Outcome
| Type |
Measure |
Description |
Time frame |
Safety issue |
| Other |
Percentage of Participants With Clinical Cure at End of Treatment (EOT) Visit: ITT Analysis Set |
Clinical cure was defined as improvement in baseline signs and symptoms such that after study treatment, no further antimicrobial treatment for the index infection (i.e., cIAI or HAP/VAP) was required. Additionally, for cIAI participants, no unplanned drainage or surgical intervention was necessary since the initial procedure. Clinical cure was determined by the Independent Clinical Adjudication Committee. 95% CI was based on Jeffrey's method. |
At EOT visit (Within 24 hours after last infusion on Day 14) |
|
| Other |
Percentage of Participants With Clinical Cure at EOT Visit: Micro-ITT Analysis Set |
Clinical cure was defined as improvement in baseline signs and symptoms such that after study treatment, no further antimicrobial treatment for the index infection (i.e., cIAI or HAP/VAP) was required. For cIAI participants, no unplanned drainage or surgical intervention was necessary since the initial procedure. Clinical cure was determined by the Independent Clinical Adjudication Committee. 95% CI was based on Jeffrey's method. |
At EOT visit (Within 24 hours after last infusion on Day 14) |
|
| Other |
Percentage of Participants With Clinical Cure at EOT Visit: CE Analysis Set |
Clinical cure = improvement in baseline signs and symptoms such that after study treatment, no further antimicrobial treatment for the index infection (i.e., cIAI or HAP/VAP) was required. Additionally, for cIAI participants, no unplanned drainage or surgical intervention was necessary since the initial procedure. Clinical cure was determined by the Independent Clinical Adjudication Committee. 95% CI was based on Jeffrey's method. CE analysis set: all participants in ITT analysis set; met criteria for cIAI, or HAP/VAP; received at least 48 hours of study treatment or <48 hours of treatment before discontinuing study drug due to AE; no concomitant antibiotics for any baseline pathogens between first dose and TOC (except protocol-allowed antibiotics); no prior antibiotics other than allowed per protocol; no important protocol deviations; no clinical outcome of indeterminate at TOC; no monomicrobial infections due to non-eligible pathogens and did not have only Gram-positive pathogens. |
At EOT visit (Within 24 hours after last infusion on Day 14) |
|
| Other |
Percentage of Participants With Clinical Cure at EOT Visit: ME Analysis Set |
Clinical cure was defined as improvement in baseline signs and symptoms such that after study treatment, no further antimicrobial treatment for the index infection (i.e., cIAI or HAP/VAP) was required. Additionally, for cIAI participants, no unplanned drainage or surgical intervention was necessary since the initial procedure. Clinical cure was determined by the Independent Clinical Adjudication Committee. 95% CI was based on Jeffrey's method. |
At EOT visit (Within 24 hours after last infusion on Day 14) |
|
| Other |
Percentage of Participants With Clinical Cure by Type of Infection at EOT Visit: ITT Analysis Set |
Clinical cure was defined as improvement in baseline signs and symptoms such that after study treatment, no further antimicrobial treatment for the index infection (i.e., cIAI or HAP/VAP) was required. Additionally, for cIAI participants, no unplanned drainage or surgical intervention was necessary since the initial procedure. Clinical cure was determined by the Independent Clinical Adjudication Committee. 95% CI was based on Jeffrey's method. |
At EOT visit (Within 24 hours after last infusion on Day 14) |
|
| Other |
Percentage of Participants With Clinical Cure by Type of Infection at EOT Visit: CE Analysis Set |
Clinical cure = improvement in baseline signs and symptoms such that after study treatment, no further antimicrobial treatment for the index infection (i.e., cIAI or HAP/VAP) was required. Additionally, for cIAI participants, no unplanned drainage or surgical intervention was necessary since the initial procedure. Clinical cure was determined by the Independent Clinical Adjudication Committee. 95% CI was based on Jeffrey's method. CE analysis set: all participants in ITT analysis set; met criteria for cIAI, or HAP/VAP; received at least 48 hours of study treatment or <48 hours of treatment before discontinuing study drug due to AE; no concomitant antibiotics for any baseline pathogens between first dose and TOC (except protocol-allowed antibiotics); no prior antibiotics other than allowed per protocol; no important protocol deviations; no clinical outcome of indeterminate at TOC; no monomicrobial infections due to non-eligible pathogens and did not have only Gram-positive pathogens. |
At EOT visit (Within 24 hours after last infusion on Day 24) |
|
| Other |
Percentage of Participants With Clinical Cure by Pathogen Resistance Type at EOT Visit: Micro-ITT Analysis Set |
Clinical cure was defined as improvement in baseline signs and symptoms such that after study treatment, no further antimicrobial treatment for the index infection (i.e., cIAI or HAP/VAP) was required. Additionally, for cIAI participants, no unplanned drainage or surgical intervention was necessary since the initial procedure. Clinical cure was determined by the Independent Clinical Adjudication Committee. Percentage of participants with clinical cure by pathogen resistance type (ATM non-susceptible and Meropenem non-susceptible based on European Committee on Antimicrobial Susceptibility Testing [EUCAST] criteria and Clinical and Laboratory Standards Institute [CLSI] criteria, Extended spectrum beta-lactamases [ESBL]-positive, Carbapenemase-positive, Serene Carbapenemase and Metallo-beta-lactamase-positive) is reported in this outcome measure. |
At EOT visit (Within 24 hours after last infusion on Day 14) |
|
| Other |
Percentage of Participants With Clinical Cure by Pathogen Resistance Type at TOC Visit: Micro-ITT Analysis Set |
Clinical cure was defined as improvement in baseline signs and symptoms such that after study treatment, no further antimicrobial treatment for the index infection (i.e., cIAI or HAP/VAP) was required. Additionally, for cIAI participants, no unplanned drainage or surgical intervention was necessary since the initial procedure. Clinical cure was determined by the Independent Clinical Adjudication Committee. Percentage of participants with clinical cure by pathogen resistance type (ATM non-susceptible and Meropenem non-susceptible based on EUCAST criteria and CLSI criteria, ESBL-positive, Carbapenemase-positive, Serene Carbapenemase and Metallo-beta-lactamase-positive) is reported in this outcome measure. |
At TOC (Day 28) |
|
| Other |
Percentage of Participants With Clinical Cure by Pathogen Resistance Type at EOT Visit: ME Analysis Set |
