Gram-Negative Bacterial Infections
Conditions
Keywords
Complicated urinary tract infection (cUTI), Complicated intra-abdominal infection (cIAI), Hospital-acquired bacterial pneumonia (HABP), Ventilator-associated (VABP), Bloodstream infection (BSI)/sepsis
Brief summary
The primary purpose of this study is to understand the pharmacokinetics (PK) of single and multiple doses of cefiderocol in children from birth to less than 3 months of age with suspected or confirmed aerobic Gram-negative bacterial infections.
Interventions
DRUGCefiderocol
Administered via intravenous (IV) infusion
DRUGStandard of Care
Antibiotics selected by the investigator based on the participant's symptoms, in accordance with local standards
Sponsors
Shionogi
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 3 Months
Healthy volunteers
No
Inclusion criteria
Eligibility Criteria: Key Inclusion Criteria: 1. Written informed consent has been provided by parent(s) or legally authorized representative(s) in accordance with local regulatory requirements 2. Hospitalized infants from birth to \< 3 months (\< 90 days) of age at the time written informed consent is provided. Enrollment of premature infants will not be restricted, but they must have a GA ≥ 26 weeks, PNA of 0 to 3 months, and weight of at least 1 kilogram (kg) 3. Require systemic IV antibiotic treatment for suspected or confirmed aerobic Gram-negative infections including, but not limited to, complicated urinary tract infection, complicated intra-abdominal infection, hospital-acquired/ ventilator-associated bacterial pneumonia, and BSI/sepsis 4. For the multiple-dose phase, within 72 hours of the start of potentially effective treatment with SOC antibiotics for the suspected or confirmed primary aerobic Gram-negative infection Key
Exclusion criteria
1. Documented history of any moderate or severe hypersensitivity or allergic reaction to any β-lactam antibiotic 2. Life expectancy of \< 72 hours after enrollment 3. Urine output \< 1.0 milliliter (mL)/kg/hour within the 24 hours prior to study drug administration on Day 1 4. Serum creatinine value greater than the maximum for GA and PNA shown below within the 24 hours prior to study drug administration on Day 1 5. Neonatal acute kidney injury (AKI), defined as a serum creatinine level greater than 1.5 milligrams per decilieter (mg/dL) (133 micromoles\[μmol\]/liter \[L\]) or an increase of 0.3 mg/dL (17 to 27 μmol/L) per day from a previous lower value 6. Acute kidney injury based on an increase in serum creatinine ≥ 0.3 mg/dL within 48 hours from an established baseline value 7. Any condition or circumstance that, in the opinion of the investigator, would compromise the safety of the participant or the quality of the study data 8. Receiving renal replacement therapy 9. Received any other investigational medicinal product within 30 days of study drug administration 10. Receiving treatment with a vasopressor at Screening 11. Has a confirmed or strongly suspected infection at Screening with a pathogen known to be resistant to cefiderocol or only a Gram-positive pathogen or viral, fungal, or parasitic pathogen as the sole cause of infection 12. Anticipated need for antibacterial therapy longer than 14 days (example , osteomyelitis or endocarditis); this applies to both study treatment with cefiderocol, as well as adjunctive IV antibacterial treatment for suspected coinfection with Gram-positive organisms or multidrug resistant Gram-negative organisms 13. Suspected or confirmed central nervous system (CNS) infection, including suspected CNS infection who do not have a lumbar puncture (LP) but who are treated for potential CNS infection, evidence suggestive of CNS infection based on LP results (polymorphonuclear pleocytosis, hypoglycorrhachia, and increased protein concentration), regardless of culture results, LP with organisms on Gram stain or culture-positive cerebrospinal fluid Note: Other protocol-defined Inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum Observed Plasma Concentration (Cmax) After a Single Dose of Cefiderocol | Up to 8 hours postdose |
| Cmax After a Minimum of 4 Doses of Cefiderocol | Up to 8 hours postdose |
| Area Under the Concentration-Time Curve Extrapolated From Time 0 to Infinity (AUC0-inf) After Single Dose of Cefiderocol | Up to 8 hours postdose |
| Area Under the Concentration-Time Curve Over the Dosing Interval (AUC0-†) After a Minimum of 4 Doses of Cefiderocol | Up to 3 hours |
| Terminal Elimination Half-Life (t1/2) After a Single Dose of Cefiderocol | Up to 8 hours postdose |
| Terminal Elimination Half-Life (t1/2) After a Minimum of 4 Doses of Cefiderocol | Up to 8 hours postdose |
Secondary
| Measure | Time frame |
|---|---|
| Number of Participants With Adverse Events (AEs) | Up to 28 days |
Countries
South Africa, Taiwan, United States
Contacts
STUDY_DIRECTORMedical Director
Shionogi
Outcome results
None listed