Trial Outcomes & Findings for Pharmacokinetic Study of Aztreonam-Avibactam in Severe Renal Impairment (NCT NCT04486625)

NCT ID: NCT04486625

Last Updated: 2023-07-28

Results Overview

AUC0-24,ss of ATM in Cohort 1 was calculated by 4\*AUC0-tau (tau = 6 hours), where AUC0-tau was area under the concentration-time profile from time 0 to time tau (the dosing interval). AUC0-24,ss of ATM in Cohort 2 was calculated by 3\*AUC0-tau (tau = 8 hours), where AUC0-tau was area under the plasma concentration-time profile from time 0 to time tau (the dosing interval).

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 11 participants
• Primary outcome timeframe: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.
• Results posted on: 2023-07-28

Participant Flow

This was a Phase 1, open-label, parallel-group study where an intravenous (IV) loading dose (30-minute infusion) followed by multiple IV doses (3-hour infusion) of aztreonam-avibactam (ATM-AVI) were administered to participants with severe renal impairment (not on dialysis) (Cohort 1) and to healthy participants with normal renal function (Cohort 2).

Participant milestones

Measure	Cohort 1: Normal Renal Function Participants with normal renal function received 30-minute IV loading dose infusion (500/167 mg aztreonam \[ATM\]/avibactam \[AVI\]), followed by 3-hour IV extended loading infusion (1500/500 mg ATM/AVI), then 3-hour 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours on Days 1 to 3.	Cohort 2: Severe Renal Impairment Participants with severe renal impairment (not on dialysis) received 30-minute IV loading dose infusion (675/255 mg aztreonam \[ATM\]/avibactam \[AVI\]), followed by 3-hour IV extended loading infusion (675/255 mg ATM/AVI), then 3-hour 675/255 mg ATM/AVI maintenance dose infusion every 8 hours on Days 1 to 3.
Overall Study STARTED	6	5
Overall Study COMPLETED	6	5
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Pharmacokinetic Study of Aztreonam-Avibactam in Severe Renal Impairment

Baseline characteristics by cohort

Measure	Cohort 1: Normal Renal Function n=6 Participants Participants with normal renal function received 30-minute IV loading dose infusion (500/167 mg aztreonam \[ATM\]/avibactam \[AVI\]), followed by 3-hour IV extended loading infusion (1500/500 mg ATM/AVI), then 3-hour 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours on Days 1 to 3.	Cohort 2: Severe Renal Impairment n=5 Participants Participants with severe renal impairment (not on dialysis) received 30-minute IV loading dose infusion (675/255 mg aztreonam \[ATM\]/avibactam \[AVI\]), followed by 3-hour IV extended loading infusion (675/255 mg ATM/AVI), then 3-hour 675/255 mg ATM/AVI maintenance dose infusion every 8 hours on Days 1 to 3.	Total n=11 Participants Total of all reporting groups
Age, Continuous Mean	61.0 Years STANDARD_DEVIATION 1.67 • n=5 Participants	67.8 Years STANDARD_DEVIATION 8.56 • n=7 Participants	64.1 Years STANDARD_DEVIATION 6.58 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	5 Participants n=7 Participants	11 Participants n=5 Participants
Race/Ethnicity, Customized Race · White	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Race/Ethnicity, Customized Race · Black or African American	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity · Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity · Not Hispanic or Latino	6 Participants n=5 Participants	5 Participants n=7 Participants	11 Participants n=5 Participants
Body Weight	98.65 kilogram (kg) STANDARD_DEVIATION 6.354 • n=5 Participants	101.06 kilogram (kg) STANDARD_DEVIATION 13.068 • n=7 Participants	99.75 kilogram (kg) STANDARD_DEVIATION 9.491 • n=5 Participants

PRIMARY outcome

Timeframe: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.

Population: The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.

AUC0-24,ss of ATM in Cohort 1 was calculated by 4*AUC0-tau (tau = 6 hours), where AUC0-tau was area under the concentration-time profile from time 0 to time tau (the dosing interval). AUC0-24,ss of ATM in Cohort 2 was calculated by 3*AUC0-tau (tau = 8 hours), where AUC0-tau was area under the plasma concentration-time profile from time 0 to time tau (the dosing interval).

Outcome measures

Measure	Cohort 1: Normal Renal Function n=6 Participants Participants with normal renal function received 30-minute IV loading dose infusion (500/167 mg aztreonam \[ATM\]/avibactam \[AVI\]), followed by 3-hour IV extended loading infusion (1500/500 mg ATM/AVI), then 3-hour 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours on Days 1 to 3.	Cohort 2: Severe Renal Impairment n=5 Participants Participants with severe renal impairment (not on dialysis) received 30-minute IV loading dose infusion (675/255 mg aztreonam \[ATM\]/avibactam \[AVI\]), followed by 3-hour IV extended loading infusion (675/255 mg ATM/AVI), then 3-hour 675/255 mg ATM/AVI maintenance dose infusion every 8 hours on Days 1 to 3.
Total Daily Area Under the Plasma Concentration-time Profile From Time 0 to 24 Hours at Steady-state (AUC0-24,ss) of Aztreonam (ATM)	922.9 Microgram*hour per milliliter (ug*hr/mL) Geometric Coefficient of Variation 16	733.5 Microgram*hour per milliliter (ug*hr/mL) Geometric Coefficient of Variation 16

PRIMARY outcome

Timeframe: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.

Population: The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.

The Cmax of ATM was observed directly from data.

