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.
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 48
- 试验地点
- 5
- 主要终点
- Maximum Predicted Plasma Concentration of Drug
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 盲法
- None
入排标准
- 年龄范围
- 0.00 Day(s) 至 9.00 Month(s)（—）
- 性别
- All
入选标准
- •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.
排除标准
- •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).
- •Participation in studies of other investigational products (drug or vaccine) at any time during their participation in this study.
- •Previous enrollment in this study.
- •Diagnostic Assessments:
- •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.
- •Hepatic dysfunction as indicated by screening AST or ALT equal to or more than 3.0 × ULN.
- •Other Exclusion Criteria:
- •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.
- •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.
结局指标
主要结局
Maximum Predicted Plasma Concentration of Drug
时间窗: Baseline up to Day 50
Area under the Concentration-Time Curve of Drug
时间窗: Baseline up to Day 50
Plasma Elimination Half-Life
时间窗: Baseline up to Day 50
Apparent Clearance
时间窗: Baseline up to Day 50
Plasma concentrations of Drug by nominal sampling time
时间窗: 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
时间窗: Baseline up to Day 50
次要结局
- 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)
研究者
Dr Seema Pai
Pfizer Limited