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TerminatedNCT04126031NOORUpdated Mar 26, 2024Results posted

Evaluation of Pharmacokinetics, Safety, and Tolerability of Ceftazidime-avibactam in Neonates and Infants.

A Phase 2 interventional study of Part A: Single Dose Ceftazidime-Avibactam, Cohorts 1-3 and Part B: Multiple-dose Ceftazidime-Avibactam, Cohorts 1-3 in Gram-negative Bacterial Infection, sponsored by Pfizer. Terminated at 18 sites in 8 countries. Open to participants aged 0 Days to 88 Days. Per ClinicalTrials.gov, last updated 2024-03-26.

Sponsored by Pfizer · Phase 2, Interventional, and Basic science

Why this study was terminated
Following regulatory consultation, the Sponsor has decided to terminate the study and analyze the current dataset. The decision to terminate was solely based on a business decision, not due to safety concerns.
Phase
Phase 2
Study type
Interventional
Enrollment
48
Allocation
Non-randomized
Ages
0 Days to 88 Days
Sex
All
01

Study summary

This study will assess the pharmacokinetics, safety, and tolerability of single and multiple doses of intravenous ceftazidime-avibactam in hospitalized infants and neonates from 26 weeks gestation to 3 months of age. In Part A of the study all patients will receive a single dose of ceftazidime-avibactam. In Part B all patients will received multiple doses of ceftazidime-avibactam. Efficacy will be assessed in the infants and neonates receiving multiple doses of ceftazidime-avibactam.

Read the detailed description

This is a 2-part, Phase 2a, non-randomized, open-label multicenter, multinational study of intravenous ceftazidime-avibactam in hospitalized neonates and infants with suspected or confirmed bacterial infection. In Part A of the study, patients already receiving intravenous antibacterial therapy with another antibiotic will receive a single intravenous dose of ceftazidime-avibactam followed by observation for 48 hours and a Late Follow-Up assessment 4-5 weeks later. In Part B of the study, patients with suspected or confirmed Gram-negative bacterial infections requiring intravenous antibacterial therapy will receive multiple doses of intravenous ceftazidime-avibactam for up to 14 days. At the discretion of the investigator, patients may also receive other antibiotics if the infection is suspected to include Gram-positive bacteria, multi-drug resistant Gram-negative bacteria, or anaerobic bacteria. At the discretion of the investigator, patients may be switched to oral therapy or outpatient parenteral antimicrobial therapy with an alternative antibiotic after receiving intravenous ceftazidime-avibactam for at least 48 yhours. Clinical outcomes will be assessed at the End of Intravenous (EOIV) treatment with ceftazidime-avibactam, the End-of-Therapy (EOT), the Test-of-Cure (TOC) at 7-14 days after the last study therapy and at a Late Follow-Up (LFU) visit, 28-55 days after the last dose of ceftazidime-avibactam. Safety assessments will occur throughout the study. Ceftazidime-avibactam blood levels will be assessed during the first 12 hours after the single dose of ceftazidime-avibactam in Part A and during 12 hours after at least 3 consecutive doses of ceftazidime-avibactam in Part B.

02

Conditions studied

  • Gram-negative Bacterial Infection

Keywords

  • Gram-negative, ceftazidime-avibactam, neonate, infant
03

In context

Infections

6,687 studies on the registry are indexed under Infections; 807 are open to participants now.

This study's enrollment of 48 is below the median of 120 across 4,200 interventional studies indexed under Infections.

Browse Infections studies →

Lead sponsor

Pfizer is the lead sponsor of 3,244 studies on the registry; 139 are open to participants now.

Of its 582 completed or terminated interventional studies of FDA-regulated products, 381 (65%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
0 Days to 88 Days
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

Inclusion Criteria (All Subjects):

  1. Evidence of a personally signed and dated informed consent document indicating that the subject's parent(s), legal guardian, or legally acceptable representative has been informed of all pertinent aspects of the study.
  2. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
  3. Male or female neonates and infants with age at Screening:

Cohort 1: Full term infants (gestational age ≥ 37 weeks) with chronological age >28 days to \<3 months (\<89 days) or pre-term infants with corrected age >28 days to \<3 months (\<89 days). A maximum of 3 pre-term corrected age infants may be enrolled in each part (A and B) of Cohort 1. Sites will be notified in writing if this limit is reached.

Cohort 2: Full term neonates (gestational age ≥ 37 weeks) from birth to ≤ 28 days.

Cohort 3: Pre-term neonates (gestational age ≥ 26 to \<37 weeks) from birth to ≤ 28 days.

Corrected age = Subtract the number of weeks born before 40 weeks of gestation from the chronological age.

Inclusion Criteria for Part A Subjects Only:

  1. Hospitalized and receiving intravenous antibacterial therapy for the treatment of a suspected or confirmed bacterial infection.