Outcome measures

Measure	Cohort 1: Normal Renal Function n=6 Participants Participants with normal renal function received 30-minute IV loading dose infusion (500/167 mg aztreonam \[ATM\]/avibactam \[AVI\]), followed by 3-hour IV extended loading infusion (1500/500 mg ATM/AVI), then 3-hour 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours on Days 1 to 3.	Cohort 2: Severe Renal Impairment n=5 Participants Participants with severe renal impairment (not on dialysis) received 30-minute IV loading dose infusion (675/255 mg aztreonam \[ATM\]/avibactam \[AVI\]), followed by 3-hour IV extended loading infusion (675/255 mg ATM/AVI), then 3-hour 675/255 mg ATM/AVI maintenance dose infusion every 8 hours on Days 1 to 3.
Maximum Plasma Concentration (Cmax) of ATM	57.34 Microgram per milliliter (ug/mL) Geometric Coefficient of Variation 13	43.34 Microgram per milliliter (ug/mL) Geometric Coefficient of Variation 11

PRIMARY outcome

Timeframe: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.

Population: The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.

AUC0-24,ss of AVI in Cohort 1 was calculated by 4*AUC0-tau (tau = 6 hours), where AUC0-tau was area under the concentration-time profile from time 0 to time tau (the dosing interval). AUC0-24,ss of AVI in Cohort 2 was calculated by 3*AUC0-tau (tau = 8 hours), where AUC0-tau was area under the plasma concentration-time profile from time 0 to time tau (the dosing interval).

Outcome measures

Measure	Cohort 1: Normal Renal Function n=6 Participants Participants with normal renal function received 30-minute IV loading dose infusion (500/167 mg aztreonam \[ATM\]/avibactam \[AVI\]), followed by 3-hour IV extended loading infusion (1500/500 mg ATM/AVI), then 3-hour 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours on Days 1 to 3.	Cohort 2: Severe Renal Impairment n=5 Participants Participants with severe renal impairment (not on dialysis) received 30-minute IV loading dose infusion (675/255 mg aztreonam \[ATM\]/avibactam \[AVI\]), followed by 3-hour IV extended loading infusion (675/255 mg ATM/AVI), then 3-hour 675/255 mg ATM/AVI maintenance dose infusion every 8 hours on Days 1 to 3.
AUC0-24,ss of Avibactam (AVI)	164.8 ug*hr/mL Geometric Coefficient of Variation 18	204.6 ug*hr/mL Geometric Coefficient of Variation 20

PRIMARY outcome

Timeframe: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.

Population: The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.

The Cmax of AVI was observed directly from data.

Outcome measures

Measure	Cohort 1: Normal Renal Function n=6 Participants Participants with normal renal function received 30-minute IV loading dose infusion (500/167 mg aztreonam \[ATM\]/avibactam \[AVI\]), followed by 3-hour IV extended loading infusion (1500/500 mg ATM/AVI), then 3-hour 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours on Days 1 to 3.	Cohort 2: Severe Renal Impairment n=5 Participants Participants with severe renal impairment (not on dialysis) received 30-minute IV loading dose infusion (675/255 mg aztreonam \[ATM\]/avibactam \[AVI\]), followed by 3-hour IV extended loading infusion (675/255 mg ATM/AVI), then 3-hour 675/255 mg ATM/AVI maintenance dose infusion every 8 hours on Days 1 to 3.
Cmax of AVI	11.08 ug/mL Geometric Coefficient of Variation 14	11.35 ug/mL Geometric Coefficient of Variation 14

SECONDARY outcome

Timeframe: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.

Population: The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.

The AUC0-tau was calculated by linear/log trapezoidal method. The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).

Outcome measures

Measure	Cohort 1: Normal Renal Function n=6 Participants Participants with normal renal function received 30-minute IV loading dose infusion (500/167 mg aztreonam \[ATM\]/avibactam \[AVI\]), followed by 3-hour IV extended loading infusion (1500/500 mg ATM/AVI), then 3-hour 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours on Days 1 to 3.	Cohort 2: Severe Renal Impairment n=5 Participants Participants with severe renal impairment (not on dialysis) received 30-minute IV loading dose infusion (675/255 mg aztreonam \[ATM\]/avibactam \[AVI\]), followed by 3-hour IV extended loading infusion (675/255 mg ATM/AVI), then 3-hour 675/255 mg ATM/AVI maintenance dose infusion every 8 hours on Days 1 to 3.
Area Under the Plasma Concentration-time Profile From Time 0 to Time Tau (The Dosing Interval)(AUC0-tau) of ATM	230.8 ug*hr/mL Geometric Coefficient of Variation 16	244.3 ug*hr/mL Geometric Coefficient of Variation 16

SECONDARY outcome

Timeframe: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.

Population: The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.

The Tmax was observed directly from data as time of first occurrence.

Outcome measures

Measure	Cohort 1: Normal Renal Function n=6 Participants Participants with normal renal function received 30-minute IV loading dose infusion (500/167 mg aztreonam \[ATM\]/avibactam \[AVI\]), followed by 3-hour IV extended loading infusion (1500/500 mg ATM/AVI), then 3-hour 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours on Days 1 to 3.	Cohort 2: Severe Renal Impairment n=5 Participants Participants with severe renal impairment (not on dialysis) received 30-minute IV loading dose infusion (675/255 mg aztreonam \[ATM\]/avibactam \[AVI\]), followed by 3-hour IV extended loading infusion (675/255 mg ATM/AVI), then 3-hour 675/255 mg ATM/AVI maintenance dose infusion every 8 hours on Days 1 to 3.
Time for Cmax (Tmax) of ATM	2.92 Hours Interval 2.0 to 2.92	2.92 Hours Interval 2.92 to 3.75

SECONDARY outcome

Timeframe: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.

Population: The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.

The Ctau was observed directly from data. The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).

Outcome measures

Measure	Cohort 1: Normal Renal Function n=6 Participants Participants with normal renal function received 30-minute IV loading dose infusion (500/167 mg aztreonam \[ATM\]/avibactam \[AVI\]), followed by 3-hour IV extended loading infusion (1500/500 mg ATM/AVI), then 3-hour 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours on Days 1 to 3.	Cohort 2: Severe Renal Impairment n=5 Participants Participants with severe renal impairment (not on dialysis) received 30-minute IV loading dose infusion (675/255 mg aztreonam \[ATM\]/avibactam \[AVI\]), followed by 3-hour IV extended loading infusion (675/255 mg ATM/AVI), then 3-hour 675/255 mg ATM/AVI maintenance dose infusion every 8 hours on Days 1 to 3.
Observed Plasma Concentration at the End of the Dosing Interval (Tau) (Ctau) of ATM	21.43 ug/mL Geometric Coefficient of Variation 19	18.55 ug/mL Geometric Coefficient of Variation 24

SECONDARY outcome

Timeframe: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.

Population: The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.

The t1/2 was calculated by loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log linear concentration time curve. Only those data points judged to describe the terminal log linear decline were used in the regression.

Outcome measures

Measure	Cohort 1: Normal Renal Function n=6 Participants Participants with normal renal function received 30-minute IV loading dose infusion (500/167 mg aztreonam \[ATM\]/avibactam \[AVI\]), followed by 3-hour IV extended loading infusion (1500/500 mg ATM/AVI), then 3-hour 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours on Days 1 to 3.	Cohort 2: Severe Renal Impairment n=5 Participants Participants with severe renal impairment (not on dialysis) received 30-minute IV loading dose infusion (675/255 mg aztreonam \[ATM\]/avibactam \[AVI\]), followed by 3-hour IV extended loading infusion (675/255 mg ATM/AVI), then 3-hour 675/255 mg ATM/AVI maintenance dose infusion every 8 hours on Days 1 to 3.
Terminal Elimination Half-life (t1/2) of ATM	2.605 Hours Standard Deviation 0.34944	4.902 Hours Standard Deviation 1.4286

SECONDARY outcome

Timeframe: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.

Population: The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.

The CL was calculated by dose/AUC0-tau, where AUC0-tau was area under the concentration-time profile from time 0 to time tau (the dosing interval). The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).

Outcome measures

Measure	Cohort 1: Normal Renal Function n=6 Participants Participants with normal renal function received 30-minute IV loading dose infusion (500/167 mg aztreonam \[ATM\]/avibactam \[AVI\]), followed by 3-hour IV extended loading infusion (1500/500 mg ATM/AVI), then 3-hour 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours on Days 1 to 3.	Cohort 2: Severe Renal Impairment n=5 Participants Participants with severe renal impairment (not on dialysis) received 30-minute IV loading dose infusion (675/255 mg aztreonam \[ATM\]/avibactam \[AVI\]), followed by 3-hour IV extended loading infusion (675/255 mg ATM/AVI), then 3-hour 675/255 mg ATM/AVI maintenance dose infusion every 8 hours on Days 1 to 3.
Clearance (CL) of ATM	6.499 Liters per hour (L/hr) Geometric Coefficient of Variation 16	2.761 Liters per hour (L/hr) Geometric Coefficient of Variation 16

SECONDARY outcome

Timeframe: In Cohort 1, at predose on Day 3, during 0-2, 2-4, and 4-6 hours after the start of a maintenance dose infusion. In Cohort 2, at predose on Day 3, during 0-2, 2-4, 4-6, and 6-8 hours after the start of a maintenance dose infusion.

Population: The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.

The CLr was calculated by Ae0-tau/AUC0-tau, where Ae0-tau was cumulative amount of drug recovered unchanged in urine up to time tau and AUC0-tau was area under the plasma concentration time profile from time 0 to time tau (the dosing interval). The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).

Outcome measures

Measure	Cohort 1: Normal Renal Function n=6 Participants Participants with normal renal function received 30-minute IV loading dose infusion (500/167 mg aztreonam \[ATM\]/avibactam \[AVI\]), followed by 3-hour IV extended loading infusion (1500/500 mg ATM/AVI), then 3-hour 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours on Days 1 to 3.	Cohort 2: Severe Renal Impairment n=5 Participants Participants with severe renal impairment (not on dialysis) received 30-minute IV loading dose infusion (675/255 mg aztreonam \[ATM\]/avibactam \[AVI\]), followed by 3-hour IV extended loading infusion (675/255 mg ATM/AVI), then 3-hour 675/255 mg ATM/AVI maintenance dose infusion every 8 hours on Days 1 to 3.
Renal Clearance (CLr) of ATM	4.527 L/hr Geometric Coefficient of Variation 18	1.477 L/hr Geometric Coefficient of Variation 23

SECONDARY outcome

Timeframe: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.

Population: The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.

The Vz was calculated by dose/(AUC0-tau*kel), where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve and AUC0-tau was area under the concentration-time profile from time 0 to time tau (the dosing interval). The dosing interval (tau) was 6 hours for the normal renal function group (Cohort 1) and 8 hours for the severe renal impairment group (Cohort 2).

Outcome measures

Measure	Cohort 1: Normal Renal Function n=6 Participants Participants with normal renal function received 30-minute IV loading dose infusion (500/167 mg aztreonam \[ATM\]/avibactam \[AVI\]), followed by 3-hour IV extended loading infusion (1500/500 mg ATM/AVI), then 3-hour 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours on Days 1 to 3.	Cohort 2: Severe Renal Impairment n=5 Participants Participants with severe renal impairment (not on dialysis) received 30-minute IV loading dose infusion (675/255 mg aztreonam \[ATM\]/avibactam \[AVI\]), followed by 3-hour IV extended loading infusion (675/255 mg ATM/AVI), then 3-hour 675/255 mg ATM/AVI maintenance dose infusion every 8 hours on Days 1 to 3.
Apparent Volume of Distribution (Vz) of ATM	24.25 Liters (L) Geometric Coefficient of Variation 23	18.79 Liters (L) Geometric Coefficient of Variation 21

SECONDARY outcome

Timeframe: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.

Population: The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.

Vss was calculated by CL*MRT, where CL was clearance and MRT was mean residence time.

Outcome measures

Measure	Cohort 1: Normal Renal Function n=6 Participants Participants with normal renal function received 30-minute IV loading dose infusion (500/167 mg aztreonam \[ATM\]/avibactam \[AVI\]), followed by 3-hour IV extended loading infusion (1500/500 mg ATM/AVI), then 3-hour 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours on Days 1 to 3.	Cohort 2: Severe Renal Impairment n=5 Participants Participants with severe renal impairment (not on dialysis) received 30-minute IV loading dose infusion (675/255 mg aztreonam \[ATM\]/avibactam \[AVI\]), followed by 3-hour IV extended loading infusion (675/255 mg ATM/AVI), then 3-hour 675/255 mg ATM/AVI maintenance dose infusion every 8 hours on Days 1 to 3.
Apparent Volume of Distribution at Steady-state (Vss) of ATM	23.70 L Geometric Coefficient of Variation 29	18.46 L Geometric Coefficient of Variation 19

SECONDARY outcome

Timeframe: In Cohort 1, at predose on Day 3, during 0-2, 2-4, and 4-6 hours after the start of a maintenance dose infusion. In Cohort 2, at predose on Day 3, during 0-2, 2-4, 4-6, and 6-8 hours after the start of a maintenance dose infusion.

Population: The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.

The Ae0-tau was the sum of (urine concentration*sample volume). The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).

Outcome measures

Measure	Cohort 1: Normal Renal Function n=6 Participants Participants with normal renal function received 30-minute IV loading dose infusion (500/167 mg aztreonam \[ATM\]/avibactam \[AVI\]), followed by 3-hour IV extended loading infusion (1500/500 mg ATM/AVI), then 3-hour 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours on Days 1 to 3.	Cohort 2: Severe Renal Impairment n=5 Participants Participants with severe renal impairment (not on dialysis) received 30-minute IV loading dose infusion (675/255 mg aztreonam \[ATM\]/avibactam \[AVI\]), followed by 3-hour IV extended loading infusion (675/255 mg ATM/AVI), then 3-hour 675/255 mg ATM/AVI maintenance dose infusion every 8 hours on Days 1 to 3.
Cumulative Amount of Drug Recovered Unchanged in Urine up to Time Tau (Ae0-tau) of ATM	1047 Milligram (mg) Geometric Coefficient of Variation 11	361.2 Milligram (mg) Geometric Coefficient of Variation 19

SECONDARY outcome

Timeframe: In Cohort 1, at predose on Day 3, during 0-2, 2-4, and 4-6 hours after the start of a maintenance dose infusion. In Cohort 2, at predose on Day 3, during 0-2, 2-4, 4-6, and 6-8 hours after the start of a maintenance dose infusion.

Population: The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.

The Ae0-tau was calculated by 100*Ae0-tau/dose, where Ae0-tau was cumulative amount of drug recovered unchanged in urine up to time tau. The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).

Outcome measures

Measure	Cohort 1: Normal Renal Function n=6 Participants Participants with normal renal function received 30-minute IV loading dose infusion (500/167 mg aztreonam \[ATM\]/avibactam \[AVI\]), followed by 3-hour IV extended loading infusion (1500/500 mg ATM/AVI), then 3-hour 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours on Days 1 to 3.	Cohort 2: Severe Renal Impairment n=5 Participants Participants with severe renal impairment (not on dialysis) received 30-minute IV loading dose infusion (675/255 mg aztreonam \[ATM\]/avibactam \[AVI\]), followed by 3-hour IV extended loading infusion (675/255 mg ATM/AVI), then 3-hour 675/255 mg ATM/AVI maintenance dose infusion every 8 hours on Days 1 to 3.
Percent of Dose Recovered Unchanged in Urine up to Time Tau (Ae0-tau%) of ATM	69.68 Percent of dose Geometric Coefficient of Variation 11	53.51 Percent of dose Geometric Coefficient of Variation 19

SECONDARY outcome

Timeframe: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.

Population: The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.

The UC0-tau was calculated by linear/log trapezoidal method. The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).A

Outcome measures

Measure	Cohort 1: Normal Renal Function n=6 Participants Participants with normal renal function received 30-minute IV loading dose infusion (500/167 mg aztreonam \[ATM\]/avibactam \[AVI\]), followed by 3-hour IV extended loading infusion (1500/500 mg ATM/AVI), then 3-hour 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours on Days 1 to 3.	Cohort 2: Severe Renal Impairment n=5 Participants Participants with severe renal impairment (not on dialysis) received 30-minute IV loading dose infusion (675/255 mg aztreonam \[ATM\]/avibactam \[AVI\]), followed by 3-hour IV extended loading infusion (675/255 mg ATM/AVI), then 3-hour 675/255 mg ATM/AVI maintenance dose infusion every 8 hours on Days 1 to 3.
AUC0-tau of AVI	41.19 ug*hr/mL Geometric Coefficient of Variation 18	68.31 ug*hr/mL Geometric Coefficient of Variation 20

SECONDARY outcome

Timeframe: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.

Population: The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.

The Tmax was observed directly from data as time of first occurrence.

Outcome measures

Measure	Cohort 1: Normal Renal Function n=6 Participants Participants with normal renal function received 30-minute IV loading dose infusion (500/167 mg aztreonam \[ATM\]/avibactam \[AVI\]), followed by 3-hour IV extended loading infusion (1500/500 mg ATM/AVI), then 3-hour 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours on Days 1 to 3.	Cohort 2: Severe Renal Impairment n=5 Participants Participants with severe renal impairment (not on dialysis) received 30-minute IV loading dose infusion (675/255 mg aztreonam \[ATM\]/avibactam \[AVI\]), followed by 3-hour IV extended loading infusion (675/255 mg ATM/AVI), then 3-hour 675/255 mg ATM/AVI maintenance dose infusion every 8 hours on Days 1 to 3.
Tmax of AVI	2.46 Hours Interval 2.0 to 2.92	2.92 Hours Interval 2.0 to 3.25

SECONDARY outcome

Timeframe: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.

Population: The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.

The Ctau was observed directly from data. The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).

Outcome measures

Measure	Cohort 1: Normal Renal Function n=6 Participants Participants with normal renal function received 30-minute IV loading dose infusion (500/167 mg aztreonam \[ATM\]/avibactam \[AVI\]), followed by 3-hour IV extended loading infusion (1500/500 mg ATM/AVI), then 3-hour 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours on Days 1 to 3.	Cohort 2: Severe Renal Impairment n=5 Participants Participants with severe renal impairment (not on dialysis) received 30-minute IV loading dose infusion (675/255 mg aztreonam \[ATM\]/avibactam \[AVI\]), followed by 3-hour IV extended loading infusion (675/255 mg ATM/AVI), then 3-hour 675/255 mg ATM/AVI maintenance dose infusion every 8 hours on Days 1 to 3.
Ctau of AVI	3.100 ug/mL Geometric Coefficient of Variation 24	5.597 ug/mL Geometric Coefficient of Variation 39

SECONDARY outcome

Timeframe: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.

Population: The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.

The t1/2 was calculated by loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log linear concentration time curve. Only those data points judged to describe the terminal log linear decline were used in the regression.

Outcome measures

Measure	Cohort 1: Normal Renal Function n=6 Participants Participants with normal renal function received 30-minute IV loading dose infusion (500/167 mg aztreonam \[ATM\]/avibactam \[AVI\]), followed by 3-hour IV extended loading infusion (1500/500 mg ATM/AVI), then 3-hour 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours on Days 1 to 3.	Cohort 2: Severe Renal Impairment n=5 Participants Participants with severe renal impairment (not on dialysis) received 30-minute IV loading dose infusion (675/255 mg aztreonam \[ATM\]/avibactam \[AVI\]), followed by 3-hour IV extended loading infusion (675/255 mg ATM/AVI), then 3-hour 675/255 mg ATM/AVI maintenance dose infusion every 8 hours on Days 1 to 3.
t1/2 of AVI	3.188 Hours Standard Deviation 0.071391	6.524 Hours Standard Deviation 1.6469

SECONDARY outcome

Timeframe: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.

Population: The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.

The CL was calculated by dose/AUC0-tau, where AUC0-tau was area under the plasma concentration-time profile from time 0 to to time tau (the dosing interval). The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).

Outcome measures

Measure	Cohort 1: Normal Renal Function n=6 Participants Participants with normal renal function received 30-minute IV loading dose infusion (500/167 mg aztreonam \[ATM\]/avibactam \[AVI\]), followed by 3-hour IV extended loading infusion (1500/500 mg ATM/AVI), then 3-hour 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours on Days 1 to 3.	Cohort 2: Severe Renal Impairment n=5 Participants Participants with severe renal impairment (not on dialysis) received 30-minute IV loading dose infusion (675/255 mg aztreonam \[ATM\]/avibactam \[AVI\]), followed by 3-hour IV extended loading infusion (675/255 mg ATM/AVI), then 3-hour 675/255 mg ATM/AVI maintenance dose infusion every 8 hours on Days 1 to 3.
CL of AVI	12.16 L/hr Geometric Coefficient of Variation 18	3.295 L/hr Geometric Coefficient of Variation 20

SECONDARY outcome

Timeframe: In Cohort 1, at predose on Day 3, during 0-2, 2-4, and 4-6 hours after the start of a maintenance dose infusion. In Cohort 2, at predose on Day 3, during 0-2, 2-4, 4-6, and 6-8 hours after the start of a maintenance dose infusion.

Population: The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.

The CLr was calculated by Ae0-tau/AUC0-tau, where Ae0-tau was cumulative amount of drug recovered unchanged in urine up to time tau and AUC0-tau was area under the plasma concentration time profile from time 0 to time tau (the dosing interval). The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).

Outcome measures

Measure	Cohort 1: Normal Renal Function n=6 Participants Participants with normal renal function received 30-minute IV loading dose infusion (500/167 mg aztreonam \[ATM\]/avibactam \[AVI\]), followed by 3-hour IV extended loading infusion (1500/500 mg ATM/AVI), then 3-hour 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours on Days 1 to 3.	Cohort 2: Severe Renal Impairment n=5 Participants Participants with severe renal impairment (not on dialysis) received 30-minute IV loading dose infusion (675/255 mg aztreonam \[ATM\]/avibactam \[AVI\]), followed by 3-hour IV extended loading infusion (675/255 mg ATM/AVI), then 3-hour 675/255 mg ATM/AVI maintenance dose infusion every 8 hours on Days 1 to 3.
CLr of AVI	11.30 L/hr Geometric Coefficient of Variation 20	3.948 L/hr Geometric Coefficient of Variation 36

SECONDARY outcome

Timeframe: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.

Population: The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.

The Vz was calculated by dose/(AUC0-tau*kel), where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve and AUC0-tau was area under the concentration-time profile from time 0 to time tau (the dosing interval). The dosing interval (tau) was 6 hours for the normal renal function group (Cohort 1) and 8 hours for the severe renal impairment group (Cohort 2).

Outcome measures

Measure	Cohort 1: Normal Renal Function n=6 Participants Participants with normal renal function received 30-minute IV loading dose infusion (500/167 mg aztreonam \[ATM\]/avibactam \[AVI\]), followed by 3-hour IV extended loading infusion (1500/500 mg ATM/AVI), then 3-hour 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours on Days 1 to 3.	Cohort 2: Severe Renal Impairment n=5 Participants Participants with severe renal impairment (not on dialysis) received 30-minute IV loading dose infusion (675/255 mg aztreonam \[ATM\]/avibactam \[AVI\]), followed by 3-hour IV extended loading infusion (675/255 mg ATM/AVI), then 3-hour 675/255 mg ATM/AVI maintenance dose infusion every 8 hours on Days 1 to 3.
Vz of AVI	55.83 L Geometric Coefficient of Variation 19	30.14 L Geometric Coefficient of Variation 16

SECONDARY outcome

Timeframe: Predose, 2, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 16, and 24 hours after start of a maintenance dose infusion on Day 3.

Population: The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.

Vss was calculated by CL*MRT, where CL was clearance and MRT was mean residence time.

Outcome measures

Measure	Cohort 1: Normal Renal Function n=6 Participants Participants with normal renal function received 30-minute IV loading dose infusion (500/167 mg aztreonam \[ATM\]/avibactam \[AVI\]), followed by 3-hour IV extended loading infusion (1500/500 mg ATM/AVI), then 3-hour 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours on Days 1 to 3.	Cohort 2: Severe Renal Impairment n=5 Participants Participants with severe renal impairment (not on dialysis) received 30-minute IV loading dose infusion (675/255 mg aztreonam \[ATM\]/avibactam \[AVI\]), followed by 3-hour IV extended loading infusion (675/255 mg ATM/AVI), then 3-hour 675/255 mg ATM/AVI maintenance dose infusion every 8 hours on Days 1 to 3.
Vss of AVI	37.37 L Geometric Coefficient of Variation 30	27.78 L Geometric Coefficient of Variation 16

SECONDARY outcome

Timeframe: In Cohort 1, at predose on Day 3, during 0-2, 2-4, and 4-6 hours after the start of a maintenance dose infusion. In Cohort 2, at predose on Day 3, during 0-2, 2-4, 4-6, and 6-8 hours after the start of a maintenance dose infusion.

Population: The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.

The Ae0-tau was the sum of (urine concentration*sample volume). The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).

Outcome measures

Measure	Cohort 1: Normal Renal Function n=6 Participants Participants with normal renal function received 30-minute IV loading dose infusion (500/167 mg aztreonam \[ATM\]/avibactam \[AVI\]), followed by 3-hour IV extended loading infusion (1500/500 mg ATM/AVI), then 3-hour 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours on Days 1 to 3.	Cohort 2: Severe Renal Impairment n=5 Participants Participants with severe renal impairment (not on dialysis) received 30-minute IV loading dose infusion (675/255 mg aztreonam \[ATM\]/avibactam \[AVI\]), followed by 3-hour IV extended loading infusion (675/255 mg ATM/AVI), then 3-hour 675/255 mg ATM/AVI maintenance dose infusion every 8 hours on Days 1 to 3.
Ae0-tau of AVI	465.6 mg Geometric Coefficient of Variation 11	270.0 mg Geometric Coefficient of Variation 17

SECONDARY outcome

Timeframe: In Cohort 1, at predose on Day 3, during 0-2, 2-4, and 4-6 hours after the start of a maintenance dose infusion. In Cohort 2, at predose on Day 3, during 0-2, 2-4, 4-6, and 6-8 hours after the start of a maintenance dose infusion.

Population: The analysis population included all participants treated with study medication who had at least 1 of the PK parameters of interest.

The Ae0-tau was calculated by 100*Ae0-tau/dose, where Ae0-tau was cumulative amount of drug recovered unchanged in urine up to time tau. The dosing interval (tau) was 6 hours for normal renal function (Cohort 1) and 8 hours for severe renal impairment (Cohort 2).

Outcome measures

Measure	Cohort 1: Normal Renal Function n=6 Participants Participants with normal renal function received 30-minute IV loading dose infusion (500/167 mg aztreonam \[ATM\]/avibactam \[AVI\]), followed by 3-hour IV extended loading infusion (1500/500 mg ATM/AVI), then 3-hour 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours on Days 1 to 3.	Cohort 2: Severe Renal Impairment n=5 Participants Participants with severe renal impairment (not on dialysis) received 30-minute IV loading dose infusion (675/255 mg aztreonam \[ATM\]/avibactam \[AVI\]), followed by 3-hour IV extended loading infusion (675/255 mg ATM/AVI), then 3-hour 675/255 mg ATM/AVI maintenance dose infusion every 8 hours on Days 1 to 3.
Ae0-tau% of AVI	93.19 Percent of dose Geometric Coefficient of Variation 11	119.9 Percent of dose Geometric Coefficient of Variation 17

SECONDARY outcome

Timeframe: Day 1 up to at least 28 days after last dose of study medication (maximum of 33 days).

Population: The analysis population included all participants who received at least 1 dose of study medication.

An adverse event (AE) is any untoward medical occurrence in a study participant administered a product; the event need not necessarily have a causal relationship with the treatment or usage. A serious adverse event is any untoward medical occurrence at any dose that: (1) results in death; (2) is life threatening (immediate risk of death); (3) requires inpatient hospitalization or prolongation of existing hospitalization; (4) results in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); (5) results in congenital anomaly/birth defect; or that is considered to be an important medical event. Treatment-emergent are events between first dose of study medication and up to at least 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. A severe AE is defined as a event interferes significantly with participant's usual function.

Outcome measures

Measure	Cohort 1: Normal Renal Function n=6 Participants Participants with normal renal function received 30-minute IV loading dose infusion (500/167 mg aztreonam \[ATM\]/avibactam \[AVI\]), followed by 3-hour IV extended loading infusion (1500/500 mg ATM/AVI), then 3-hour 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours on Days 1 to 3.	Cohort 2: Severe Renal Impairment n=5 Participants Participants with severe renal impairment (not on dialysis) received 30-minute IV loading dose infusion (675/255 mg aztreonam \[ATM\]/avibactam \[AVI\]), followed by 3-hour IV extended loading infusion (675/255 mg ATM/AVI), then 3-hour 675/255 mg ATM/AVI maintenance dose infusion every 8 hours on Days 1 to 3.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) (All-causality) Participants with AEs	2 Participants	3 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) (All-causality) Participants with serious AEs	0 Participants	0 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) (All-causality) Participants with severe AEs	0 Participants	0 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) (All-causality) Participants discontinued from study due to AEs	0 Participants	0 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) (All-causality) Participants discontinued study drug due to AEs and continue study	0 Participants	0 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) (All-causality) Participants with dose reduced or temporary discontinuation due to AEs	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Day 1 up to at least 28 days after last dose of study medication (maximum of 33 days).

Population: The analysis population included all participants who received at least 1 dose of study medication.

An adverse event (AE) is any untoward medical occurrence in a study participant administered a product; the event attributed to the study medication. A serious AE is any untoward medical occurrence at any dose that: (1) results in death; (2) is life threatening (immediate risk of death); (3) requires inpatient hospitalization or prolongation of existing hospitalization; (4) results in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); (5) results in congenital anomaly/birth defect; or that is considered to be an important medical event. Treatment-emergent are events between first dose of study medication and up to at least 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. A severe AE is defined as a event interferes significantly with participant's usual function.

Outcome measures

Measure	Cohort 1: Normal Renal Function n=6 Participants Participants with normal renal function received 30-minute IV loading dose infusion (500/167 mg aztreonam \[ATM\]/avibactam \[AVI\]), followed by 3-hour IV extended loading infusion (1500/500 mg ATM/AVI), then 3-hour 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours on Days 1 to 3.	Cohort 2: Severe Renal Impairment n=5 Participants Participants with severe renal impairment (not on dialysis) received 30-minute IV loading dose infusion (675/255 mg aztreonam \[ATM\]/avibactam \[AVI\]), followed by 3-hour IV extended loading infusion (675/255 mg ATM/AVI), then 3-hour 675/255 mg ATM/AVI maintenance dose infusion every 8 hours on Days 1 to 3.
Number of Participants With TEAEs (Treatment-related) Participants with AEs	0 Participants	3 Participants
Number of Participants With TEAEs (Treatment-related) Participants with serious AEs	0 Participants	0 Participants
Number of Participants With TEAEs (Treatment-related) Participants with severe AEs	0 Participants	0 Participants
Number of Participants With TEAEs (Treatment-related) Participants discontinued from study due to AEs	0 Participants	0 Participants
Number of Participants With TEAEs (Treatment-related) Participants discontinued study drug due to AEs and continue study	0 Participants	0 Participants
Number of Participants With TEAEs (Treatment-related) Participants with dose reduced or temporary discontinuation due to AEs	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Days 1 to 3

Population: The analysis population included all participants who received at least 1 dose of study medication.

Categorical post-baseline vital signs included: (1) pulse rate: value less than (<) 40 beats per minute (bpm), lager than (>) 120 bpm; (2) supine diastolic blood pressure (DBP): value <50 mmHg, change of more than or equal to (>=) 20 mmHg increase, change of >=20 mmHg decrease; (3) supine systolic blood pressure (SBP): value <90 mmHg, change of >=30 mmHg increase, change of >=30 mmHg decrease.

Outcome measures

Measure	Cohort 1: Normal Renal Function n=6 Participants Participants with normal renal function received 30-minute IV loading dose infusion (500/167 mg aztreonam \[ATM\]/avibactam \[AVI\]), followed by 3-hour IV extended loading infusion (1500/500 mg ATM/AVI), then 3-hour 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours on Days 1 to 3.	Cohort 2: Severe Renal Impairment n=5 Participants Participants with severe renal impairment (not on dialysis) received 30-minute IV loading dose infusion (675/255 mg aztreonam \[ATM\]/avibactam \[AVI\]), followed by 3-hour IV extended loading infusion (675/255 mg ATM/AVI), then 3-hour 675/255 mg ATM/AVI maintenance dose infusion every 8 hours on Days 1 to 3.
Number of Participants With Categorical Post-Baseline Vital Signs Data Pulse rate <40 bpm	0 Participants	0 Participants
Number of Participants With Categorical Post-Baseline Vital Signs Data Pulse rate >120 bpm	0 Participants	0 Participants
Number of Participants With Categorical Post-Baseline Vital Signs Data Supine DBP <50 mmHg	0 Participants	0 Participants
Number of Participants With Categorical Post-Baseline Vital Signs Data Supine DBP change >=20 mmHg increase	0 Participants	0 Participants
Number of Participants With Categorical Post-Baseline Vital Signs Data Supine DBP change >=20 mmHg decrease	0 Participants	0 Participants
Number of Participants With Categorical Post-Baseline Vital Signs Data Supine SBP <90 mmHg	0 Participants	0 Participants
Number of Participants With Categorical Post-Baseline Vital Signs Data Supine SBP change >=30 mmHg increase	0 Participants	1 Participants
Number of Participants With Categorical Post-Baseline Vital Signs Data Supine SBP change >=30 mmHg decrease	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Days 1 to 3

Population: The analysis population included all participants who received at least 1 dose of study medication.

Criteria for ECG abnormalities: maximum QT interval >500 milliseconds (msec); maximum QTc interval of >=450 msec to less than or equal to (<=) 480 msec, >480 msec, and >500 msec and a maximum change of <30 change<=60 or >60 msec from baseline; maximum QTcF (Fridericia's Correction) interval of >=450 msec to <=480 msec, >480 msec, and >500 msec and a maximum change of <30 change<=60 or >60 msec from baseline.

Outcome measures

Measure	Cohort 1: Normal Renal Function n=6 Participants Participants with normal renal function received 30-minute IV loading dose infusion (500/167 mg aztreonam \[ATM\]/avibactam \[AVI\]), followed by 3-hour IV extended loading infusion (1500/500 mg ATM/AVI), then 3-hour 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours on Days 1 to 3.	Cohort 2: Severe Renal Impairment n=5 Participants Participants with severe renal impairment (not on dialysis) received 30-minute IV loading dose infusion (675/255 mg aztreonam \[ATM\]/avibactam \[AVI\]), followed by 3-hour IV extended loading infusion (675/255 mg ATM/AVI), then 3-hour 675/255 mg ATM/AVI maintenance dose infusion every 8 hours on Days 1 to 3.
Number of Participants With Abnormal Electrocardiogram (ECG) QT interval value > 500 msec	0 Participants	0 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) 450 msec<= QTc interval value <=480 msec	0 Participants	2 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) QTc interval value >480 msec	0 Participants	0 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) QTc interval value >500 msec	0 Participants	0 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) 30 msec< QTc interval change <=60 msec	0 Participants	0 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) QTc interval change >60 msec	0 Participants	0 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) 450 msec<= QTcF interval value <=480 msec	0 Participants	2 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) QTcF interval value >480 msec	0 Participants	0 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) QTcF interval value >500 msec	0 Participants	0 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) 30 msec< QTcF interval change <=60 msec	0 Participants	0 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) QTcF interval change >60 msec	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Days 1 to 3

Population: The analysis population included all participants who received at least 1 dose of study medication.

Following laboratory parameters were abnormal (without regard to baseline abnormality): hemoglobin, hematocrit, erythrocytes, lymphocytes, neutrophils, activated partial thromboplastin time, protein, urea nitrogen, creatinine, urate, urine glucose, and urine protein.

Outcome measures

Measure	Cohort 1: Normal Renal Function n=6 Participants Participants with normal renal function received 30-minute IV loading dose infusion (500/167 mg aztreonam \[ATM\]/avibactam \[AVI\]), followed by 3-hour IV extended loading infusion (1500/500 mg ATM/AVI), then 3-hour 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours on Days 1 to 3.	Cohort 2: Severe Renal Impairment n=5 Participants Participants with severe renal impairment (not on dialysis) received 30-minute IV loading dose infusion (675/255 mg aztreonam \[ATM\]/avibactam \[AVI\]), followed by 3-hour IV extended loading infusion (675/255 mg ATM/AVI), then 3-hour 675/255 mg ATM/AVI maintenance dose infusion every 8 hours on Days 1 to 3.
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) Hemoglobin (gram per deciliter [g/dL]) <0.8*lower limit of normal (LLN)	0 Participants	3 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) Hematocrit (%) <0.8*LLN	0 Participants	3 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) Erythrocytes (10^6 per cubic millimeter [10^6/mm^3]) <0.8*LLN	0 Participants	4 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) Lymphocytes (10^3 per cubic millimeter [10^3/mm^3]) <0.8*LLN	0 Participants	1 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) Neutrophils (10^3/mm^3) >1.2*upper limit of normal (ULN)	0 Participants	1 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) Activated partial thromboplastin time (second) >1.1*ULN	0 Participants	1 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) Protein (g/dL) <0.8*LLN	0 Participants	1 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) Urea Nitrogen (milligram per deciliter [mg/dL]) >1.3*ULN	0 Participants	5 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) Creatinine (mg/dL) >1.3*ULN	0 Participants	5 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) Urate (mg/dL) >1.2*ULN	0 Participants	3 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) Urine glucose (mg/dL) >=1	0 Participants	3 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) Urine protein (mg/dL) >=1	0 Participants	1 Participants

Adverse Events

Cohort 1: Normal Renal Function

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Cohort 2: Severe Renal Impairment

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Cohort 1: Normal Renal Function n=6 participants at risk Participants with normal renal function received 30-minute IV loading dose infusion (500/167 mg aztreonam \[ATM\]/avibactam \[AVI\]), followed by 3-hour IV extended loading infusion (1500/500 mg ATM/AVI), then 3-hour 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours on Days 1 to 3.	Cohort 2: Severe Renal Impairment n=5 participants at risk Participants with severe renal impairment (not on dialysis) received 30-minute IV loading dose infusion (675/255 mg aztreonam \[ATM\]/avibactam \[AVI\]), followed by 3-hour IV extended loading infusion (675/255 mg ATM/AVI), then 3-hour 675/255 mg ATM/AVI maintenance dose infusion every 8 hours on Days 1 to 3.
Gastrointestinal disorders Diarrhoea	0.00% 0/6 • Day 1 up to at least 28 days after last dose of study drug (maximum of 33 days). Participants were only counted once per treatment for each category.	20.0% 1/5 • Day 1 up to at least 28 days after last dose of study drug (maximum of 33 days). Participants were only counted once per treatment for each category.
Metabolism and nutrition disorders Decreased appetite	0.00% 0/6 • Day 1 up to at least 28 days after last dose of study drug (maximum of 33 days). Participants were only counted once per treatment for each category.	20.0% 1/5 • Day 1 up to at least 28 days after last dose of study drug (maximum of 33 days). Participants were only counted once per treatment for each category.
Nervous system disorders Headache	0.00% 0/6 • Day 1 up to at least 28 days after last dose of study drug (maximum of 33 days). Participants were only counted once per treatment for each category.	20.0% 1/5 • Day 1 up to at least 28 days after last dose of study drug (maximum of 33 days). Participants were only counted once per treatment for each category.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/6 • Day 1 up to at least 28 days after last dose of study drug (maximum of 33 days). Participants were only counted once per treatment for each category.	20.0% 1/5 • Day 1 up to at least 28 days after last dose of study drug (maximum of 33 days). Participants were only counted once per treatment for each category.
Skin and subcutaneous tissue disorders Dermatitis contact	16.7% 1/6 • Day 1 up to at least 28 days after last dose of study drug (maximum of 33 days). Participants were only counted once per treatment for each category.	0.00% 0/5 • Day 1 up to at least 28 days after last dose of study drug (maximum of 33 days). Participants were only counted once per treatment for each category.
Skin and subcutaneous tissue disorders Pruritus	16.7% 1/6 • Day 1 up to at least 28 days after last dose of study drug (maximum of 33 days). Participants were only counted once per treatment for each category.	0.00% 0/5 • Day 1 up to at least 28 days after last dose of study drug (maximum of 33 days). Participants were only counted once per treatment for each category.

Additional Information

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Phone: 1-800-718-1021

Email: ClinicalTrials.gov_Inquiries@pfizer.com

Results disclosure agreements

• Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
• Publication restrictions are in place

Restriction type: OTHER