- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04973826
Study to Assess the Pharmacokinetics, Safety and Tolerability of Aztreonam-Avibactam in Healthy Chinese Participants.
A PHASE I, SINGLE CENTER, OPEN-LABEL STUDY TO ASSESS THE PHARMACOKINETICS, SAFETY AND TOLERABILITY OF AZTREONAM-AVIBACTAM ADMINISTERED AS SINGLE AND REPEATED INTRAVENOUS DOSES IN HEALTHY CHINESE PARTICIPANTS
Study Overview
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Shanghai
-
Shanghai, Shanghai, China, 201107
- Huashan Hospital Fudan University
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Healthy Chinese male and female participants
- No clinical relevant abnormalities
- willing and able to comply with all study procedures
- BMI:17.5-30.5
- Sign informed consent
Exclusion Criteria:
- Any clinical significant illness
- History of alcohol abuse
- Use within 14 days prior the first study dose
- CL>80ml/min
- Abnormal vital signs, such 12-ECG, blood pressure and pulse rate
- Blood donation within 60days
- History of HIV, HBsAg, HBcAb, HCVAb
- Other medical or psychiatric may inappropriate for the study
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Other
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: ATM-AVI treatment arm
Chinese healthy volunteers
|
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
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum Observed Plasma Concentration (Cmax) on Day 1 & 4 of Aztreonam
Time Frame: Post dose on day 1 and day 4
|
Cmax was the maximum observed plasma concentration and was directly observed from data.
Concentration values below the lower limit of quantification (LLQ) were set to zero.
Geometric Mean analysis was on the log scale.
Zero values were not included in geometric mean and geometric coefficient of variation calculation.
The geometric coefficient of variation is expressed in percentage.
|
Post dose on day 1 and day 4
|
Maximum Observed Plasma Concentration (Cmax) on Day 1 & 4 of Avibactam
Time Frame: Post dose on day 1 and day 4
|
Cmax was the maximum observed plasma concentration and was directly observed from data.
Concentration values below the lower limit of quantification (LLQ) were set to zero.
Geometric Mean analysis was on the log scale.
Zero values were not included in geometric mean and geometric coefficient of variation calculation.
The geometric coefficient of variation is expressed in percentage.
|
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
Time Frame: Post dose on day 1
|
The area under the plasma drug concentration-time curve (AUC) was estimated from time 0 to 6 hours post dose.
AUC6 was computed using the Linear/Log trapezoidal method.
The geometric coefficient of variation is expressed in percentage.
|
Post dose on day 1
|
Area Under the Plasma Concentration-Time Profile From Time 0 to 6 Hours (AUC6) on Day 1 of Avibactam
Time Frame: Post dose on day 1
|
The area under the plasma drug concentration-time curve (AUC) was estimated from time 0 to 6 hours post dose.
AUC6 was computed using the Linear/Log trapezoidal method.
The geometric coefficient of variation is expressed in percentage.
|
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
Time Frame: Post dose on day 1 and day 4
|
AUClast is area under the plasma concentration time-curve from zero (pre-dose) to the last measured concentration.
The geometric coefficient of variation is expressed in percentage.
|
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
Time Frame: Post dose on day 1 and day 4
|
AUClast is area under the plasma concentration time-curve from zero (pre-dose) to the last measured concentration.
The geometric coefficient of variation is expressed in percentage.
|
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
Time Frame: Post dose on day 1 and day 4
|
AUC24 was defined as area under the plasma concentration-time profile from time zero to 24 hours post dose.
The geometric coefficient of variation is expressed in percentage.
|
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
Time Frame: Post dose on day 1 and day 4
|
AUC24 was defined as area under the plasma concentration-time profile from time zero to 24 hours post dose.
The geometric coefficient of variation is expressed in percentage.
|
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
Time Frame: Post dose on day 1 and day 4
|
AUCinf was defined as area under the plasma concentration-time curve from time zero to infinity.
The geometric coefficient of variation is expressed in percentage.
|
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
Time Frame: Post dose on day 1 and day 4
|
AUCinf was defined as area under the plasma concentration-time curve from time zero to infinity.
The geometric coefficient of variation is expressed in percentage.
|
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
Time Frame: Post dose on day 4
|
AUCtau was defined as area under the concentration-time profile from time 0 to time tau.
The geometric coefficient of variation is expressed in percentage.
|
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
Time Frame: Post dose on day 4
|
AUCtau was defined as area under the concentration-time profile from time 0 to time tau.
The geometric coefficient of variation is expressed in percentage.
|
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
Time Frame: Post dose on day 4
|
AUC24,ss was defined as total daily area under the plasma concentration-time profile from time 0 to 24 hours at steady-state.
The geometric coefficient of variation is expressed in percentage.
|
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
Time Frame: Post dose on day 4
|
AUC24,ss was defined as total daily area under the plasma concentration-time profile from time 0 to 24 hours at steady-state.
The geometric coefficient of variation is expressed in percentage.
|
Post dose on day 4
|
Renal Clearance (CLr) on Day 1 & 4 of Aztreonam
Time Frame: Post dose on day 1 and day 4
|
CLr was calculated as cumulative amount of drug recovered unchanged in urine during the dosing interval (Ae) divided by area under the plasma concentration time-curve from time zero to end of dosing interval (AUCtau).
AUCtau was defined as area under the concentration-time profile from time 0 to time tau.
The geometric coefficient of variation is expressed in percentage.
|
Post dose on day 1 and day 4
|
Renal Clearance (CLr) on Day 1 & 4 of Avibactam
Time Frame: Post dose on day 1 and day 4
|
CLr was calculated as cumulative amount of drug recovered unchanged in urine during the dosing interval (Ae) divided by area under the plasma concentration time-curve from time zero to end of dosing interval (AUCtau).
AUCtau was defined as area under the concentration-time profile from time 0 to time tau.
The geometric coefficient of variation is expressed in percentage.
|
Post dose on day 1 and day 4
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Terminal Elimination Half-Life (T1/2) on Day 1 & 4 of Aztreonam
Time Frame: 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
|
Terminal Elimination Half-Life (T1/2) on Day 1 & 4 of Avibactam
Time Frame: 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
Time Frame: Post dose on day 1 and day 4
|
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
Time Frame: Post dose on day 1 and day 4
|
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
Time Frame: Post dose on day 1 and day 4
|
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
Time Frame: Post dose on day 1 and day 4
|
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
Time Frame: Post dose on day 1 and day 4
|
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
Time Frame: Post dose on day 1 and day 4
|
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
Time Frame: Post dose on day 1 and day 4
|
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
Time Frame: Post dose on day 1 and day 4
|
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
Time Frame: Post dose on day 4
|
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
Time Frame: Post dose on day 4
|
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
Time Frame: Post dose on day 4
|
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
Time Frame: Post dose on day 4
|
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)
Time Frame: From the first dose of study treatment to the last dose of study treatment date +28 +7 days (up to 2 months)
|
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
Time Frame: From the first dose of study treatment to the last dose of study treatment date +28 +7 days (up to 2 months)
|
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)
Time Frame: From the first dose of study treatment to the last dose of study treatment date +28 +7 days (up to 2 months)
|
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
Time Frame: From the first dose of study treatment to the last dose of study treatment date +28 +7 days (up to 2 months)
|
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)
|
Collaborators and Investigators
Sponsor
Investigators
- Study Director: Pfizer CT.gov Call Center, Pfizer
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- C3601007
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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