Health Condition 1: A498- Other bacterial infections of unspecified site
Conditions
Interventions
Intervention1: Aztreonam-avibactam with or without Metronidazole (MTZ) (required for cIAI): Study Intervention:
Part A: ATM-AVI Single Dose
Single intravenous infusion of aztreonam-avibactam over 3
Sponsors
Pfizer Limited
Eligibility
Inclusion criteria
Inclusion criteria: 1. Neonates and infants age birth to less than 9 months at Screening, divided into 4 age cohorts: Cohort 1: equal to or more than 3 months (13 weeks) to less than 9 months (39 weeks) Cohort 2: equal to or more than 28 days (4 weeks) to less than 3 months (13 weeks) Cohort 3: Full term (GA equal to or more than 37 weeks) birth to less than 28 days (4 weeks) Cohort 4: Preterm (GA equal to or more than 26 to less than 37 weeks) birth to less than 28 days (less than 4 weeks) Disease Characteristics: 2. Part A: Hospitalized, receiving IV antibiotics for treatment of suspected or confirmed bacterial infection, including but not limited to cIAI, cUTI, HAP/VAP, BSI, or sepsis 3. Part B: Hospitalized with suspected or confirmed gram-negative bacterial infection requiring IV antibiotics, including but not limited to cIAI, cUTI, HAP/VAP, BSI, or sepsis
Exclusion criteria
Exclusion criteria: Medical Conditions: 1. Any medical or laboratory abnormality that may increase the risk of study participation or, in the investigator’s judgment, make the participant inappropriate for the study. 2. Documented history of serious allergic reaction such as anaphylaxis, angioedema or bronchospasm to aztreonam or any ß-lactam antibiotic. 3. Part B only, participant with cystic fibrosis, suspected or confirmed CNS infection (eg, meningitis, shunt infection), or gram-negative species not expected to respond to ATM-AVI in equal to or less than 14 days. Prior/Concomitant Therapy: 4. Treatment with aztreonam or ceftazidime-avibactam within 12 hours of ATM-AVI administration. 5. Part B Only: Received more than 24 hours of systemic antibiotic treatment for gram-negative organisms during the 48 hours before screening unless documented treatment failure or lack of improvement in at least one objective sign or symptom of infection after equal to or less than 48 hours of antibiotic therapy. 6. Current use of any prohibited concomitant medication(s) or participants with cIAI or known anaerobic infection unwilling or unable to use MTZ. Prior/Concurrent Clinical Study Experience: 7. Previous administration with an investigational product (drug or vaccine) within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer). Participation in studies of other investigational products (drug or vaccine) at any time during their participation in this study. 8. Previous enrollment in this study. Diagnostic Assessments: 9. Renal impairment or known significant renal disease, as evidenced by a serum creatinine at screening above the 97.5th percentile for age, or urinary output less than 0.5 mL/kg/h for 6 consecutive hours or requirement for dialysis. 10. Hepatic dysfunction as indicated by screening AST or ALT equal to or more than 3.0 × ULN. Other Exclusion Criteria: 11. Participant is expected to be discharged less than 24 hours after the start of ATM-AVI infusion for Part A or less than 48 hours for Part B. 12. Investigator site staff directly involved in the conduct of the study and their family members, site staff otherwise supervised by the investigator, and sponsor and sponsor delegate employees directly involved in the conduct of the study and their family members.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum Predicted Plasma Concentration of Drug Area under the Concentration-Time Curve of Drug Plasma Elimination Half-Life Apparent Clearance Plasma concentrations of Drug by nominal sampling time Proportion of Participants reporting Adverse Events, Serious Adverse Events, AEs leading to discontinuation of study drug, AEs resulting in death,liver injury and acute kidney injuryTimepoint: Baseline up to Day 50 | — |
Secondary
| Measure | Time frame |
|---|---|
| Part B: Proportion of participants with each clinical outcome & with a favorable clinical outcome at end of IV study treatment (EOIV)Timepoint: Up to 15 days after start of IV study treatment;Part B: Proportion of participants with each clinical outcome & with a favorable clinical outcome at end of treatment (EOT)Timepoint: Within 48 hours after last dose of oral switch treatment;Part B: Proportion of participants with each clinical outcome & with a favorable clinical outcome at test of cure (TOC)Timepoint: 7-14 days after the last study treatment;Part B: Proportion of participants with a favorable microbiological response at TOCTimepoint: 7-14 days after the last study treatment;Part B: Counts & proportions of pathogens with each per-pathogen microbiological response at EOIV/EOTTimepoint: Up to 15 days after start of IV study treatment;Part B: Counts & proportions of pathogens with each per-pathogen microbiological response at TOCTimepoint: 7-14 days after the last study treatment;Part B: Counts & proportions of participants with emergent infections (new infections or superinfections) during the studyTimepoint: Through study completion, up to Day 50 | — |
Countries
Bulgaria, Czech Republic, Greece, Hungary, India, Israel, Italy, Slovakia, Spain, Taiwan, United States of America
Contacts
Public ContactDr Seema Pai
Pfizer Limited
Outcome results
None listed