Clinical cure was defined as improvement in baseline signs and symptoms such that after study treatment, no further antimicrobial treatment for the index infection (i.e., cIAI or HAP/VAP) was required. Additionally, for cIAI participants, no unplanned drainage or surgical intervention was necessary since the initial procedure. Clinical cure was determined by the Independent Clinical Adjudication Committee. Percentage of participants with clinical cure by pathogen resistance type (ATM non-susceptible and Meropenem non-susceptible based on EUCAST criteria and CLSI criteria, ESBL-positive, Carbapenemase-positive, Serene Carbapenemase and Metallo-beta-lactamase-positive) is reported in this outcome measure. |
At EOT (Within 24 hours after last infusion on Day 14) |
|
| Other |
Percentage of Participants With Clinical Cure by Pathogen Resistance Type at TOC Visit: ME Analysis Set |
Clinical cure was defined as improvement in baseline signs and symptoms such that after study treatment, no further antimicrobial treatment for the index infection (i.e., cIAI or HAP/VAP) was required. Additionally, for cIAI participants, no unplanned drainage or surgical intervention was necessary since the initial procedure. Clinical cure was determined by the Independent Clinical Adjudication Committee. Percentage of participants with clinical cure by pathogen resistance type (ATM non-susceptible and Meropenem non-susceptible based on EUCAST criteria and CLSI criteria, ESBL-positive, Carbapenemase-positive, Serene Carbapenemase and Metallo-beta-lactamase-positive) is reported in this outcome measure. |
At TOC visit (Day 28) |
|
| Other |
Percentage of Participants With Favorable Per Participant Microbiological Response at EOT Visit: Micro-ITT Analysis Set |
Participants were determined to have a favorable microbiological response if all baseline pathogens for that participant had a favorable outcome (eradicated or presumed eradicated). Eradication: Absence of causative pathogen from an appropriately obtained specimen at the site of infection. Presumed eradication: repeat culture of specimens were not performed/clinically indicated in a participant who had a clinical response of cure. |
At EOT visit (Within 24 hours after last infusion on Day 14) |
|
| Other |
Percentage of Participants With Favorable Per Participant Microbiological Response at EOT Visit : ME Analysis Set |
Participants were determined to have a favorable microbiological response if all baseline pathogens for that participant had a favorable outcome (eradicated or presumed eradicated). Eradication: Absence of causative pathogen from an appropriately obtained specimen at the site of infection. Presumed eradication: repeat culture of specimens were not performed/clinically indicated in a participant who had a clinical response of cure. |
At EOT visit (Within 24 hours after last infusion on Day 14) |
|
| Other |
Number of Participants With Favorable Microbiological Response Per-Pathogen at EOT Visit: Micro-ITT Analysis Set |
Participants were determined to have a favorable microbiological response if all baseline pathogens for that participant had a favorable outcome (eradicated or presumed eradicated). Eradication: Absence of causative pathogen from an appropriately obtained specimen at the site of infection. Presumed eradication: repeat culture of specimens were not performed/clinically indicated in a participant who had a clinical response of cure. Only those pathogens are reported which had more than or equal to 10 isolates for either treatment group. |
At EOT (Within 24 hours after last infusion on Day 14) |
|
| Other |
Number of Participants With Favorable Microbiological Response Per-Pathogen at at TOC Visit: Micro-ITT Analysis Set |
Participants were determined to have a favorable microbiological response if all baseline pathogens for that participant had a favorable outcome (eradicated or presumed eradicated). Eradication: Absence of causative pathogen from an appropriately obtained specimen at the site of infection. Presumed eradication: repeat culture of specimens were not performed/clinically indicated in a participant who had a clinical response of cure. Only those pathogens are reported which had more than or equal to 10 isolates for either treatment group. |
At TOC visit (Day 28) |
|
| Other |
Number of Participants With Favorable Microbiological Response Per-Pathogen at EOT Visit: ME Analysis Set |
Participants were determined to have a favorable microbiological response if all baseline pathogens for that participant had a favorable outcome (eradicated or presumed eradicated). Eradication: Absence of causative pathogen from an appropriately obtained specimen at the site of infection. Presumed eradication: repeat culture of specimens were not performed/clinically indicated in a participant who had a clinical response of cure. Only those pathogens are reported which had more than or equal to 10 isolates for either treatment group. |
At EOT (Within 24 hours after last infusion on Day 14) |
|
| Other |
Number of Participants With Favorable Microbiological Response Per-Pathogen at TOC Visit: ME Analysis Set |
Participants were determined to have a favorable microbiological response if all baseline pathogens for that participant had a favorable outcome (eradicated or presumed eradicated). Eradication: Absence of causative pathogen from an appropriately obtained specimen at the site of infection. Presumed eradication: repeat culture of specimens were not performed/clinically indicated in a participant who had a clinical response of cure. Only those pathogens are reported which had more than or equal to 10 isolates for either treatment group. |
At TOC visit (Day 28) |
|
| Other |
Percentage of Participants With Favorable Per-Participant Microbiological Response by Pathogen Resistance Type at EOT Visit: Micro-ITT Analysis Set |
Participants were determined to have a favorable microbiological response if all baseline pathogens for that participant had a favorable outcome (eradicated or presumed eradicated). Eradication: Absence of causative pathogen from an appropriately obtained specimen at the site of infection. Presumed eradication: repeat culture of specimens were not performed/clinically indicated in a participant who had a clinical response of cure. Percentage of participants with favorable microbiological response by pathogen resistance type (ATM non-susceptible and Meropenem non-susceptible based on EUCAST criteria and CLSI criteria, ESBL-positive, Carbapenemase-positive, Serene Carbapenemase and Metallo-beta-lactamase-positive) is reported in this outcome measure. |
At EOT (Within 24 hours after last infusion on Day 14) |
|
| Other |
Percentage of Participants With Favorable Per-Participant Microbiological Response by Pathogen Resistance Type at TOC Visit: Micro-ITT Analysis Set |
Participants were determined to have a favorable microbiological response if all baseline pathogens for that participant had a favorable outcome (eradicated or presumed eradicated). Eradication: Absence of causative pathogen from an appropriately obtained specimen at the site of infection. Presumed eradication: repeat culture of specimens were not performed/clinically indicated in a participant who had a clinical response of cure. Percentage of participants with favorable microbiological response by pathogen resistance type (ATM non-susceptible and Meropenem non-susceptible based on EUCAST criteria and CLSI criteria, ESBL-positive, Carbapenemase-positive, Serene Carbapenemase and Metallo-beta-lactamase-positive) is reported in this outcome measure. |
At TOC visit (Day 28) |
|
| Other |
Percentage of Participants With Favorable Per-Participant Microbiological Response by Pathogen Resistance Type at EOT Visit: ME Analysis Set |
Participants were determined to have a favorable microbiological response if all baseline pathogens for that participant had a favorable outcome (eradicated or presumed eradicated). Eradication: Absence of causative pathogen from an appropriately obtained specimen at the site of infection. Presumed eradication: repeat culture of specimens were not performed/clinically indicated in a participant who had a clinical response of cure. Percentage of participants with favorable microbiological response by pathogen resistance type (ATM non-susceptible, Meropenem non-susceptible based on EUCAST criteria and CLSI criteria, ESBL-positive, Carbapenemase-positive, Serene Carbapenemase and Metallo-beta-lactamase-positive) is reported in this outcome measure. |
At EOT (Within 24 hours after last infusion on Day 14) |
|
| Other |
Percentage of Participants With Favorable Per-Participant Microbiological Response by Pathogen Resistance Type at TOC Visit: ME Analysis Set |
Participants were determined to have a favorable microbiological response if all baseline pathogens for that participant had a favorable outcome (eradicated or presumed eradicated). Eradication: Absence of causative pathogen from an appropriately obtained specimen at the site of infection. Presumed eradication: repeat culture of specimens were not performed/clinically indicated in a participant who had a clinical response of cure. Percentage of participants with favorable microbiological response by pathogen resistance type (ATM non-susceptible, Meropenem non-susceptible based on EUCAST criteria and CLSI criteria, ESBL-positive, Carbapenemase-positive, Serene Carbapenemase and Metallo-beta-lactamase-positive) is reported in this outcome measure. |
At TOC visit (Day 28) |
|
| Other |
Percentage of Participants With Favorable Per-Pathogen Microbiological Response by Pathogen Resistance Type at EOT Visit: Micro-ITT Analysis Set |
Participants were determined to have a favorable microbiological response if all baseline pathogens for that participant had a favorable outcome (eradicated or presumed eradicated). Eradication: Absence of causative pathogen from an appropriately obtained specimen at the site of infection. Presumed eradication: repeat culture of specimens were not performed/clinically indicated in a participant who had a clinical response of cure. Percentage of participants with favorable per-pathogen microbiological response by pathogen resistance type (ATM non-susceptible, Meropenem non-susceptible based on EUCAST criteria and CLSI criteria, ESBL-positive, Carbapenemase-positive, Serene Carbapenemase and Metallo-beta-lactamase-positive) is reported in this outcome measure. |
At EOT (Within 24 hours after last infusion on Day 14) |
|
| Other |
Percentage of Participants With Favorable Per-Pathogen Microbiological Response by Pathogen Resistance Type at TOC Visit: Micro-ITT Analysis Set |
Participants were determined to have a favorable microbiological response if all baseline pathogens for that participant had a favorable outcome (eradicated or presumed eradicated). Eradication: Absence of causative pathogen from an appropriately obtained specimen at the site of infection. Presumed eradication: repeat culture of specimens were not performed/clinically indicated in a participant who had a clinical response of cure. Percentage of participants with favorable per-pathogen microbiological response by pathogen resistance type (ATM non-susceptible, Meropenem non-susceptible based on EUCAST criteria and CLSI criteria, ESBL-positive, Carbapenemase-positive, Serene Carbapenemase and Metallo-beta-lactamase-positive) is reported in this outcome measure. |
At TOC visit (Day 28) |
|
| Other |
Percentage of Participants With Favorable Per-Pathogen Microbiological Response by Pathogen Resistance Type at EOT Visit: ME Analysis Set |
Participants were determined to have a favorable microbiological response if all baseline pathogens for that participant had a favorable outcome (eradicated or presumed eradicated). Eradication: Absence of causative pathogen from an appropriately obtained specimen at the site of infection. Presumed eradication: repeat culture of specimens were not performed/clinically indicated in a participant who had a clinical response of cure. Percentage of participants with favorable per-pathogen microbiological response by pathogen resistance type (ATM non-susceptible, Meropenem non-susceptible based on EUCAST criteria and CLSI criteria, ESBL-positive, Carbapenemase-positive, Serene Carbapenemase and Metallo-beta-lactamase-positive) is reported in this outcome measure. |
At EOT (Within 24 hours after last infusion on Day 14) |
|
| Other |
Percentage of Participants With Favorable Per-Pathogen Microbiological Response by Pathogen Resistance Type at TOC Visit: ME Analysis Set |
Participants were determined to have a favorable microbiological response if all baseline pathogens for that participant had a favorable outcome (eradicated or presumed eradicated). Eradication: Absence of causative pathogen from an appropriately obtained specimen at the site of infection. Presumed eradication: repeat culture of specimens were not performed/clinically indicated in a participant who had a clinical response of cure. Percentage of participants with favorable per-pathogen microbiological response by pathogen resistance type (ATM non-susceptible, Meropenem non-susceptible based on EUCAST criteria and CLSI criteria, ESBL-positive, Carbapenemase-positive, Serene Carbapenemase and Metallo-beta-lactamase-positive) is reported in this outcome measure. |
At TOC visit (Day 28) |
|
| Other |
Number of Participants According to Total Score for the Composite Endpoint of Symptom-Based Objective Clinical Measures: ITT Analysis Set |
|
Up to Day 28 |
|
| Other |
Number of Participants According to Total Score for the Composite Endpoint of Symptom-Based Objective Clinical Measures: CE Analysis Set |
