<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/NCT03006679</url>
  </required_header>
  <id_info>
    <org_study_id>Rempex 509</org_study_id>
    <nct_id>NCT03006679</nct_id>
  </id_info>
  <brief_title>A Study of Meropenem-Vaborbactam Versus Piperacillin/Tazobactam in Participants With Hospital-Acquired and Ventilator-Associated Bacterial Pneumonia</brief_title>
  <acronym>TANGOIII</acronym>
  <official_title>A Phase IIIb, Multicenter, Double-Blind, Randomized, Comparative Study to Evaluate the Efficacy, Safety, and Tolerability of Meropenem-Vaborbactam Versus Piperacillin/Tazobactam in the Treatment of Hospital-Acquired Bacterial Pneumonia and Ventilator-Associated Bacterial Pneumonia in Hospitalized Adults (TANGO III)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Melinta Therapeutics, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Melinta Therapeutics, Inc.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine the efficacy, safety, tolerability, and&#xD;
      pharmacokinetics (PK) of meropenem-vaborbactam compared to piperacillin/tazobactam for 7 to&#xD;
      14 days in the treatment of hospitalized adults who meet clinical, radiographic, and&#xD;
      microbiological criteria for hospital-acquired bacterial pneumonia (HABP) or&#xD;
      ventilator-associated bacterial pneumonia (VABP).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Sponsor Decision&#xD;
  </why_stopped>
  <start_date type="Anticipated">August 2018</start_date>
  <completion_date type="Anticipated">December 2020</completion_date>
  <primary_completion_date type="Anticipated">June 2020</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Rate of Participants with All-Cause Mortality at Day 28 in the Intent-to-Treat (ITT) Population</measure>
    <time_frame>Day 28</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of Participants who Achieve a Clinical Outcome of Cure at the Test of Cure (TOC) Visit in the ITT and Clinically Evaluable (CE) Populations</measure>
    <time_frame>12-23 days (TOC visit) after first dose of study drug</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Rate of Participants with All-Cause Mortality at Day 14 in the ITT, microbiological Modified ITT (mMITT), CE, and Microbiologically Evaluable (ME) Populations</measure>
    <time_frame>Day 14</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of Participants with All-Cause Mortality at Day 28 in the mMITT, CE, and ME Populations</measure>
    <time_frame>Day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants with Clinical Outcome of Cure at EOT, TOC, and Last Follow Up (LFU) Visits in the ITT, CE, and ME Populations</measure>
    <time_frame>1 day (EOT visit), 12-23 days (TOC visit), and 19-30 days (LFU visit) after first dose of study drug</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants with Clinical Outcome of Cure per Pathogen at EOT, TOC, and LFU Visits in the mMITT and ME Populations</measure>
    <time_frame>1 day (EOT visit), 12-23 days (TOC visit), and 19-30 days (LFU visit) after first dose of study drug</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants with Microbiological Eradication Per-Participant and Per-Pathogen Microbiological Response at EOT and TOC visits in the mMITT and ME Populations</measure>
    <time_frame>1 day (EOT visit) and 12-23 days (TOC visit) after first dose of study drug</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants who Survive and Did Not Have a &quot;Major Nonfatal Event&quot; (Treatment-Emergent Events of Acute Respiratory Distress Syndrome, Septic Shock, or Pleural Empyema) up to Day 28 in the ITT and CE Populations</measure>
    <time_frame>Up to Day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of Meropenem</measure>
    <time_frame>Days 1 and 3</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics: Maximum Plasma Concentration (Cmax) of Meropenem</measure>
    <time_frame>Days 1 and 3</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics: Time to Maximum Plasma Concentration (Tmax) of Meropenem</measure>
    <time_frame>Days 1 and 3</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of Vaborbactam</measure>
    <time_frame>Days 1 and 3</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics: Maximum Plasma Concentration (Cmax) of Vaborbactam</measure>
