Trial Outcomes & Findings for Study to Assess the Pharmacokinetics, Safety and Tolerability of Aztreonam-Avibactam in Healthy Chinese Participants. (NCT NCT04973826)
NCT ID: NCT04973826
Last Updated: 2023-07-28
Results Overview
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.
COMPLETED
PHASE1
12 participants
Post dose on day 1 and day 4
2023-07-28
Participant Flow
A total of 12 participants received assigned treatment of AZTREONAM-AVIBACTAM (ATM-AVI) and completed the treatment and follow-up phases.
Participant milestones
| Measure |
AZTREONAM-AVIBACTAM (ATM-AVI)
ATM-AVI was dosed in a fixed 3:1 ratio (ATM:AVI=3:1) in 12 healthy participants. On Day 1, participants received a 3-hour intravenous (IV) infusion of a single dose of 1500 mg ATM plus 500 mg AVI. On Day 2, participants received a loading (500 mg ATM plus 167 mg AVI infused over a 30-minute period)/extended loading dose (1500 mg ATM plus 500 mg AVI over a 3-hour period), followed by multiple maintenance doses of ATM-AVI IV infusion: 1500 mg ATM and 500 mg AVI were infused over 3 hours and administered every 6 hours (q6h) till morning of Study Day 4.
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Overall Study
STARTED
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12
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Overall Study
COMPLETED
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12
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Overall Study
NOT COMPLETED
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0
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Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Study to Assess the Pharmacokinetics, Safety and Tolerability of Aztreonam-Avibactam in Healthy Chinese Participants.
Baseline characteristics by cohort
| Measure |
AZTREONAM-AVIBACTAM (ATM-AVI)
n=12 Participants
ATM-AVI was dosed in a fixed 3:1 ratio (ATM:AVI=3:1) in 12 healthy participants. On Day 1, participants received a 3-hour intravenous (IV) infusion of a single dose of 1500 mg ATM plus 500 mg AVI. On Day 2, participants received a loading (500 mg ATM plus 167 mg AVI infused over a 30-minute period)/extended loading dose (1500 mg ATM plus 500 mg AVI over a 3-hour period), followed by multiple maintenance doses of ATM-AVI IV infusion: 1500 mg ATM and 500 mg AVI were infused over 3 hours and administered every 6 hours (q6h) till morning of Study Day 4.
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Age, Continuous
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27.08 Years
STANDARD_DEVIATION 5.30 • n=5 Participants
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Sex: Female, Male
Female
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4 Participants
n=5 Participants
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Sex: Female, Male
Male
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8 Participants
n=5 Participants
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Ethnicity (NIH/OMB)
Hispanic or Latino
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0 Participants
n=5 Participants
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Ethnicity (NIH/OMB)
Not Hispanic or Latino
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12 Participants
n=5 Participants
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Ethnicity (NIH/OMB)
Unknown or Not Reported
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0 Participants
n=5 Participants
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Race/Ethnicity, Customized
Asian
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12 Participants
n=5 Participants
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PRIMARY outcome
Timeframe: Post dose on day 1 and day 4Population: The analysis population included all participants who received at least one dose of investigational product (ATM-AVI) and had at least one of the PK parameters of interest.
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.
Outcome measures
| Measure |
AZTREONAM-AVIBACTAM (ATM-AVI)
n=12 Participants
ATM-AVI was dosed in a fixed 3:1 ratio (ATM:AVI=3:1) in 12 healthy participants. On Day 1, participants received a 3-hour intravenous (IV) infusion of a single dose of 1500 mg ATM plus 500 mg AVI. On Day 2, participants received a loading (500 mg ATM plus 167 mg AVI infused over a 30-minute period)/extended loading dose (1500 mg ATM plus 500 mg AVI over a 3-hour period), followed by multiple maintenance doses of ATM-AVI IV infusion: 1500 mg ATM and 500 mg AVI were infused over 3 hours and administered every 6 hours (q6h) till morning of Study Day 4.
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Maximum Observed Plasma Concentration (Cmax) on Day 1 & 4 of Aztreonam
Day 1
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69.44 micrograms per milliliter (ug/mL)
Geometric Coefficient of Variation 15
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Maximum Observed Plasma Concentration (Cmax) on Day 1 & 4 of Aztreonam
Day 4
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79.66 micrograms per milliliter (ug/mL)
Geometric Coefficient of Variation 12
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PRIMARY outcome
Timeframe: Post dose on day 1 and day 4Population: The analysis population included all participants who received at least one dose of investigational product (ATM-AVI) and had at least one of the PK parameters of interest.
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.
Outcome measures
| Measure |
AZTREONAM-AVIBACTAM (ATM-AVI)
n=12 Participants
ATM-AVI was dosed in a fixed 3:1 ratio (ATM:AVI=3:1) in 12 healthy participants. On Day 1, participants received a 3-hour intravenous (IV) infusion of a single dose of 1500 mg ATM plus 500 mg AVI. On Day 2, participants received a loading (500 mg ATM plus 167 mg AVI infused over a 30-minute period)/extended loading dose (1500 mg ATM plus 500 mg AVI over a 3-hour period), followed by multiple maintenance doses of ATM-AVI IV infusion: 1500 mg ATM and 500 mg AVI were infused over 3 hours and administered every 6 hours (q6h) till morning of Study Day 4.
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Maximum Observed Plasma Concentration (Cmax) on Day 1 & 4 of Avibactam
Day 1
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13.93 ug/mL
Geometric Coefficient of Variation 16
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Maximum Observed Plasma Concentration (Cmax) on Day 1 & 4 of Avibactam
Day 4
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14.03 ug/mL
Geometric Coefficient of Variation 14
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PRIMARY outcome
Timeframe: Post dose on day 1Population: The analysis population included all participants who received at least one dose of investigational product (ATM-AVI) and had at least one of the PK parameters of interest.
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.
Outcome measures
| Measure |
AZTREONAM-AVIBACTAM (ATM-AVI)
n=12 Participants
ATM-AVI was dosed in a fixed 3:1 ratio (ATM:AVI=3:1) in 12 healthy participants. On Day 1, participants received a 3-hour intravenous (IV) infusion of a single dose of 1500 mg ATM plus 500 mg AVI. On Day 2, participants received a loading (500 mg ATM plus 167 mg AVI infused over a 30-minute period)/extended loading dose (1500 mg ATM plus 500 mg AVI over a 3-hour period), followed by multiple maintenance doses of ATM-AVI IV infusion: 1500 mg ATM and 500 mg AVI were infused over 3 hours and administered every 6 hours (q6h) till morning of Study Day 4.