CE analysis set: all participants in ITT analysis set; met criteria for cIAI, or HAP/VAP; received at least 48 hours of study treatment or <48 hours of treatment before discontinuing study drug due to AE; no concomitant antibiotics for any baseline pathogens between first dose and TOC (except protocol-allowed antibiotics); no prior antibiotics other than allowed per protocol; no important protocol deviations; no clinical outcome of indeterminate at TOC; no monomicrobial infections due to non-eligible pathogens and did not have only Gram-positive pathogens. |
Up to Day 28 |
|
| Other |
Percentage of Participants Who Died on or Before 14 Days From Randomization: ITT Analysis Set |
Percentage of participants who died on or before 14 days from randomization is reported in this outcome measure. |
From randomization up to 14 days |
|
| Other |
Total Length of Hospital Stay up to TOC Visit: ITT Analysis Set |
The total length of hospital stay was defined as the total number of calendar days on which the participant was in the hospital from the date of randomization up to and including the specified time point of TOC. |
From randomization up to Day 28 |
|
| Other |
Total Length of Hospital Stay up to TOC Visit: CE Analysis Set |
The total length of hospital stay was defined as the total number of calendar days on which the participant was in the hospital from the date of randomization up to and including the specified time point of TOC. CE analysis set: all participants in ITT analysis set; met criteria for cIAI, or HAP/VAP; received at least 48 hours of study treatment or <48 hours of treatment before discontinuing study drug due to AE; no concomitant antibiotics for any baseline pathogens between first dose and TOC (except protocol-allowed antibiotics); no prior antibiotics other than allowed per protocol; no important protocol deviations; no clinical outcome of indeterminate at TOC; no monomicrobial infections due to non-eligible pathogens and did not have only Gram-positive pathogens. |
From randomization up to Day 28 |
|
| Other |
Duration of Study Treatment |
The duration of therapy in calendar days were calculated as follows: Date of last dose of study drug - date of first dose of study drug +1. |
From first dose of study treatment until last dose of treatment (Up to 14 days) |
|
| Other |
Length of Intensive Care Unit (ICU) Stay: ITT Analysis Set |
The total length of ICU stay was defined as the total number of calendar days on which the participant was in ICU for the period from date of randomization until the TOC visit. |
From randomization until TOC visit (Up to Day 28) |
|
| Other |
Length of Intensive Care Unit (ICU) Stay: CE Analysis Set |
The total length of ICU stay was defined as the total number of calendar days on which the participant was in ICU for the period from date of randomization until the TOC visit. CE analysis set: all participants in ITT analysis set; met criteria for cIAI, or HAP/VAP; received at least 48 hours of study treatment or <48 hours of treatment before discontinuing study drug due to AE; no concomitant antibiotics for any baseline pathogens between first dose and TOC (except protocol-allowed antibiotics); no prior antibiotics other than allowed per protocol; no important protocol deviations; no clinical outcome of indeterminate at TOC; no monomicrobial infections due to non-eligible pathogens and did not have only Gram-positive pathogens. |
From randomization until TOC visit (Up to Day 28) |
|
| Other |
Number of Participants Admitted to the ICU: ITT Analysis Set |
Number of participants admitted to the ICU up to TOC were reported in this outcome measure. |
From randomization until TOC visit (Up to Day 28) |
|
| Other |
Number of Participants Admitted to the ICU: CE Analysis Set |
The number of participants admitted to the ICU were reported in this outcome measure. CE analysis set: all participants in ITT analysis set; met criteria for cIAI, or HAP/VAP; received at least 48 hours of study treatment or <48 hours of treatment before discontinuing study drug due to AE; no concomitant antibiotics for any baseline pathogens between first dose and TOC (except protocol-allowed antibiotics); no prior antibiotics other than allowed per protocol; no important protocol deviations; no clinical outcome of indeterminate at TOC; no monomicrobial infections due to non-eligible pathogens and did not have only Gram-positive pathogens. |
From randomization until TOC visit (Up to Day 28) |
|
| Other |
Number of Participants With Mechanical Ventilation: ITT Analysis Set |
Number of participants with mechanical ventilation were reported in this outcome measure. |
From randomization until TOC visit (Up to Day 28) |
|
| Other |
Number of Participants With Mechanical Ventilation: CE Analysis Set |
Number of participants with mechanical ventilation were reported in this outcome measure. CE analysis set: all participants in ITT analysis set; met criteria for cIAI, or HAP/VAP; received at least 48 hours of study treatment or <48 hours of treatment before discontinuing study drug due to AE; no concomitant antibiotics for any baseline pathogens between first dose and TOC (except protocol-allowed antibiotics); no prior antibiotics other than allowed per protocol; no important protocol deviations; no clinical outcome of indeterminate at TOC; no monomicrobial infections due to non-eligible pathogens and did not have only Gram-positive pathogens. |
From randomization until TOC visit (Up to Day 28) |
|
| Other |
Duration of Mechanical Ventilation in HAP/VAP Participants: ITT Analysis Set |
Duration of mechanical ventilation was defined as the total number of calendar days on which the participant required mechanical ventilation from the date of randomization up to TOC. |
From randomization until TOC visit (Up to Day 28) |
|
| Other |
Duration of Mechanical Ventilation in HAP/VAP Participants: CE Analysis Set |
Duration of mechanical ventilation was defined as the total number of calendar days on which the participant required mechanical ventilation from the date of randomization up to TOC. CE analysis set: all participants in ITT analysis set; met criteria for cIAI, or HAP/VAP; received at least 48 hours of study treatment or <48 hours of treatment before discontinuing study drug due to AE; no concomitant antibiotics for any baseline pathogens between first dose and TOC (except protocol-allowed antibiotics); no prior antibiotics other than allowed per protocol; no important protocol deviations; no clinical outcome of indeterminate at TOC; no monomicrobial infections due to non-eligible pathogens and did not have only Gram-positive pathogens. |
From randomization until TOC visit (Up to Day 28) |
|
| Other |
Number of Participants With Unplanned Surgical Interventions in Complicated Intra-abdominal Infections (cIAI) Participants: ITT Analysis Set |
Unplanned surgical interventions was defined as those occurring after the initial qualifying surgical intervention and prior to the TOC visit. Number of cIAI participants with unplanned surgical intervention according to clinical response categories of cure and failure is reported in this outcome measure. |
