The analysis population included all participants who received at least 1 dose of study medication.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Participants with AEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participants with serious AEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participants with severe AEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participants discontinued from study due to AEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participants discontinued study drug due to AEs and continue study</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participants with dose reduced or temporary discontinuation due to AEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Categorical Post-Baseline Vital Signs Data</title>
        <description>Categorical post-baseline vital signs included: (1) pulse rate: value less than (&lt;) 40 beats per minute (bpm), lager than (&gt;) 120 bpm; (2) supine diastolic blood pressure (DBP): value &lt;50 mmHg, change of more than or equal to (&gt;=) 20 mmHg increase, change of &gt;=20 mmHg decrease; (3) supine systolic blood pressure (SBP): value &lt;90 mmHg, change of &gt;=30 mmHg increase, change of &gt;=30 mmHg decrease.</description>
        <time_frame>Days 1 to 3</time_frame>
        <population>The analysis population included all participants who received at least 1 dose of study medication.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: Normal Renal Function</title>
            <description>Participants with normal renal function received 30-minute IV loading dose infusion (500/167 mg aztreonam [ATM]/avibactam [AVI]), followed by 3-hour IV extended loading infusion (1500/500 mg ATM/AVI), then 3-hour 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours on Days 1 to 3.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2: Severe Renal Impairment</title>
            <description>Participants with severe renal impairment (not on dialysis) received 30-minute IV loading dose infusion (675/255 mg aztreonam [ATM]/avibactam [AVI]), followed by 3-hour IV extended loading infusion (675/255 mg ATM/AVI), then 3-hour 675/255 mg ATM/AVI maintenance dose infusion every 8 hours on Days 1 to 3.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Categorical Post-Baseline Vital Signs Data</title>
          <description>Categorical post-baseline vital signs included: (1) pulse rate: value less than (&lt;) 40 beats per minute (bpm), lager than (&gt;) 120 bpm; (2) supine diastolic blood pressure (DBP): value &lt;50 mmHg, change of more than or equal to (&gt;=) 20 mmHg increase, change of &gt;=20 mmHg decrease; (3) supine systolic blood pressure (SBP): value &lt;90 mmHg, change of &gt;=30 mmHg increase, change of &gt;=30 mmHg decrease.</description>
          <population>The analysis population included all participants who received at least 1 dose of study medication.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Pulse rate &lt;40 bpm</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pulse rate &gt;120 bpm</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Supine DBP &lt;50 mmHg</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Supine DBP change &gt;=20 mmHg increase</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Supine DBP change &gt;=20 mmHg decrease</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Supine SBP &lt;90 mmHg</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Supine SBP change &gt;=30 mmHg increase</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Supine SBP change &gt;=30 mmHg decrease</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Abnormal Electrocardiogram (ECG)</title>
        <description>Criteria for ECG abnormalities: maximum QT interval &gt;500 milliseconds (msec); maximum QTc interval of &gt;=450 msec to less than or equal to (&lt;=) 480 msec, &gt;480 msec, and &gt;500 msec and a maximum change of &lt;30 change&lt;=60 or &gt;60 msec from baseline; maximum QTcF (Fridericia's Correction) interval of &gt;=450 msec to &lt;=480 msec, &gt;480 msec, and &gt;500 msec and a maximum change of &lt;30 change&lt;=60 or &gt;60 msec from baseline.</description>
        <time_frame>Days 1 to 3</time_frame>
        <population>The analysis population included all participants who received at least 1 dose of study medication.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: Normal Renal Function</title>
            <description>Participants with normal renal function received 30-minute IV loading dose infusion (500/167 mg aztreonam [ATM]/avibactam [AVI]), followed by 3-hour IV extended loading infusion (1500/500 mg ATM/AVI), then 3-hour 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours on Days 1 to 3.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2: Severe Renal Impairment</title>
            <description>Participants with severe renal impairment (not on dialysis) received 30-minute IV loading dose infusion (675/255 mg aztreonam [ATM]/avibactam [AVI]), followed by 3-hour IV extended loading infusion (675/255 mg ATM/AVI), then 3-hour 675/255 mg ATM/AVI maintenance dose infusion every 8 hours on Days 1 to 3.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Abnormal Electrocardiogram (ECG)</title>
