Bacterial Infections
Conditions
Brief summary
This study characterized the pharmacokinetics and safety of a single dose of ceftobiprole in neonates and infants aged ≤ 3 months.
Interventions
Ceftobiprole medocaril was administered as a single intravenous infusion, with a bodyweight-adjusted volume, at a constant rate over 4 hours. The ceftobiprole dose was 7.5 mg/kg, which corresponds to 10.0 mg ceftobiprole medocaril.
Sponsors
Basilea Pharmaceutica
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 3 Months
Healthy volunteers
No
Inclusion criteria
* Neonates and infants ≤3 months, with gestational age ≥28 weeks * Documented or presumed (or at risk of) bacterial infections, and currently receiving antibiotic treatment * Expected to survive beyond the first 7 days after enrollment * Sufficient vascular access to receive study drug, and to allow blood sampling at a site separate from the study drug infusion site * Parent's / legally acceptable representative's informed consent to participate in the study
Exclusion criteria
* Major birth defect or malformation syndrome * Proven presence of an immunodeficiency * HIV or other congenital viral or fungal infection * Significant laboratory abnormalities including: hematocrit \<20%; absolute neutrophil count \<0.5x10⁹/L; platelet count \< 50x10⁹/L; alanine aminotransferase or aspartate aminotransferase \>3 times the age-specific upper limit of normal * Impaired renal function or known significant renal disease * Any condition which would make the subject or caregiver, in the opinion of the investigator, unsuitable for the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax | Blood samples for pharmacokinetic (PK) analysis were obtained pre-dose, and at 2, 4, 6, 8, and 12 hours after the start of dosing. | The maximum observed plasma concentration (Cmax) |
| Tmax | Blood samples for PK analysis were obtained pre-dose, and at 2, 4, 6, 8, and 12 hours after the start of dosing. | The time of maximum observed plasma concentration (Tmax) |
| AUC0-last | Blood samples for PK analysis were obtained pre-dose, and at 2, 4, 6, 8, and 12 hours after the start of dosing. | The area under the plasma concentration-time curve from time zero to the time of the last measurable concentration (AUC0-last) |
| T>MIC of 4 mg/L | Blood samples for PK analysis were obtained pre-dose, and at 2, 4, 6, 8, and 12 hours after the start of dosing. | The duration of time after dose for which free-drug concentrations remained above a value of 4 mg/L (T\>MIC of 4 mg/L) |
Countries
Belgium, Germany, Latvia, Lithuania, Poland, United States
Participant flow
Pre-assignment details
Subjects with documented or presumed bacterial infection receiving standard-of-care antibiotic treatment were screened.
Participants by arm
| Arm | Count |
|---|---|
| Ceftobiprole ITT/Safety Population All subjects who received any quantity of study drug. | 15 |
| Total | 15 |
Baseline characteristics
| Characteristic | Ceftobiprole ITT/Safety Population |
|---|---|
| Age, Categorical <=18 years | 15 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age, Continuous | 13 days |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 13 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 15 |
| other Total, other adverse events | 4 / 15 |
| serious Total, serious adverse events | 2 / 15 |
Outcome results
Primary
AUC0-last
The area under the plasma concentration-time curve from time zero to the time of the last measurable concentration (AUC0-last)
Time frame: Blood samples for PK analysis were obtained pre-dose, and at 2, 4, 6, 8, and 12 hours after the start of dosing.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ceftobiprole PK Population | AUC0-last | 60.6 μg•hours/mL |
Primary
Cmax
The maximum observed plasma concentration (Cmax)
Time frame: Blood samples for pharmacokinetic (PK) analysis were obtained pre-dose, and at 2, 4, 6, 8, and 12 hours after the start of dosing.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ceftobiprole PK Population | Cmax | 11.2 μg/mL |
Primary
Tmax
The time of maximum observed plasma concentration (Tmax)
Time frame: Blood samples for PK analysis were obtained pre-dose, and at 2, 4, 6, 8, and 12 hours after the start of dosing.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ceftobiprole PK Population | Tmax | 4.00 hours |
Primary
T>MIC of 4 mg/L
The duration of time after dose for which free-drug concentrations remained above a value of 4 mg/L (T\>MIC of 4 mg/L)
Time frame: Blood samples for PK analysis were obtained pre-dose, and at 2, 4, 6, 8, and 12 hours after the start of dosing.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ceftobiprole PK Population | T>MIC of 4 mg/L | 5.40 hours |