From randomization until TOC visit (Up to Day 28) |
|
| Other |
Number of Participants With Unplanned Surgical Interventions in cIAI Participants: CE Analysis Set |
Unplanned surgical interventions was defined as those occurring after the initial qualifying surgical intervention and prior to the TOC visit. Number of cIAI participants with unplanned surgical intervention according to clinical response categories of cure and failure is reported in this outcome measure. |
From randomization until TOC visit (Up to Day 28) |
|
| Primary |
Percentage of Participants With Clinical Cure at Test of Cure (TOC) Visit: Intent-To-Treat (ITT) Analysis Set |
Clinical cure was defined as improvement in baseline signs and symptoms such that after study treatment, no further antimicrobial treatment for the index infection (i.e., cIAI or HAP/VAP) was required. Additionally, for cIAI participants, no unplanned drainage or surgical intervention was necessary since the initial procedure. Clinical cure was determined by the Independent Clinical Adjudication Committee. 95% confidence interval (CI) was based on Jeffrey's method. |
At TOC visit (Day 28) |
|
| Primary |
Percentage of Participants With Clinical Cure at TOC Visit: Clinically Evaluable (CE) Analysis Set |
Clinical cure = improvement in baseline signs and symptoms such that after study treatment, no further antimicrobial treatment for the index infection (i.e., cIAI or HAP/VAP) was required. Additionally for cIAI participants, no unplanned drainage or surgical intervention was necessary since the initial procedure. Clinical cure was determined by Independent Clinical Adjudication Committee. 95% CI was based on Jeffrey's method. CE analysis set:all participants in ITT analysis set; met criteria for cIAI, or HAP/VAP; received at least 48 hours of study treatment or <48 hours of treatment before discontinuing study drug due to AE; no concomitant antibiotics for any baseline pathogens between first dose and TOC (except protocol-allowed antibiotics); no prior antibiotics other than allowed per protocol; no important protocol deviations; no clinical outcome of indeterminate at TOC; no monomicrobial infections due to non-eligible pathogens and did not have only Gram-positive pathogens. |
At TOC visit (Day 28) |
|
| Secondary |
Percentage of Participants With Clinical Cure at TOC Visit: Microbiological Intent-To-Treat (Micro-ITT) Analysis Set |
Clinical cure was defined as improvement in baseline signs and symptoms such that after study treatment, no further antimicrobial treatment for the index infection (i.e., cIAI or HAP/VAP) was required. Additionally, for cIAI participants, no unplanned drainage or surgical intervention was necessary since the initial procedure. Clinical cure was determined by the Independent Clinical Adjudication Committee. 95% CI was based on Jeffrey's method. |
At TOC visit (Day 28) |
|
| Secondary |
Percentage of Participants With Clinical Cure at TOC Visit: Microbiologically Evaluable (ME) Analysis Set |
Clinical cure was defined as improvement in baseline signs and symptoms such that after study treatment, no further antimicrobial treatment for the index infection (i.e., cIAI or HAP/VAP) was required. Additionally, for cIAI participants, no unplanned drainage or surgical intervention was necessary since the initial procedure. Clinical cure was determined by the Independent Clinical Adjudication Committee. 95% CI was based on Jeffrey's method. |
At TOC visit (Day 28) |
|
| Secondary |
Percentage of Participants With Clinical Cure at TOC Visit by Type of Infection: ITT Analysis Set |
Clinical cure was defined as improvement in baseline signs and symptoms such that after study treatment, no further antimicrobial treatment for the index infection (i.e., cIAI or HAP/VAP) was required. Additionally, for cIAI participants, no unplanned drainage or surgical intervention was necessary since the initial procedure. Clinical cure was determined by the Independent Clinical Adjudication Committee. 95% CI was based on Jeffrey's method. |
At TOC visit (Day 28) |
|
| Secondary |
Percentage of Participants With Clinical Cure at TOC Visit by Type of Infection: CE Analysis Set |
Clinical cure = improvement in baseline signs and symptoms such that after study treatment, no further antimicrobial treatment for the index infection (i.e., cIAI or HAP/VAP) was required. Additionally, for cIAI participants, no unplanned drainage or surgical intervention was necessary since the initial procedure. Clinical cure was determined by the Independent Clinical Adjudication Committee. 95% CI was based on Jeffrey's method. CE analysis set:all participants in ITT analysis set; met criteria for cIAI, or HAP/VAP; received at least 48 hours of study treatment or <48 hours of treatment before discontinuing study drug due to AE; no concomitant antibiotics for any baseline pathogens between first dose and TOC (except protocol-allowed antibiotics); no prior antibiotics other than allowed per protocol; no important protocol deviations; no clinical outcome of indeterminate at TOC; no monomicrobial infections due to non-eligible pathogens and did not have only Gram-positive pathogens. |
At TOC visit (Day 28) |
|
| Secondary |
Percentage of Participants With Clinical Cure in Participants With Metallo-beta-lactamase (MBL) Positive Pathogen at TOC Visit: Micro-ITT Analysis Set |
Clinical cure was defined as improvement in baseline signs and symptoms such that after study treatment, no further antimicrobial treatment for the index infection (i.e., cIAI or HAP/VAP) was required. Additionally, for cIAI participants, no unplanned drainage or surgical intervention was necessary since the initial procedure. Clinical cure was determined by the Independent Clinical Adjudication Committee. |
At TOC visit (Day 28) |
|
| Secondary |
Percentage of Participants With Clinical Cure in Participants With MBL Positive Pathogen at TOC Visit: ME Analysis Set |
Clinical cure was defined as improvement in baseline signs and symptoms such that after study treatment, no further antimicrobial treatment for the index infection (i.e., cIAI or HAP/VAP) was required. For cIAI participants, no unplanned drainage or surgical intervention was necessary since the initial procedure. Clinical cure was determined by the Independent Clinical Adjudication Committee. |
At TOC visit (Day 28) |
|
| Secondary |
Percentage of Participants With Favorable Per-Participant Microbiological Response at TOC Visit: Micro- ITT Analysis Set |
Participants were determined to have a favorable microbiological response if all baseline pathogens for that participant had a favorable outcome (eradicated or presumed eradicated). Eradication: Absence of causative pathogen from an appropriately obtained specimen at the site of infection. Presumed eradication: repeat culture of specimens were not performed/clinically indicated in a participant who had a clinical response of cure. |