          <description>Criteria for ECG abnormalities: maximum QT interval &gt;500 milliseconds (msec); maximum QTc interval of &gt;=450 msec to less than or equal to (&lt;=) 480 msec, &gt;480 msec, and &gt;500 msec and a maximum change of &lt;30 change&lt;=60 or &gt;60 msec from baseline; maximum QTcF (Fridericia's Correction) interval of &gt;=450 msec to &lt;=480 msec, &gt;480 msec, and &gt;500 msec and a maximum change of &lt;30 change&lt;=60 or &gt;60 msec from baseline.</description>
          <population>The analysis population included all participants who received at least 1 dose of study medication.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>QT interval value &gt; 500 msec</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>450 msec&lt;= QTc interval value &lt;=480 msec</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>QTc interval value &gt;480 msec</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>QTc interval value &gt;500 msec</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>30 msec&lt; QTc interval change &lt;=60 msec</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>QTc interval change &gt;60 msec</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>450 msec&lt;= QTcF interval value &lt;=480 msec</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>QTcF interval value &gt;480 msec</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>QTcF interval value &gt;500 msec</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>30 msec&lt; QTcF interval change &lt;=60 msec</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>QTcF interval change &gt;60 msec</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)</title>
        <description>Following laboratory parameters were abnormal (without regard to baseline abnormality): hemoglobin, hematocrit, erythrocytes, lymphocytes, neutrophils, activated partial thromboplastin time, protein, urea nitrogen, creatinine, urate, urine glucose, and urine protein.</description>
        <time_frame>Days 1 to 3</time_frame>
        <population>The analysis population included all participants who received at least 1 dose of study medication.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: Normal Renal Function</title>
            <description>Participants with normal renal function received 30-minute IV loading dose infusion (500/167 mg aztreonam [ATM]/avibactam [AVI]), followed by 3-hour IV extended loading infusion (1500/500 mg ATM/AVI), then 3-hour 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours on Days 1 to 3.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2: Severe Renal Impairment</title>
            <description>Participants with severe renal impairment (not on dialysis) received 30-minute IV loading dose infusion (675/255 mg aztreonam [ATM]/avibactam [AVI]), followed by 3-hour IV extended loading infusion (675/255 mg ATM/AVI), then 3-hour 675/255 mg ATM/AVI maintenance dose infusion every 8 hours on Days 1 to 3.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)</title>
          <description>Following laboratory parameters were abnormal (without regard to baseline abnormality): hemoglobin, hematocrit, erythrocytes, lymphocytes, neutrophils, activated partial thromboplastin time, protein, urea nitrogen, creatinine, urate, urine glucose, and urine protein.</description>
          <population>The analysis population included all participants who received at least 1 dose of study medication.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Hemoglobin (gram per deciliter [g/dL]) &lt;0.8*lower limit of normal (LLN)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hematocrit (%) &lt;0.8*LLN</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Erythrocytes (10^6 per cubic millimeter [10^6/mm^3]) &lt;0.8*LLN</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lymphocytes (10^3 per cubic millimeter [10^3/mm^3]) &lt;0.8*LLN</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Neutrophils (10^3/mm^3) &gt;1.2*upper limit of normal (ULN)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Activated partial thromboplastin time (second) &gt;1.1*ULN</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Protein (g/dL) &lt;0.8*LLN</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Urea Nitrogen (milligram per deciliter [mg/dL]) &gt;1.3*ULN</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Creatinine (mg/dL) &gt;1.3*ULN</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Urate (mg/dL) &gt;1.2*ULN</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Urine glucose (mg/dL) &gt;=1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Urine protein (mg/dL) &gt;=1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Day 1 up to at least 28 days after last dose of study drug (maximum of 33 days).</time_frame>
      <desc>Participants were only counted once per treatment for each category.</desc>
      <group_list>
        <group group_id="E1">
          <title>Cohort 1: Normal Renal Function</title>
          <description>Participants with normal renal function received 30-minute IV loading dose infusion (500/167 mg aztreonam [ATM]/avibactam [AVI]), followed by 3-hour IV extended loading infusion (1500/500 mg ATM/AVI), then 3-hour 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours on Days 1 to 3.</description>