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Area Under the Plasma Concentration-Time Profile From Time 0 to 6 Hours (AUC6) on Day 1 of Aztreonam
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236.7 nanograms/millilitre/hour (ng*hr/mL)
Geometric Coefficient of Variation 14
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PRIMARY outcome
Timeframe: Post dose on day 1Population: The analysis population included all participants who received at least one dose of investigational product (ATM-AVI) and had at least one of the PK parameters of interest.
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.
Outcome measures
| Measure |
AZTREONAM-AVIBACTAM (ATM-AVI)
n=12 Participants
ATM-AVI was dosed in a fixed 3:1 ratio (ATM:AVI=3:1) in 12 healthy participants. On Day 1, participants received a 3-hour intravenous (IV) infusion of a single dose of 1500 mg ATM plus 500 mg AVI. On Day 2, participants received a loading (500 mg ATM plus 167 mg AVI infused over a 30-minute period)/extended loading dose (1500 mg ATM plus 500 mg AVI over a 3-hour period), followed by multiple maintenance doses of ATM-AVI IV infusion: 1500 mg ATM and 500 mg AVI were infused over 3 hours and administered every 6 hours (q6h) till morning of Study Day 4.
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Area Under the Plasma Concentration-Time Profile From Time 0 to 6 Hours (AUC6) on Day 1 of Avibactam
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42.36 ng*hr/mL
Geometric Coefficient of Variation 15
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PRIMARY outcome
Timeframe: Post dose on day 1 and day 4Population: The analysis population included all participants who received at least one dose of investigational product (ATM-AVI) and had at least one of the PK parameters of interest.
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.
Outcome measures
| Measure |
AZTREONAM-AVIBACTAM (ATM-AVI)
n=12 Participants
ATM-AVI was dosed in a fixed 3:1 ratio (ATM:AVI=3:1) in 12 healthy participants. On Day 1, participants received a 3-hour intravenous (IV) infusion of a single dose of 1500 mg ATM plus 500 mg AVI. On Day 2, participants received a loading (500 mg ATM plus 167 mg AVI infused over a 30-minute period)/extended loading dose (1500 mg ATM plus 500 mg AVI over a 3-hour period), followed by multiple maintenance doses of ATM-AVI IV infusion: 1500 mg ATM and 500 mg AVI were infused over 3 hours and administered every 6 hours (q6h) till morning of Study Day 4.
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Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUClast) on Day 1 & 4 of Aztreonam
Day 1
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287.8 ug*hr/mL
Geometric Coefficient of Variation 14
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Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUClast) on Day 1 & 4 of Aztreonam
Day 4
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336.4 ug*hr/mL
Geometric Coefficient of Variation 15
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PRIMARY outcome
Timeframe: Post dose on day 1 and day 4Population: The analysis population included all participants who received at least one dose of investigational product (ATM-AVI) and had at least one of the PK parameters of interest.
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.
Outcome measures
| Measure |
AZTREONAM-AVIBACTAM (ATM-AVI)
n=12 Participants
ATM-AVI was dosed in a fixed 3:1 ratio (ATM:AVI=3:1) in 12 healthy participants. On Day 1, participants received a 3-hour intravenous (IV) infusion of a single dose of 1500 mg ATM plus 500 mg AVI. On Day 2, participants received a loading (500 mg ATM plus 167 mg AVI infused over a 30-minute period)/extended loading dose (1500 mg ATM plus 500 mg AVI over a 3-hour period), followed by multiple maintenance doses of ATM-AVI IV infusion: 1500 mg ATM and 500 mg AVI were infused over 3 hours and administered every 6 hours (q6h) till morning of Study Day 4.
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Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUClast) on Day 1 & 4 of Avibactam
Day 1
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47.23 ug*hr/mL
Geometric Coefficient of Variation 15
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Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUClast) on Day 1 & 4 of Avibactam
Day 4
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49.47 ug*hr/mL
Geometric Coefficient of Variation 18
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PRIMARY outcome
Timeframe: Post dose on day 1 and day 4Population: The analysis population included all participants who received at least one dose of investigational product (ATM-AVI) and had at least one of the PK parameters of interest.
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.
Outcome measures
| Measure |
AZTREONAM-AVIBACTAM (ATM-AVI)
n=12 Participants
ATM-AVI was dosed in a fixed 3:1 ratio (ATM:AVI=3:1) in 12 healthy participants. On Day 1, participants received a 3-hour intravenous (IV) infusion of a single dose of 1500 mg ATM plus 500 mg AVI. On Day 2, participants received a loading (500 mg ATM plus 167 mg AVI infused over a 30-minute period)/extended loading dose (1500 mg ATM plus 500 mg AVI over a 3-hour period), followed by multiple maintenance doses of ATM-AVI IV infusion: 1500 mg ATM and 500 mg AVI were infused over 3 hours and administered every 6 hours (q6h) till morning of Study Day 4.
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Area Under the Plasma Concentration-Time Profile From Time 0 to 24 Hours (AUC24) on Day 1 & 4 of Aztreonam
Day 1
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289.6 ug*hr/mL
Geometric Coefficient of Variation 14
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Area Under the Plasma Concentration-Time Profile From Time 0 to 24 Hours (AUC24) on Day 1 & 4 of Aztreonam
Day 4
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337.5 ug*hr/mL
Geometric Coefficient of Variation 15
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PRIMARY outcome
Timeframe: Post dose on day 1 and day 4Population: The analysis population included all participants who received at least one dose of investigational product (ATM-AVI) and had at least one of the PK parameters of interest.
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.
Outcome measures
| Measure |
AZTREONAM-AVIBACTAM (ATM-AVI)
n=12 Participants
ATM-AVI was dosed in a fixed 3:1 ratio (ATM:AVI=3:1) in 12 healthy participants. On Day 1, participants received a 3-hour intravenous (IV) infusion of a single dose of 1500 mg ATM plus 500 mg AVI. On Day 2, participants received a loading (500 mg ATM plus 167 mg AVI infused over a 30-minute period)/extended loading dose (1500 mg ATM plus 500 mg AVI over a 3-hour period), followed by multiple maintenance doses of ATM-AVI IV infusion: 1500 mg ATM and 500 mg AVI were infused over 3 hours and administered every 6 hours (q6h) till morning of Study Day 4.