At TOC visit day (28) |
|
| Secondary |
Percentage of Participants With Favorable Per-Participant Microbiological Response at TOC Visit: ME Analysis Set |
Participants were determined to have a favorable microbiological response if all baseline pathogens for that participant had a favorable outcome (eradicated or presumed eradicated). Eradication: Absence of causative pathogen from an appropriately obtained specimen at the site of infection. Presumed eradication: repeat culture of specimens were not performed/clinically indicated in a participant who had a clinical response of cure. |
At TOC Visit (Day 28) |
|
| Secondary |
Percentage of Participants Who Died on or Before 28 Days After Randomization: ITT Analysis Set |
Percentage of participants who died on or before 28 days after randomization is reported in this outcome measure. |
From randomization up to 28 days |
|
| Secondary |
Percentage of Participants Who Died on or Before 28 Days After Randomization: Micro-ITT Analysis Set |
Percentage of participants who died on or before 28 days after randomization is reported in this outcome measure. |
From randomization up to 28 days |
|
| Secondary |
Plasma Concentration of Aztreonam |
Plasma concentration for aztreonam according to renal function (augmented, normal and mild, moderate and severe is presented in this outcome measure. Augmented = Creatinine clearance (CrCL) > 150 milliliters per minute (mL/min); Normal & Mild = CrCL > 50 to <=150 mL/min; Moderate = CrCL > 30 to = 50 mL/min; Severe = CrCL > 15 to = 30 mL/min. |
Anytime between 25 to 30 minutes, 3.25 to 3.5 hours, 5.5 to 6.5 hours, 7.5 to 8.5 hours post start of infusion on Day 1; 2.75 to 3 hours, 3.5 to 4.5 hours, 5 to 6 and 7 to 8 hours post start of infusion on Day 4 |
|
| Secondary |
Plasma Concentration of Avibactam |
Plasma concentration for avibactam according to renal function (augmented, normal and mild, moderate and severe is presented in this outcome measure. Augmented = CrCL > 150 mL/min; Normal & Mild = CrCL > 50 to <=150 mL/min; Moderate = CrCL > 30 to = 50 mL/min; Severe = CrCL > 15 to = 30 mL/min. |
Anytime between 25 to 30 minutes, 3.25 to 3.5 hours, 5.5 to 6.5 hours, 7.5 to 8.5 hours post start of infusion on Day 1; 2.75 to 3 hours, 3.5 to 4.5 hours, 5 to 6 and 7 to 8 hours post start of infusion on Day 4 |
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| Secondary |
Maximum Plasma Concentration for a Dosing Interval at Steady-State (Cmax, ss) According to Clinical Response by Infection Type at TOC: Aztreonam |
Population PK predicted maximum plasma concentration for a dosing interval at steady-state (Cmax,ss) for participants who received aztreonam-avibactam in studies C3601002 (NCT03329092) and C3601009 (NCT03580044). Clinical response categories included, clinical cure=improvement in baseline signs and symptoms such that after study treatment, no further antimicrobial treatment for the index infection (i.e., cIAI or HAP/VAP) was required. For cIAI participants, no unplanned drainage or surgical intervention was necessary since the initial procedure. Failure was defined as participants who met any of the following criteria like death (after receiving at least 48 hours of study treatment) and participants who received treatment with further antibiotics for the index infection. Indeterminate was defined as death (after receiving less than 48 hours of study treatment) and for cIAI participants inadequate infection source control at time of initial surgical procedure. |
At TOC (Day 28) |
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| Secondary |
Percentage of Time That Free Plasma Concentrations Are Above the Minimum Inhibitory Concentration Over a Dosing Interval (%fT>MIC Aztreonam (ATM) of 8 mg/L) According to Clinical Response by Infection Type at TOC: Aztreonam |
Population PK predicted (%fT>MIC ATM of 8 mg/L) for participants who received aztreonam-avibactam in studies C3601002 (NCT03329092) and C3601009 (NCT03580044). Clinical response categories included, clinical cure=improvement in baseline signs and symptoms such that after study treatment, no further antimicrobial treatment for the index infection (i.e., cIAI or HAP/VAP) was required. For cIAI participants, no unplanned drainage or surgical intervention was necessary since the initial procedure. Failure was defined as participants who met any of the following criteria like death (after receiving at least 48 hours of study treatment) and participants who received treatment with further antibiotics for the index infection. Indeterminate was defined as death (after receiving less than 48 hours of study treatment) and for cIAI participants inadequate infection source control at time of initial surgical procedure. |
At TOC (Day 28) |
|
| Secondary |
Area Under the Plasma Concentration-time Curve Over 24 Hours at Steady-state (AUC24,ss ) According to Clinical Response by Infection Type at TOC: Aztreonam |
Population PK predicted (AUC24,ss) for participants who received aztreonam-avibactam in studies C3601002 (NCT03329092) and C3601009 (NCT03580044). Clinical response categories included, clinical cure=improvement in baseline signs and symptoms such that after study treatment, no further antimicrobial treatment for the index infection (i.e., cIAI or HAP/VAP) was required. For cIAI participants, no unplanned drainage or surgical intervention was necessary since the initial procedure. Failure was defined as participants who met any of the following criteria like death (after receiving at least 48 hours of study treatment) and participants who received treatment with further antibiotics for the index infection. Indeterminate was defined as death (after receiving less than 48 hours of study treatment) and for cIAI participants inadequate infection source control at time of initial surgical procedure. |
0 to 24 hours at TOC (Day 28) |
|
| Secondary |
Maximum Plasma Concentration for a Dosing Interval at Steady-state (Cmax,ss) According to Microbiological Response by Infection Type at TOC: Aztreonam |
Population PK predicted (Cmax,ss) for participants who received ATM-AVI in studies C3601002 (NCT03329092) and C3601009 (NCT03580044). Microbiological response included Favorable =baseline pathogens for participant had a favorable outcome. Eradication: Absence of causative pathogen from an appropriately obtained specimen at site of infection. Presumed eradication: repeat culture of specimens were not performed/clinically indicated in a participant who had a clinical response of cure. Unfavorable=persistence, persistence with increasing MIC, or presumed persistence. Persistence= Causative organism still present from appropriately obtained specimen at site of infection. Presumed persistence= Participant assessed as a clinical failure and repeat culture of specimens were not performed/clinically indicated. Indeterminate = death (after receiving < 48 hours of study treatment) and for cIAI participants inadequate infection source control at time of initial surgical procedure. |
