Study of ceftazidime and avibactam in neonates and infants from birth to less than 3 months of age who is having infection or can have infaction and require antibiotic treatment.
- Conditions
- Health Condition 1: B968- Other specified bacterial agents as the cause of diseases classified elsewhere
- Registration Number
- CTRI/2020/02/023439
- Lead Sponsor
- Pfizer Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Yet Recruiting
- Sex
- Not specified
- Target Recruitment
- 0
1. Male or female neonates and infants with age at Screening:
a. Cohort 1: Full term (or pre-term corrected age), age greater than 28 days to less than 3 months
b. Cohort 2: Full term, age birth to less than or equal to 28 days
c. Cohort 3: Pre-term, age birth to less than or equal to 28 days
2. Part A: Hospitalized and receiving intravenous antibacterial therapy for the treatment of a suspected or confirmed bacterial infection.
3. Part B: Hospitalized with suspected or confirmed aerobic Gram-negative bacterial infection requiring intravenous antibacterial therapy,
a. plus Must meet at least 1 clinical and 1 laboratory criterion OR
b. Meet at least 2 of the clinical criteria
Clinical Criteria:
a. Hypothermia (less than 36°C) OR fever (greater than 38.5°C);
b. Bradycardia OR tachycardia OR rhythm instability;
c. Urine output 0.5 to 1 mL/kg/h OR hypotension OR mottled skin OR impaired peripheral perfusion;
d. Petechial rash OR sclerema neonatorum;
e. New onset or worsening of apnea episodes OR tachypnea episodes OR increased oxygen requirements OR requirement for ventilation support;
f. Feeding intolerance OR poor suckling OR abdominal distension;
g. Irritability;
h. Lethargy;
i. Hypotonia.
Laboratory Criteria:
a. White blood cell count less than or equal to 4.0 Ã? 109/L OR greater than or equal to 20.0 Ã? 109/L;
b. Immature to total neutrophil ratio greater than 0.2;
c. Platelet count less than or equal to 100 Ã? 109/L;
d. C reactive protein (CRP) greater than 15 mg/L OR procalcitonin greater than or equal to 2 ng/mL;
e. Hyperglycemia OR Hypoglycemia;
f. 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 greater than or equal to 2 times the upper limit of normal (ULN) for age OR urine output less than 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 less than or equal to 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 CNS infection (meningitis, brain abscess, subdural abscess etc.)
3. Anticipated need for antibacterial therapy longer than 14 days (osteomyelitis, endocarditis etc.). This applies to both study treatment with CAZ AVI as well as adju
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Part A: Ceftazidime and avibactam plasma conc. by nominal sampling time using appropriate descriptive statistics, eg, no., mean, SD, minimum, median, maximum, geometric mean, and coefficient of variation <br/ ><br>Part B: Number of subjects with adverse events (AEs) and Serious Adverse Events (SAEs) <br/ ><br>Part B: Number of deaths reported for study subjects <br/ ><br>Part B: Number of subjects discontinued due to adverse events (AEs) <br/ ><br>Part B: Number of subjects with clinically significant abnormal laboratory resultsTimepoint: Part A: Day 1-2 <br/ ><br>Part B: Day 1 until Late Follow-up Visit (up to a maximum study duration of 49 days)
- Secondary Outcome Measures
Name Time Method Part A:AEs & SAEs; Deaths; Discontinuation due to AEs & No. of subj. with abnormal lab results; Part B: Drug plasma conc. by using statistics; Efficacy Assessments: All-cause mortality ; Clinical outcome, clinical imprmnt., clinical failure, or indeterminate at End-of-IV, EoT, Test-of-Cure & Late f-up Visits; Cure defined as clinical imprmnt. & no need for further antibacterial treatment, 7-14 days after EoT ; Microbiological eradication 7 to 14 days after EoT & Emergent infections.Timepoint: Part A: Day 1 until Late Follow-up Visit (up to a maximum study duration of 35 days). <br/ ><br>Part B: Day 2 until Late Follow-up Visit (up to a maximum study duration of 49 days) <br/ ><br>