The primary objectives of this study are: * To assess the safety and tolerability of cefiderocol after single-dose administration in hospitalized paediatric participants 3 months to \< 18 years of age with suspected or confirmed aerobic Gram-negative bacterial infections * To assess the pharmacokinetics (PK) of cefiderocol after single-dose administration of cefiderocol in hospitalized paediatric participants 3 months to \< 18 years of age with suspected or confirmed aerobic Gram-negative bacterial infections * To assess the safety and tolerability of cefiderocol after multiple-dose administration in hospitalized paediatric participants 3 months to \< 12 years of age with suspected or confirmed aerobic Gram-negative bacterial infections * To assess the PK of cefiderocol after multiple-dose administration in hospitalized paediatric participants 3 months to \< 12 years of age with suspected or confirmed aerobic Gram-negative bacterial infections
This is a multicenter, single-arm, open-label, single- and multiple-dose study to assess the safety, tolerability, and PK of cefiderocol in hospitalized paediatric participants. The single-dose phase will include 4 separate cohorts of participants, grouped according to age range: * Cohort 1: 12 to \< 18 years * Cohort 2: 6 to \< 12 years * Cohort 3: 2 to \< 6 years * Cohort 4: 3 months to \< 2 years Cohorts 1, 2, and 3 in the single-dose phase will be initiated in parallel. Cohort 4 will begin after safety and PK data from at least 6 participants from the single-dose Cohorts 1, 2, and 3 (with a minimum of 3 participants from Cohort 3) have been assessed. The multiple-dose phase will include 3 cohorts according to age range (Cohorts 2, 3, and 4) and will begin after safety and PK data from 6 participants in the corresponding single-dose cohort have been assessed.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
53
Administered intravenously over 3 hours
Standard of care antibiotics will be selected by the investigator based on the suspected or confirmed pathogen(s) for the infection in accordance with local standards.
Universitair Ziekenhuis Brussel
Brussels, Belgium
Cliniques Universitaires Saint-Luc
Brussels, Belgium
Tallinn Childrens Hospital
Tallinn, Estonia
Tartu Ulikooli Kliinikum - Anestesioloogia ja Intensiivravi Kliinik
Tartu, Estonia
JSC "Medical Corporation Evex" " M. Iashvili Batumi Maternal and Child Central Hospital"
Batumi, Georgia
JSC "EVEX Medical Corporation"- M Lashvili Childrens Central Hospital
Tbilisi, Georgia
Ltd Unimedi Kakheti Childrens New Clinic
Tbilisi, Georgia
Heim Pl Orszgos Gyermekgygyszati Intzet
Pilisborosjenő, Hungary
Szegedi Tudomnyegyetem
Szegedi Tudomnyegyetem, Hungary
Daugavpils regional Hospital
Daugavpils, Latvia
...and 13 more locations
Single-Dose Phase: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
An adverse event (AE) was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. SAEs included death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized the participant and required medical intervention to prevent 1 of the outcomes listed in this definition. TEAEs were defined as AEs reported after the initial dose of study drug. A summary of serious and non-serious AEs regardless of causality is located in 'Reported Adverse Events module'.
Time frame: Day 1 up to Day 28
Multiple-Dose Phase: Number of Participants With TEAEs
An AE was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. SAEs included death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized the participant and required medical intervention to prevent 1 of the outcomes listed in this definition. TEAEs were defined as AEs reported after the initial dose of study drug. A summary of serious and non-serious AEs regardless of causality is located in 'Reported Adverse Events module'.
Time frame: Day 1 up to Day 42
Single Dose Phase: Maximum Observed Plasma Concentration (Cmax) of Cefiderocol
Time frame: Up to 8 hours postdose
Single Dose Phase: Area Under the Plasma Concentration Time Curve Extrapolated From Time 0 to Infinity (AUCinf) of Cefiderocol
Time frame: Up to 8 hours postdose
Single Dose Phase: Apparent Terminal Elimination Half-life (t1/2) of Cefiderocol
Time frame: Up to 8 hours postdose
Multiple Dose Phase: Cmax of Cefiderocol
Time frame: Up to 8 hours postdose
Multiple Dose Phase: Area Under the Plasma Concentration Time Curve Extrapolated From Time 0 to the Last Measurable Concentration (AUC0-t) of Cefiderocol
Time frame: Up to 8 hours postdose
Multiple Dose Phase: t1/2 of Cefiderocol
Time frame: Up to 8 hours postdose
Multiple-Dose Phase: Number of Participants With a Clinical Outcome, as Assessed by the Investigator
The clinical outcomes were clinical cure, clinical failure, and indeterminate. Clinical Cure: Resolution or substantial improvement of baseline signs and symptoms. Participants with bacteremia must have had eradication of bacteremia caused by the Gram-negative pathogen. Clinical Failure: No apparent response to therapy; persistence or worsening of baseline signs and/or symptoms, reappearance of signs and/or symptoms; development of new signs and/or symptoms requiring antibiotic therapy other than, or in addition to, study treatment therapy; or death due to pneumonia/complicated intra-abdominal infection (cIAI) or complicated urinary tract infections (cUTI) or bloodstream infection (BSI)/sepsis. Indeterminate: Lost to follow-up such that a determination of clinical cure/failure could not be made.
Time frame: End of treatment (EOT; up to Day 14), post-treatment (7 days after EOT [up to Day 21]), and end of study (EOS; 28 days after last dose [up to Day 42])
Multiple-Dose Phase: Number of Participants With a Microbiological Outcome, as Assessed by the Investigator
Microbiological outcomes were eradication, persistence, and indeterminate. For hospital-acquired pneumonia (HAP)/ventilator-acquired pneumonia (VAP)/cIAI and BSI/sepsis- Eradication: Absence of baseline Gram-negative pathogen from an appropriate clinical specimen; Persistence: Continued presence of baseline Gram-negative pathogen from an appropriate clinical specimen; Indeterminate: No culture obtained from an appropriate clinical specimen or additional antibiotic therapy for the treatment of current infection including missed sampling. For cUTI- Eradication: A urine culture showed baseline Gram-negative uropathogen found at entry at ≥10\^5 colony forming units (CFU)/milliliters (mL) was reduced to \<10\^3 CFU/mL; Persistence: A urine culture showed that the baseline Gram-negative uropathogen found at entry at ≥10\^5 CFU/mL remained at ≥10\^3 CFU/mL; Indeterminate: No urine culture obtained or additional antibiotic therapy for the treatment of current infection including missed sampling.
Time frame: EOT (up to Day 14), post-treatment (7 days after EOT [up to Day 21]), and EOS (28 days after last dose [up to Day 42])
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