Inclusion Criteria for Part B Subjects Only:

  1. Hospitalized with suspected or confirmed aerobic Gram-negative bacterial infection requiring intravenous antibacterial therapy.
  2. Subjects must meet at least 1 clinical and 1 laboratory criterion or meet at least 2 of the clinical criteria:

Clinical Criteria:

  1. Hypothermia (\<36ºC) OR fever (>38.5ºC);
  2. Bradycardia OR tachycardia OR rhythm instability;
  3. Urine output 0.5 to 1 mL/kg/h OR hypotension OR mottled skin OR impaired peripheral perfusion;
  4. Petechial rash OR sclerema neonatorum;
  5. New onset or worsening of apnea episodes OR tachypnea episodes OR increased oxygen requirements OR requirement for ventilation support;
  6. Feeding intolerance OR poor suckling OR abdominal distension;
  7. Irritability;
  8. Lethargy;
  9. Hypotonia.

Laboratory Criteria:

  1. White blood cell count ≤ 4.0 × 10\^9/L OR ≥ 20.0 × 10\^9/L;
  2. Immature to total neutrophil ratio >0.2;
  3. Platelet count ≤ 100 × 10\^9/L;
  4. C reactive protein (CRP) >15 mg/L OR procalcitonin ≥ 2 ng/mL;
  5. Hyperglycemia OR Hypoglycemia;
  6. Metabolic acidosis.

Exclusion Criteria (All Subjects):

  1. Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the Investigator, or subjects who are Pfizer employees, including their family members, directly involved in the conduct of the study.
  2. Participation in another clinical study involving investigational drug(s) within 30 days prior to study entry and/or during this study participation or have previously participated in the current study or in another study of CAZ-AVI (in which an active agent was received).
  3. Use of potent inhibitors of organic anion transporters OAT1 and/or OAT3 (eg, probenecid, p-aminohippuric acid (PAH), or teriflunomide) are prohibited. This prohibition of OAT1 and/or OAT3 inhibitors also applies to the mothers of any neonates or infants who are breast feeding during the trial.
  4. Other acute or chronic medical or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the subject inappropriate for entry into this study.
  5. Documented history of any hypersensitivity or allergic reaction to any beta-lactam antibiotic.
  6. Refractory septic shock within 24 hours before screening that does not resolve after 60 minutes of vasopressor therapy.
  7. Moderate or severe renal impairment defined as serum creatinine ≥ 2 times the upper limit of normal (ULN) for age OR urine output \<0.5 mL/kg/h (measured over at least 8 hours) OR requirement for dialysis. Deterioration of renal function after enrollment during Part B of the study will be handled on a case-by-case basis in discussion with the Medical Monitor.
  8. Evidence of progressively fatal underlying disease, or life expectancy of ≤ 60 days.
  9. Documented history of seizure.
  10. Active acute viral hepatitis or acute hepatic failure.
  11. Known Clostridium difficile associated diarrhea.
  12. Requiring or currently taking antiretroviral therapy for human immunodeficiency virus (HIV) or known HIV positive mother.
  13. Any condition (eg, cystic fibrosis, urea cycle disorders), antepartum/peripartum factors, or procedures that would, in the opinion of the Investigator, make the subject unsuitable for the study, place a subject at risk, or compromise the quality of data.
  14. Treatment with ceftazidime within 12 hours of CAZ-AVI administration.

Exclusion Criteria for Part A Subjects Only:

  1. Subject received a blood or a blood component transfusion within 24 hours of the start of CAZ AVI infusion.
  2. Subject is expected to be discharged less than 24 hours after the start of CAZ AVI infusion.

Exclusion Criteria for Part B Subjects Only:

  1. At study entry, subject has confirmed or strongly suspected infection with a pathogen known to be resistant to CAZ-AVI or only a Gram-positive pathogen or viral, fungal, or parasitic pathogens as the sole cause of infection.
  2. Confirmed or suspected central nervous system (CNS) infection (eg, meningitis, brain abscess, subdural abscess).
  3. Anticipated need for antibacterial therapy longer than 14 days (eg, osteomyelitis, endocarditis). This applies to both study treatment with CAZ-AVI as well as adjunctive IV antibacterial treatment for suspected co infection with Gram-positive organisms or multi drug resistant Gram-negative organisms.
  4. Receipt of more than 24 hours of nonstudy systemic antibacterial treatment for Gram-negative organisms after culture and before administration of study doses of CAZ-AVI. Empiric coverage with an aminoglycoside for suspected multidrug resistant organisms is permitted, provided CAZ-AVI is initiated within 24 hours after culture.
  5. Intravenous treatment with chloramphenicol within 24 hours of administration of study doses of CAZ-AVI.
  6. Subject is expected to be discharged less than 48 hours after the start of CAZ-AVI infusion.
05

Study design

Phase
Phase 2
Primary purpose
Basic science
Allocation
Non-randomized
Intervention model
Single group
Masking
None (open label)
Enrollment
48 participants (actual)

Study arms

  • Experimental
    Part A, Cohorts 1-3

    Single dose pharmacokinetics. This arm will include three age cohorts.

    Drug: Part A: Single Dose Ceftazidime-Avibactam, Cohorts 1-3

  • Experimental
    Part B, Cohorts 1-3

    Multi-dose pharmacokinetics. This arm will include three age cohorts.

