Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
A Phase 1, single center, single arm, open-label study to assess the PK, safety and tolerability of Aztreonam-Avibactam after single and repeated IV infusion of doses in healthy Chinese participants.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ATM-AVI treatment arm | Experimental | Chinese healthy volunteers |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Aztreonam-Avibactam | Drug | 500/167 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) on Day 1 & 4 of Aztreonam | 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. | Post dose on day 1 and day 4 |
| Maximum Observed Plasma Concentration (Cmax) on Day 1 & 4 of Avibactam | 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. | Post dose on day 1 and day 4 |
| Area Under the Plasma Concentration-Time Profile From Time 0 to 6 Hours (AUC6) on Day 1 of Aztreonam | 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. | Post dose on day 1 |
| Area Under the Plasma Concentration-Time Profile From Time 0 to 6 Hours (AUC6) on Day 1 of Avibactam | 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. | Post dose on day 1 |
| Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUClast) on Day 1 & 4 of Aztreonam |
| Measure | Description | Time Frame |
|---|---|---|
| Terminal Elimination Half-Life (T1/2) on Day 1 & 4 of Aztreonam | Plasma terminal elimination half-life (T1/2) is the time measured for the plasma concentration to decrease by one half at the terminal phase. | Post dose on day 1 and day 4 |
| Terminal Elimination Half-Life (T1/2) on Day 1 & 4 of Avibactam |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Pfizer CT.gov Call Center | Pfizer | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Huashan Hospital Fudan University | Shanghai | Shanghai Municipality | 201107 | China |
Not provided
| Label | URL |
|---|---|
| To obtain contact information for a study center near you, click here. | View source |
Not provided
Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.
Not provided
Not provided
Not provided
Not provided
A total of 12 participants received assigned treatment of AZTREONAM-AVIBACTAM (ATM-AVI) and completed the treatment and follow-up phases.
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
All enrolled participants who received at least one dose of study medication.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Maximum Observed Plasma Concentration (Cmax) on Day 1 & 4 of Aztreonam | 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | micrograms per milliliter (ug/mL) | Post dose on day 1 and day 4 |
|
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.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Alanine aminotransferase increased | Investigations | MedDRA v24.0 | Non-systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Pfizer ClinicalTrials.gov Call Center | Pfizer, Inc. | 1-800-718-1021 | ClinicalTrials.gov_Inquiries@pfizer.com |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Sep 20, 2018 | Sep 9, 2022 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Dec 31, 2020 | Sep 9, 2022 | SAP_001.pdf |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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. |
| Post dose on day 1 and day 4 |
| Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUClast) on Day 1 & 4 of Avibactam | 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. | Post dose on day 1 and day 4 |
| Area Under the Plasma Concentration-Time Profile From Time 0 to 24 Hours (AUC24) on Day 1 & 4 of Aztreonam | 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. | Post dose on day 1 and day 4 |
| Area Under the Plasma Concentration-Time Profile From Time 0 to 24 Hours (AUC24) on Day 1 & 4 of Avibactam | 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. | Post dose on day 1 and day 4 |
| Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) on Day 1 & 4 of Aztreonam | 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. | Post dose on day 1 and day 4 |
| Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) on Day 1 & 4 of Avibactam | 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. | Post dose on day 1 and day 4 |
| 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 | 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. | Post dose on day 4 |
| 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 | 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. | Post dose on day 4 |
| 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 | 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. | Post dose on day 4 |
| 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 | 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. | Post dose on day 4 |
| Renal Clearance (CLr) on Day 1 & 4 of Aztreonam | 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. | Post dose on day 1 and day 4 |
| Renal Clearance (CLr) on Day 1 & 4 of Avibactam | 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. | Post dose on day 1 and day 4 |
Plasma terminal elimination half-life (T1/2) is the time measured for the plasma concentration to decrease by one half at the terminal phase. |
| Post dose on day 1 and day 4 |
| Apparent Volume of Distribution at Steady-State (Vss) on Day 1 & 4 of Aztreonam | 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. | Post dose on day 1 and day 4 |
| Apparent Volume of Distribution at Steady-State (Vss) on Day 1 & 4 of Avibactam | 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. | Post dose on day 1 and day 4 |