        </group>
        <group group_id="E2">
          <title>Cohort 2: Severe Renal Impairment</title>
          <description>Participants with severe renal impairment (not on dialysis) received 30-minute IV loading dose infusion (675/255 mg aztreonam [ATM]/avibactam [AVI]), followed by 3-hour IV extended loading infusion (675/255 mg ATM/AVI), then 3-hour 675/255 mg ATM/AVI maintenance dose infusion every 8 hours on Days 1 to 3.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA v24.1</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="5"/>
              </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="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
              </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="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Dermatitis contact</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Pfizer ClinicalTrials.gov Call Center</name_or_title>
      <organization>Pfizer Inc.</organization>
      <phone>1-800-718-1021</phone>
      <email>ClinicalTrials.gov_Inquiries@pfizer.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/NCT04486625
org study id: C3601006
nct id: NCT04486625
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This Phase 1 study is being conducted to evaluate the effect of severe renal impairment on
      the PK, safety and tolerability of Aztreonam-Avibactam. Results from this study along with
      previous renal impairment data from each of the Aztreonam-Avibactam components will be used
      to confirm the proposed dosing adjustment in severe renal impairment which was based on
      modelling/simulation.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: None (Open Label)
measure: Total Daily Area Under the Plasma Concentration-time Profile From Time 0 to 24 Hours at Steady-state (AUC0-24,ss) of Aztreonam (ATM)
time frame: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.
description: AUC0-24,ss of ATM in Cohort 1 was calculated by 4*AUC0-tau (tau = 6 hours), where AUC0-tau was area under the concentration-time profile from time 0 to time tau (the dosing interval). AUC0-24,ss of ATM in Cohort 2 was calculated by 3*AUC0-tau (tau = 8 hours), where AUC0-tau was area under the plasma concentration-time profile from time 0 to time tau (the dosing interval).
measure: Maximum Plasma Concentration (Cmax) of ATM
time frame: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.
description: The Cmax of ATM was observed directly from data.
measure: AUC0-24,ss of Avibactam (AVI)
time frame: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.
description: AUC0-24,ss of AVI in Cohort 1 was calculated by 4*AUC0-tau (tau = 6 hours), where AUC0-tau was area under the concentration-time profile from time 0 to time tau (the dosing interval). AUC0-24,ss of AVI in Cohort 2 was calculated by 3*AUC0-tau (tau = 8 hours), where AUC0-tau was area under the plasma concentration-time profile from time 0 to time tau (the dosing interval).
measure: Cmax of AVI
time frame: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.
description: The Cmax of AVI was observed directly from data.
measure: Area Under the Plasma Concentration-time Profile From Time 0 to Time Tau (The Dosing Interval)(AUC0-tau) of ATM
time frame: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.
description: The AUC0-tau was calculated by linear/log trapezoidal method. The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).
measure: Time for Cmax (Tmax) of ATM
time frame: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.
description: The Tmax was observed directly from data as time of first occurrence.
measure: Observed Plasma Concentration at the End of the Dosing Interval (Tau) (Ctau) of ATM
time frame: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.
description: The Ctau was observed directly from data. The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).
measure: Terminal Elimination Half-life (t1/2) of ATM
time frame: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.
description: The t1/2 was calculated by loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log linear concentration time curve. Only those data points judged to describe the terminal log linear decline were used in the regression.
measure: Clearance (CL) of ATM
time frame: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.
description: The CL was calculated by dose/AUC0-tau, where AUC0-tau was area under the concentration-time profile from time 0 to time tau (the dosing interval). The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).
measure: Renal Clearance (CLr) of ATM
time frame: In Cohort 1, at predose on Day 3, during 0-2, 2-4, and 4-6 hours after the start of a maintenance dose infusion. In Cohort 2, at predose on Day 3, during 0-2, 2-4, 4-6, and 6-8 hours after the start of a maintenance dose infusion.
description: The CLr was calculated by Ae0-tau/AUC0-tau, where Ae0-tau was cumulative amount of drug recovered unchanged in urine up to time tau and AUC0-tau was area under the plasma concentration time profile from time 0 to time tau (the dosing interval). The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).