    Drug: Part B: Multiple-dose Ceftazidime-Avibactam, Cohorts 1-3

Interventions

  • DrugPart A: Single Dose Ceftazidime-Avibactam, Cohorts 1-3

    Single intravenous infusion of ceftazidime-avibactam over 2 hours

  • DrugPart B: Multiple-dose Ceftazidime-Avibactam, Cohorts 1-3

    Multiple intravenous infusions of ceftazidime-avibactam over 2 hours, repeated every 8 hours up to 14 days

06

What researchers measure

Primary outcomes

  1. Plasma Concentrations of Ceftazidime and Avibactam 2 Hours Post-dose: Part A

    Time frame: 2 hours post dose on Day 1

  2. Plasma Concentrations of Ceftazidime and Avibactam 2 Hours and 30 Minutes Post-dose: Part A

    Time frame: 2 hours and 30 minutes post dose on Day 1

  3. Plasma Concentrations of Ceftazidime and Avibactam of 7 Hours Post-dose: Part A

    Time frame: 7 hours post dose on Day 1

  4. Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs): Part B

    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in participant hospitalization; life-threatening experience (immediate risk of dying) ; persistent or significant disability/incapacity; congenital anomaly.

    Time frame: Day 1 up to maximum of Day 49

  5. Number of Participants Who Died: Part B

    Time frame: Day 1 up to maximum of Day 49

  6. Number of Participants Who Discontinued Treatment and Study Due to AEs: Part B

    Time frame: Day 1 up to maximum of Day 49

  7. Number of Participants With Clinically Significant Laboratory Parameters Occurred in More Than 2 Participants: Part B

    Number of participants in Part B with clinically significant abnormal laboratory parameters that occurred in more than 2 participants from Day 1 up to 35 days after the last dose of CAZ-AVI were reported in this outcome measure. Clinically significant labs were abnormal laboratory results which the investigator reported as being clinically significant. Only parameters with non-zero values are reported.

    Time frame: Day 1 up to maximum of Day 49

Secondary outcomes

  1. Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs): Part A

    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in-patient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.

    Time frame: Day 1 up to maximum of Day 35

  2. Number of Participants Who Died: Part A

    Time frame: Day 1 up to maximum of Day 35

  3. Number of Participants Who Discontinued Treatment and Study Due to AEs: Part A

    Time frame: Day 1 up to maximum of Day 35

  4. Plasma Concentrations of Ceftazidime and Avibactam 2 Hours, 2 Hours and 30 Minutes, 7 Hours Post Doses on Day 1: Part B

    Time frame: 2 hours, 2 hours 30 mins, and 7 hours post dose on Day 1

  5. Number of Participants According to Clinical Outcome At End of IV Treatment(EOIV), End of Treatment(EOT), Test of Cure(TOC) and Late Follow-Up(LFU): Intent to Treat (ITT) Analysis Population: Part B

    Clinical outcome assessed based on clinical cure, improvement, failure, indeterminate. Clinical cure=resolution of acute signs, symptoms.Clinical improvement=participants switched to oral therapy;met following criteria at EOIV:afebrile for 24 hours(H);improvement in at least 1 symptom,sign.Clinical failure=received \>48H of therapy, met any of these:therapy discontinuation due to insufficient effect, AE, death. Indeterminate=data not available for evaluation(death;lost to follow up;diagnosis of CNS infection, osteomyelitis, endocarditis or necrotizing enterocolitis after enrollment). EOIV (Up to 14 days), EOT (Up to 27 days), TOC (Up to 34 days), LFU (Up to 49 days).

    Time frame: EOIV, EOT, TOC, LFU

  6. Number of Participants According to Clinical Outcome At End of IV Treatment(EOIV), End of Treatment(EOT), Test of Cure(TOC) and Late Follow-Up(LFU) in Micro-ITT Analysis Population: Part B

    Clinical outcome assessed based on clinical cure, improvement, failure, indeterminate. Clinical cure=resolution of acute signs, symptoms.Clinical improvement=participants switched to oral therapy;met following criteria at EOIV:afebrile for 24 hours(H);improvement in at least 1 symptom,sign.Clinical failure=received \>48H of therapy, met any of these:therapy discontinuation due to insufficient effect, AE, death. Indeterminate=data not available for evaluation(death;lost to follow up;diagnosis of CNS infection, osteomyelitis, endocarditis or necrotizing enterocolitis after enrollment). EOIV (Up to 14 days), EOT (Up to 27 days), TOC (Up to 34 days), LFU (Up to 49 days).

    Time frame: EOIV, EOT, TOC, LFU

  7. Number of Participants According to Clinical Outcome At End of IV Treatment(EOIV), End of Treatment(EOT), Test of Cure(TOC) and Late Follow-Up(LFU) in Modified-ITT Analysis Population: Part B

    Clinical outcome assessed based on clinical cure, improvement, failure, indeterminate. Clinical cure=resolution of acute signs, symptoms.Clinical improvement=participants switched to oral therapy;met following criteria at EOIV:afebrile for 24 hours(H);improvement in at least 1 symptom,sign.Clinical failure=received \>48H of therapy, met any of these:therapy discontinuation due to insufficient effect, AE, death. Indeterminate=data not available for evaluation(death;lost to follow up;diagnosis of CNS infection, osteomyelitis, endocarditis or necrotizing enterocolitis after enrollment). EOIV (Up to 14 days), EOT (Up to 27 days), TOC (Up to 34 days), LFU (Up to 49 days).

