Gram-negative Bacterial InfectionPhase 2NOORNCT04126031
Evaluation of Pharmacokinetics, Safety, and Tolerability of Ceftazidime-avibactam in Neonates and Infants.
A Phase 2 study testing Part A: Single Dose Ceftazidime-Avibactam, Cohorts 1-3 and Part B: Multiple-dose Ceftazidime-Avibactam, Cohorts 1-3 in people with Gram-negative Bacterial Infection, run by Pfizer at 18 sites in 8 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 0 to 88 days
- Conditions the study is for
- Gram-negative Bacterial Infection
- What is being tested?
- Part A: Single Dose Ceftazidime-Avibactam, Cohorts 1-3 and Part B: Multiple-dose Ceftazidime-Avibactam, Cohorts 1-3
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 18 sitesin 8 countries
- Study dates
- 14 Jan 2020to 30 Dec 2022
- Phase
- Phase 2
- 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 0 to 88 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
- Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
- 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.
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- Corrected age = Subtract the number of weeks born before 40 weeks of gestation from the chronological age.
- 1. Hospitalized and receiving intravenous antibacterial therapy for the treatment of a suspected or confirmed bacterial infection.
- Hospitalized with suspected or confirmed aerobic Gram-negative bacterial infection requiring intravenous antibacterial therapy.
- Subjects must meet at least 1 clinical and 1 laboratory criterion or meet at least 2 of the clinical criteria:
- Clinical Criteria:
- Hypothermia (<36ºC) OR fever (>38.5ºC);
- Bradycardia OR tachycardia OR rhythm instability;
- Urine output 0.5 to 1 mL/kg/h OR hypotension OR mottled skin OR impaired peripheral perfusion;
- Petechial rash OR sclerema neonatorum;
- New onset or worsening of apnea episodes OR tachypnea episodes OR increased oxygen requirements OR requirement for ventilation support;
- Feeding intolerance OR poor suckling OR abdominal distension;
- Irritability;
- Lethargy;
- Hypotonia.
- Laboratory Criteria:
- White blood cell count ≤ 4.0 × 10^9/L OR ≥ 20.0 × 10^9/L;
- Immature to total neutrophil ratio >0.2;
- Platelet count ≤ 100 × 10^9/L;
- C reactive protein (CRP) >15 mg/L OR procalcitonin ≥ 2 ng/mL;
- Hyperglycemia OR Hypoglycemia;
- Metabolic acidosis.
Who cannot join
- 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.
- 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).
- 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.
- 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.
- Documented history of any hypersensitivity or allergic reaction to any beta-lactam antibiotic.
- Refractory septic shock within 24 hours before screening that does not resolve after 60 minutes of vasopressor therapy.
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- 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.
- Evidence of progressively fatal underlying disease, or life expectancy of ≤ 60 days.
- Documented history of seizure.
- Active acute viral hepatitis or acute hepatic failure.
- Known Clostridium difficile associated diarrhea.
- Requiring or currently taking antiretroviral therapy for human immunodeficiency virus (HIV) or known HIV positive mother.
- 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.
- Treatment with ceftazidime within 12 hours of CAZ-AVI administration.
- Subject received a blood or a blood component transfusion within 24 hours of the start of CAZ AVI infusion.
- Subject is expected to be discharged less than 24 hours after the start of CAZ AVI infusion.
- 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.
- Confirmed or suspected central nervous system (CNS) infection (eg, meningitis, brain abscess, subdural abscess).
- 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.
- 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.
- Intravenous treatment with chloramphenicol within 24 hours of administration of study doses of CAZ-AVI.
- Subject is expected to be discharged less than 48 hours after the start of CAZ-AVI infusion.
Trial locations and contacts
18 sites in 8 countries.
