Study to Assess the Pharmacokinetics, Safety and Tolerability of Aztreonam-Avibactam in Healthy Chinese Participants.
- Conditions
- Healthy
- Interventions
- Drug: Aztreonam-Avibactam
- Registration Number
- NCT04973826
- Lead Sponsor
- Pfizer
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 12
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description ATM-AVI treatment arm Aztreonam-Avibactam Chinese healthy volunteers
- Primary Outcome Measures
Name Time Method Area Under the Plasma Concentration-Time Profile From Time 0 to 24 Hours (AUC24) on Day 1 & 4 of Aztreonam Post dose on day 1 and day 4 AUC24 was defined as area under the plasma concentration-time profile from time zero to 24 hours post dose. The geometric coefficient of variation is expressed in percentage.
Maximum Observed Plasma Concentration (Cmax) on Day 1 & 4 of Avibactam Post dose on day 1 and day 4 Cmax was the maximum observed plasma concentration and was directly observed from data. Concentration values below the lower limit of quantification (LLQ) were set to zero. Geometric Mean analysis was on the log scale. Zero values were not included in geometric mean and geometric coefficient of variation calculation. The geometric coefficient of variation is expressed in percentage.
Area Under the Plasma Concentration-Time Profile From Time 0 to 6 Hours (AUC6) on Day 1 of Aztreonam Post dose on day 1 The area under the plasma drug concentration-time curve (AUC) was estimated from time 0 to 6 hours post dose. AUC6 was computed using the Linear/Log trapezoidal method. The geometric coefficient of variation is expressed in percentage.
Area Under the Plasma Concentration-Time Profile From Time 0 to 6 Hours (AUC6) on Day 1 of Avibactam Post dose on day 1 The area under the plasma drug concentration-time curve (AUC) was estimated from time 0 to 6 hours post dose. AUC6 was computed using the Linear/Log trapezoidal method. The geometric coefficient of variation is expressed in percentage.
Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) on Day 1 & 4 of Aztreonam Post dose on day 1 and day 4 AUCinf was defined as area under the plasma concentration-time curve from time zero to infinity. The geometric coefficient of variation is expressed in percentage.
Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUClast) on Day 1 & 4 of Aztreonam Post dose on day 1 and day 4 AUClast is area under the plasma concentration time-curve from zero (pre-dose) to the last measured concentration. The geometric coefficient of variation is expressed in percentage.
Maximum Observed Plasma Concentration (Cmax) on Day 1 & 4 of Aztreonam Post dose on day 1 and day 4 Cmax was the maximum observed plasma concentration and was directly observed from data. Concentration values below the lower limit of quantification (LLQ) were set to zero. Geometric Mean analysis was on the log scale. Zero values were not included in geometric mean and geometric coefficient of variation calculation. The geometric coefficient of variation is expressed in percentage.
Area Under the Plasma Concentration-Time Profile From Time 0 to 24 Hours (AUC24) on Day 1 & 4 of Avibactam Post dose on day 1 and day 4 AUC24 was defined as area under the plasma concentration-time profile from time zero to 24 hours post dose. The geometric coefficient of variation is expressed in percentage.
Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) on Day 1 & 4 of Avibactam Post dose on day 1 and day 4 AUCinf was defined as area under the plasma concentration-time curve from time zero to infinity. The geometric coefficient of variation is expressed in percentage.
Area Under the Plasma Concentration-Time Profile From Time 0 to the Time of the End of the Dosing Interval (τ), Where τ=6 Hours (AUCtau) on Day 4 of Avibactam Post dose on day 4 AUCtau was defined as area under the concentration-time profile from time 0 to time tau. The geometric coefficient of variation is expressed in percentage.
Renal Clearance (CLr) on Day 1 & 4 of Aztreonam Post dose on day 1 and day 4 CLr was calculated as cumulative amount of drug recovered unchanged in urine during the dosing interval (Ae) divided by area under the plasma concentration time-curve from time zero to end of dosing interval (AUCtau). AUCtau was defined as area under the concentration-time profile from time 0 to time tau. The geometric coefficient of variation is expressed in percentage.
Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUClast) on Day 1 & 4 of Avibactam Post dose on day 1 and day 4 AUClast is area under the plasma concentration time-curve from zero (pre-dose) to the last measured concentration. The geometric coefficient of variation is expressed in percentage.
Area Under the Plasma Concentration-Time Profile From Time 0 to the Time of the End of the Dosing Interval (τ), Where τ=6 Hours (AUCtau) on Day 4 of Aztreonam Post dose on day 4 AUCtau was defined as area under the concentration-time profile from time 0 to time tau. The geometric coefficient of variation is expressed in percentage.
Total Daily Area Under the Plasma Concentration-Time Profile From Time 0 to 24 Hours at Steady-State (AUC24,ss) on Day 4 of Avibactam Post dose on day 4 AUC24,ss was defined as total daily area under the plasma concentration-time profile from time 0 to 24 hours at steady-state. The geometric coefficient of variation is expressed in percentage.
Renal Clearance (CLr) on Day 1 & 4 of Avibactam Post dose on day 1 and day 4 CLr was calculated as cumulative amount of drug recovered unchanged in urine during the dosing interval (Ae) divided by area under the plasma concentration time-curve from time zero to end of dosing interval (AUCtau). AUCtau was defined as area under the concentration-time profile from time 0 to time tau. The geometric coefficient of variation is expressed in percentage.
Total Daily Area Under the Plasma Concentration-Time Profile From Time 0 to 24 Hours at Steady-State (AUC24,ss) on Day 4 of Aztreonam Post dose on day 4 AUC24,ss was defined as total daily area under the plasma concentration-time profile from time 0 to 24 hours at steady-state. The geometric coefficient of variation is expressed in percentage.
- Secondary Outcome Measures
Name Time Method Terminal Elimination Half-Life (T1/2) on Day 1 & 4 of Avibactam 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.
Time of Observed Maximum Plasma Concentration (Tmax) on Day 1 & 4 of Avibactam Post dose on day 1 and day 4 Tmax was defined as time to reach maximum observed plasma concentration.
Clearance (CL) on Day 1 & 4 of Aztreonam 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.
Clearance (CL) on Day 1 & 4 of Avibactam 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.
Number of Participants With an Adverse Event (AE) 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.
Terminal Elimination Half-Life (T1/2) on Day 1 & 4 of Aztreonam 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.
Apparent Volume of Distribution at Steady-State (Vss) on Day 1 & 4 of Avibactam 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.
Accumulation Ratio for Cmax (Rac,Cmax) on Day 4 of Avibactam 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.
Apparent Volume of Distribution at Steady-State (Vss) on Day 1 & 4 of Aztreonam 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.
Apparent Volume of Distribution During Terminal Phase (Vz) on Day 1 & 4 of Aztreonam 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.
Apparent Volume of Distribution During Terminal Phase (Vz) on Day 1 & 4 of Avibactam 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.
Time of Observed Maximum Plasma Concentration (Tmax) on Day 1 & 4 of Aztreonam Post dose on day 1 and day 4 Tmax was defined as time to reach maximum observed plasma concentration.
Number of Participants With Abnormal Laboratory Assessments 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).
Accumulation Ratio for AUCτ Following Multiple Dosing (Rac) on Day 4 of Aztreonam 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.
Accumulation Ratio for Cmax (Rac,Cmax) on Day 4 of Aztreonam 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.
Accumulation Ratio for AUCτ Following Multiple Dosing (Rac) on Day 4 of Avibactam 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.
Number of Participants With Abnormal Vital Signs 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.
Number of Participants With Abnormal Electrocardiograms (ECGs) 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.
Trial Locations
- Locations (1)
Huashan Hospital Fudan University
🇨🇳Shanghai, Shanghai, China