measure: Apparent Volume of Distribution (Vz) of ATM
time frame: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.
description: The Vz was calculated by dose/(AUC0-tau*kel), where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve and AUC0-tau was area under the concentration-time profile from time 0 to time tau (the dosing interval). The dosing interval (tau) was 6 hours for the normal renal function group (Cohort 1) and 8 hours for the severe renal impairment group (Cohort 2).
measure: Apparent Volume of Distribution at Steady-state (Vss) of ATM
time frame: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.
description: Vss was calculated by CL*MRT, where CL was clearance and MRT was mean residence time.
measure: Cumulative Amount of Drug Recovered Unchanged in Urine up to Time Tau (Ae0-tau) of ATM
time frame: In Cohort 1, at predose on Day 3, during 0-2, 2-4, and 4-6 hours after the start of a maintenance dose infusion. In Cohort 2, at predose on Day 3, during 0-2, 2-4, 4-6, and 6-8 hours after the start of a maintenance dose infusion.
description: The Ae0-tau was the sum of (urine concentration*sample volume). The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).
measure: Percent of Dose Recovered Unchanged in Urine up to Time Tau (Ae0-tau%) of ATM
time frame: In Cohort 1, at predose on Day 3, during 0-2, 2-4, and 4-6 hours after the start of a maintenance dose infusion. In Cohort 2, at predose on Day 3, during 0-2, 2-4, 4-6, and 6-8 hours after the start of a maintenance dose infusion.
description: The Ae0-tau was calculated by 100*Ae0-tau/dose, where Ae0-tau was cumulative amount of drug recovered unchanged in urine up to time tau. The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).
measure: AUC0-tau of AVI
time frame: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.
description: The UC0-tau was calculated by linear/log trapezoidal method. The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).A
measure: Tmax of AVI
time frame: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.
description: The Tmax was observed directly from data as time of first occurrence.
measure: Ctau of AVI
time frame: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.
description: The Ctau was observed directly from data. The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).
measure: t1/2 of AVI
time frame: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.
description: The t1/2 was calculated by loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log linear concentration time curve. Only those data points judged to describe the terminal log linear decline were used in the regression.
measure: CL of AVI
time frame: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.
description: The CL was calculated by dose/AUC0-tau, where AUC0-tau was area under the plasma concentration-time profile from time 0 to to time tau (the dosing interval). The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).
measure: CLr of AVI
time frame: In Cohort 1, at predose on Day 3, during 0-2, 2-4, and 4-6 hours after the start of a maintenance dose infusion. In Cohort 2, at predose on Day 3, during 0-2, 2-4, 4-6, and 6-8 hours after the start of a maintenance dose infusion.
description: The CLr was calculated by Ae0-tau/AUC0-tau, where Ae0-tau was cumulative amount of drug recovered unchanged in urine up to time tau and AUC0-tau was area under the plasma concentration time profile from time 0 to time tau (the dosing interval). The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).
measure: Vz of AVI
time frame: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.
description: The Vz was calculated by dose/(AUC0-tau*kel), where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve and AUC0-tau was area under the concentration-time profile from time 0 to time tau (the dosing interval). The dosing interval (tau) was 6 hours for the normal renal function group (Cohort 1) and 8 hours for the severe renal impairment group (Cohort 2).
measure: Vss of AVI
time frame: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.
description: Vss was calculated by CL*MRT, where CL was clearance and MRT was mean residence time.
measure: Ae0-tau of AVI
time frame: In Cohort 1, at predose on Day 3, during 0-2, 2-4, and 4-6 hours after the start of a maintenance dose infusion. In Cohort 2, at predose on Day 3, during 0-2, 2-4, 4-6, and 6-8 hours after the start of a maintenance dose infusion.
description: The Ae0-tau was the sum of (urine concentration*sample volume). The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).
measure: Ae0-tau% of AVI
time frame: In Cohort 1, at predose on Day 3, during 0-2, 2-4, and 4-6 hours after the start of a maintenance dose infusion. In Cohort 2, at predose on Day 3, during 0-2, 2-4, 4-6, and 6-8 hours after the start of a maintenance dose infusion.