| Apparent Volume of Distribution During Terminal Phase (Vz) on Day 1 & 4 of Aztreonam | 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. | Post dose on day 1 and day 4 |
| Apparent Volume of Distribution During Terminal Phase (Vz) on Day 1 & 4 of Avibactam | 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. | Post dose on day 1 and day 4 |
| Clearance (CL) on Day 1 & 4 of Aztreonam | 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. | Post dose on day 1 and day 4 |
| Clearance (CL) on Day 1 & 4 of Avibactam | 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. | Post dose on day 1 and day 4 |
| Time of Observed Maximum Plasma Concentration (Tmax) on Day 1 & 4 of Aztreonam | Tmax was defined as time to reach maximum observed plasma concentration. | Post dose on day 1 and day 4 |
| Time of Observed Maximum Plasma Concentration (Tmax) on Day 1 & 4 of Avibactam | Tmax was defined as time to reach maximum observed plasma concentration. | Post dose on day 1 and day 4 |
| Accumulation Ratio for Cmax (Rac,Cmax) on Day 4 of Aztreonam | 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. | Post dose on day 4 |
| Accumulation Ratio for Cmax (Rac,Cmax) on Day 4 of Avibactam | 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. | Post dose on day 4 |
| Accumulation Ratio for AUCτ Following Multiple Dosing (Rac) on Day 4 of Aztreonam | 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. | Post dose on day 4 |
| Accumulation Ratio for AUCτ Following Multiple Dosing (Rac) on Day 4 of Avibactam | 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. | Post dose on day 4 |
| Number of Participants With an Adverse Event (AE) | 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. | From the first dose of study treatment to the last dose of study treatment date +28 +7 days (up to 2 months) |
| Number of Participants With Abnormal Vital Signs | 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. | From the first dose of study treatment to the last dose of study treatment date +28 +7 days (up to 2 months) |
| Number of Participants With Abnormal Electrocardiograms (ECGs) | 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. | From the first dose of study treatment to the last dose of study treatment date +28 +7 days (up to 2 months) |
| Number of Participants With Abnormal Laboratory Assessments | Following laboratory parameters were assessed against pre-defined abnormality criteria: hematology (basophils); clinical chemistry (urate); urinalysis (urine hemoglobin, nitrite, urine erythrocytes). | From the first dose of study treatment to the last dose of study treatment date +28 +7 days (up to 2 months) |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
|
|
| Primary | Maximum Observed Plasma Concentration (Cmax) on Day 1 & 4 of Avibactam | 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ug/mL | Post dose on day 1 and day 4 |
|
|
|
| Primary | Area Under the Plasma Concentration-Time Profile From Time 0 to 6 Hours (AUC6) on Day 1 of Aztreonam | 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanograms/millilitre/hour (ng*hr/mL) | Post dose on day 1 |
|
|
|
| Primary | Area Under the Plasma Concentration-Time Profile From Time 0 to 6 Hours (AUC6) on Day 1 of Avibactam | 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | Post dose on day 1 |
|
|
|
| Primary | Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUClast) on Day 1 & 4 of Aztreonam | 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ug*hr/mL | Post dose on day 1 and day 4 |
|
|
|
| Primary | Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUClast) on Day 1 & 4 of Avibactam | 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ug*hr/mL | Post dose on day 1 and day 4 |
|
|
|
| Primary | Area Under the Plasma Concentration-Time Profile From Time 0 to 24 Hours (AUC24) on Day 1 & 4 of Aztreonam | 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ug*hr/mL | Post dose on day 1 and day 4 |
|
|
|
| Primary | Area Under the Plasma Concentration-Time Profile From Time 0 to 24 Hours (AUC24) on Day 1 & 4 of Avibactam | 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ug*hr/mL | Post dose on day 1 and day 4 |
|
|
|
| Primary | Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) on Day 1 & 4 of Aztreonam | 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ug*hr/mL | Post dose on day 1 and day 4 |
|
|
|
| Primary | Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) on Day 1 & 4 of Avibactam | 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ug*hr/mL | Post dose on day 1 and day 4 |
|
|
|
| Primary | 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 | 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ug*hr/mL | Post dose on day 4 |
|
|
|
| Primary | 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 | 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ug*hr/mL | Post dose on day 4 |
|
|
|
| Primary | 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 | 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ug*hr/mL | Post dose on day 4 |
|
|
|
| Primary | 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 | 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ug*hr/mL | Post dose on day 4 |
|
|
|
| Primary | Renal Clearance (CLr) on Day 1 & 4 of Aztreonam | 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | litre per hour (L/hr) | Post dose on day 1 and day 4 |
|
|
|
| Primary | Renal Clearance (CLr) on Day 1 & 4 of Avibactam | 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | litre per hour (L/hr) | Post dose on day 1 and day 4 |
|
|
|
| Secondary | Terminal Elimination Half-Life (T1/2) on Day 1 & 4 of Aztreonam | Plasma terminal elimination half-life (T1/2) is the time measured for the plasma concentration to decrease by one half at the terminal phase. | 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. | Posted | Mean | Standard Deviation | hours | Post dose on day 1 and day 4 |
|
|
|
| Secondary | Terminal Elimination Half-Life (T1/2) on Day 1 & 4 of Avibactam | Plasma terminal elimination half-life (T1/2) is the time measured for the plasma concentration to decrease by one half at the terminal phase. | 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. | Posted | Mean | Standard Deviation | hours | Post dose on day 1 and day 4 |
|
|
|
| Secondary | Apparent Volume of Distribution at Steady-State (Vss) on Day 1 & 4 of Aztreonam | 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | Liter | Post dose on day 1 and day 4 |
|
|
|
| Secondary | Apparent Volume of Distribution at Steady-State (Vss) on Day 1 & 4 of Avibactam | 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | Liter | Post dose on day 1 and day 4 |
|
|
|
| Secondary | Apparent Volume of Distribution During Terminal Phase (Vz) on Day 1 & 4 of Aztreonam | 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | Liter | Post dose on day 1 and day 4 |
|
|
|
| Secondary | Apparent Volume of Distribution During Terminal Phase (Vz) on Day 1 & 4 of Avibactam | 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | Liter | Post dose on day 1 and day 4 |
|
|
|
| Secondary | Clearance (CL) on Day 1 & 4 of Aztreonam | 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | litre per hour (L/hr) | Post dose on day 1 and day 4 |
|
|
|
| Secondary | Clearance (CL) on Day 1 & 4 of Avibactam | 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | litre per hour (L/hr) | Post dose on day 1 and day 4 |
|
|
|
| Secondary | Time of Observed Maximum Plasma Concentration (Tmax) on Day 1 & 4 of Aztreonam | Tmax was defined as time to reach maximum observed plasma concentration. | 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. | Posted | Median | Full Range | hours | Post dose on day 1 and day 4 |
|
|
|
| Secondary | Time of Observed Maximum Plasma Concentration (Tmax) on Day 1 & 4 of Avibactam | Tmax was defined as time to reach maximum observed plasma concentration. | 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. | Posted | Median | Full Range | hours | Post dose on day 1 and day 4 |
|
|
|
| Secondary | Accumulation Ratio for Cmax (Rac,Cmax) on Day 4 of Aztreonam | 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ratio | Post dose on day 4 |
|
|
|
| Secondary | Accumulation Ratio for Cmax (Rac,Cmax) on Day 4 of Avibactam | 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ratio | Post dose on day 4 |
|
|
|
| Secondary | Accumulation Ratio for AUCτ Following Multiple Dosing (Rac) on Day 4 of Aztreonam | 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ratio | Post dose on day 4 |
|
|
|
| Secondary | Accumulation Ratio for AUCτ Following Multiple Dosing (Rac) on Day 4 of Avibactam | 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ratio | Post dose on day 4 |
|
|
|
| Secondary | Number of Participants With an Adverse Event (AE) | 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. | The safety analysis set included all healthy Chinese participants who received at least one dose of investigational product (ATM-AVI). | Posted | Count of Participants | Participants | From the first dose of study treatment to the last dose of study treatment date +28 +7 days (up to 2 months) |
|
|
|
| Secondary | Number of Participants With Abnormal Vital Signs | 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. | The safety analysis set included all healthy Chinese participants who received at least one dose of investigational product (ATM-AVI). | Posted | Count of Participants | Participants | From the first dose of study treatment to the last dose of study treatment date +28 +7 days (up to 2 months) |
|
|
|
| Secondary | Number of Participants With Abnormal Electrocardiograms (ECGs) | 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. | The safety analysis set included all healthy Chinese participants who received at least one dose of investigational product (ATM-AVI). | Posted | Count of Participants | Participants | From the first dose of study treatment to the last dose of study treatment date +28 +7 days (up to 2 months) |
|
|
|
| Secondary | Number of Participants With Abnormal Laboratory Assessments | Following laboratory parameters were assessed against pre-defined abnormality criteria: hematology (basophils); clinical chemistry (urate); urinalysis (urine hemoglobin, nitrite, urine erythrocytes). | The safety analysis set included all healthy Chinese participants who received at least one dose of investigational product (ATM-AVI). | Posted | Count of Participants | Participants | From the first dose of study treatment to the last dose of study treatment date +28 +7 days (up to 2 months) |
|
|
|
| 0 |
| 12 |
| 0 |
| 12 |
| 2 |
| 12 |
| Aspartate aminotransferase increased | Investigations | MedDRA v24.0 | Non-systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA v24.0 | Non-systematic Assessment |
|
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.
|
|
|
| Supine Systolic Blood Pressure (mmHg): Change >= 30 mmHg decrease from baseline |
|
|
| QTCF - FRIDERICIA'S CORRECTION FORMULA NOT OTHERWISE SPECIFIED (msec): Change > 60 |
|
|
| URINALYSIS: URINE Hemoglobin >= 1 |
|
|
| URINALYSIS: URINE Erythrocytes >= 20 |
|
|