At TOC (Day 28) |
|
| Secondary |
Area Under the Plasma Concentration-time Curve Over 24 Hours at Steady-state (AUC24,ss) According to Microbiological Response by Infection Type at TOC: Aztreonam |
Population PK predicted (AUC24,ss) for participants who received ATM-AVI in studies C3601002 (NCT03329092) and C3601009 (NCT03580044). Microbiological response included Favorable =baseline pathogens for participant had a favorable outcome. Eradication: Absence of causative pathogen from an appropriately obtained specimen at site of infection. Presumed eradication: repeat culture of specimens were not performed/clinically indicated in a participant who had a clinical response of cure. Unfavorable=persistence, persistence with increasing MIC, or presumed persistence. Persistence= Causative organism still present from appropriately obtained specimen at site of infection. Presumed persistence= Participant assessed as a clinical failure and repeat culture of specimens were not performed/clinically indicated. Indeterminate = death (after receiving < 48 hours of study treatment) and for cIAI participants inadequate infection source control at time of initial surgical procedure. |
0 to 24 hours at TOC (Day 28) |
|
| Secondary |
Percentage of Time That Free Plasma Concentrations Are Above the Minimum Inhibitory Concentration Over a Dosing Interval (%fT>MIC Aztreonam (ATM) of 8 mg/L) According to Microbiological Response by Infection Type at TOC: Aztreonam |
Population PK predicted (%fT>MIC ATM of 8 mg/L) for participants who received ATM-AVI in studies C3601002 (NCT03329092) and C3601009 (NCT03580044). Microbiological response included Favorable =baseline pathogens for participant had a favorable outcome. Eradication: Absence of causative pathogen from an appropriately obtained specimen at site of infection. Presumed eradication: repeat culture of specimens were not performed/clinically indicated in a participant who had a clinical response of cure. Unfavorable=persistence, persistence with increasing MIC, or presumed persistence. Persistence= Causative organism still present from appropriately obtained specimen at site of infection. Presumed persistence= Participant assessed as a clinical failure and repeat culture of specimens were not performed/clinically indicated. Indeterminate = death (after receiving < 48 hours of study treatment) and for cIAI participants inadequate infection source control at time of initial surgical procedure. |
At TOC (Day 28) |
|
| Secondary |
Area Under the Plasma Concentration-time Curve Over 24 Hours at Steady-state (AUC24,ss) According to Clinical Response by Infection Type at TOC: Avibactam |
Population PK predicted (AUC24,ss) for participants who received aztreonam-avibactam in studies C3601002 (NCT03329092) and C3601009 (NCT03580044). Clinical response categories included, clinical cure=improvement in baseline signs and symptoms such that after study treatment, no further antimicrobial treatment for the index infection (i.e., cIAI or HAP/VAP) was required. For cIAI participants, no unplanned drainage or surgical intervention was necessary since the initial procedure. Failure was defined as participants who met any of the following criteria like death (after receiving at least 48 hours of study treatment) and participants who received treatment with further antibiotics for the index infection. Indeterminate was defined as death (after receiving less than 48 hours of study treatment) and for cIAI participants inadequate infection source control at time of initial surgical procedure. |
0 to 24 hours at TOC (Day 28) |
|
| Secondary |
Maximum Plasma Concentration for a Dosing Interval at Steady-state (Cmax,ss ) According to Clinical Response by Infection Type at TOC: Avibactam |
Population PK predicted (Cmax,ss) for participants who received aztreonam-avibactam in studies C3601002 (NCT03329092) and C3601009 (NCT03580044). Clinical response categories included, clinical cure=improvement in baseline signs and symptoms such that after study treatment, no further antimicrobial treatment for the index infection (i.e., cIAI or HAP/VAP) was required. For cIAI participants, no unplanned drainage or surgical intervention was necessary since the initial procedure. Failure was defined as participants who met any of the following criteria like death (after receiving at least 48 hours of study treatment) and participants who received treatment with further antibiotics for the index infection. Indeterminate was defined as death (after receiving less than 48 hours of study treatment) and for cIAI participants inadequate infection source control at time of initial surgical procedure. |
At TOC (Day 28) |
|
| Secondary |
Percent of Time That Free Plasma Concentrations Are Above the Threshold Concentration Over a Dosing Interval (%fT>CT of 2.5mg/L) According to Clinical Response by Infection Type at TOC: Avibactam |
Population PK predicted (%fT>CT of 2.5mg/L) for participants who received aztreonam-avibactam in studies C3601002 (NCT03329092) and C3601009 (NCT03580044). Clinical response categories included, clinical cure=improvement in baseline signs and symptoms such that after study treatment, no further antimicrobial treatment for the index infection (i.e., cIAI or HAP/VAP) was required. For cIAI participants, no unplanned drainage or surgical intervention was necessary since the initial procedure. Failure was defined as participants who met any of the following criteria like death (after receiving at least 48 hours of study treatment) and participants who received treatment with further antibiotics for the index infection. Indeterminate was defined as death (after receiving less than 48 hours of study treatment) and for cIAI participants inadequate infection source control at time of initial surgical procedure. |
At TOC (Day 28) |
|
| Secondary |
Area Under the Plasma Concentration-time Curve Over 24 Hours at Steady-state (AUC24,ss) According to Microbiological Response by Infection Type at TOC: Avibactam |
Population PK predicted (AUC24,ss) for participants who received ATM-AVI in studies C3601002 (NCT03329092) and C3601009 (NCT03580044). Microbiological response included Favorable =baseline pathogens for participant had a favorable outcome. Eradication: Absence of causative pathogen from an appropriately obtained specimen at site of infection. Presumed eradication: repeat culture of specimens were not performed/clinically indicated in a participant who had a clinical response of cure. Unfavorable=persistence, persistence with increasing MIC, or presumed persistence. Persistence= Causative organism still present from appropriately obtained specimen at site of infection. Presumed persistence= Participant assessed as a clinical failure and repeat culture of specimens were not performed/clinically indicated. Indeterminate = death (after receiving<48 hours of study treatment) and for cIAI participants inadequate infection source control at time of initial surgical procedure. |