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Area Under the Plasma Concentration-Time Profile From Time 0 to 24 Hours (AUC24) on Day 1 & 4 of Avibactam
Day 1
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47.33 ug*hr/mL
Geometric Coefficient of Variation 15
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Area Under the Plasma Concentration-Time Profile From Time 0 to 24 Hours (AUC24) on Day 1 & 4 of Avibactam
Day 4
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49.47 ug*hr/mL
Geometric Coefficient of Variation 18
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PRIMARY outcome
Timeframe: Post dose on day 1 and day 4Population: The analysis population included all participants who received at least one dose of investigational product (ATM-AVI) and had at least one of the PK parameters of interest.
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.
Outcome measures
| Measure |
AZTREONAM-AVIBACTAM (ATM-AVI)
n=12 Participants
ATM-AVI was dosed in a fixed 3:1 ratio (ATM:AVI=3:1) in 12 healthy participants. On Day 1, participants received a 3-hour intravenous (IV) infusion of a single dose of 1500 mg ATM plus 500 mg AVI. On Day 2, participants received a loading (500 mg ATM plus 167 mg AVI infused over a 30-minute period)/extended loading dose (1500 mg ATM plus 500 mg AVI over a 3-hour period), followed by multiple maintenance doses of ATM-AVI IV infusion: 1500 mg ATM and 500 mg AVI were infused over 3 hours and administered every 6 hours (q6h) till morning of Study Day 4.
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Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) on Day 1 & 4 of Aztreonam
Day 1
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289.2 ug*hr/mL
Geometric Coefficient of Variation 14
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Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) on Day 1 & 4 of Aztreonam
Day 4
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337.6 ug*hr/mL
Geometric Coefficient of Variation 15
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PRIMARY outcome
Timeframe: Post dose on day 1 and day 4Population: The analysis population included all participants who received at least one dose of investigational product (ATM-AVI) and had at least one of the PK parameters of interest.
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.
Outcome measures
| Measure |
AZTREONAM-AVIBACTAM (ATM-AVI)
n=12 Participants
ATM-AVI was dosed in a fixed 3:1 ratio (ATM:AVI=3:1) in 12 healthy participants. On Day 1, participants received a 3-hour intravenous (IV) infusion of a single dose of 1500 mg ATM plus 500 mg AVI. On Day 2, participants received a loading (500 mg ATM plus 167 mg AVI infused over a 30-minute period)/extended loading dose (1500 mg ATM plus 500 mg AVI over a 3-hour period), followed by multiple maintenance doses of ATM-AVI IV infusion: 1500 mg ATM and 500 mg AVI were infused over 3 hours and administered every 6 hours (q6h) till morning of Study Day 4.
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Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) on Day 1 & 4 of Avibactam
Day 1
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47.29 ug*hr/mL
Geometric Coefficient of Variation 15
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Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) on Day 1 & 4 of Avibactam
Day 4
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49.59 ug*hr/mL
Geometric Coefficient of Variation 18
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PRIMARY outcome
Timeframe: Post dose on day 4Population: The analysis population included all participants who received at least one dose of investigational product (ATM-AVI) and had at least one of the PK parameters of interest.
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.
Outcome measures
| Measure |
AZTREONAM-AVIBACTAM (ATM-AVI)
n=12 Participants
ATM-AVI was dosed in a fixed 3:1 ratio (ATM:AVI=3:1) in 12 healthy participants. On Day 1, participants received a 3-hour intravenous (IV) infusion of a single dose of 1500 mg ATM plus 500 mg AVI. On Day 2, participants received a loading (500 mg ATM plus 167 mg AVI infused over a 30-minute period)/extended loading dose (1500 mg ATM plus 500 mg AVI over a 3-hour period), followed by multiple maintenance doses of ATM-AVI IV infusion: 1500 mg ATM and 500 mg AVI were infused over 3 hours and administered every 6 hours (q6h) till morning of Study Day 4.
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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
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285.2 ug*hr/mL
Geometric Coefficient of Variation 14
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PRIMARY outcome
Timeframe: Post dose on day 4Population: The analysis population included all participants who received at least one dose of investigational product (ATM-AVI) and had at least one of the PK parameters of interest.
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.
Outcome measures
| Measure |
AZTREONAM-AVIBACTAM (ATM-AVI)
n=12 Participants
ATM-AVI was dosed in a fixed 3:1 ratio (ATM:AVI=3:1) in 12 healthy participants. On Day 1, participants received a 3-hour intravenous (IV) infusion of a single dose of 1500 mg ATM plus 500 mg AVI. On Day 2, participants received a loading (500 mg ATM plus 167 mg AVI infused over a 30-minute period)/extended loading dose (1500 mg ATM plus 500 mg AVI over a 3-hour period), followed by multiple maintenance doses of ATM-AVI IV infusion: 1500 mg ATM and 500 mg AVI were infused over 3 hours and administered every 6 hours (q6h) till morning of Study Day 4.
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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
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44.41 ug*hr/mL
Geometric Coefficient of Variation 16
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PRIMARY outcome
Timeframe: Post dose on day 4Population: The analysis population included all participants who received at least one dose of investigational product (ATM-AVI) and had at least one of the PK parameters of interest.
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.
Outcome measures
| Measure |
AZTREONAM-AVIBACTAM (ATM-AVI)
n=12 Participants
ATM-AVI was dosed in a fixed 3:1 ratio (ATM:AVI=3:1) in 12 healthy participants. On Day 1, participants received a 3-hour intravenous (IV) infusion of a single dose of 1500 mg ATM plus 500 mg AVI. On Day 2, participants received a loading (500 mg ATM plus 167 mg AVI infused over a 30-minute period)/extended loading dose (1500 mg ATM plus 500 mg AVI over a 3-hour period), followed by multiple maintenance doses of ATM-AVI IV infusion: 1500 mg ATM and 500 mg AVI were infused over 3 hours and administered every 6 hours (q6h) till morning of Study Day 4.
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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
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1142 ug*hr/mL
Geometric Coefficient of Variation 14
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PRIMARY outcome
Timeframe: Post dose on day 4Population: The analysis population included all participants who received at least one dose of investigational product (ATM-AVI) and had at least one of the PK parameters of interest.
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.