description: The Ae0-tau was calculated by 100*Ae0-tau/dose, where Ae0-tau was cumulative amount of drug recovered unchanged in urine up to time tau. The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) (All-causality)
time frame: Day 1 up to at least 28 days after last dose of study medication (maximum of 33 days).
description: An adverse event (AE) is any untoward medical occurrence in a study participant administered a product; the event need not necessarily have a causal relationship with the treatment or usage. A serious adverse event is any untoward medical occurrence at any dose that: (1) results in death; (2) is life threatening (immediate risk of death); (3) requires inpatient hospitalization or prolongation of existing hospitalization; (4) results in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); (5) results in congenital anomaly/birth defect; or that is considered to be an important medical event. Treatment-emergent are events between first dose of study medication and up to at least 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. A severe AE is defined as a event interferes significantly with participant's usual function.
measure: Number of Participants With TEAEs (Treatment-related)
time frame: Day 1 up to at least 28 days after last dose of study medication (maximum of 33 days).
description: An adverse event (AE) is any untoward medical occurrence in a study participant administered a product; the event attributed to the study medication. A serious AE is any untoward medical occurrence at any dose that: (1) results in death; (2) is life threatening (immediate risk of death); (3) requires inpatient hospitalization or prolongation of existing hospitalization; (4) results in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); (5) results in congenital anomaly/birth defect; or that is considered to be an important medical event. Treatment-emergent are events between first dose of study medication and up to at least 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. A severe AE is defined as a event interferes significantly with participant's usual function.
measure: Number of Participants With Categorical Post-Baseline Vital Signs Data
time frame: Days 1 to 3
description: Categorical post-baseline vital signs included: (1) pulse rate: value less than (<) 40 beats per minute (bpm), lager than (>) 120 bpm; (2) supine diastolic blood pressure (DBP): value <50 mmHg, change of more than or equal to (>=) 20 mmHg increase, change of >=20 mmHg decrease; (3) supine systolic blood pressure (SBP): value <90 mmHg, change of >=30 mmHg increase, change of >=30 mmHg decrease.
measure: Number of Participants With Abnormal Electrocardiogram (ECG)
time frame: Days 1 to 3
description: Criteria for ECG abnormalities: maximum QT interval >500 milliseconds (msec); maximum QTc interval of >=450 msec to less than or equal to (<=) 480 msec, >480 msec, and >500 msec and a maximum change of <30 change<=60 or >60 msec from baseline; maximum QTcF (Fridericia's Correction) interval of >=450 msec to <=480 msec, >480 msec, and >500 msec and a maximum change of <30 change<=60 or >60 msec from baseline.
measure: Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)
time frame: Days 1 to 3
description: Following laboratory parameters were abnormal (without regard to baseline abnormality): hemoglobin, hematocrit, erythrocytes, lymphocytes, neutrophils, activated partial thromboplastin time, protein, urea nitrogen, creatinine, urate, urine glucose, and urine protein.
arm group label: Cohort 1
arm group type: Experimental
description: Normal renal function
arm group label: Cohort 2
arm group type: Experimental
description: Severe renal impairment (not on dialysis)
intervention type: Drug
intervention name: Aztreonam-Avibactam
description: 500/167 mg ATM/AVI loading infusion, followed by 1500/500 mg ATM/AVI extended loading infusion, then 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours
arm group label: Cohort 1
intervention type: Drug
intervention name: Aztreonam-Avibactam
description: 675/225 mg ATM/AVI loading infusion, followed by 675/225 mg ATM/AVI extended loading infusion, then 675/225 mg ATM/AVI maintenance dose infusion every 8 hours
arm group label: Cohort 2
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Pfizer CT.gov Call Center
role: Study Director
affiliation: Pfizer
facility: 
country: United States
url: https://pmiform.com/clinical-trial-info-request?StudyID=C3601006
description: To obtain contact information for a study center near you, click here.
responsible party type: Sponsor
mesh term: Renal Insufficiency
mesh term: Aztreonam
mesh term: Avibactam
sharing ipd: No
ipd description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 