    <time_frame>Days 1 and 3</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics: Time to Maximum Plasma Concentration (Tmax) of Vaborbactam</measure>
    <time_frame>Days 1 and 3</time_frame>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Hospital-Acquired Bacterial Pneumonia</condition>
  <condition>Ventilator-Associated Bacterial Pneumonia</condition>
  <condition>Hospital-Acquired Pneumonia</condition>
  <condition>Ventilator-Associated Pneumonia</condition>
  <arm_group>
    <arm_group_label>Meropenem-Vaborbactam HABP</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants with a clinical diagnosis of HABP will be treated with meropenem 2 grams (g) and vaborbactam 2 g in 250 milliliters (mL) infused intravenously for 3 hours every 8 hours for 7 days to a maximum of 14 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Piperacillin/Tazobactam HABP</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants with a clinical diagnosis of HABP will be treated with piperacillin 4 g and tazobactam 0.5 g in 100 mL infused intravenously for 30 minutes every 6 hours for 7 days to a maximum of 14 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Meropenem-Vaborbactam VABP</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants with a clinical diagnosis of VABP will be treated with meropenem 2 g and vaborbactam 2 g in 250 mL infused intravenously for 3 hours every 8 hours for 7 days to a maximum of 14 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Piperacillin/Tazobactam VABP</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants with a clinical diagnosis of VABP will be treated with piperacillin 4 g and tazobactam 0.5 g in 100 mL infused intravenously for 30 minutes every 6 hours for 7 days to a maximum of 14 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Meropenem-Vaborbactam</intervention_name>
    <description>meropenem 2 g and vaborbactam 2 g</description>
    <arm_group_label>Meropenem-Vaborbactam HABP</arm_group_label>
    <arm_group_label>Meropenem-Vaborbactam VABP</arm_group_label>
    <other_name>Carbavance</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Piperacillin/Tazobactam</intervention_name>
    <description>piperacillin 4 g and tazobactam 0.5 g</description>
    <arm_group_label>Piperacillin/Tazobactam HABP</arm_group_label>
    <arm_group_label>Piperacillin/Tazobactam VABP</arm_group_label>
    <other_name>Zosyn</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Willingness to comply with all study procedures and provide a signed written informed&#xD;
             consent prior to any study-specific procedures; however, if unable to do so, the&#xD;
             participant's legally authorized representative may provide written consent as&#xD;
             approved by institutional-specific guidelines. Participants who are unconscious or&#xD;
             considered by the investigator to be clinically unable to consent at Screening and who&#xD;
             are entered into the study by the consent of a legally authorized representative,&#xD;
             should provide their own written informed consent for continuing to participate in the&#xD;
             study as soon as possible on recovery, as applicable in accordance with local&#xD;
             regulations.&#xD;
&#xD;
          2. Hospitalized male or female participants, ≥18 years of age.&#xD;
&#xD;
          3. Females must be surgically sterile or at least 2 years postmenopausal, or if of&#xD;
             childbearing potential, have a negative screening urine pregnancy test and be willing&#xD;
             to practice sexual abstinence or use an accepted form of contraception with her&#xD;
             partner (for example, barrier or hormonal methods) during treatment and for at least&#xD;
             28 days after the last dose of study drug.&#xD;
&#xD;
          4. Expectation, in the opinion of the Investigator, that the participant's infection will&#xD;
             require treatment with IV antibiotics for a minimum of 7 days.&#xD;
&#xD;
          5. Have a confirmed diagnosis of HABP or VABP requiring antibiotic therapy by meeting all&#xD;
