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
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Pfizer
- Enrollment
- 12
- Locations
- 1
- Primary Endpoint
- Area Under the Plasma Concentration-Time Profile From Time 0 to 24 Hours (AUC24) on Day 1 & 4 of Aztreonam
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Other
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 55 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
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
Arms & Interventions
ATM-AVI treatment arm
Chinese healthy volunteers
Intervention: Aztreonam-Avibactam (Drug)
Outcomes
Primary Outcomes
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Secondary Outcomes
- Terminal Elimination Half-Life (T1/2) on Day 1 & 4 of Avibactam(Post dose on day 1 and day 4)
- Time of Observed Maximum Plasma Concentration (Tmax) on Day 1 & 4 of Avibactam(Post dose on day 1 and day 4)
- Clearance (CL) on Day 1 & 4 of Aztreonam(Post dose on day 1 and day 4)
- Clearance (CL) on Day 1 & 4 of Avibactam(Post dose on day 1 and day 4)
- 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))
- Terminal Elimination Half-Life (T1/2) on Day 1 & 4 of Aztreonam(Post dose on day 1 and day 4)
- Apparent Volume of Distribution at Steady-State (Vss) on Day 1 & 4 of Avibactam(Post dose on day 1 and day 4)
- Accumulation Ratio for Cmax (Rac,Cmax) on Day 4 of Avibactam(Post dose on day 4)
- 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 During Terminal Phase (Vz) on Day 1 & 4 of Aztreonam(Post dose on day 1 and day 4)
- Apparent Volume of Distribution During Terminal Phase (Vz) on Day 1 & 4 of Avibactam(Post dose on day 1 and day 4)
- Time of Observed Maximum Plasma Concentration (Tmax) on Day 1 & 4 of Aztreonam(Post dose on day 1 and day 4)
- 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))
- Accumulation Ratio for Cmax (Rac,Cmax) on Day 4 of Aztreonam(Post dose on day 4)
- Accumulation Ratio for AUCτ Following Multiple Dosing (Rac) on Day 4 of Avibactam(Post dose on day 4)
- 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))
- 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))
- Accumulation Ratio for AUCτ Following Multiple Dosing (Rac) on Day 4 of Aztreonam(Post dose on day 4)