Clinical Trials List
Protocol NumberC3591025
NCT Number(ClinicalTrials.gov Identfier)NCT04040621
2019-08-22 - 2021-08-25
Phase I
Recruiting7
ICD-10J18.8
Other pneumonia, unspecified organism
ICD-10J18.9
Pneumonia, unspecified organism
ICD-9486
Pneumonia, organism unspecified
A PHASE 1, OPEN-LABEL, SINGLE-DOSE STUDY TO ASSESS THE PHARMACOKINETICS, SAFETY AND TOLERABILITY OF CEFTAZIDIME-AVIBACTAM (CAZ-AVI) IN CHILDREN FROM 3 MONTHS TO LESS THAN 18 YEARS OF AGE WHO ARE HOSPITALIZED AND RECEIVING SYSTEMIC ANTIBIOTIC THERAPY FOR SUSPECTED OR CONFIRMED NOSOCOMIAL PNEUMONIA, INCLUDING VENTILATOR-ASSOCIATED PNEUMONIA
-
Trial Applicant
Syneos Health
-
Sponsor
Pfizer, Inc.
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Liang-Ti Huang Division of Pediatrics
- Jinn-Li Wang Division of Pediatrics
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 黃競瑩 Division of Pediatrics
- Nan-Chang Chiu Division of Pediatrics
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 鄭名芳 Division of Pediatrics
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Chun-yi Lu Division of Pediatrics
- 邢子芸 Division of Pediatrics
- 陳立倫 Division of Pediatrics
- Luan-Yin Chang Division of Pediatrics
- 林筱琪 Division of Pediatrics
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Hospitalized Children With Suspected or Confirmed Nosocomial Pneumonia
Objectives
Primary Objective:
To characterize the pharmacokinetics (PK) of a single intravenous dose of CAZ-AVI in pediatric subjects aged 3 months to less than 18 years who are receiving systemic antibiotic therapy for suspected or confirmed nosocomial pneumonia, including
ventilator-associated pneumonia.
Secondary Objective(s):
To evaluate the safety and tolerability of a single intravenous dose of CAZ-AVI in pediatric subjects aged 3 months to less than 18 years with nosocomial pneumonia, including ventilator-associated pneumonia.
Tertiary/Exploratory Objective(s):
To determine CAZ-AVI concentrations in bronchial epithelial lining fluid (ELF) by bronchoalveolar lavage (BAL) from subjects undergoing bronchoscopy for their clinical management if bronchoscopy is performed within the PK sampling interval after CAZ-AVI infusion.
Test Drug
ceftazidime-avibactam
Active Ingredient
ceftazidime/avibactam
Dosage Form
injection
Dosage
2/0.5
Endpoints
Primary Endpoint:
CAZ and AVI plasma concentrations by nominal time.
CAZ and AVI PK parameters calculated by non-compartmental analysis (Cohorts 1 and 2 only).
Secondary Endpoint(s):
Safety and tolerability endpoints include adverse events (AEs), serious adverse events (SAEs), deaths, discontinuations due to AEs and laboratory abnormalities.
Tertiary/Exploratory Endpoint(s):
CAZ and AVI ELF: plasma concentration ratios
CAZ and AVI plasma concentrations by nominal time.
CAZ and AVI PK parameters calculated by non-compartmental analysis (Cohorts 1 and 2 only).
Secondary Endpoint(s):
Safety and tolerability endpoints include adverse events (AEs), serious adverse events (SAEs), deaths, discontinuations due to AEs and laboratory abnormalities.
Tertiary/Exploratory Endpoint(s):
CAZ and AVI ELF: plasma concentration ratios
Inclution Criteria
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. As appropriate per local requirements
informed assent of subjects must also be documented.
2. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and
other study procedures.
3. Male or female children age ≥3 months to <18 years at Screening:
a. Cohort 1: age 12 years to <18 years;
b. Cohort 2: age 6 years to <12 years;
c. Cohort 3: age 2 years to <6 years;
d. Cohort 4: age 3 months to <2 years (must be born ≥37 weeks gestational age).