18 sites in 8 countries
United States5 sites
Tufts Children's Hospital at Tufts Medical Center
Boston, Massachusetts, 02111
Duke University Investigational Drug Services
Durham, North Carolina, 27710
Duke University Medical Center
Durham, North Carolina, 27710
University of Utah
Salt Lake City, Utah, 84108
Primary Children's Hospital
Salt Lake City, Utah, 84113
Greece3 sites
Athens General Children's Hospital "Panagioti and Aglaias Kyriakou"
Athens, Ampelokipi, 11 527
"ATTIKON" University General Hospital
Chaïdári, Athens, 124 62
"Hippokration" General Hospital of Thessaloniki
Thessaloniki, 546 42
Hungary3 sites
Debreceni Egyetem Klinikai Központ
Debrecen, 4032
Kanizsai Dorottya Korhaz
Nagykanizsa, 8800
Szabolcs-Szatmár-Bereg Megyei Kórházak és Oktatókórház, Jósa András Oktatókórház
Nyíregyháza, 4400
Taiwan3 sites
Hsinchu Mackay Memorial Hospital, Department of Pharmacy
Hsinchu, R.o.c, 300
Hsinchu Mackay Memorial Hospital
Hsinchu, 30071
National Taiwan University Hospital
Taipei, 10041
About this study
Official title: A PHASE 2A, 2-PART, OPEN-LABEL, NON-RANDOMIZED, MULTICENTER, SINGLE AND MULTIPLE DOSE TRIAL TO EVALUATE PHARMACOKINETICS, SAFETY AND TOLERABILITY OF CEFTAZIDIME AND AVIBACTAM IN NEONATES AND INFANTS FROM BIRTH TO LESS THAN 3 MONTHS OF AGE WITH SUSPECTED OR CONFIRMED INFECTIONS DUE TO GRAM-NEGATIVE PATHOGENS REQUIRING INTRAVENOUS ANTIBIOTIC TREATMENT
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.
- Conditions
- Gram-negative Bacterial Infection
- Being tested
- Part A: Single Dose Ceftazidime-Avibactam, Cohorts 1-3, Part B: Multiple-dose Ceftazidime-Avibactam, Cohorts 1-3
- Keywords
- Gram-negative, ceftazidime-avibactam, neonate, infant
- Medical subject headings
- Gram-Negative Bacterial Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Part A: Single Dose Ceftazidime-Avibactam, Cohorts 1-3Drug
Single intravenous infusion of ceftazidime-avibactam over 2 hours
Part B: Multiple-dose Ceftazidime-Avibactam, Cohorts 1-3Drug
Multiple intravenous infusions of ceftazidime-avibactam over 2 hours, repeated every 8 hours up to 14 days
| Study group | Role | What they receive |
|---|---|---|
| Part A, Cohorts 1-3 | Experimental | Single dose pharmacokinetics. This arm will include three age cohorts. Receives: Drug: Part A: Single Dose Ceftazidime-Avibactam, Cohorts 1-3 |
| Part B, Cohorts 1-3 | Experimental | Multi-dose pharmacokinetics. This arm will include three age cohorts. Receives: Drug: Part B: Multiple-dose Ceftazidime-Avibactam, Cohorts 1-3 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma Concentrations of Ceftazidime and Avibactam 2 Hours Post-dose: Part A
Measured: 2 hours post dose on Day 1
Plasma Concentrations of Ceftazidime and Avibactam 2 Hours and 30 Minutes Post-dose: Part A
Measured: 2 hours and 30 minutes post dose on Day 1
Plasma Concentrations of Ceftazidime and Avibactam of 7 Hours Post-dose: Part A
Measured: 7 hours post dose on Day 1
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.
Measured: Day 1 up to maximum of Day 49
Number of Participants Who Died: Part B
Measured: Day 1 up to maximum of Day 49
Number of Participants Who Discontinued Treatment and Study Due to AEs: Part B
Measured: Day 1 up to maximum of Day 49
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.
Measured: Day 1 up to maximum of Day 49
Secondary outcomes (10)
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.