             clinical, microbiological, and radiographic criteria as defined in the following:&#xD;
&#xD;
        For HABP participants:&#xD;
&#xD;
        To meet the study definition of HABP, participants must meet all of the following clinical,&#xD;
        microbiological, and radiographic criteria:&#xD;
&#xD;
          1. A chest radiograph (chest X-ray [CXR], magnetic resonance imaging [MRI] or computed&#xD;
             tomography [CT]) reveals the presence of new or progressive pulmonary infiltrate(s)&#xD;
             consistent with bacterial pneumonia within 48 hours prior to randomization.&#xD;
&#xD;
          2. Onset of symptoms at least 48 hours after hospitalization or within 7 days after&#xD;
             discharge from an inpatient acute or chronic care facility (for example, long-term&#xD;
             care, rehabilitation center, hospital, or skilled nursing home).&#xD;
&#xD;
          3. Have at least one of the following:&#xD;
&#xD;
               1. Temperature ≥38.0 degrees Celsius (100.4 degrees Fahrenheit) or ≤35 degrees&#xD;
                  Celsius (95.0 degrees Fahrenheit).&#xD;
&#xD;
               2. Peripheral white blood cell (WBC) count ≥10,000 cells/cubic millimeter (mm^3) or&#xD;
                  ≤4,500 cells/mm^3.&#xD;
&#xD;
               3. ≥15 percent immature neutrophils (band forms) regardless of total WBC count.&#xD;
&#xD;
          4. Have at least one of the following:&#xD;
&#xD;
               1. New onset of cough or expectorated sputum production (or worsening of baseline&#xD;
                  cough).&#xD;
&#xD;
               2. Auscultatory findings on pulmonary examination consistent with bacterial&#xD;
                  pneumonia or pulmonary consolidation (for example, rales, dullness on percussion,&#xD;
                  bronchial breath sounds, or ego phony).&#xD;
&#xD;
               3. Dyspnea or tachypnea (that is, respiratory rate greater than 25 breaths/minute).&#xD;
&#xD;
               4. Hypoxemia (O2 saturation ≤90 percent or pO2 ≤60 millimeters of mercury [mmHg]&#xD;
                  while breathing room air, or worsening of the O2 saturation/FiO2).&#xD;
&#xD;
               5. New onset need for mechanical ventilation.&#xD;
&#xD;
               6. A deep respiratory secretion specimen that was collected within 48 hours prior to&#xD;
                  randomization and after development of clinical signs and symptoms of HABP&#xD;
                  (ideally prior to administration of systemic antimicrobial therapy). This can be&#xD;
                  obtained via a sputum sample (expectorated sputum), bronchoalveolar lavage (BAL)&#xD;
                  (including protected BAL or mini-BAL), protected specimen brush (PSB),&#xD;
                  endotracheal tube aspirate (ETA), pleural fluid, or lung parenchyma (open-lung,&#xD;
                  transthoracic, or transbronchial biopsy).&#xD;
&#xD;
               7. This deep respiratory secretion sample must meet adequacy criteria for testing,&#xD;
                  and be sent to the local or regional laboratory for Gram stain and culture&#xD;
                  (results of Gram stain and culture do not have to be available for enrollment).&#xD;
&#xD;
        For VABP participants:&#xD;
&#xD;
        To meet the study definition of VABP, participants must meet all of the following clinical,&#xD;
        microbiological, and radiographic criteria:&#xD;
&#xD;
          1. A chest radiograph (CXR, MRI or CT) revealing the presence of new or progressive&#xD;
             pulmonary infiltrate(s) consistent with bacterial pneumonia within 48 hours prior to&#xD;
             randomization.&#xD;
&#xD;
          2. Receiving mechanical ventilation via endotracheal intubation or tracheostomy for&#xD;
             greater than or equal to 48 hours.&#xD;
&#xD;
          3. Have at least one of the following:&#xD;
&#xD;
               1. Temperature ≥38.0 degrees Celsius (100.4 degrees Fahrenheit) or ≤35 degrees&#xD;
                  Celsius (95.0 degrees Fahrenheit).&#xD;
&#xD;
               2. Peripheral white blood cell (WBC) count ≥10,000 cells/mm^3 or ≤4,500 cells/mm^3.&#xD;
&#xD;
               3. ≥15 percent immature neutrophils (band forms) regardless of total WBC count.&#xD;
&#xD;
          4. Have at least one of the following:&#xD;
&#xD;
               1. New onset of purulent respiratory secretions from the lungs or new onset of or&#xD;
                  increased need for respiratory secretion suctioning.&#xD;
&#xD;
               2. Auscultatory findings on pulmonary examination consistent with bacterial&#xD;
                  pneumonia or pulmonary consolidation (for example, rales, dullness on percussion,&#xD;
                  bronchial breath sounds, or egophony).&#xD;
&#xD;
               3. Worsening gas exchange (ratio of partial pressure of arterial oxygen to fraction&#xD;
                  of inspired oxygen [PaO2/FiO2] ≤240 or PaO2 ≤60 mmHg) leading to acute changes to&#xD;
                  the ventilator support system (minimum daily FiO2 values increased by at least&#xD;
                  0.20 over the daily minimum FiO2 in the preceding 48 hours, or minimum daily&#xD;
                  positive end- expiratory pressure (PEEP) values increased by at least 3&#xD;
                  centimeters (cm) H2O over the daily minimum PEEP in the preceding 48 hours).&#xD;
&#xD;
          5. A deep respiratory secretion specimen must be collected within 48 hours prior to&#xD;
             randomization and after development of clinical signs and symptoms of VABP (ideally&#xD;
             prior to administration of systemic antimicrobial therapy). This can be obtained via&#xD;
             BAL (including protected BAL or mini-BAL), PSB, or ETA, pleural fluid, or lung&#xD;
             parenchyma (open-lung, transthoracic, or transbronchial biopsy).&#xD;
&#xD;
          6. The above deep respiratory secretion sample must meet adequacy criteria for testing&#xD;
             and be sent to the local or regional laboratory for Gram stain and culture (results of&#xD;
             Gram stain and culture do not have to be available for enrollment).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Participants who meet any of the following exclusion criteria will not be enrolled in the&#xD;
        study:&#xD;
&#xD;
          1. History of any severe hypersensitivity to any beta-lactam antibiotic (for example,&#xD;
             cephalosporins, penicillins, or carbapenems).&#xD;
&#xD;
          2. History of any severe allergic reaction that would preclude the use of either all&#xD;
             aminoglycosides or adjunctive gram-positive antimicrobials (that is, allergy to both&#xD;
             glycopeptides and oxazolidinones).&#xD;
&#xD;
          3. Requirement or anticipated need for additional systemic antibiotic (other than study&#xD;
             drug) or antifungal, including prophylactic antimicrobials and antifungals.&#xD;
&#xD;
          4. Requirement or anticipated need for more than 14 days of systemic antimicrobial&#xD;
             therapy to treat HABP or VABP.&#xD;
&#xD;
          5. Known deep-tissue infection (including undrained abscess, meningitis, endocarditis, or&#xD;
             osteomyelitis) within 7 days prior to randomization.&#xD;
&#xD;
          6. Participant has received more than 24 hours of any potentially effective systemic&#xD;
             antibacterial therapy for the current episode of HABP or VABP within 72 hours before&#xD;
             randomization. Exceptions:&#xD;
&#xD;
               1. Evidence of clinical failure of the current episode of HABP or VABP (for example,&#xD;
                  worsening signs and symptoms) following at least 48 hours of prior systemic&#xD;
                  antimicrobial therapy (participants with evidence of clinical failure of&#xD;
                  piperacillin/tazobactam are not eligible for inclusion), or&#xD;
&#xD;
               2. The clinical symptoms and signs of the current episode of HABP or VABP started at&#xD;
                  least 48 hours after the prior antibacterial therapy was initiated.&#xD;
&#xD;
          7. Pulmonary disease that precludes evaluation of a therapeutic response (including, but&#xD;
             not limited to, lung cancer, active tuberculosis, cystic fibrosis, granulomatous&#xD;
             disease, fungal pulmonary infection, pulmonary embolism, lung abscess, pleural&#xD;
             empyema, or post obstructive pneumonia).&#xD;