4. Hospitalized, receiving systemic antibiotic therapy for the treatment of a suspected or
confirmed HAP, including VAP, meeting the following criteria, and expected to
require hospitalization until after the follow-up evaluations are completed on Day 3
(48 hours after the end of infusion):
a. Onset of symptoms ≥48 hours after admission or <7 days after discharge from an
inpatient acute or chronic care facility;
b. Evidence of new or worsening infiltrate as demonstrated on chest X-ray or other
imaging modality that has been performed as part of the subject’s regular medical
care;
c. At least 1 of the following systemic signs prior to the initiation of treatment for
Nosocomial Pneumonia:
i. Fever (temperature >38°C) or hypothermia (rectal/core temperature
<35°C);
ii. White blood cell (WBC) count >10,000 cells/mm
3
, or WBC count
<4,500 cells/mm3
, or >15% band forms.
d. At least 2 of the following respiratory signs or symptoms:
i. A new onset of cough (or worsening of cough);
ii. Production of purulent sputum or endotracheal secretions;
iii. Auscultatory findings consistent with pneumonia/pulmonary consolidation
(eg, rales, rhonchi, bronchial breath sounds, dullness to percussion,
egophony);
iv. Dyspnea, tachypnea or hypoxemia (O2 saturation <90% or PaO2
<60 mmHg while breathing room air);
v. A need for mechanical ventilation or, for already ventilated subjects, acute
changes made in the ventilator support system to enhance oxygenation, as
determined by, for example arterial blood gas or worsening PaO2/FiO2.
5. Likely to survive the current illness or hospitalization.
6. Sufficient IV access (peripheral or central) to receive study drug and dedicated access
for PK sampling.
the subject’s parent(s), legal guardian, or legally acceptable representative has been
informed of all pertinent aspects of the study. As appropriate per local requirements
informed assent of subjects must also be documented.
2. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and
other study procedures.
3. Male or female children age ≥3 months to <18 years at Screening:
a. Cohort 1: age 12 years to <18 years;
b. Cohort 2: age 6 years to <12 years;
c. Cohort 3: age 2 years to <6 years;
d. Cohort 4: age 3 months to <2 years (must be born ≥37 weeks gestational age).
4. Hospitalized, receiving systemic antibiotic therapy for the treatment of a suspected or
confirmed HAP, including VAP, meeting the following criteria, and expected to
require hospitalization until after the follow-up evaluations are completed on Day 3
(48 hours after the end of infusion):
a. Onset of symptoms ≥48 hours after admission or <7 days after discharge from an
inpatient acute or chronic care facility;
b. Evidence of new or worsening infiltrate as demonstrated on chest X-ray or other
imaging modality that has been performed as part of the subject’s regular medical
care;
c. At least 1 of the following systemic signs prior to the initiation of treatment for
Nosocomial Pneumonia:
i. Fever (temperature >38°C) or hypothermia (rectal/core temperature
<35°C);
ii. White blood cell (WBC) count >10,000 cells/mm
3
, or WBC count
<4,500 cells/mm3
, or >15% band forms.
d. At least 2 of the following respiratory signs or symptoms:
i. A new onset of cough (or worsening of cough);
ii. Production of purulent sputum or endotracheal secretions;
iii. Auscultatory findings consistent with pneumonia/pulmonary consolidation
(eg, rales, rhonchi, bronchial breath sounds, dullness to percussion,
egophony);
iv. Dyspnea, tachypnea or hypoxemia (O2 saturation <90% or PaO2
<60 mmHg while breathing room air);
v. A need for mechanical ventilation or, for already ventilated subjects, acute
changes made in the ventilator support system to enhance oxygenation, as
determined by, for example arterial blood gas or worsening PaO2/FiO2.
5. Likely to survive the current illness or hospitalization.
6. Sufficient IV access (peripheral or central) to receive study drug and dedicated access
for PK sampling.
Exclusion Criteria
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 other studies involving investigational drug(s) within 30 days prior to
study entry and/or during study participation.
3. Other acute or chronic medical or psychiatric condition including recent (within the
past year) or active suicidal ideation or behavior 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.
4. Past or current history of epilepsy or seizure disorder (excluding childhood febrile
seizures.
5. Severe renal impairment defined as creatinine clearance (CrCL) ≤30 mL/min/1.73 m2
calculated using the child’s measured height (length) and serum creatinine with the
Bedside Schwartz equation (Schwartz, Munoz, et al., 2009)
6. Documented history of any hypersensitivity or allergic reaction to any β-lactam
antibiotic.
7. Pregnant female subjects; breastfeeding female subjects; fertile male subjects and
female subjects of childbearing potential who are sexually active and unwilling or
unable to use a highly effective method of contraception as outlined in this protocol
for the duration of the study and for at least 28 days after the last dose of CAZ-AVI.
8. Acute hepatitis in the prior 6 months, a prior history of cirrhosis, acute hepatic failure,
or acute decompensation of chronic hepatic failure; and/or any of the following blood
test results, for any individual, when assessed for eligibility:
a. Bilirubin >3 × upper limit of normal (ULN), unless isolated hyperbilirubinemia is
directly related to the acute infection or due to known Gilbert’s disease;
b. ALT or AST >3 × ULN values used by the laboratory performing the test.
