Clinical Trials List
Protocol NumberC3591024
NCT Number(ClinicalTrials.gov Identfier)NCT04126031
2019-09-20 - 2022-12-31
Phase II
Recruiting7
ICD-10B96.89
Other specified bacterial agents as the cause of diseases classified elsewhere
ICD-9041.85
Other Gram-negative organisms infections of unspecified site
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
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Trial Applicant
Syneos Health
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Sponsor
Pfizer
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- 朱世明 Division of Pediatrics
- 傅仁煇 Division of Pediatrics
- 賴美吟 Division of Pediatrics
- 陳愛華 Division of Pediatrics
- Jen Fu Hsu Division of Pediatrics
- 許凱翔 Division of Pediatrics
- 夏紹軒 Division of Pediatrics
- 林瑞瑩 Division of Pediatrics
- 李建忠 Division of Pediatrics
- 吳怡萱 Division of Pediatrics
- 李恩沛 Division of Pediatrics
- 宋聿翔 Division of Pediatrics
- 江明洲 Division of Pediatrics
- 楊長佑 Division of Pediatrics
- 林建志 Division of Pediatrics
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
- 張弘洋 Division of Pediatrics
- Nan-Chang Chiu Division of Pediatrics
- 陳佳慧 Division of Pediatrics
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 許雅淇 Division of Pediatrics
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 李冠霖 Division of Pediatrics
- 陳立倫 Division of Pediatrics
- 白孟丘 無
- Chun-yi Lu Division of Pediatrics
- 楊德亮 Division of Pediatrics
- 邢子芸 Division of Pediatrics
- 吳季憲 Division of Pediatrics
- 李杰明 Division of Pediatrics
- 林筱琪 Division of Pediatrics
- 黃筱倫 無
- Luan-Yin Chang Division of Pediatrics
- 鄭芳渝 Division of Pediatrics
- 陳婉真 Division of Pediatrics
- 黃崧銘 Division of Pediatrics
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Gram-negative Bacterial Infection
Objectives
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.
Test Drug
ceftazidime-avibactam
Active Ingredient
ceftazidime-avibactam
Dosage Form
Injection
Dosage
ceftazidime 2 g, avibactam 0.5 g
Endpoints
Primary Outcome Measures :
Part A: Ceftazidime and avibactam plasma concentrations by nominal sampling time using appropriate descriptive statistics, eg, number, mean, standard deviation (SD), minimum, median, maximum, geometric mean, and coefficient of variation [ Time Frame: Part A: Day 1-2. ]
Characterize the pharmacokinetics (PK) of a single intravenous dose of ceftazidime-avibactam in hospitalized neonates and infants from birth to <3 months of age.
Part B: Number of subjects with adverse events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Part B: Day 1 until Late Follow-up Visit (up to a maximum study duration of 49 days). ]
Evaluate the safety and tolerability of ceftazidime-avibactam for the treatment of aerobic Gram-negative infection in neonates and infants from birth to <3 months.
Part B: Number of deaths reported for study subjects [ Time Frame: Part B: Day 1 until Late Follow-up Visit (up to a maximum study duration of 49 days). ]
Evaluate the safety and tolerability of ceftazidime-avibactam for the treatment of aerobic Gram-negative infection in neonates and infants from birth to <3 months.
Part B: Number of subjects discontinued due to adverse events (AEs) [ Time Frame: Part B: Day 1 until Late Follow-up Visit (up to a maximum study duration of 49 days). ]
Evaluate the safety and tolerability of ceftazidime-avibactam for the treatment of aerobic Gram-negative infection in neonates and infants from birth to <3 months.
Part B: Number of subjects with clinically significant abnormal laboratory results [ Time Frame: Part B: Day 1 until Late Follow-up Visit (up to a maximum study duration of 49 days). ]
Evaluate the safety and tolerability of ceftazidime-avibactam for the treatment of aerobic Gram-negative infection in neonates and infants from birth to <3 months.
Part A: Ceftazidime and avibactam plasma concentrations by nominal sampling time using appropriate descriptive statistics, eg, number, mean, standard deviation (SD), minimum, median, maximum, geometric mean, and coefficient of variation [ Time Frame: Part A: Day 1-2. ]
Characterize the pharmacokinetics (PK) of a single intravenous dose of ceftazidime-avibactam in hospitalized neonates and infants from birth to <3 months of age.
Part B: Number of subjects with adverse events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Part B: Day 1 until Late Follow-up Visit (up to a maximum study duration of 49 days). ]
Evaluate the safety and tolerability of ceftazidime-avibactam for the treatment of aerobic Gram-negative infection in neonates and infants from birth to <3 months.
Part B: Number of deaths reported for study subjects [ Time Frame: Part B: Day 1 until Late Follow-up Visit (up to a maximum study duration of 49 days). ]
Evaluate the safety and tolerability of ceftazidime-avibactam for the treatment of aerobic Gram-negative infection in neonates and infants from birth to <3 months.
Part B: Number of subjects discontinued due to adverse events (AEs) [ Time Frame: Part B: Day 1 until Late Follow-up Visit (up to a maximum study duration of 49 days). ]
Evaluate the safety and tolerability of ceftazidime-avibactam for the treatment of aerobic Gram-negative infection in neonates and infants from birth to <3 months.
Part B: Number of subjects with clinically significant abnormal laboratory results [ Time Frame: Part B: Day 1 until Late Follow-up Visit (up to a maximum study duration of 49 days). ]
Evaluate the safety and tolerability of ceftazidime-avibactam for the treatment of aerobic Gram-negative infection in neonates and infants from birth to <3 months.
Inclution Criteria
Inclusion Criteria (All Subjects):
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.
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:
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.
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.
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:
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.
Exclusion Criteria
Exclusion Criteria (All Subjects):
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.
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.
Exclusion Criteria for Part A Subjects Only:
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.
Exclusion Criteria for Part B Subjects Only:
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.
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.
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.
Exclusion Criteria for Part A Subjects Only:
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.
Exclusion Criteria for Part B Subjects Only:
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.
The Estimated Number of Participants
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Taiwan
8 participants
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Global
48 participants