Outcome measures
| Measure |
AZTREONAM-AVIBACTAM (ATM-AVI)
n=12 Participants
ATM-AVI was dosed in a fixed 3:1 ratio (ATM:AVI=3:1) in 12 healthy participants. On Day 1, participants received a 3-hour intravenous (IV) infusion of a single dose of 1500 mg ATM plus 500 mg AVI. On Day 2, participants received a loading (500 mg ATM plus 167 mg AVI infused over a 30-minute period)/extended loading dose (1500 mg ATM plus 500 mg AVI over a 3-hour period), followed by multiple maintenance doses of ATM-AVI IV infusion: 1500 mg ATM and 500 mg AVI were infused over 3 hours and administered every 6 hours (q6h) till morning of Study Day 4.
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|---|---|
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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
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177.7 ug*hr/mL
Geometric Coefficient of Variation 16
|
PRIMARY outcome
Timeframe: Post dose on day 1 and day 4Population: The analysis population included all participants who received at least one dose of investigational product (ATM-AVI) and had at least one of the PK parameters of interest.
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.
Outcome measures
| Measure |
AZTREONAM-AVIBACTAM (ATM-AVI)
n=12 Participants
ATM-AVI was dosed in a fixed 3:1 ratio (ATM:AVI=3:1) in 12 healthy participants. On Day 1, participants received a 3-hour intravenous (IV) infusion of a single dose of 1500 mg ATM plus 500 mg AVI. On Day 2, participants received a loading (500 mg ATM plus 167 mg AVI infused over a 30-minute period)/extended loading dose (1500 mg ATM plus 500 mg AVI over a 3-hour period), followed by multiple maintenance doses of ATM-AVI IV infusion: 1500 mg ATM and 500 mg AVI were infused over 3 hours and administered every 6 hours (q6h) till morning of Study Day 4.
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Renal Clearance (CLr) on Day 1 & 4 of Aztreonam
Day 1
|
4.277 litre per hour (L/hr)
Geometric Coefficient of Variation 14
|
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Renal Clearance (CLr) on Day 1 & 4 of Aztreonam
Day 4
|
4.487 litre per hour (L/hr)
Geometric Coefficient of Variation 23
|
PRIMARY outcome
Timeframe: Post dose on day 1 and day 4Population: The analysis population included all participants who received at least one dose of investigational product (ATM-AVI) and had at least one of the PK parameters of interest.
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.
Outcome measures
| Measure |
AZTREONAM-AVIBACTAM (ATM-AVI)
n=12 Participants
ATM-AVI was dosed in a fixed 3:1 ratio (ATM:AVI=3:1) in 12 healthy participants. On Day 1, participants received a 3-hour intravenous (IV) infusion of a single dose of 1500 mg ATM plus 500 mg AVI. On Day 2, participants received a loading (500 mg ATM plus 167 mg AVI infused over a 30-minute period)/extended loading dose (1500 mg ATM plus 500 mg AVI over a 3-hour period), followed by multiple maintenance doses of ATM-AVI IV infusion: 1500 mg ATM and 500 mg AVI were infused over 3 hours and administered every 6 hours (q6h) till morning of Study Day 4.
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|---|---|
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Renal Clearance (CLr) on Day 1 & 4 of Avibactam
Day 1
|
12.09 litre per hour (L/hr)
Geometric Coefficient of Variation 18
|
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Renal Clearance (CLr) on Day 1 & 4 of Avibactam
Day 4
|
12.65 litre per hour (L/hr)
Geometric Coefficient of Variation 25
|
SECONDARY outcome
Timeframe: Post dose on day 1 and day 4Population: The analysis population included all participants who received at least one dose of investigational product (ATM-AVI) and had at least one of the PK parameters of interest.
Plasma terminal elimination half-life (T1/2) is the time measured for the plasma concentration to decrease by one half at the terminal phase.
Outcome measures
| Measure |
AZTREONAM-AVIBACTAM (ATM-AVI)
n=12 Participants
ATM-AVI was dosed in a fixed 3:1 ratio (ATM:AVI=3:1) in 12 healthy participants. On Day 1, participants received a 3-hour intravenous (IV) infusion of a single dose of 1500 mg ATM plus 500 mg AVI. On Day 2, participants received a loading (500 mg ATM plus 167 mg AVI infused over a 30-minute period)/extended loading dose (1500 mg ATM plus 500 mg AVI over a 3-hour period), followed by multiple maintenance doses of ATM-AVI IV infusion: 1500 mg ATM and 500 mg AVI were infused over 3 hours and administered every 6 hours (q6h) till morning of Study Day 4.
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|---|---|
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Terminal Elimination Half-Life (T1/2) on Day 1 & 4 of Aztreonam
Day 1
|
1.890 hours
Standard Deviation 0.16597
|
|
Terminal Elimination Half-Life (T1/2) on Day 1 & 4 of Aztreonam
Day 4
|
1.886 hours
Standard Deviation 0.20304
|
SECONDARY outcome
Timeframe: Post dose on day 1 and day 4Population: The analysis population included all participants who received at least one dose of investigational product (ATM-AVI) and had at least one of the PK parameters of interest.
Plasma terminal elimination half-life (T1/2) is the time measured for the plasma concentration to decrease by one half at the terminal phase.
Outcome measures
| Measure |
AZTREONAM-AVIBACTAM (ATM-AVI)
n=12 Participants
ATM-AVI was dosed in a fixed 3:1 ratio (ATM:AVI=3:1) in 12 healthy participants. On Day 1, participants received a 3-hour intravenous (IV) infusion of a single dose of 1500 mg ATM plus 500 mg AVI. On Day 2, participants received a loading (500 mg ATM plus 167 mg AVI infused over a 30-minute period)/extended loading dose (1500 mg ATM plus 500 mg AVI over a 3-hour period), followed by multiple maintenance doses of ATM-AVI IV infusion: 1500 mg ATM and 500 mg AVI were infused over 3 hours and administered every 6 hours (q6h) till morning of Study Day 4.
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|---|---|
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Terminal Elimination Half-Life (T1/2) on Day 1 & 4 of Avibactam
Day 1
|
2.003 hours
Standard Deviation 0.34613
|
|
Terminal Elimination Half-Life (T1/2) on Day 1 & 4 of Avibactam
Day 4
|
4.061 hours
Standard Deviation 0.59180
|
SECONDARY outcome
Timeframe: Post dose on day 1 and day 4Population: The analysis population included all participants who received at least one dose of investigational product (ATM-AVI) and had at least one of the PK parameters of interest.
Apparent volume of distribution (Vz) was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Vss was the Vz at steady-state. The geometric coefficient of variation is expressed in percentage.