Subjects with values >3 × ULN and <5 × ULN are eligible if this value is acute
and directly related to the infectious process being treated. This must be
documented;
c. ALP >3 × ULN. Subjects with values >3 × ULN and <5 × ULN are eligible if this
value is acute and directly related to the infectious process being treated. This
must be documented.
9. Any condition (eg, septic shock, burns, cystic fibrosis, acute hemodynamic
instability, including those conditions not responding to pressor support) that would
make the patient, in the opinion of the Investigator, unsuitable for the study (eg,
would place a patient at risk; compromise the quality of the data; or interfere with the
absorption, distribution, metabolism, or excretion of CAZ-AVI).
10. Receipt of a blood or blood component or scheduled for transfusion within the PK
sampling period (eg, red blood cells, fresh frozen plasma, platelets) transfusion during
the 24-hour period before enrollment.
11. Body mass index (BMI) below the 5th percentile or above the 95th percentile for
height, age, and weight except for children <2 years of age as BMI is not considered a
screening tool for healthy weight in children under 2 years of age.
12. Treatment with ceftazidime within 12 hours of CAZ-AVI administration or treatment
with ceftazidime within 24 hours of CAZ-AVI administration in subjects with renal
impairment (CrCL ≤50 mL/min/1.73 m2
).
13. Treatment with potent inhibitors of OAT1 and/or OAT3 (eg, probenecid,
p-aminohippuric acid (PAH), or teriflunomide).
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 other studies involving investigational drug(s) within 30 days prior to
study entry and/or during study participation.
3. Other acute or chronic medical or psychiatric condition including recent (within the
past year) or active suicidal ideation or behavior 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.
4. Past or current history of epilepsy or seizure disorder (excluding childhood febrile
seizures.
5. Severe renal impairment defined as creatinine clearance (CrCL) ≤30 mL/min/1.73 m2
calculated using the child’s measured height (length) and serum creatinine with the
Bedside Schwartz equation (Schwartz, Munoz, et al., 2009)
6. Documented history of any hypersensitivity or allergic reaction to any β-lactam
antibiotic.
7. Pregnant female subjects; breastfeeding female subjects; fertile male subjects and
female subjects of childbearing potential who are sexually active and unwilling or
unable to use a highly effective method of contraception as outlined in this protocol
for the duration of the study and for at least 28 days after the last dose of CAZ-AVI.
8. Acute hepatitis in the prior 6 months, a prior history of cirrhosis, acute hepatic failure,
or acute decompensation of chronic hepatic failure; and/or any of the following blood
test results, for any individual, when assessed for eligibility:
a. Bilirubin >3 × upper limit of normal (ULN), unless isolated hyperbilirubinemia is
directly related to the acute infection or due to known Gilbert’s disease;
b. ALT or AST >3 × ULN values used by the laboratory performing the test.
Subjects with values >3 × ULN and <5 × ULN are eligible if this value is acute
and directly related to the infectious process being treated. This must be
documented;
c. ALP >3 × ULN. Subjects with values >3 × ULN and <5 × ULN are eligible if this
value is acute and directly related to the infectious process being treated. This
must be documented.
9. Any condition (eg, septic shock, burns, cystic fibrosis, acute hemodynamic
instability, including those conditions not responding to pressor support) that would
make the patient, in the opinion of the Investigator, unsuitable for the study (eg,
would place a patient at risk; compromise the quality of the data; or interfere with the
absorption, distribution, metabolism, or excretion of CAZ-AVI).
10. Receipt of a blood or blood component or scheduled for transfusion within the PK
sampling period (eg, red blood cells, fresh frozen plasma, platelets) transfusion during
the 24-hour period before enrollment.
11. Body mass index (BMI) below the 5th percentile or above the 95th percentile for
height, age, and weight except for children <2 years of age as BMI is not considered a
screening tool for healthy weight in children under 2 years of age.
12. Treatment with ceftazidime within 12 hours of CAZ-AVI administration or treatment
with ceftazidime within 24 hours of CAZ-AVI administration in subjects with renal
impairment (CrCL ≤50 mL/min/1.73 m2
).
13. Treatment with potent inhibitors of OAT1 and/or OAT3 (eg, probenecid,
p-aminohippuric acid (PAH), or teriflunomide).
The Estimated Number of Participants
-
Taiwan
12 participants
-
Global
32 participants