&#xD;
          8. Known human immunodeficiency virus (HIV) positivity and meets an acquired immune&#xD;
             deficiency syndrome (AIDS)-defining illness or has a documented CD4 count &lt;200/&#xD;
             microliter (μL) within the past year.&#xD;
&#xD;
          9. Treatment within 30 days prior to enrollment with bone-marrow suppressive chemotherapy&#xD;
             (non-bone marrow suppressive chemotherapy is permitted), high dose steroids,&#xD;
             immunosuppressive medications for transplantation, or medications for rejection of&#xD;
             transplantation.&#xD;
&#xD;
         10. Fulminant hepatitis; current cirrhosis or clinical manifestations of end-stage liver&#xD;
             disease (for example, ascites or hepatic encephalopathy); acute hepatic failure or&#xD;
             acute decompensation of chronic hepatic failure; or aspartate aminotransferase (AST)&#xD;
             or alanine aminotransferase (ALT) level greater than 5-fold the upper limit of normal&#xD;
             or total bilirubin greater than 3-fold the upper limit of normal using local or&#xD;
             regional laboratory reference values.&#xD;
&#xD;
         11. Requirement for peritoneal dialysis or continuous renal replacement therapy (including&#xD;
             continuous venovenous hemofiltration [CVVH], continuous venovenous hemodialysis&#xD;
             [CVVHD], and continuous venovenous hemodiafiltration [CVVHDF]) (Note, standard&#xD;
             intermittent hemodialysis is not exclusionary).&#xD;
&#xD;
         12. Females who are pregnant or breastfeeding.&#xD;
&#xD;
         13. Participation in any study involving administration of an investigational agent or&#xD;
             device within 30 days prior to randomization into this study or previous participation&#xD;
             in the current study or any study of vaborbactam or meropenem vaborbactam.&#xD;
&#xD;
         14. Any condition that would make the participant, in the opinion of the Investigator,&#xD;
             unsuitable for the study (for example, would place a participant at risk or compromise&#xD;
             the quality of the data), including participants with a high likelihood of death&#xD;
             within 72 hours after randomization despite adequate antimicrobial therapy for HABP or&#xD;
             VABP or participants with a &quot;do not resuscitate&quot; order.&#xD;
&#xD;
         15. An employee of the Investigator or study center with direct involvement in the&#xD;
             proposed study or other studies under the direction of that Investigator or study&#xD;
             center, or a family member of the employee or the Investigator.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>December 15, 2016</study_first_submitted>
  <study_first_submitted_qc>December 27, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 30, 2016</study_first_posted>
  <last_update_submitted>January 9, 2019</last_update_submitted>
  <last_update_submitted_qc>January 9, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 11, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pneumonia</mesh_term>
    <mesh_term>Pneumonia, Ventilator-Associated</mesh_term>
    <mesh_term>Pneumonia, Bacterial</mesh_term>
    <mesh_term>Healthcare-Associated Pneumonia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Meropenem</mesh_term>
    <mesh_term>Tazobactam</mesh_term>
    <mesh_term>Piperacillin</mesh_term>
    <mesh_term>Piperacillin, Tazobactam Drug Combination</mesh_term>
    <mesh_term>Vaborbactam</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03006679
org study id: Rempex 509
nct id: NCT03006679
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to determine the efficacy, safety, tolerability, and
      pharmacokinetics (PK) of meropenem-vaborbactam compared to piperacillin/tazobactam for 7 to
      14 days in the treatment of hospitalized adults who meet clinical, radiographic, and
      microbiological criteria for hospital-acquired bacterial pneumonia (HABP) or
      ventilator-associated bacterial pneumonia (VABP).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Rate of Participants with All-Cause Mortality at Day 28 in the Intent-to-Treat (ITT) Population
