Efficacy and Safety of Ceftazidime-Avibactam (CAZ-AVI) in Chinese Participants With HAP (Including VAP)

Clinical cure: participants were considered to be a success for clinical response at TOC visit if the participants were not a clinical failure at end of treatment (EOT), and the participants were alive and all signs and symptoms of pneumonia were resolved or improved to an extent that no antibacterial therapy for HAP was taken between EOT and TOC inclusive. Gram negative is abbreviated as gram -ve and gram positive as gram +ve.

Time frame: TOC visit: any day from Day 21 to 25

Population: cMITT: MITT subset and participants whose baseline respiratory or blood culture showed gram -ve pathogens with or without concomitant gram +ve pathogens (excluding those with gram -ve pathogens unexpected to respond to either study drug \[participants with only monomicrobial gram -ve infection: any Acinetobacter species/ Legionella species/ Stenotrophomonas maltophilia/ Elizabethkingia meningoseptica\]) or in whom no etiologic pathogens identified from respiratory or blood culture at baseline.

Hematology: Hemoglobin (Hg), hematocrit, erythrocytes: less than (\<)0.8\*lower limit of normal (LLN) & change (chg) more than (\>)20% decrease (dec); platelets: \<0.65\*LLN & chg \>50% dec &, \>1.5\* upper limit of normal (ULN) & chg \>100% increase (inc); leukocytes: \<0.65\*LLN & chg \>60% dec &, \>1.6\*ULN & chg \>100% inc; lymphocytes, \<0.25\*LLN & chg \>75% dec; neutrophils: \<0.65\*LLN & chg \>75% dec &, \>1.6\*ULN & chg \>100% inc; basophils, monocytes: \>4.0\* ULN & chg \>300% inc. Clinical chemistry: bilirubin: \>2.0\*ULN & chg \>150% inc; aspartate aminotransferase (AT) & Alanine AT: \>3.0\*ULN & chg \>200% inc; alkaline phosphatase \<0.5\*LLN & chg \>80% dec & \>2.0\*ULN & chg \>100% inc; creatinine: \>2.0\*ULN & \>chg 100% inc; sodium: \<0.85\*LLN & chg \>10% dec & \>1.1\*ULN & chg \>10% inc; potassium & chloride: \<0.8\*LLN & chg \>20% dec & \>1.2\*ULN & chg \>20% dec; calcium: \<0.7\*LLN & chg \>30% dec & bicarbonate: \<0.7\*LLN & chg \>40% dec. Clinical significance was judged by investigator.

Time frame: Day 1 up to 32 days after last dose of CAZ-AVI (maximum up to 46 days; maximum treatment duration was of 14 days)

Population: SAS included all participants who had taken at least 1 dose of study intervention. Here Number of Participants Analyzed includes number of participants evaluable for laboratory abnormalities.

An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and all non-SAEs that occurred in the study. TEAEs were AEs between first dose of study treatment and up to 32 days post last dose that were absent before treatment or that worsened relative to pretreatment state.

Time frame: Day 1 up to 32 days after last dose of CAZ-AVI (maximum up to 46 days; maximum treatment duration was of 14 days)

Population: SAS included all participants who had taken at least 1 dose of study intervention.

Vital signs included diastolic blood pressure (millimeters of mercury \[mmHg\]); pulse rate (beats per minute \[bpm\]) and systolic blood pressure (mmHg). Pre-defined criteria: Diastolic blood pressure: Value \<50 mmHg, Diastolic blood pressure: Change more than or equal to (\>=) 20 mmHg increase, Diastolic blood pressure: Change \>= 20 mmHg decrease, Pulse rate: Value \<40 bpm, Pulse rate: Value \>120 bpm, Systolic blood pressure: Value \<90 mmHg, Systolic blood pressure: Change \>= 30 mmHg increase, Systolic blood pressure: Change \>= 30 mmHg decrease. One participant could have more than one vital sign abnormality.

Time frame: Day 1 up to 32 days after last dose of CAZ-AVI (maximum up to 46 days; maximum treatment duration was of 14 days)

Population: SAS included all participants who had taken at least 1 dose of study intervention.

Clinical cure at EOT: participants were considered to be a success for clinical response at EOT visit if the participants were alive and all signs and symptoms of pneumonia were resolved or improved such that all antibacterial therapies for HAP/VAP were stopped. No antibacterial therapy other than those outlined by the protocol was administered for HAP prior to EOT. Clinical cure at TOC: participants were considered to be a success for clinical response at TOC visit if the participants were not a clinical failure at EOT, and the participants were alive and all signs and symptoms of pneumonia were resolved or improved to an extent that no antibacterial therapy for HAP was taken between EOT and TOC inclusive.

Time frame: EOT visit: within 24 hours after the completion of the last infusion of study intervention (study treatment was a minimum of 7 days and maximum of 14 days); TOC visit: any day from Day 21 to 25

Population: mMITT:MITT subset and participants with proper respiratory culture (RC) showing gram-ve pathogens,excluding participants unexpected to respond to CAZ-AVI (participants with only monomicrobial gram-ve infections:any Acinetobacter species/Legionella species/Stenotrophomonas maltophilia/Elizabethkingia meningoseptica).If baseline RC unavailable or didn't identify respiratory pathogen, but gram-ve organism causing pneumonia was identified from baseline blood cultures,participant qualified for mMITT.

Clinical cure: participants were considered to be a success for clinical response at EOT visit if the participants were alive and all signs and symptoms of pneumonia were resolved or improved such that all antibacterial therapies for HAP/ VAP were stopped. No antibacterial therapy other than those outlined by the protocol was administered for HAP prior to EOT.