Outcome measures
| Measure |
AZTREONAM-AVIBACTAM (ATM-AVI)
n=12 Participants
ATM-AVI was dosed in a fixed 3:1 ratio (ATM:AVI=3:1) in 12 healthy participants. On Day 1, participants received a 3-hour intravenous (IV) infusion of a single dose of 1500 mg ATM plus 500 mg AVI. On Day 2, participants received a loading (500 mg ATM plus 167 mg AVI infused over a 30-minute period)/extended loading dose (1500 mg ATM plus 500 mg AVI over a 3-hour period), followed by multiple maintenance doses of ATM-AVI IV infusion: 1500 mg ATM and 500 mg AVI were infused over 3 hours and administered every 6 hours (q6h) till morning of Study Day 4.
|
|---|---|
|
Apparent Volume of Distribution at Steady-State (Vss) on Day 1 & 4 of Aztreonam
Day 1
|
13.69 Liter
Geometric Coefficient of Variation 15
|
|
Apparent Volume of Distribution at Steady-State (Vss) on Day 1 & 4 of Aztreonam
Day 4
|
12.81 Liter
Geometric Coefficient of Variation 15
|
SECONDARY outcome
Timeframe: Post dose on day 1 and day 4Population: The analysis population included all participants who received at least one dose of investigational product (ATM-AVI) and had at least one of the PK parameters of interest.
Vz was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Vss was the Vz at steady-state. The geometric coefficient of variation is expressed in percentage.
Outcome measures
| Measure |
AZTREONAM-AVIBACTAM (ATM-AVI)
n=12 Participants
ATM-AVI was dosed in a fixed 3:1 ratio (ATM:AVI=3:1) in 12 healthy participants. On Day 1, participants received a 3-hour intravenous (IV) infusion of a single dose of 1500 mg ATM plus 500 mg AVI. On Day 2, participants received a loading (500 mg ATM plus 167 mg AVI infused over a 30-minute period)/extended loading dose (1500 mg ATM plus 500 mg AVI over a 3-hour period), followed by multiple maintenance doses of ATM-AVI IV infusion: 1500 mg ATM and 500 mg AVI were infused over 3 hours and administered every 6 hours (q6h) till morning of Study Day 4.
|
|---|---|
|
Apparent Volume of Distribution at Steady-State (Vss) on Day 1 & 4 of Avibactam
Day 1
|
21.36 Liter
Geometric Coefficient of Variation 14
|
|
Apparent Volume of Distribution at Steady-State (Vss) on Day 1 & 4 of Avibactam
Day 4
|
17.96 Liter
Geometric Coefficient of Variation 16
|
SECONDARY outcome
Timeframe: Post dose on day 1 and day 4Population: The analysis population included all participants who received at least one dose of investigational product (ATM-AVI) and had at least one of the PK parameters of interest.
Vz was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. The geometric coefficient of variation is expressed in percentage.
Outcome measures
| Measure |
AZTREONAM-AVIBACTAM (ATM-AVI)
n=12 Participants
ATM-AVI was dosed in a fixed 3:1 ratio (ATM:AVI=3:1) in 12 healthy participants. On Day 1, participants received a 3-hour intravenous (IV) infusion of a single dose of 1500 mg ATM plus 500 mg AVI. On Day 2, participants received a loading (500 mg ATM plus 167 mg AVI infused over a 30-minute period)/extended loading dose (1500 mg ATM plus 500 mg AVI over a 3-hour period), followed by multiple maintenance doses of ATM-AVI IV infusion: 1500 mg ATM and 500 mg AVI were infused over 3 hours and administered every 6 hours (q6h) till morning of Study Day 4.
|
|---|---|
|
Apparent Volume of Distribution During Terminal Phase (Vz) on Day 1 & 4 of Aztreonam
Day 1
|
14.09 Liter
Geometric Coefficient of Variation 16
|
|
Apparent Volume of Distribution During Terminal Phase (Vz) on Day 1 & 4 of Aztreonam
Day 4
|
14.22 Liter
Geometric Coefficient of Variation 16
|
SECONDARY outcome
Timeframe: Post dose on day 1 and day 4Population: The analysis population included all participants who received at least one dose of investigational product (ATM-AVI) and had at least one of the PK parameters of interest.
Vz was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. The geometric coefficient of variation is expressed in percentage.
Outcome measures
| Measure |
AZTREONAM-AVIBACTAM (ATM-AVI)
n=12 Participants
ATM-AVI was dosed in a fixed 3:1 ratio (ATM:AVI=3:1) in 12 healthy participants. On Day 1, participants received a 3-hour intravenous (IV) infusion of a single dose of 1500 mg ATM plus 500 mg AVI. On Day 2, participants received a loading (500 mg ATM plus 167 mg AVI infused over a 30-minute period)/extended loading dose (1500 mg ATM plus 500 mg AVI over a 3-hour period), followed by multiple maintenance doses of ATM-AVI IV infusion: 1500 mg ATM and 500 mg AVI were infused over 3 hours and administered every 6 hours (q6h) till morning of Study Day 4.
|
|---|---|
|
Apparent Volume of Distribution During Terminal Phase (Vz) on Day 1 & 4 of Avibactam
Day 1
|
30.14 Liter
Geometric Coefficient of Variation 22
|
|
Apparent Volume of Distribution During Terminal Phase (Vz) on Day 1 & 4 of Avibactam
Day 4
|
65.41 Liter
Geometric Coefficient of Variation 26
|
SECONDARY outcome
Timeframe: Post dose on day 1 and day 4Population: The analysis population included all participants who received at least one dose of investigational product (ATM-AVI) and had at least one of the PK parameters of interest.
CL was a quantitative measure of the rate at which a drug substance was removed from the body. The geometric coefficient of variation is expressed in percentage.
Outcome measures
| Measure |
AZTREONAM-AVIBACTAM (ATM-AVI)
n=12 Participants
ATM-AVI was dosed in a fixed 3:1 ratio (ATM:AVI=3:1) in 12 healthy participants. On Day 1, participants received a 3-hour intravenous (IV) infusion of a single dose of 1500 mg ATM plus 500 mg AVI. On Day 2, participants received a loading (500 mg ATM plus 167 mg AVI infused over a 30-minute period)/extended loading dose (1500 mg ATM plus 500 mg AVI over a 3-hour period), followed by multiple maintenance doses of ATM-AVI IV infusion: 1500 mg ATM and 500 mg AVI were infused over 3 hours and administered every 6 hours (q6h) till morning of Study Day 4.
|
|---|---|
|
Clearance (CL) on Day 1 & 4 of Aztreonam
Day 1
|
5.188 litre per hour (L/hr)
Geometric Coefficient of Variation 14
|
|
Clearance (CL) on Day 1 & 4 of Aztreonam
Day 4
|
5.261 litre per hour (L/hr)
Geometric Coefficient of Variation 14
|
SECONDARY outcome
Timeframe: Post dose on day 1 and day 4Population: The analysis population included all participants who received at least one dose of investigational product (ATM-AVI) and had at least one of the PK parameters of interest.
CL was a quantitative measure of the rate at which a drug substance was removed from the body. The geometric coefficient of variation is expressed in percentage.
Outcome measures
| Measure |
AZTREONAM-AVIBACTAM (ATM-AVI)
n=12 Participants
ATM-AVI was dosed in a fixed 3:1 ratio (ATM:AVI=3:1) in 12 healthy participants. On Day 1, participants received a 3-hour intravenous (IV) infusion of a single dose of 1500 mg ATM plus 500 mg AVI. On Day 2, participants received a loading (500 mg ATM plus 167 mg AVI infused over a 30-minute period)/extended loading dose (1500 mg ATM plus 500 mg AVI over a 3-hour period), followed by multiple maintenance doses of ATM-AVI IV infusion: 1500 mg ATM and 500 mg AVI were infused over 3 hours and administered every 6 hours (q6h) till morning of Study Day 4.
|
|---|---|
|
Clearance (CL) on Day 1 & 4 of Avibactam
Day 4
|
11.26 litre per hour (L/hr)
Geometric Coefficient of Variation 16
|
|
Clearance (CL) on Day 1 & 4 of Avibactam
Day 1
|
10.56 litre per hour (L/hr)
Geometric Coefficient of Variation 15
|
SECONDARY outcome
Timeframe: Post dose on day 1 and day 4Population: The analysis population included all participants who received at least one dose of investigational product (ATM-AVI) and had at least one of the PK parameters of interest.
Tmax was defined as time to reach maximum observed plasma concentration.
Outcome measures
| Measure |
AZTREONAM-AVIBACTAM (ATM-AVI)
n=12 Participants
ATM-AVI was dosed in a fixed 3:1 ratio (ATM:AVI=3:1) in 12 healthy participants. On Day 1, participants received a 3-hour intravenous (IV) infusion of a single dose of 1500 mg ATM plus 500 mg AVI. On Day 2, participants received a loading (500 mg ATM plus 167 mg AVI infused over a 30-minute period)/extended loading dose (1500 mg ATM plus 500 mg AVI over a 3-hour period), followed by multiple maintenance doses of ATM-AVI IV infusion: 1500 mg ATM and 500 mg AVI were infused over 3 hours and administered every 6 hours (q6h) till morning of Study Day 4.
|
|---|---|
|
Time of Observed Maximum Plasma Concentration (Tmax) on Day 1 & 4 of Aztreonam
Day 1
|
2.92 hours
Interval 2.0 to 2.95
|
|
Time of Observed Maximum Plasma Concentration (Tmax) on Day 1 & 4 of Aztreonam
Day 4
|
2.92 hours
Interval 2.92 to 2.92
|
SECONDARY outcome
Timeframe: Post dose on day 1 and day 4Population: The analysis population included all participants who received at least one dose of investigational product (ATM-AVI) and had at least one of the PK parameters of interest.
Tmax was defined as time to reach maximum observed plasma concentration.
Outcome measures
| Measure |
AZTREONAM-AVIBACTAM (ATM-AVI)
n=12 Participants
ATM-AVI was dosed in a fixed 3:1 ratio (ATM:AVI=3:1) in 12 healthy participants. On Day 1, participants received a 3-hour intravenous (IV) infusion of a single dose of 1500 mg ATM plus 500 mg AVI. On Day 2, participants received a loading (500 mg ATM plus 167 mg AVI infused over a 30-minute period)/extended loading dose (1500 mg ATM plus 500 mg AVI over a 3-hour period), followed by multiple maintenance doses of ATM-AVI IV infusion: 1500 mg ATM and 500 mg AVI were infused over 3 hours and administered every 6 hours (q6h) till morning of Study Day 4.
|
|---|---|
|
Time of Observed Maximum Plasma Concentration (Tmax) on Day 1 & 4 of Avibactam
Day 1
|
2.44 hours
Interval 2.0 to 2.95
|
|
Time of Observed Maximum Plasma Concentration (Tmax) on Day 1 & 4 of Avibactam
Day 4
|
2.46 hours
Interval 2.0 to 2.92
|
SECONDARY outcome
Timeframe: Post dose on day 4Population: The analysis population included all participants who received at least one dose of investigational product (ATM-AVI) and had at least one of the PK parameters of interest.
Accumulation ratio based on maximum plasma concentration (Rac,cmax) was calculated as: Rac,Cmax = Cmax at steady state (Day 4) divided by Cmax at first dose (Day 1). The geometric coefficient of variation is expressed in percentage.
Outcome measures
| Measure |
AZTREONAM-AVIBACTAM (ATM-AVI)
n=12 Participants
ATM-AVI was dosed in a fixed 3:1 ratio (ATM:AVI=3:1) in 12 healthy participants. On Day 1, participants received a 3-hour intravenous (IV) infusion of a single dose of 1500 mg ATM plus 500 mg AVI. On Day 2, participants received a loading (500 mg ATM plus 167 mg AVI infused over a 30-minute period)/extended loading dose (1500 mg ATM plus 500 mg AVI over a 3-hour period), followed by multiple maintenance doses of ATM-AVI IV infusion: 1500 mg ATM and 500 mg AVI were infused over 3 hours and administered every 6 hours (q6h) till morning of Study Day 4.
|
|---|---|
|
Accumulation Ratio for Cmax (Rac,Cmax) on Day 4 of Aztreonam
|
1.149 ratio
Geometric Coefficient of Variation 5
|
SECONDARY outcome
Timeframe: Post dose on day 4Population: The analysis population included all participants who received at least one dose of investigational product (ATM-AVI) and had at least one of the PK parameters of interest.
Accumulation ratio based on maximum plasma concentration (Rac,cmax) was calculated as: Rac,Cmax = Cmax at steady state (Day 4) divided by Cmax at first dose (Day 1). The geometric coefficient of variation is expressed in percentage.
Outcome measures
| Measure |
AZTREONAM-AVIBACTAM (ATM-AVI)
n=12 Participants
ATM-AVI was dosed in a fixed 3:1 ratio (ATM:AVI=3:1) in 12 healthy participants. On Day 1, participants received a 3-hour intravenous (IV) infusion of a single dose of 1500 mg ATM plus 500 mg AVI. On Day 2, participants received a loading (500 mg ATM plus 167 mg AVI infused over a 30-minute period)/extended loading dose (1500 mg ATM plus 500 mg AVI over a 3-hour period), followed by multiple maintenance doses of ATM-AVI IV infusion: 1500 mg ATM and 500 mg AVI were infused over 3 hours and administered every 6 hours (q6h) till morning of Study Day 4.
|
|---|---|
|
Accumulation Ratio for Cmax (Rac,Cmax) on Day 4 of Avibactam
|
1.006 ratio
Geometric Coefficient of Variation 7
|
SECONDARY outcome
Timeframe: Post dose on day 4Population: The analysis population included all participants who received at least one dose of investigational product (ATM-AVI) and had at least one of the PK parameters of interest.
Rac was obtained from AUCtau at steady state (Day 4) divided by AUCtau after single dose (Day 1). 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.
Outcome measures
| Measure |
AZTREONAM-AVIBACTAM (ATM-AVI)
n=12 Participants
ATM-AVI was dosed in a fixed 3:1 ratio (ATM:AVI=3:1) in 12 healthy participants. On Day 1, participants received a 3-hour intravenous (IV) infusion of a single dose of 1500 mg ATM plus 500 mg AVI. On Day 2, participants received a loading (500 mg ATM plus 167 mg AVI infused over a 30-minute period)/extended loading dose (1500 mg ATM plus 500 mg AVI over a 3-hour period), followed by multiple maintenance doses of ATM-AVI IV infusion: 1500 mg ATM and 500 mg AVI were infused over 3 hours and administered every 6 hours (q6h) till morning of Study Day 4.
|
|---|---|
|
Accumulation Ratio for AUCτ Following Multiple Dosing (Rac) on Day 4 of Aztreonam
|
1.204 ratio
Geometric Coefficient of Variation 6
|
SECONDARY outcome
Timeframe: Post dose on day 4Population: The analysis population included all participants who received at least one dose of investigational product (ATM-AVI) and had at least one of the PK parameters of interest.
Rac was obtained from AUCtau at steady state (Day 4) divided by AUCtau after single dose (Day 1). 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.
Outcome measures
| Measure |
AZTREONAM-AVIBACTAM (ATM-AVI)
n=12 Participants
ATM-AVI was dosed in a fixed 3:1 ratio (ATM:AVI=3:1) in 12 healthy participants. On Day 1, participants received a 3-hour intravenous (IV) infusion of a single dose of 1500 mg ATM plus 500 mg AVI. On Day 2, participants received a loading (500 mg ATM plus 167 mg AVI infused over a 30-minute period)/extended loading dose (1500 mg ATM plus 500 mg AVI over a 3-hour period), followed by multiple maintenance doses of ATM-AVI IV infusion: 1500 mg ATM and 500 mg AVI were infused over 3 hours and administered every 6 hours (q6h) till morning of Study Day 4.
|
|---|---|
|
Accumulation Ratio for AUCτ Following Multiple Dosing (Rac) on Day 4 of Avibactam
|
1.049 ratio
Geometric Coefficient of Variation 6
|
SECONDARY outcome
Timeframe: From the first dose of study treatment to the last dose of study treatment date +28 +7 days (up to 2 months)Population: The safety analysis set included all healthy Chinese participants who received at least one dose of investigational product (ATM-AVI).
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent adverse event (TEAE) means event between first dose of study treatment and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state. An SAE was an AE resulting in any of death; inpatient hospitalization; life-threatening experience; disability; congenital anomaly or deemed significant for any other reason. Symptoms of infusion-related reactions (IRRs) may include, but were not limited to, fever, chills, flushing, hypotension, dyspnea, wheezing, back pain, abdominal pain, and urticaria. Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE.
Outcome measures
| Measure |
AZTREONAM-AVIBACTAM (ATM-AVI)
n=12 Participants
ATM-AVI was dosed in a fixed 3:1 ratio (ATM:AVI=3:1) in 12 healthy participants. On Day 1, participants received a 3-hour intravenous (IV) infusion of a single dose of 1500 mg ATM plus 500 mg AVI. On Day 2, participants received a loading (500 mg ATM plus 167 mg AVI infused over a 30-minute period)/extended loading dose (1500 mg ATM plus 500 mg AVI over a 3-hour period), followed by multiple maintenance doses of ATM-AVI IV infusion: 1500 mg ATM and 500 mg AVI were infused over 3 hours and administered every 6 hours (q6h) till morning of Study Day 4.
|
|---|---|
|
Number of Participants With an Adverse Event (AE)
Participants with treatment-emergent adverse events (all-causality)
|
2 Participants
|
|
Number of Participants With an Adverse Event (AE)
Participants with treatment-emergent adverse events (treatment-related)
|
1 Participants
|
SECONDARY outcome
Timeframe: From the first dose of study treatment to the last dose of study treatment date +28 +7 days (up to 2 months)Population: The safety analysis set included all healthy Chinese participants who received at least one dose of investigational product (ATM-AVI).
Criteria for vital signs abnormalities: increase or decrease from baseline in supine Systolic Blood Pressure (SBP) \>=30 mm Hg and increase or decrease from baseline in supine Diastolic Blood Pressure (DBP) \>=20 mm Hg.
Outcome measures
| Measure |
AZTREONAM-AVIBACTAM (ATM-AVI)
n=12 Participants
ATM-AVI was dosed in a fixed 3:1 ratio (ATM:AVI=3:1) in 12 healthy participants. On Day 1, participants received a 3-hour intravenous (IV) infusion of a single dose of 1500 mg ATM plus 500 mg AVI. On Day 2, participants received a loading (500 mg ATM plus 167 mg AVI infused over a 30-minute period)/extended loading dose (1500 mg ATM plus 500 mg AVI over a 3-hour period), followed by multiple maintenance doses of ATM-AVI IV infusion: 1500 mg ATM and 500 mg AVI were infused over 3 hours and administered every 6 hours (q6h) till morning of Study Day 4.
|
|---|---|
|
Number of Participants With Abnormal Vital Signs
Supine Diastolic Blood Pressure (mmHg): Change >= 20 mmHg increase from baseline
|
0 Participants
|
|
Number of Participants With Abnormal Vital Signs
Supine Systolic Blood Pressure (mmHg): Change >= 30 mmHg increase from baseline
|
0 Participants
|
|
Number of Participants With Abnormal Vital Signs
Supine Diastolic Blood Pressure (mmHg): Change >= 20 mmHg decrease from baseline
|
0 Participants
|
|
Number of Participants With Abnormal Vital Signs
Supine Systolic Blood Pressure (mmHg): Change >= 30 mmHg decrease from baseline
|
0 Participants
|
SECONDARY outcome
Timeframe: From the first dose of study treatment to the last dose of study treatment date +28 +7 days (up to 2 months)Population: The safety analysis set included all healthy Chinese participants who received at least one dose of investigational product (ATM-AVI).
ECG categorical summarization criteria: 1. PR interval (the interval between the start of the P wave and the start of the QRS complex, corresponding to the time between the onset of the atrial depolarization and onset of ventricular depolarization): a) greater than or equal to (\>=) 300 millisecond (msec), b) \>=25% increase when baseline is \> 200 msec or \>=50% increase when baseline is less than or equal to (\<=) 200 msec. 2\. QRS duration (time from ECG Q wave to the end of the S wave corresponding to ventricle depolarization): a) \>=140 msec, b) \>=50% increase from baseline. 3\. QTcF interval (QT corrected using the Fridericia formula): a) \>450 msec and \<=480 msec, b) \>480 msec and \<=500 msec, c) \>500 msec, d) \>30 msec and \<=60 msec increase from baseline, e) \>60 msec increase from baseline.
Outcome measures
| Measure |
AZTREONAM-AVIBACTAM (ATM-AVI)
n=12 Participants
ATM-AVI was dosed in a fixed 3:1 ratio (ATM:AVI=3:1) in 12 healthy participants. On Day 1, participants received a 3-hour intravenous (IV) infusion of a single dose of 1500 mg ATM plus 500 mg AVI. On Day 2, participants received a loading (500 mg ATM plus 167 mg AVI infused over a 30-minute period)/extended loading dose (1500 mg ATM plus 500 mg AVI over a 3-hour period), followed by multiple maintenance doses of ATM-AVI IV infusion: 1500 mg ATM and 500 mg AVI were infused over 3 hours and administered every 6 hours (q6h) till morning of Study Day 4.
|
|---|---|
|
Number of Participants With Abnormal Electrocardiograms (ECGs)
PR INTERVAL NOT OTHERWISE SPECIFIED (msec): %Change >= 25/50%
|
0 Participants
|
|
Number of Participants With Abnormal Electrocardiograms (ECGs)
QRS INTERVAL NOT OTHERWISE SPECIFIED (msec): %Change >= 50%
|
0 Participants
|
|
Number of Participants With Abnormal Electrocardiograms (ECGs)
QTCF - FRIDERICIA'S CORRECTION FORMULA NOT OTHERWISE SPECIFIED (msec): 30 < Change <= 60
|
0 Participants
|
|
Number of Participants With Abnormal Electrocardiograms (ECGs)
QTCF - FRIDERICIA'S CORRECTION FORMULA NOT OTHERWISE SPECIFIED (msec): Change > 60
|
0 Participants
|
SECONDARY outcome
Timeframe: From the first dose of study treatment to the last dose of study treatment date +28 +7 days (up to 2 months)Population: The safety analysis set included all healthy Chinese participants who received at least one dose of investigational product (ATM-AVI).
Following laboratory parameters were assessed against pre-defined abnormality criteria: hematology (basophils); clinical chemistry (urate); urinalysis (urine hemoglobin, nitrite, urine erythrocytes).
Outcome measures
| Measure |
AZTREONAM-AVIBACTAM (ATM-AVI)
n=12 Participants
ATM-AVI was dosed in a fixed 3:1 ratio (ATM:AVI=3:1) in 12 healthy participants. On Day 1, participants received a 3-hour intravenous (IV) infusion of a single dose of 1500 mg ATM plus 500 mg AVI. On Day 2, participants received a loading (500 mg ATM plus 167 mg AVI infused over a 30-minute period)/extended loading dose (1500 mg ATM plus 500 mg AVI over a 3-hour period), followed by multiple maintenance doses of ATM-AVI IV infusion: 1500 mg ATM and 500 mg AVI were infused over 3 hours and administered every 6 hours (q6h) till morning of Study Day 4.
|
|---|---|
|
Number of Participants With Abnormal Laboratory Assessments
HEMATOLOGY: Basophils (10^3/mm^3) > 1.2x upper limit of normal (ULN)
|
1 Participants
|
|
Number of Participants With Abnormal Laboratory Assessments
CLINICAL CHEMISTRY: Urate (mg/dL) > 1.2x ULN
|
1 Participants
|
|
Number of Participants With Abnormal Laboratory Assessments
URINALYSIS: URINE Hemoglobin >= 1
|
3 Participants
|
|
Number of Participants With Abnormal Laboratory Assessments
URINALYSIS: URINE Erythrocytes >= 20
|
2 Participants
|
Adverse Events
AZTREONAM-AVIBACTAM (ATM-AVI)
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
AZTREONAM-AVIBACTAM (ATM-AVI)
n=12 participants at risk
ATM-AVI was dosed in a fixed 3:1 ratio (ATM:AVI=3:1) in 12 healthy participants. On Day 1, participants received a 3-hour intravenous (IV) infusion of a single dose of 1500 mg ATM plus 500 mg AVI. On Day 2, participants received a loading (500 mg ATM plus 167 mg AVI infused over a 30-minute period)/extended loading dose (1500 mg ATM plus 500 mg AVI over a 3-hour period), followed by multiple maintenance doses of ATM-AVI IV infusion: 1500 mg ATM and 500 mg AVI were infused over 3 hours and administered every 6 hours (q6h) till morning of Study Day 4.
|
|---|---|
|
Investigations
Alanine aminotransferase increased
|
8.3%
1/12 • From the first dose of study treatment to the last dose of study treatment date +28 +7 days (up to 2 months)
The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
|
|
Investigations
Aspartate aminotransferase increased
|
8.3%
1/12 • From the first dose of study treatment to the last dose of study treatment date +28 +7 days (up to 2 months)
The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
8.3%
1/12 • From the first dose of study treatment to the last dose of study treatment date +28 +7 days (up to 2 months)
The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
|
Additional Information
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