    Time frame: EOIV, EOT, TOC, LFU

  8. Number of Participants According to Microbiological Response at TOC Visit in Micro-ITT Population: Part B

    Microbiological response was assessed based on eradication, presumed eradication, persistence, presumed persistence, indeterminate. Eradication: source specimen demonstrated absence of the original baseline pathogen. Presumed eradication: source specimen was not available to culture and the participant was assessed as a clinical cure. Persistence: source specimen demonstrated continued presence of the original baseline pathogen. Presumed persistence: source specimen was not available to culture and the participant was assessed as a clinical failure. Indeterminate: source specimen was not available to culture and the participant's clinical outcome was assessed as indeterminate.

    Time frame: Up to 34 days

  9. Number of Participants With Emergent Infections in Micro-ITT Analysis Population: Part B

    Emergent infections included superinfection and new infection. Superinfection: a culture identified pathogen other than a baseline pathogen during the course of active treatment with study therapy requiring alternative antimicrobial therapy. New infection: a culture identified pathogen other than a baseline pathogen at any time after study treatment has finished requiring alternative antimicrobial therapy.

    Time frame: Day 1 up to maximum of Day 49

  10. Number of Participants With Clinically Significant Laboratory Parameters Occurred in More Than 2 Participants: Part A

    Number of participants in Part A with clinically significant abnormal laboratory parameters that occurred in more than 2 participants from Day 1 up to 35 days after the last dose of CAZ-AVI were reported in this outcome measure. Clinically significant labs were abnormal laboratory results which the investigator reported as being clinically significant.

    Time frame: Day 1 up to maximum of Day 35

07

Results

Posted Mar 26, 2024

Participant flow

Part A
Participant flow — Part A
MilestonePart A: Cohort 1Part A: Cohort 2Part A: Cohort 3Part B: Cohort 1Part B: Cohort 2Part B: Cohort 3
Started1089000
Treated988000
Completed988000
Not completed101000
Withdrew: Withdrawal by subject001000
Withdrew: Other100000
Part B
Participant flow — Part B
MilestonePart A: Cohort 1Part A: Cohort 2Part A: Cohort 3Part B: Cohort 1Part B: Cohort 2Part B: Cohort 3
Started000858
Completed000846
Not completed000012
Withdrew: Adverse event000002
Withdrew: Pre-existing hypertransaminasemia000010

Outcome measures

PrimaryPlasma Concentrations of Ceftazidime and Avibactam 2 Hours Post-dose: Part A
Time frame:
2 hours post dose on Day 1
Reported as:
Mean · Nanogram per milliliter
Plasma Concentrations of Ceftazidime and Avibactam 2 Hours Post-dose: Part A
Nanogram per milliliterPart A: Cohort 1Part A: Cohort 2Part A: Cohort 3
Ceftazidime104544.4 ± 113161.3435537.5 ± 13473.8853212.5 ± 25972.32
Avibactam19210.0 ± 18747.866910.0 ± 2553.5010570.0 ± 4342.69
PrimaryPlasma Concentrations of Ceftazidime and Avibactam 2 Hours and 30 Minutes Post-dose: Part A
Time frame:
2 hours and 30 minutes post dose on Day 1
Reported as:
Mean · Nanogram per milliliter
Plasma Concentrations of Ceftazidime and Avibactam 2 Hours and 30 Minutes Post-dose: Part A
Nanogram per milliliterPart A: Cohort 1Part A: Cohort 2Part A: Cohort 3
Ceftazidime76822.2 ± 106423.7632571.4 ± 10842.0049012.5 ± 18832.45
Avibactam13250.0 ± 16906.676251.4 ± 2363.999788.8 ± 2956.39
PrimaryPlasma Concentrations of Ceftazidime and Avibactam of 7 Hours Post-dose: Part A
Time frame:
7 hours post dose on Day 1
Reported as:
Mean · Nanogram per milliliter
Plasma Concentrations of Ceftazidime and Avibactam of 7 Hours Post-dose: Part A
Nanogram per milliliterPart A: Cohort 1Part A: Cohort 2Part A: Cohort 3
Ceftazidime15635.6 ± 15243.228305.0 ± 6728.5017608.8 ± 8165.42
Avibactam2058.2 ± 1670.321190.4 ± 998.693475.6 ± 1931.10
PrimaryNumber of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs): Part B

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in participant hospitalization; life-threatening experience (immediate risk of dying) ; persistent or significant disability/incapacity; congenital anomaly.