time frame: Day 28
measure: Percentage of Participants who Achieve a Clinical Outcome of Cure at the Test of Cure (TOC) Visit in the ITT and Clinically Evaluable (CE) Populations
time frame: 12-23 days (TOC visit) after first dose of study drug
measure: Rate of Participants with All-Cause Mortality at Day 14 in the ITT, microbiological Modified ITT (mMITT), CE, and Microbiologically Evaluable (ME) Populations
time frame: Day 14
measure: Rate of Participants with All-Cause Mortality at Day 28 in the mMITT, CE, and ME Populations
time frame: Day 28
measure: Percentage of Participants with Clinical Outcome of Cure at EOT, TOC, and Last Follow Up (LFU) Visits in the ITT, CE, and ME Populations
time frame: 1 day (EOT visit), 12-23 days (TOC visit), and 19-30 days (LFU visit) after first dose of study drug
measure: Percentage of Participants with Clinical Outcome of Cure per Pathogen at EOT, TOC, and LFU Visits in the mMITT and ME Populations
time frame: 1 day (EOT visit), 12-23 days (TOC visit), and 19-30 days (LFU visit) after first dose of study drug
measure: Percentage of Participants with Microbiological Eradication Per-Participant and Per-Pathogen Microbiological Response at EOT and TOC visits in the mMITT and ME Populations
time frame: 1 day (EOT visit) and 12-23 days (TOC visit) after first dose of study drug
measure: Percentage of Participants who Survive and Did Not Have a "Major Nonfatal Event" (Treatment-Emergent Events of Acute Respiratory Distress Syndrome, Septic Shock, or Pleural Empyema) up to Day 28 in the ITT and CE Populations
time frame: Up to Day 28
measure: Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of Meropenem
time frame: Days 1 and 3
measure: Pharmacokinetics: Maximum Plasma Concentration (Cmax) of Meropenem
time frame: Days 1 and 3
measure: Pharmacokinetics: Time to Maximum Plasma Concentration (Tmax) of Meropenem
time frame: Days 1 and 3
measure: Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of Vaborbactam
time frame: Days 1 and 3
measure: Pharmacokinetics: Maximum Plasma Concentration (Cmax) of Vaborbactam
time frame: Days 1 and 3
measure: Pharmacokinetics: Time to Maximum Plasma Concentration (Tmax) of Vaborbactam
time frame: Days 1 and 3
arm group label: Meropenem-Vaborbactam HABP
arm group type: Experimental
description: Participants with a clinical diagnosis of HABP will be treated with meropenem 2 grams (g) and vaborbactam 2 g in 250 milliliters (mL) infused intravenously for 3 hours every 8 hours for 7 days to a maximum of 14 days.
arm group label: Piperacillin/Tazobactam HABP
arm group type: Active Comparator
description: Participants with a clinical diagnosis of HABP will be treated with piperacillin 4 g and tazobactam 0.5 g in 100 mL infused intravenously for 30 minutes every 6 hours for 7 days to a maximum of 14 days.
arm group label: Meropenem-Vaborbactam VABP
arm group type: Experimental
description: Participants with a clinical diagnosis of VABP will be treated with meropenem 2 g and vaborbactam 2 g in 250 mL infused intravenously for 3 hours every 8 hours for 7 days to a maximum of 14 days.
arm group label: Piperacillin/Tazobactam VABP
arm group type: Active Comparator
description: Participants with a clinical diagnosis of VABP will be treated with piperacillin 4 g and tazobactam 0.5 g in 100 mL infused intravenously for 30 minutes every 6 hours for 7 days to a maximum of 14 days.
intervention type: Drug
intervention name: Meropenem-Vaborbactam
description: meropenem 2 g and vaborbactam 2 g
arm group label: Meropenem-Vaborbactam HABP
arm group label: Meropenem-Vaborbactam VABP
other name: Carbavance
intervention type: Drug
intervention name: Piperacillin/Tazobactam
description: piperacillin 4 g and tazobactam 0.5 g
arm group label: Piperacillin/Tazobactam HABP
arm group label: Piperacillin/Tazobactam VABP
other name: Zosyn
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
responsible party type: Sponsor
mesh term: Pneumonia
mesh term: Pneumonia, Ventilator-Associated
mesh term: Pneumonia, Bacterial
mesh term: Healthcare-Associated Pneumonia
mesh term: Meropenem
mesh term: Tazobactam
mesh term: Piperacillin
mesh term: Piperacillin, Tazobactam Drug Combination
mesh term: Vaborbactam