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HealthyPhase 1NCT04973826

Study to Assess the Pharmacokinetics, Safety and Tolerability of Aztreonam-Avibactam in Healthy Chinese Participants.

A Phase 1 study testing Aztreonam-Avibactam in people with Healthy, run by Pfizer at 1 site in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for
Healthy
What is being tested?
Aztreonam-Avibactam
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
1 siteChina
Study dates
20 Aug 2021to 27 Sep 2021
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 55 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

China1 site
  • Huashan Hospital Fudan University

    Shanghai, Shanghai Municipality, 201107

Other trials in China

About this study

Official title: 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

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.

Conditions
Healthy
Being tested
Aztreonam-Avibactam
Keywords
no clinically relevant abnormalities

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Aztreonam-AvibactamDrug

    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

Study groups in NCT04973826
Study groupRoleWhat they receive
ATM-AVI treatment armExperimentalChinese healthy volunteers
Receives: Drug: Aztreonam-Avibactam

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Post dose on day 1 and day 4

  2. 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.

    Measured: Post dose on day 1 and day 4

  3. 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.

    Measured: Post dose on day 1

  4. 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.

    Measured: Post dose on day 1

  5. 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.

    Measured: Post dose on day 1 and day 4

  6. 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.

    Measured: Post dose on day 1 and day 4

  7. 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.

    Measured: Post dose on day 1 and day 4

  8. 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.

    Measured: Post dose on day 1 and day 4

  9. 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.

    Measured: Post dose on day 1 and day 4

  10. 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.

    Measured: Post dose on day 1 and day 4

  11. 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.

    Measured: Post dose on day 4

  12. 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.

    Measured: Post dose on day 4

  13. 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.

    Measured: Post dose on day 4

  14. 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.

    Measured: Post dose on day 4

  15. 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.

    Measured: Post dose on day 1 and day 4

  16. 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.

    Measured: Post dose on day 1 and day 4

Secondary outcomes (18)
  1. 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.

    Measured: Post dose on day 1 and day 4

  2. 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.

    Measured: Post dose on day 1 and day 4

  3. 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.

    Measured: Post dose on day 1 and day 4

  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.

    Measured: Post dose on day 1 and day 4

  5. 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.

    Measured: Post dose on day 1 and day 4

  6. 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.

    Measured: Post dose on day 1 and day 4

  7. 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.

    Measured: Post dose on day 1 and day 4

  8. 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.

    Measured: Post dose on day 1 and day 4

  9. Time of Observed Maximum Plasma Concentration (Tmax) on Day 1 & 4 of Aztreonam

    Tmax was defined as time to reach maximum observed plasma concentration.

    Measured: Post dose on day 1 and day 4

  10. Time of Observed Maximum Plasma Concentration (Tmax) on Day 1 & 4 of Avibactam

    Tmax was defined as time to reach maximum observed plasma concentration.

    Measured: Post dose on day 1 and day 4

  11. 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.

    Measured: Post dose on day 4

  12. 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.

    Measured: Post dose on day 4

  13. 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.

    Measured: Post dose on day 4

  14. 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.

    Measured: Post dose on day 4

  15. 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.

    Measured: From the first dose of study treatment to the last dose of study treatment date +28 +7 days (up to 2 months)

  16. 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.

    Measured: From the first dose of study treatment to the last dose of study treatment date +28 +7 days (up to 2 months)

  17. 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.

    1. 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.
    2. 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.

    Measured: From the first dose of study treatment to the last dose of study treatment date +28 +7 days (up to 2 months)

  18. 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).

    Measured: From the first dose of study treatment to the last dose of study treatment date +28 +7 days (up to 2 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Jul 2021
  2. Study start20 Aug 2021
  3. Primary completion27 Sep 2021
  4. Study completion27 Sep 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Other
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
12 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04973826
Sponsor's protocol ID
C3601007
Status last verified
Sep 2022
First submitted
13 Jul 2021
Last updated
28 Jul 2023
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: 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.

Publications

  • Wang J, He J, Wu J, Zhang J, Ma Y, Ren X, Wei H, Zhang C, Zhu H, Raber SR, Cong S. Pharmacokinetics of Aztreonam-Avibactam After Single- and Multiple-Dose Administration: A Phase 1, Open-Label Study in Healthy Chinese Participants and Ethnic Comparison with Non-Chinese Participants. Clin Pharmacol Drug Dev. 2026 Feb;15(2):e70040. doi: 10.1002/cpdd.70040.

    PubMed 41709845

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Aztreonam-Avibactam in people with Healthy, run by Pfizer at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Jul 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Observed Plasma Concentration (Cmax) on Day 1 & 4 of Aztreonam (time frame: Post dose on day 1 and day 4). The study lists 16 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04973826, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jul 2023.

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