E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Pharmacokinetics of a Single Dose of Ceftaroline
fosamil in Children Ages Birth to Younger Than 12
Years With Suspected or Confirmed Infection |
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10021881 |
E.1.2 | Term | Infections and infestations |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evalutate the single-dose pharmacokinetic profile, safety and
tolerability of ceftaroline fosamil administered by intravenous infusion
in children with ages from birth to younger than 12 years |
|
E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Written informed consent from parent(s) (or other legally acceptable
representative[s]) and verbal informed assent from subject (if age
appropriate; according to local requirements)
2. Male or female children with ages from birth to younger than 12
years
3. Hospitalized and receiving antibiotic therapy for treatment of a
suspected or confirmed systemic
4. Negative urine pregnancy test (if female and has reached menarche)
5. Sufficient intravascular access (peripheral or central) to receive
study drug |
|
E.4 | Principal exclusion criteria |
1. History of any hypersensitivity or allergic reaction to any β-lactam
antimicrobial (eg, cephalosporins, penicillins)
2. Past or current history of epilepsy or seizure disorder (excluding
childhood febrile seizures)
3. Moderate or severe renal impairment such that: ○ Cohorts 1, and 2 ,
and 3: Creatinine clearance (CrCl) < 50 mL/min
calculated using the modified Schwartz equation (Schwartz et al, 1987):
CrCl (mL/min/1.73m2) = [length (cm) x k] / Serum creatinine
(mg/dL)
where:
- k = 0.45 for infants 1 to 52 weeks old
- k = 0.55 for children 1 to 12 years old
○ Cohorts 4 and 5:
- Urine output with value of < 1 mL/min/kg (measured in diapered
children as diaper weight
change where 1 g = 1 mL of urine) and
- Serum creatinine value of > 1.3 mg/dL
Note: For Cohort 3, if calculated CrCl is between 50-60
mL/min/1.73m2, and the child is age
24 months or under, please ensure urine output and serum creatinine
values are within normal or mild renal impairment criteria as for
Cohorts 4 and 5 (ie, urine output ≥ 1mL/kg/min [measured in diapered
children as diaper weight change where 1 g = 1 mL of urine] and serum
creatinine ≤ 1.3 mg/dL)
4. Aspartate aminotransferase, alanine aminotransferase, or total
bilirubin level > 3 times upper limit of
normal (neonates with elevated total bilirubin may participate if
conjugated bilirubin is normal)
5. Any condition (eg, septic shock, acute hemodynamic instability
including those requiring pressor
support) that would make the subject, in the opinion of the
Investigator, unsuitable for the study (eg,
would place a subject at risk or compromise the quality of the data)
6. Receipt of a blood transfusion during the 24-hour period before
enrollment
7. Use of probenecid within 3 days prior to dosing
8. If female, currently pregnant or nursing
9. Previous participation in this study or in any study involving
administration of an investigational agent
within 30 days prior to enrollment into this study where the subject
was randomized and received an
active investigational product (not placebo)
10. Unwilling or unable to adhere to study procedures or restrictions |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The Safety Population (all subjects who receive any amount of
ceftaroline fosamil)
PK Analysis Population (all subjects who received the entire
ceftaroline fosamil infusion on
Study Day 1 and from whom any PK samples are collected)
Outcome Variables:
• Evaluation of pharmacokinetics (Cmax, AUC, clearance and T½ will
be derived from population PK
analysis)
• Plasma concentrations-time profiles of ceftaroline by patient, age
cohort, and dosage level
• Evaluation of safety and tolerablility of ceftaroline following a single dose
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
|
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |