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Aztreonam-Avibactam

Phase 1

Healthy | Small molecule | Other |Pfizer, Inc.|Last Updated: Jul 28, 2023

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Trial Design

UNCONTROLLED
Total Trials1
Total Enrollment12

FDA Designations

No designations recorded

Clinical trial landscape

Aztreonam-Avibactam · 2 trials · 2 indications

Phase 1 2
NCT04973826Study to Assess the Pharmacokinetics, Safety and Tolerability of Aztreonam-Avibactam in Healthy Chinese Participants.Healthy
COMPLETED12 Analytics
NCT04486625Pharmacokinetic Study of Aztreonam-Avibactam in Severe Renal ImpairmentRenal Insufficiency
COMPLETED11 Analytics
PHASE1COMPLETED
Study to Assess the Pharmacokinetics, Safety and Tolerability of Aztreonam-Avibactam in Healthy Chinese Participants.
HealthyUnlock trial analytics
PHASE1COMPLETED
Pharmacokinetic Study of Aztreonam-Avibactam in Severe Renal Impairment
Renal InsufficiencyUnlock trial analytics

Study Endpoints

Primary Endpoints

Maximum Observed Plasma Concentration (Cmax) on Day 1 & 4 of Aztreonam
Post dose on day 1 and day 4

Cmax was the maximum observed plasma concentration and was directly observed from data. Concentration values below the lower limit of quantification (LLQ) were set to zero. Geometric Mean analysis was on the log scale. Zero values were not included in geometric mean and geometric coefficient of variation calculation. The geometric coefficient of variation is expressed in percentage.

Maximum Observed Plasma Concentration (Cmax) on Day 1 & 4 of Avibactam
Post dose on day 1 and day 4

Cmax was the maximum observed plasma concentration and was directly observed from data. Concentration values below the lower limit of quantification (LLQ) were set to zero. Geometric Mean analysis was on the log scale. Zero values were not included in geometric mean and geometric coefficient of variation calculation. The geometric coefficient of variation is expressed in percentage.

Area Under the Plasma Concentration-Time Profile From Time 0 to 6 Hours (AUC6) on Day 1 of Aztreonam
Post dose on day 1

The area under the plasma drug concentration-time curve (AUC) was estimated from time 0 to 6 hours post dose. AUC6 was computed using the Linear/Log trapezoidal method. The geometric coefficient of variation is expressed in percentage.

Area Under the Plasma Concentration-Time Profile From Time 0 to 6 Hours (AUC6) on Day 1 of Avibactam
Post dose on day 1

The area under the plasma drug concentration-time curve (AUC) was estimated from time 0 to 6 hours post dose. AUC6 was computed using the Linear/Log trapezoidal method. The geometric coefficient of variation is expressed in percentage.

Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUClast) on Day 1 & 4 of Aztreonam
Post dose on day 1 and day 4

AUClast is area under the plasma concentration time-curve from zero (pre-dose) to the last measured concentration. The geometric coefficient of variation is expressed in percentage.

Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUClast) on Day 1 & 4 of Avibactam
Post dose on day 1 and day 4

AUClast is area under the plasma concentration time-curve from zero (pre-dose) to the last measured concentration. The geometric coefficient of variation is expressed in percentage.

Area Under the Plasma Concentration-Time Profile From Time 0 to 24 Hours (AUC24) on Day 1 & 4 of Aztreonam
Post dose on day 1 and day 4

AUC24 was defined as area under the plasma concentration-time profile from time zero to 24 hours post dose. The geometric coefficient of variation is expressed in percentage.

Area Under the Plasma Concentration-Time Profile From Time 0 to 24 Hours (AUC24) on Day 1 & 4 of Avibactam
Post dose on day 1 and day 4

AUC24 was defined as area under the plasma concentration-time profile from time zero to 24 hours post dose. The geometric coefficient of variation is expressed in percentage.

Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) on Day 1 & 4 of Aztreonam
Post dose on day 1 and day 4

AUCinf was defined as area under the plasma concentration-time curve from time zero to infinity. The geometric coefficient of variation is expressed in percentage.

Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) on Day 1 & 4 of Avibactam
Post dose on day 1 and day 4

AUCinf was defined as area under the plasma concentration-time curve from time zero to infinity. The geometric coefficient of variation is expressed in percentage.

Area Under the Plasma Concentration-Time Profile From Time 0 to the Time of the End of the Dosing Interval (τ), Where τ=6 Hours (AUCtau) on Day 4 of Aztreonam
Post dose on day 4

AUCtau was defined as area under the concentration-time profile from time 0 to time tau. The geometric coefficient of variation is expressed in percentage.

Area Under the Plasma Concentration-Time Profile From Time 0 to the Time of the End of the Dosing Interval (τ), Where τ=6 Hours (AUCtau) on Day 4 of Avibactam
Post dose on day 4

AUCtau was defined as area under the concentration-time profile from time 0 to time tau. The geometric coefficient of variation is expressed in percentage.

