Safety, Tolerability, and Pharmacokinetics of Single and Multiple Doses of Cefiderocol in Hospitalized Pediatric Patients

• Status: Recruiting
• Trial end date: 2022-12-15
• Target enrollment: 0
• Participant gender: All

Summary

The primary objectives of this study are:

• To assess the safety and tolerability of cefiderocol after single-dose administration in hospitalized paediatric patients 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 patients 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 patients 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 patients 3 months to < 12 years of age with suspected or confirmed aerobic Gram-negative bacterial infections

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Shionogi
• Treatments: Cephalosporins

Criteria

Inclusion Criteria:

1. Subject's parent(s) or legally authorized representative (LAR) provides written informed consent in accordance with regional and country-specific laws and regulations

2. Subject provides written informed assent, when feasible (age of assent to be determined by institutional review boards/independent ethics committees [IRB's/IEC's] or be consistent with local legal requirements)

3. Hospitalized subject is 3 months to < 18 years of age at the time written informed consent/assent is obtained for the single-dose phase. Hospitalized subject is 3 months to < 12 years of age at the time written informed consent/assent is obtained for the multiple-dose phase. Premature babies will not be restricted, but the subject must have an adjusted or postnatal age of 3 months.

4. Subject has a suspected or confirmed infection (including but not limited to cUTI, cIAI, pneumonia [including HAP/VAP], sepsis, or BSI) that requires hospitalization for treatment with IV antibiotics

5. If subject is a sexually active female of childbearing potential and has reached menarche or Tanner stage 3, subject agrees to use barrier contraception (including condom, diaphragm, or cervical cap) with spermicide or agrees to use a highly effective method of contraception (including contraceptive implant, injectable contraceptive, combination oral contraceptive, or an intrauterine [IUD] contraceptive device) from Screening up to 28 days after administration of the last dose of cefiderocol.

Exclusion Criteria:

1. Subject has a documented history of any hypersensitivity or allergic reaction to any β-lactam antibiotic (Note: for β-lactams, a history of a mild rash followed by uneventful re-exposure is not a contraindication to enrollment)

2. Multiple-dose only: Subject has an infection caused only by a confirmed Gram-positive pathogen

3. Subject has a suspected or confirmed central nervous system (CNS) infection (eg, meningitis, brain abscess, shunt infection) or osteomyelitis (which would require prolonged antibiotic therapy).

4. Subject has cystic fibrosis

5. Single-dose phase: Subject has moderate or severe renal impairment based on estimated glomerular filtration rate (eGFR) (based on Schwartz equation if ≥ 3 months to < 1 year of age and modified Bedside Schwartz equation if ≥ 1 to < 18 years of age) of < 60 mL/min/1.73 m² at Screening.

Multiple-dose phase: Subject has an eGFR (based on Schwartz equation if ≥ 3 months to < 1 year of age and modified Bedside Schwartz equation if ≥ 1 to < 18 years of age) of < 15 mL/min/1.73 m² at Screening.

6. Subject has end-stage renal disease (ESRD), is on hemodialysis (HD), or receiving continuous venovenous hemofiltration (CVVH)

7. Subject has experienced shock in the prior month or is in shock at the time of Screening.

8. Subject has severe neutropenia or is severely immunocompromised

9. Subject has multiorgan failure

10. Subjects has a life expectancy of < 30 days due to severity of a concurrent illness

11. Subject is a female who has a positive pregnancy test at Screening

12. Subject is a female who is breastfeeding

13. Subject has received any other investigational medicinal product (IMP) within 30 days

14. Subject has any condition or circumstance that, in the opinion of the investigator, would compromise the safety of the subject or the quality of the study data, including acute trauma to the pelvis or urinary tract

15. Subject is receiving vasopressor therapy at Screening.