A phase 2a, 2-part, open-label, non-randomized, multicenter, single and multiple dose trial to evaluate Pharmacokinetics, Safety and Tolerability of Aztreonam and Avibactam plus or minus Metronidazole in neonates and infants from birth to less than 9 months of age with suspected or confirmed infections due to Gram-Negative pathogens requiring intravenous antibiotic treatment.
Overview
- Phase
- Phase 2
- Status
- Not yet recruiting
- Sponsor
- Pfizer Limited
- Enrollment
- 48
- Locations
- 5
- Primary Endpoint
- Maximum Predicted Plasma Concentration of Drug
Overview
Brief Summary
This is a 2-part Phase 2a, non-randomized, multicenter, open-label, single and multi-dose PK study to assess PK, safety, and tolerability of ATM-AVI in hospitalized neonates, including preterm neonates, and infants, aged birth to <9 months. Participants in Part A will be hospitalized and receiving intravenous antibiotic treatment for suspected or confirmed bacterial infections including but not limited to cIAI, cUTI, HAP/VAP, BSI, or sepsis. They will receive a single infusion of ATM-AVI to assess ATM-AVI PK, safety and tolerability, but not intended as treatment. Participants in Part B will be hospitalized with suspected or confirmed aerobic gram-negative bacterial infection requiring intravenous antibacterial therapy, including but not limited to cIAI, cUTI, HAP/VAP, BSI, or sepsis. Part B participants will receive multiple infusions of ATM-AVI in the hospital as treatment and to assess ATM-AVI PK, safety, tolerability, and efficacy. Participants with complicated intraabdominal infection (cIAI) will receive concomitant intravenous metronidazole because ATM-AVI does not treat anaerobes. The sponsor will attempt recruitment of an ethnically and racially diverse study population through selection of investigational sites. The study will use an external Data Monitoring Committee (DMC) for safety monitoring.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Masking
- None
Eligibility Criteria
- Ages
- 0.00 Day(s) to 9.00 Month(s) (—)
- Sex
- All
Inclusion Criteria
- •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:
- •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
- •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
- •Medical Conditions:
- •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.
- •Documented history of serious allergic reaction such as anaphylaxis, angioedema or bronchospasm to aztreonam or any β-lactam antibiotic.
- •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:
- •Treatment with aztreonam or ceftazidime-avibactam within 12 hours of ATM-AVI administration.
- •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.
- •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:
- •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).
Outcomes
Primary Outcomes
Maximum Predicted Plasma Concentration of Drug
Time Frame: Baseline up to Day 50
Area under the Concentration-Time Curve of Drug
Time Frame: Baseline up to Day 50
Plasma Elimination Half-Life
Time Frame: Baseline up to Day 50
Apparent Clearance
Time Frame: Baseline up to Day 50
Plasma concentrations of Drug by nominal sampling time
Time Frame: Baseline up to Day 50
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 injury
Time Frame: Baseline up to Day 50
Secondary Outcomes
- Part B: Proportion of participants with each clinical outcome & with a favorable clinical outcome at end of IV study treatment (EOIV)(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)(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)(7-14 days after the last study treatment)
- Part B: Proportion of participants with a favorable microbiological response at TOC(7-14 days after the last study treatment)
- Part B: Counts & proportions of pathogens with each per-pathogen microbiological response at EOIV/EOT(Up to 15 days after start of IV study treatment)
- Part B: Counts & proportions of pathogens with each per-pathogen microbiological response at TOC(7-14 days after the last study treatment)
- Part B: Counts & proportions of participants with emergent infections (new infections or superinfections) during the study(Through study completion, up to Day 50)
Investigators
Dr Seema Pai
Pfizer Limited