Time frame: EOT visit: within 24 hours after the completion of the last infusion of study intervention (study treatment was a minimum of 7 days and maximum of 14 days)

Population: cMITT: MITT subset and participants whose baseline respiratory or blood culture showed gram -ve pathogens with or without concomitant gram +ve pathogens (excluding those with gram -ve pathogens unexpected to respond to either study drug \[participants with only monomicrobial gram -ve infection: any Acinetobacter species/ Legionella species/ Stenotrophomonas maltophilia/ Elizabethkingia meningoseptica\]) or in whom no etiologic pathogens identified from respiratory or blood culture at baseline.

Clinical cure at EOT: participants were considered to be a success for clinical response at EOT visit if the participants were alive and all signs and symptoms of pneumonia were resolved or improved such that all antibacterial therapies for HAP/VAP were stopped. No antibacterial therapy other than those outlined by the protocol was administered for HAP prior to EOT. Clinical cure at TOC: participants were considered to be a success for clinical response at TOC visit if the participants were not a clinical failure at EOT, and the participants were alive and all signs and symptoms of pneumonia were resolved or improved to an extent that no antibacterial therapy for HAP was taken between EOT and TOC inclusive.

Time frame: EOT visit: within 24 hours after the completion of the last infusion of study intervention (study treatment was a minimum of 7 days and maximum of 14 days); TOC visit: any day from Day 21 to 25

Population: mMITT analysis set evaluated. Here, Overall Number of Participants Analyzed signifies number of participants who were evaluable for this outcome measure, i.e. participants in mMITT analysis set that with gram-negative baseline pathogens resistant to ceftazidime.

Time frame: TOC visit: any day from Day 21 to 25; Day 28

Population: cMITT: MITT subset and participants whose baseline respiratory or blood culture showed gram -ve pathogens with or without concomitant gram +ve pathogens (excluding those with gram -ve pathogens unexpected to respond to either study drug \[participants with only monomicrobial gram -ve infection: any Acinetobacter species/ Legionella species/ Stenotrophomonas maltophilia/ Elizabethkingia meningoseptica\]) or in whom no etiologic pathogens identified from respiratory or blood culture at baseline.

Time frame: TOC visit: any day from Day 21 to 25; Day 28

Population: mMITT:MITT subset and participants with proper RC showing gram-ve pathogens,excluding participants unexpected to respond to CAZ-AVI (participants with only monomicrobial gram-ve infections:any Acinetobacter species/Legionella species/Stenotrophomonas maltophilia/Elizabethkingia meningoseptica).If baseline RC unavailable or didn't identify respiratory pathogen, but gram-ve organism causing pneumonia was identified from baseline blood cultures,participant qualified for mMITT.

For participants from whom only 1 causative pathogen is isolated, the overall microbiological response assessment was based on the microbiological response assessment for that pathogen. For participants from whom more than 1 baseline pathogen was isolated, the overall microbiological response assessment was favorable only if the microbiological response assessment for each of the baseline pathogens isolated was favorable. Favorable microbiological response included eradication (an adequate source specimen demonstrated absence of the original baseline pathogen) and presumed eradication (an adequate source specimen was not available to culture and the participant was assessed as a clinical cure). In this outcome measure percentage of participants with favorable per-participant microbiological response are recorded.

Time frame: EOT visit: within 24 hours after the completion of the last infusion of study intervention (study treatment was a minimum of 7 days and maximum of 14 days); TOC visit: any day from Day 21 to 25

Population: mMITT:MITT subset and participants with proper RC showing gram-ve pathogens,excluding participants unexpected to respond to CAZ-AVI (participants with only monomicrobial gram-ve infections:any Acinetobacter species/Legionella species/Stenotrophomonas maltophilia/Elizabethkingia meningoseptica).If baseline RC unavailable or didn't identify respiratory pathogen, but gram-ve organism causing pneumonia was identified from baseline blood cultures,participant qualified for mMITT.

For participants from whom only 1 causative pathogen is isolated, the overall microbiological response assessment was based on the microbiological response assessment for that pathogen. For participants from whom more than 1 baseline pathogen was isolated, the overall microbiological response assessment was favorable only if the microbiological response assessment for each of the baseline pathogens isolated was favorable. Favorable microbiological response included eradication (an adequate source specimen demonstrated absence of the original baseline pathogen) and presumed eradication (an adequate source specimen was not available to culture and the participant was assessed as a clinical cure). In this outcome measure percentage of participants with favorable per-participant microbiological response are recorded.

Time frame: EOT visit: within 24 hours after the completion of the last infusion of study intervention (study treatment was a minimum of 7 days and maximum of 14 days); TOC visit: any day from Day 21 to 25

Population: mMITT analysis set evaluated. Here, Overall Number of Participants Analyzed signifies number of participants who were evaluable for this outcome measure, i.e. participants in mMITT analysis set that with gram-negative baseline pathogens resistant to ceftazidime.

Favorable microbiological response included eradication (an adequate source specimen demonstrated absence of the original baseline pathogen) and presumed eradication (an adequate source specimen was not available to culture and the participant was assessed as a clinical cure). In this outcome measure percentage of participants with favorable per-pathogen microbiological response are recorded.

Time frame: EOT visit: within 24 hours after the completion of the last infusion of study intervention (study treatment was a minimum of 7 days and maximum of 14 days); TOC visit: any day from Day 21 to 25

Population: mMITT analysis set evaluated. All participants reported under Number of Participants Analyzed contributed data to the table; however, may not have evaluable data for every row. Here, Number Analyzed signifies number of participants in mMITT analysis set evaluable for specified pathogens and visits.