Time frame:
Day 1 up to maximum of Day 49
Reported as:
Count of participants · Participants
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs): Part B
ParticipantsPart B: Cohort 1Part B: Cohort 2Part B: Cohort 3
AEs447
SAEs122
PrimaryNumber of Participants Who Died: Part B
Time frame:
Day 1 up to maximum of Day 49
Reported as:
Count of participants · Participants
Number of Participants Who Died: Part B
ParticipantsPart B: Cohort 1Part B: Cohort 2Part B: Cohort 3
Number of Participants Who Died: Part B001
PrimaryNumber of Participants Who Discontinued Treatment and Study Due to AEs: Part B
Time frame:
Day 1 up to maximum of Day 49
Reported as:
Count of participants · Participants
Number of Participants Who Discontinued Treatment and Study Due to AEs: Part B
ParticipantsPart B: Cohort 1Part B: Cohort 2Part B: Cohort 3
Discontinued from study due to AEs002
Discontinued study drug due to AE and continue study000
SecondaryNumber of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs): Part A

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in-patient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.

Time frame:
Day 1 up to maximum of Day 35
Reported as:
Count of participants · Participants
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs): Part A
ParticipantsPart A: Cohort 1Part A: Cohort 2Part A: Cohort 3
AEs422
SAEs201
SecondaryNumber of Participants Who Died: Part A
Time frame:
Day 1 up to maximum of Day 35
Reported as:
Count of participants · Participants
Number of Participants Who Died: Part A
ParticipantsPart A: Cohort 1Part A: Cohort 2Part A: Cohort 3
Number of Participants Who Died: Part A000
SecondaryNumber of Participants Who Discontinued Treatment and Study Due to AEs: Part A
Time frame:
Day 1 up to maximum of Day 35
Reported as:
Count of participants · Participants
Number of Participants Who Discontinued Treatment and Study Due to AEs: Part A
ParticipantsPart A: Cohort 1Part A: Cohort 2Part A: Cohort 3
Discontinued from study due to AEs000
Discontinued study drug due to AE and continue study000
SecondaryPlasma Concentrations of Ceftazidime and Avibactam 2 Hours, 2 Hours and 30 Minutes, 7 Hours Post Doses on Day 1: Part B
Time frame:
2 hours, 2 hours 30 mins, and 7 hours post dose on Day 1
Reported as:
Mean · Nanograms per milliliter
Plasma Concentrations of Ceftazidime and Avibactam 2 Hours, 2 Hours and 30 Minutes, 7 Hours Post Doses on Day 1: Part B
Nanograms per milliliterPart B: Cohort 1Part B: Cohort 2Part B: Cohort 3
Ceftazidime: 2 hours52950.0 ± 17565.4748625.0 ± 17010.4643711.3 ± 22229.93
Ceftazidime: 2 hours 30 mins43037.5 ± 17433.2139000.0 ± 4415.8842465.0 ± 26800.19
Ceftazidime: 7 hours8323.8 ± 4805.6516735.0 ± 9070.8718658.4 ± 18268.92
Avibactam: 2 hours10340.0 ± 3262.6311330.0 ± 2012.539410.1 ± 5551.00
Avibactam: 2 hours 30 mins6825.0 ± 2386.269380.0 ± 2317.149064.0 ± 5694.05
Avibactam: 7 hours1025.3 ± 592.833787.5 ± 2533.463890.5 ± 3867.47
SecondaryNumber of Participants According to Clinical Outcome At End of IV Treatment(EOIV), End of Treatment(EOT), Test of Cure(TOC) and Late Follow-Up(LFU): Intent to Treat (ITT) Analysis Population: Part B

Clinical outcome assessed based on clinical cure, improvement, failure, indeterminate. Clinical cure=resolution of acute signs, symptoms.Clinical improvement=participants switched to oral therapy;met following criteria at EOIV:afebrile for 24 hours(H);improvement in at least 1 symptom,sign.Clinical failure=received \>48H of therapy, met any of these:therapy discontinuation due to insufficient effect, AE, death. Indeterminate=data not available for evaluation(death;lost to follow up;diagnosis of CNS infection, osteomyelitis, endocarditis or necrotizing enterocolitis after enrollment). EOIV (Up to 14 days), EOT (Up to 27 days), TOC (Up to 34 days), LFU (Up to 49 days).

Time frame:
EOIV, EOT, TOC, LFU
Reported as:
Count of participants · Participants
Number of Participants According to Clinical Outcome At End of IV Treatment(EOIV), End of Treatment(EOT), Test of Cure(TOC) and Late Follow-Up(LFU): Intent to Treat (ITT) Analysis Population: Part B
ParticipantsPart B: Cohort 1Part B: Cohort 2Part B: Cohort 3
EOIV: Clinical cure223
EOIV: Clinical improvement623
EOIV: Clinical failure001
EOIV: Indeterminate011
EOIV: Missing000
EOT: Clinical cure633
EOT: Clinical improvement213
EOT: Clinical failure001
EOT: Indeterminate010
EOT: Missing001
LFU: Clinical cure846
LFU: Clinical improvement000
LFU: Clinical failure001
LFU: Indeterminate010
LFU: Missing000
TOC: Clinical cure737
TOC: Clinical improvement000
TOC: Clinical failure001
TOC: Indeterminate020
TOC: Missing000
SecondaryNumber of Participants According to Clinical Outcome At End of IV Treatment(EOIV), End of Treatment(EOT), Test of Cure(TOC) and Late Follow-Up(LFU) in Micro-ITT Analysis Population: Part B