0 to 24 hours At TOC (Day 28) |
|
| Secondary |
Maximum Plasma Concentration for a Dosing Interval at Steady-state (Cmax,ss (mg/L)) According to Microbiological Response by Infection Type at TOC: Avibactam |
Population PK predicted (Cmax,ss (mg/L)) for participants who received ATM-AVI in studies C3601002 (NCT03329092) and C3601009 (NCT03580044). Microbiological response included Favorable =baseline pathogens for participant had a favorable outcome. Eradication: Absence of causative pathogen from an appropriately obtained specimen at site of infection. Presumed eradication: repeat culture of specimens were not performed/clinically indicated in a participant who had a clinical response of cure. Unfavorable=persistence, persistence with increasing MIC, or presumed persistence. Persistence= Causative organism still present from appropriately obtained specimen at site of infection. Presumed persistence= Participant assessed as a clinical failure and repeat culture of specimens were not performed/clinically indicated. Indeterminate = death (after receiving<48 hours of study treatment) and for cIAI participants inadequate infection source control at time of initial surgical procedure. |
At TOC (Day 28) |
|
| Secondary |
Percent of Time That Free Plasma Concentrations Are Above the Threshold Concentration Over a Dosing Interval; (%fT>CT of 2.5 mg/L) According to Microbiological Response by Infection Type at TOC: Avibactam |
Population PK predicted (%fT>CT of 2.5 mg/L) for participants who received ATM-AVI in studies C3601002 (NCT03329092) and C3601009 (NCT03580044). Microbiological response included Favorable =baseline pathogens for participant had a favorable outcome. Eradication: Absence of causative pathogen from an appropriately obtained specimen at site of infection. Presumed eradication: repeat culture of specimens were not performed/clinically indicated in a participant who had a clinical response of cure. Unfavorable=persistence, persistence with increasing MIC, or presumed persistence. Persistence= Causative organism still present from appropriately obtained specimen at site of infection. Presumed persistence= Participant assessed as a clinical failure and repeat culture of specimens were not performed/clinically indicated. Indeterminate = death (after receiving < 48 hours of study treatment) and for cIAI participants inadequate infection source control at time of initial surgical procedure. |
At TOC (Day 28) |
|
| Secondary |
Number of Participants With Adverse Events (AEs) and Serious AEs |
An adverse event (AE) was any untoward medical occurrence in a study participant administered medicinal product,; the event need not necessarily have a causal relationship with product treatment or usage. A serious adverse event (SAE) was any untoward medical occurrence at any dose that: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); resulted in congenital abnormal/birth defect or considered an important medical event. |
From start of study treatment until end of late follow-up (Up to Day 45) |
|
| Secondary |
Number of Participants With Potentially Clinically Significant Hematology Abnormalities |
Criteria for potential clinically significant hematology results were as follows: hemoglobin, hematocrit and erythrocyte <0.7*lower limit of normal [LLN] and >30% decrease from Baseline (DFB); >1.3*upper limit of normal (ULN) and >30% increase from Baseline (IFB). Platelet count <0.65*LLN and > 50% decrease from baseline; > 1.5 * ULN and > 100% increase from baseline. leukocyte: < 0.65* LLN and > 60% decrease from baseline; > 1.5* ULN and 100% increase from baseline. Neutrophils/leukocytes < 0.65 * LLN and >75% decrease from baseline; > 1.6*ULN and > 100% increase from baseline. Lymphocytes/leukocytes < 0.25* LLN and > 75% decrease from baseline;> 1.5* ULN and > 100% increase from baseline, Eosinophils/leukocytes, Monocytes/leukocytes, Basophils/leukocytes > 4.0* ULN and > 300% increase from baseline. |
From start of study treatment until TOC visit (Up to Day 28) |
|
| Secondary |
Number of Participants With Potentially Clinically Significant Clinical Chemistry Abnormalities |
Albumin < 0.5* LLN and> 50% decrease from baseline (DFB);> 1.5 * ULN and> 50% increase from baseline (IFB). Alkaline phosphatase < 0.5 * LLN and> 80% DFB;> 3.0 * ULN and> 100%. Alanine and Aspartate aminotransferase > 3.0 * ULN and> 100% IFB. Bicarbonate < 0.7 * LLN and > 40% DFB;> 1.3 * ULN and> 40% IFB. Blood urea nitrogen < 0.2 * LLN and > 100% DFB; > 3.0 * ULN and > 200% IFB. Calcium < 0.7 * LLN and > 30% DFB;> 1.3 * ULN and> 30% IFB. Chloride < 0.8 * LLN >and 20% DFB; > 1.2 * ULN and > 20% IFB. Creatinine > 2.0 * ULN and> 100% IFB; Glucose < 0.6 * LLN and> 40% DFB; > 3.0 * ULN and> 200% IFB. Potassium < 0.8 * LLN and > 20% DFB; > 1.2 * ULN and> 20% IFB. Sodium < 0.85 * LLN and> 10% DFB;> 1.1 * ULN and >10% IFB. Bilirubin > 1.5 * ULN and > 100% IFB.; Direct bilirubin > 2.0 * ULN and > 150% IFB. |
From start of study treatment until At TOC visit (Up to Day 28) |
|
| Secondary |
Number of Participants With Abnormalities in Vital Signs |
Vitals signs, included blood pressure and, heart rate. Blood pressure (BP) and heart rate were measured using a semiautomatic BP recording device with the participant in a supine position after at least 10 minutes of rest. Criteria for abnormalities included: Systolic BP (millimeters of mercury [mmHg]): value more than (>) 150 and increase from baseline more than equal (>= 30) or value less than (<) 90 and decrease from baseline >= 30; DBP: value > 100 and increase from baseline >=20 or Value < 50 and decrease from baseline >= 20; Heart Rate (beats per minute [BPM]): value < 40 or > 120. |
From start of study treatment until TOC visit (Up to Day 28) |
|
| Secondary |
Number of Participants With Abnormal Physical Examination Finding |
A complete physical examination was performed and included an assessment of the following: general appearance including site of infection, skin, head and throat (head, eyes, ears, nose, and throat), lymph nodes, lungs, cardiovascular (CV), abdomen, musculoskeletal, and neurological systems. |
Screening, End of treatment (up to 24 hours post infusion on Day 14) and Test of Cure (Day 28) |
|
| Secondary |
Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings |
Standard 12-lead ECGs were recorded with the participants in the supine position after the participant had rested in this position for 10 minutes. Clinically significant findings were based on investigators assessment. |
Baseline (latest non-missing value before start of treatment) and Day 3 |
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