Total Daily Area Under the Plasma Concentration-Time Profile From Time 0 to 24 Hours at Steady-State (AUC24,ss) on Day 4 of Aztreonam
Post dose on day 4

AUC24,ss was defined as total daily area under the plasma concentration-time profile from time 0 to 24 hours at steady-state. The geometric coefficient of variation is expressed in percentage.

Total Daily Area Under the Plasma Concentration-Time Profile From Time 0 to 24 Hours at Steady-State (AUC24,ss) on Day 4 of Avibactam
Post dose on day 4

AUC24,ss was defined as total daily area under the plasma concentration-time profile from time 0 to 24 hours at steady-state. The geometric coefficient of variation is expressed in percentage.

Renal Clearance (CLr) on Day 1 & 4 of Aztreonam
Post dose on day 1 and day 4

CLr was calculated as cumulative amount of drug recovered unchanged in urine during the dosing interval (Ae) divided by area under the plasma concentration time-curve from time zero to end of dosing interval (AUCtau). AUCtau was defined as area under the concentration-time profile from time 0 to time tau. The geometric coefficient of variation is expressed in percentage.

Renal Clearance (CLr) on Day 1 & 4 of Avibactam
Post dose on day 1 and day 4

CLr was calculated as cumulative amount of drug recovered unchanged in urine during the dosing interval (Ae) divided by area under the plasma concentration time-curve from time zero to end of dosing interval (AUCtau). AUCtau was defined as area under the concentration-time profile from time 0 to time tau. The geometric coefficient of variation is expressed in percentage.

Total Daily Area Under the Plasma Concentration-time Profile From Time 0 to 24 Hours at Steady-state (AUC0-24,ss) of Aztreonam (ATM)
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.

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).

Maximum Plasma Concentration (Cmax) of ATM
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.

The Cmax of ATM was observed directly from data.

AUC0-24,ss of Avibactam (AVI)
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.

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).

Cmax of AVI
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.

The Cmax of AVI was observed directly from data.

Secondary Endpoints

Terminal Elimination Half-Life (T1/2) on Day 1 & 4 of Aztreonam
Post dose on day 1 and day 4
Terminal Elimination Half-Life (T1/2) on Day 1 & 4 of Avibactam
Post dose on day 1 and day 4
Apparent Volume of Distribution at Steady-State (Vss) on Day 1 & 4 of Aztreonam
Post dose on day 1 and day 4
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Study Design & Arms

AllocationNA
MaskingNONE
ModelSINGLE_GROUP
PurposeOTHER

Treatment Arms

ArmTypeDescription
ATM-AVI treatment armEXPERIMENTALChinese healthy volunteers
Cohort 1EXPERIMENTALNormal renal function
Cohort 2EXPERIMENTALSevere renal impairment (not on dialysis)

Interventions

NameTypeDescription
Aztreonam-AvibactamDRUG500/167 mg ATM/AVI loading infusion, followed by 1500/500 mg ATM/AVI extended loading infusion, then 1500/500 mg ATM/AVI maintenance dose infusion every 6 hours
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Eligibility Criteria

Age Range18 Years to 55 Years
SexALL
Healthy VolunteersYes
Study Sites1

Inclusion Criteria: * Healthy Chinese male and female participants * No clinical relevant abnormalities * willing and able to comply with all study procedures * BMI:17.5-30.5 * Sign informed consent Exclusion Criteria: * Any clinical significant illness * History of alcohol abuse * Use within 14 ...

Countries:ChinaUnited States
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Frequently asked questions about Aztreonam-Avibactam

What is Aztreonam-Avibactam used for?

Aztreonam-Avibactam is an investigational small molecule being studied in healthy volunteers and in people with renal insufficiency. It is being developed by Pfizer, Inc. (PFE). As of now, it is in Phase 1 clinical development and has not been approved by the FDA.

What does Aztreonam-Avibactam target?

Aztreonam-Avibactam is a combination of two antibiotics: aztreonam, which inhibits bacterial cell wall synthesis, and avibactam, which is a beta-lactamase inhibitor that protects aztreonam from degradation. This combination is designed to treat infections caused by certain resistant bacteria.

Who makes Aztreonam-Avibactam?

Aztreonam-Avibactam is being developed by Pfizer, Inc., a pharmaceutical company listed on the New York Stock Exchange under the ticker symbol PFE. The drug is currently in Phase 1 clinical trials.

What phase is Aztreonam-Avibactam in?

Aztreonam-Avibactam is in Phase 1 clinical development. It is an investigational drug and has not been approved by regulatory authorities. Two Phase 1 studies have been completed, one in the United States and one in China.

What clinical trials is Aztreonam-Avibactam in?

Aztreonam-Avibactam has completed two Phase 1 trials. NCT04486625 studied its pharmacokinetics in severe renal impairment in the United States, enrolling 11 participants. NCT04973826 assessed its pharmacokinetics, safety, and tolerability in healthy Chinese participants, enrolling 12 participants.

Is Aztreonam-Avibactam the same as Avibactam?

Aztreonam-Avibactam is a fixed-dose combination product containing two active ingredients: aztreonam and avibactam. It is not the same as avibactam alone, which is a beta-lactamase inhibitor used in other combination products. The combination is being studied for its potential to treat resistant bacterial infections.