Clinical outcome assessed based on clinical cure, improvement, failure, indeterminate. Clinical cure=resolution of acute signs, symptoms.Clinical improvement=participants switched to oral therapy;met following criteria at EOIV:afebrile for 24 hours(H);improvement in at least 1 symptom,sign.Clinical failure=received \>48H of therapy, met any of these:therapy discontinuation due to insufficient effect, AE, death. Indeterminate=data not available for evaluation(death;lost to follow up;diagnosis of CNS infection, osteomyelitis, endocarditis or necrotizing enterocolitis after enrollment). EOIV (Up to 14 days), EOT (Up to 27 days), TOC (Up to 34 days), LFU (Up to 49 days).

Time frame:
EOIV, EOT, TOC, LFU
Reported as:
Count of participants · Participants
Number of Participants According to Clinical Outcome At End of IV Treatment(EOIV), End of Treatment(EOT), Test of Cure(TOC) and Late Follow-Up(LFU) in Micro-ITT Analysis Population: Part B
ParticipantsPart B: Cohort 1Part B: Cohort 2Part B: Cohort 3
EOIV: Clinical cure2—1
EOIV: Clinical improvement5—0
EOIV: Clinical failure0—1
EOIV: Indeterminate0—1
EOIV: Missing0—0
EOT: Clinical cure6—1
EOT: Clinical improvement1—0
EOT: Clinical failure0—1
EOT: Indeterminate0—0
EOT: Missing0—1
LFU: Clinical cure7—1
LFU: Clinical improvement0—0
LFU: Clinical failure0—1
LFU: Indeterminate0—0
LFU: Missing0—0
TOC: Clinical cure6—2
TOC: Clinical improvement0—0
TOC: Clinical failure0—1
TOC: Indeterminate0—0
TOC: Missing0—0
SecondaryNumber of Participants According to Clinical Outcome At End of IV Treatment(EOIV), End of Treatment(EOT), Test of Cure(TOC) and Late Follow-Up(LFU) in Modified-ITT Analysis Population: Part B

Clinical outcome assessed based on clinical cure, improvement, failure, indeterminate. Clinical cure=resolution of acute signs, symptoms.Clinical improvement=participants switched to oral therapy;met following criteria at EOIV:afebrile for 24 hours(H);improvement in at least 1 symptom,sign.Clinical failure=received \>48H of therapy, met any of these:therapy discontinuation due to insufficient effect, AE, death. Indeterminate=data not available for evaluation(death;lost to follow up;diagnosis of CNS infection, osteomyelitis, endocarditis or necrotizing enterocolitis after enrollment). EOIV (Up to 14 days), EOT (Up to 27 days), TOC (Up to 34 days), LFU (Up to 49 days).

Time frame:
EOIV, EOT, TOC, LFU
Reported as:
Count of participants · Participants
Number of Participants According to Clinical Outcome At End of IV Treatment(EOIV), End of Treatment(EOT), Test of Cure(TOC) and Late Follow-Up(LFU) in Modified-ITT Analysis Population: Part B
ParticipantsPart B: Cohort 1Part B: Cohort 2Part B: Cohort 3
EOIV: Clinical cure213
EOIV: Clinical improvement610
EOIV: Clinical failure001
EOIV: Indeterminate011
EOIV: Missing000
EOT: Clinical cure613
EOT: Clinical improvement210
EOT: Clinical failure001
EOT: Indeterminate010
EOT: Missing001
LFU: Clinical cure823
LFU: Clinical improvement000
LFU: Clinical failure001
LFU: Indeterminate010
LFU: Missing000
TOC: Clinical cure714
TOC: Clinical improvement000
TOC: Clinical failure001
TOC: Indeterminate020
TOC: Missing000
SecondaryNumber of Participants According to Microbiological Response at TOC Visit in Micro-ITT Population: Part B

Microbiological response was assessed based on eradication, presumed eradication, persistence, presumed persistence, indeterminate. Eradication: source specimen demonstrated absence of the original baseline pathogen. Presumed eradication: source specimen was not available to culture and the participant was assessed as a clinical cure. Persistence: source specimen demonstrated continued presence of the original baseline pathogen. Presumed persistence: source specimen was not available to culture and the participant was assessed as a clinical failure. Indeterminate: source specimen was not available to culture and the participant's clinical outcome was assessed as indeterminate.

Time frame:
Up to 34 days
Reported as:
Count of participants · Participants
Number of Participants According to Microbiological Response at TOC Visit in Micro-ITT Population: Part B
ParticipantsPart B: Cohort 1Part B: Cohort 2Part B: Cohort 3
Enterobacter Cloacae Complex: F: Eradication0—0
Enterobacter Cloacae Complex: F: Presumed eradication0—0
Enterobacter Cloacae Complex: U: Persistence0—0
Enterobacter Cloacae Complex: U: Presumed persistence0—1
Enterobacter Cloacae Complex Indeterminate0—0
E.coli: F: Eradication4—0
E.coli: F: Presumed eradication2—0
E.coli: U: Persistence0—0
E.coli:U:Presumed persistence0—0
E.coli:Indeterminate0—0
Klebsiella Oxytoca:F: Eradication0—0
Klebsiella Oxytoca:F:Presumed eradication0—1
Klebsiella Oxytoca:U: Persistence0—0
Klebsiella Oxytoca:U:Presumed persistence0—0
Klebsiella Oxytoca: Indeterminate0—0
Klebsiella Pneumoniae:F: Eradication0—0
Klebsiella Pneumoniae:F:Presumed eradication0—1
Klebsiella Pneumoniae:U: Persistence0—0
Klebsiella Pneumoniae:U:Presumed persistence0—0
Klebsiella Pneumoniae: Indeterminate0—0
SecondaryNumber of Participants With Emergent Infections in Micro-ITT Analysis Population: Part B

Emergent infections included superinfection and new infection. Superinfection: a culture identified pathogen other than a baseline pathogen during the course of active treatment with study therapy requiring alternative antimicrobial therapy. New infection: a culture identified pathogen other than a baseline pathogen at any time after study treatment has finished requiring alternative antimicrobial therapy.

Time frame:
Day 1 up to maximum of Day 49
Reported as:
Count of participants · Participants
Number of Participants With Emergent Infections in Micro-ITT Analysis Population: Part B
ParticipantsPart B: Cohort 1Part B: Cohort 2Part B: Cohort 3
Superinfection000
New infection000
PrimaryNumber of Participants With Clinically Significant Laboratory Parameters Occurred in More Than 2 Participants: Part B

Number of participants in Part B with clinically significant abnormal laboratory parameters that occurred in more than 2 participants from Day 1 up to 35 days after the last dose of CAZ-AVI were reported in this outcome measure. Clinically significant labs were abnormal laboratory results which the investigator reported as being clinically significant. Only parameters with non-zero values are reported.

Time frame:
Day 1 up to maximum of Day 49
Reported as:
Count of participants · Participants
Number of Participants With Clinically Significant Laboratory Parameters Occurred in More Than 2 Participants: Part B
ParticipantsPart B: Cohort 1Part B: Cohort 2Part B: Cohort 3
Hematology: Hematocrit201
Hematology: Hemoglobin202
Hematology: Leukocytes021
Hematology: Neutrophils/Leukocytes120
Hematology: Platelets112
Clinical Chemistry:Alanine Aminotransferase111
Clinical Chemistry: Albumin122
Clinical Chemistry: Aspartate Aminotransferase121
Clinical Chemistry: Base Excess033
Clinical Chemistry: Bilirubin012
Clinical Chemistry: Blood Ph033
Clinical Chemistry: C Reactive Protein248
Clinical Chemistry: Direct Bilirubin013
Clinical Chemistry:Partial Pressure Carbon Dioxide012
Clinical Chemistry: Potassium021
Clinical Chemistry: Procalcitonin024
SecondaryNumber of Participants With Clinically Significant Laboratory Parameters Occurred in More Than 2 Participants: Part A

Number of participants in Part A with clinically significant abnormal laboratory parameters that occurred in more than 2 participants from Day 1 up to 35 days after the last dose of CAZ-AVI were reported in this outcome measure. Clinically significant labs were abnormal laboratory results which the investigator reported as being clinically significant.

Time frame:
Day 1 up to maximum of Day 35
Reported as:
Count of participants · Participants
Number of Participants With Clinically Significant Laboratory Parameters Occurred in More Than 2 Participants: Part A
ParticipantsPart A: Cohort 1Part A: Cohort 2Part A: Cohort 3
Hematology: Hematocrit112
Hematology: Hemoglobin112
Hematology: Leukocytes123
Blood chemistry000
Urinalysis000