Measured: Day 1 up to maximum of Day 35
Number of Participants Who Died: Part A
Measured: Day 1 up to maximum of Day 35
Number of Participants Who Discontinued Treatment and Study Due to AEs: Part A
Measured: Day 1 up to maximum of Day 35
Plasma Concentrations of Ceftazidime and Avibactam 2 Hours, 2 Hours and 30 Minutes, 7 Hours Post Doses on Day 1: Part B
Measured: 2 hours, 2 hours 30 mins, and 7 hours post dose on Day 1
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).
Measured: EOIV, EOT, TOC, LFU
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).
Measured: EOIV, EOT, TOC, LFU
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).
Measured: EOIV, EOT, TOC, LFU
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.
Measured: Up to 34 days
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.
Measured: Day 1 up to maximum of Day 49
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.
Measured: Day 1 up to maximum of Day 35
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Oct 2019
- Study start14 Jan 2020
- Primary completion30 Dec 2022
- Study completion30 Dec 2022
Why it stopped: 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.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Gram-negative Bacterial InfectionStudies of the same condition, open and under way.
- More trials run by PfizerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Model description
- Non-randomized, 2-part with three age cohorts in each part
- Masking
- None (open label)
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Allergan
- Responsible party
- Sponsor
- Investigators
- Pfizer CT.gov Call Center, Study director, Pfizer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04126031
- Sponsor's protocol ID
- C3591024
- Other IDs
- 2018-002800-16, NOOR, 2018
- Acronym
- NOOR
- Status last verified
- Feb 2024
- First submitted
- 27 Sep 2019
- Last updated
- 26 Mar 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- 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.
Publications
Bradley J, Roilides E, Tawadrous M, Yan JL, Soto E, Stone GG, Kamat S, Irani P, England R. Pharmacokinetics and Safety of Ceftazidime-Avibactam in Neonates and Young Infants: A Phase 2a, Multicenter Prospective Trial. J Pediatric Infect Dis Soc. 2025 May 13;14(5):piaf028. doi: 10.1093/jpids/piaf028.
PubMed 40251980
Study at a glance
From the registry record, last updated by the sponsor on 26 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A PHASE 2A, 2-PART, OPEN-LABEL, NON-RANDOMIZED, MULTICENTER, SINGLE AND MULTIPLE DOSE TRIAL TO EVALUATE PHARMACOKINETICS, SAFETY AND TOLERABILITY OF CEFTAZIDIME AND AVIBACTAM IN NEONATES AND INFANTS FROM BIRTH TO LESS THAN 3 MONTHS OF AGE WITH SUSPECTED OR CONFIRMED INFECTIONS DUE TO GRAM-NEGATIVE PATHOGENS REQUIRING INTRAVENOUS ANTIBIOTIC TREATMENT
- ClinicalTrials.gov ID
- NCT04126031
- Acronym / sponsor ID
- NOOR / C3591024
- Conditions
- Gram-negative Bacterial Infection
- Keywords
- Gram-negative, ceftazidime-avibactam, neonate, infant
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: 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.
- Enrolment
- 48 participants (actual)
- Lead sponsor
- PfizerIndustry (pharma, biotech, devices)
- Collaborators
- Allergan
- Study start
- 14 Jan 2020 (actual)
- Primary completion
- 30 Dec 2022 (actual)
- Study completion
- 30 Dec 2022 (actual)
- First posted
- 14 Oct 2019 (actual)
- Results
- Posted 26 Mar 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Non-randomized, 2-part with three age cohorts in each part
| Arm | Type | Receives |
|---|---|---|
| Part A, Cohorts 1-3 | Experimental | Drug: Part A: Single Dose Ceftazidime-Avibactam, Cohorts 1-3Single dose pharmacokinetics. This arm will include three age cohorts. |
| Part B, Cohorts 1-3 | Experimental | Drug: Part B: Multiple-dose Ceftazidime-Avibactam, Cohorts 1-3Multi-dose pharmacokinetics. This arm will include three age cohorts. |
Who may qualify
- Ages
- 0 to 88 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (27 listed)
- 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.
- Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
- 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.
Key exclusion criteria (22 listed)
- 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.
- 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).
- 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.
- 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.
- Documented history of any hypersensitivity or allergic reaction to any beta-lactam antibiotic.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Part A: Single Dose Ceftazidime-Avibactam, Cohorts 1-3Single intravenous infusion of ceftazidime-avibactam over 2 hours | Drug | Part A, Cohorts 1-3 |
| Part B: Multiple-dose Ceftazidime-Avibactam, Cohorts 1-3Multiple intravenous infusions of ceftazidime-avibactam over 2 hours, repeated every 8 hours up to 14 days | Drug | Part B, Cohorts 1-3 |
Primary outcome
Plasma Concentrations of Ceftazidime and Avibactam 2 Hours Post-dose: Part A
Time frame: 2 hours post dose on Day 1
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
Plasma Concentrations of Ceftazidime and Avibactam of 7 Hours Post-dose: Part A
Time frame: 7 hours post dose on Day 1
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs): Part B
Time frame: Day 1 up to maximum of Day 49
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.
Number of Participants Who Died: Part B
Time frame: Day 1 up to maximum of Day 49
Number of Participants Who Discontinued Treatment and Study Due to AEs: Part B
Time frame: Day 1 up to maximum of Day 49
Number of Participants With Clinically Significant Laboratory Parameters Occurred in More Than 2 Participants: Part B
Time frame: Day 1 up to maximum of Day 49
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.
10 secondary outcomes
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs): Part A
Time frame: Day 1 up to maximum of Day 35
Number of Participants Who Died: Part A
Time frame: Day 1 up to maximum of Day 35
Number of Participants Who Discontinued Treatment and Study Due to AEs: Part A
Time frame: Day 1 up to maximum of Day 35
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
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
Time frame: EOIV, EOT, TOC, LFU
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
Time frame: EOIV, EOT, TOC, LFU
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
Time frame: EOIV, EOT, TOC, LFU
Number of Participants According to Microbiological Response at TOC Visit in Micro-ITT Population: Part B
Time frame: Up to 34 days
Number of Participants With Emergent Infections in Micro-ITT Analysis Population: Part B
Time frame: Day 1 up to maximum of Day 49
Number of Participants With Clinically Significant Laboratory Parameters Occurred in More Than 2 Participants: Part A
Time frame: Day 1 up to maximum of Day 35
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Mar 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40251980Bradley J, Roilides E, Tawadrous M, Yan JL, Soto E, Stone GG, Kamat S, Irani P, England R. Pharmacokinetics and Safety of Ceftazidime-Avibactam in Neonates and Young Infants: A Phase 2a, Multicenter Prospective Trial. J Pediatric Infect Dis Soc. 2025 May 13;14(5):piaf028. doi: 10.1093/jpids/piaf028.
- To obtain contact information for a study center near you, click here.Link provided by the sponsor.
- Individual participant dataSharing planned: 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pfizer CT.gov Call Center study director
Pfizer
18 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Part A: Single Dose Ceftazidime-Avibactam, Cohorts 1-3 and Part B: Multiple-dose Ceftazidime-Avibactam, Cohorts 1-3 in people with Gram-negative Bacterial Infection, run by Pfizer at 18 sites in 8 countries.
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 27 inclusion and 22 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: stopped early, as of the sponsor's last update on 26 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites in United States, Greece, Hungary, Taiwan, Estonia and 3 more countries. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 26 Mar 2024). 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?
Plasma Concentrations of Ceftazidime and Avibactam 2 Hours Post-dose: Part A (time frame: 2 hours post dose on Day 1). The study lists 7 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 NCT04126031, 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 26 Mar 2024.