Adverse events

Collected over Part A: Day 1 up to maximum of Day 35; Part B: Day 1 up to maximum of Day 49. Non-serious events are listed at a 4% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Part A: Cohort 10/9 (0%)2/9 (22.2%)1/9 (11.1%)
Part A: Cohort 20/8 (0%)0/8 (0%)0/8 (0%)
Part A: Cohort 30/8 (0%)1/8 (12.5%)1/8 (12.5%)
Part B: Cohort 10/8 (0%)1/8 (12.5%)3/8 (37.5%)
Part B: Cohort 20/5 (0%)2/5 (40%)1/5 (20%)
Part B: Cohort 31/8 (12.5%)2/8 (25%)4/8 (50%)
Most frequent serious events
Showing 10 of 14
Most frequent serious events
EventPart A: Cohort 1Part A: Cohort 2Part A: Cohort 3Part B: Cohort 1Part B: Cohort 2Part B: Cohort 3
NeutropeniaBlood and lymphatic system disorders0/90/80/80/81/50/8
Enterococcal sepsisInfections and infestations0/90/80/80/81/50/8
SepsisInfections and infestations0/90/80/80/81/51/8
OliguriaRenal and urinary disorders0/90/80/80/81/50/8
Acute respiratory failureRespiratory, thoracic and mediastinal disorders0/90/80/80/81/50/8
Cardiac failure acuteCardiac disorders0/90/80/80/80/51/8
Necrotising colitisGastrointestinal disorders1/90/80/80/80/51/8
COVID-19Infections and infestations0/90/81/80/80/50/8
Enterobacter sepsisInfections and infestations0/90/80/81/80/50/8
Septic shockInfections and infestations0/90/80/80/80/51/8
Most frequent other events
Most frequent other events
EventPart A: Cohort 1Part A: Cohort 2Part A: Cohort 3Part B: Cohort 1Part B: Cohort 2Part B: Cohort 3
AnaemiaBlood and lymphatic system disorders0/90/80/80/81/52/8
SepsisInfections and infestations0/90/80/80/81/52/8
Transaminases increasedInvestigations0/90/80/82/80/50/8
Decubitus ulcerSkin and subcutaneous tissue disorders0/90/80/80/80/52/8
VomitingGastrointestinal disorders1/90/80/81/80/51/8
PyrexiaGeneral disorders1/90/80/80/80/51/8
Oxygen saturation decreasedInvestigations0/90/81/80/80/51/8

Baseline characteristics

Safety analysis sets for Part A and Part B included participants who received any amount of the investigational drug (CAZ-AVI) in the respective part.

Age, Continuous
Age, Continuous(Days)Part A: Cohort 1Part A: Cohort 2Part A: Cohort 3Part B: Cohort 1Part B: Cohort 2Part B: Cohort 3Total
Mean59.0 ± 15.7319.3 ± 9.0014.6 ± 7.4651.1 ± 18.1615.80 ± 7.6317.8 ± 8.9931.13 ± 22.19
Sex: Female, Male
Sex: Female, Male(Participants)Part A: Cohort 1Part A: Cohort 2Part A: Cohort 3Part B: Cohort 1Part B: Cohort 2Part B: Cohort 3Total
Female54631625
Male44254221
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Part A: Cohort 1Part A: Cohort 2Part A: Cohort 3Part B: Cohort 1Part B: Cohort 2Part B: Cohort 3Total
Hispanic or Latino1010002
Not Hispanic or Latino77785842
Unknown or Not Reported1100002
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Part A: Cohort 1Part A: Cohort 2Part A: Cohort 3Part B: Cohort 1Part B: Cohort 2Part B: Cohort 3Total
American Indian or Alaska Native00000000
Asian2201005
Native Hawaiian or Other Pacific Islander0000000
Black or African American1102004
White65755836
More than one race0000000
Unknown or Not Reported0010001
08

Study locations

18 sites
  • Tufts Children's Hospital at Tufts Medical Center
    Boston, Massachusetts 02111, United States
  • Duke University Investigational Drug Services
    Durham, North Carolina 27710, United States
  • Duke University Medical Center
    Durham, North Carolina 27710, United States
  • University of Utah
    Salt Lake City, Utah 84108, United States
  • Primary Children's Hospital
    Salt Lake City, Utah 84113, United States
  • Tallinn Children's Hospital
    Tallinn, 13419, Estonia
  • Athens General Children's Hospital "Panagioti and Aglaias Kyriakou"
    Athens, Ampelokipi 11 527, Greece
  • "ATTIKON" University General Hospital
    Chaidari, Athens 124 62, Greece
  • "Hippokration" General Hospital of Thessaloniki
    Thessaloniki, 546 42, Greece
  • Debreceni Egyetem Klinikai Központ
    Debrecen, 4032, Hungary
  • Kanizsai Dorottya Korhaz
    Nagykanizsa, 8800, Hungary
  • Szabolcs-Szatmár-Bereg Megyei Kórházak és Oktatókórház, Jósa András Oktatókórház
    Nyíregyháza, 4400, Hungary
  • Kasturba Medical College and Hospital
    Manipal, Karnataka 576104, India
  • Ospedale Pediatrico Bambino Gesu
    Rome, RM 00165, Italy
  • Univerzitna nemocnica Martin
    Martin, 036 59, Slovakia
  • Hsinchu Mackay Memorial Hospital, Department of Pharmacy
    Hsinchu City, R.o.c 300, Taiwan
  • Hsinchu Mackay Memorial Hospital
    Hsinchu, 30071, Taiwan
  • National Taiwan University Hospital
    Taipei, 10041, Taiwan
09

References and documents

Study documents

  • Study protocol · Jun 27, 2019
  • Statistical analysis plan · Sep 18, 2019

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — 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.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Mar 26, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT04126031
Lead sponsor
Pfizer
Collaborators
Allergan
Responsible party
Sponsor
First posted
Oct 14, 2019
Start date
Jan 14, 2020
Primary completion
Dec 30, 2022
Completion
Dec 30, 2022
Results posted
Mar 26, 2024
Last update
Mar 26, 2024

Study contacts

Pfizer CT.gov Call Center
study director · Pfizer

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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This study is terminated, as verified in Feb 2024. You cannot join it, but the record below documents what was studied.

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