Pharmacokinetics and Safety of Ceftobiprole in Neonates and Infants up to 3 Months Treated With Systemic Antibiotics

An Open-label Study to Evaluate the Single-dose Pharmacokinetics and Safety of Ceftobiprole in Neonate and Infant Subjects Aged up to 3 Months Undergoing Treatment With Systemic Antibiotics

This study characterized the pharmacokinetics and safety of a single dose of ceftobiprole in neonates and infants aged ≤ 3 months.

Study Overview

• Status: Terminated
• Conditions: Bacterial Infections
• Intervention / Treatment: Drug: Ceftobiprole medocaril

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium
    • UZ Leuven
• Germany
  • Munich, Germany
    • Klinikum der Universität München
• Latvia
  • Riga, Latvia
    • Children Clinical University Hospital
• Lithuania
  • Vilnius, Lithuania
    • Vilnius University Children's Hospital
• Poland
  • Kraków, Poland
    • University Children's Hospital of Kraków
• United States
  • California
    • Loma Linda, California, United States, 92354
      • Loma Linda University Medical Center
    • Los Angeles, California, United States, 90095
      • University of California Los Angeles
    • Los Angeles, California, United States, 90089
      • University of Southern California
  • Indiana
    • South Bend, Indiana, United States, 46601
      • Beacon Children's Hospital
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Norton Children's Hospital
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University Hospital
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • University of Pittsburgh Medical Center Cancer Center at Magee-Womens Hospital
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas Health Science Center at Houston
  • West Virginia
    • Morgantown, West Virginia, United States, 26506-9214
      • West Virginia University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 3 years (Child)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ceftobiprole; Ceftobiprole medocaril is the water-soluble prodrug of ceftobiprole, an advanced-generation cephalosporin developed for intravenous administration. Ceftobiprole is characterized by potent, broad-spectrum antimicrobial activity against both Gram-positive and Gram-negative pathogens.	Drug: Ceftobiprole medocaril; 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.; Other Names: ceftobiprole

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	The maximum observed plasma concentration (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.
Tmax	The time of maximum observed plasma concentration (Tmax)	Blood samples for PK analysis were obtained pre-dose, and at 2, 4, 6, 8, and 12 hours after the start of dosing.
AUC0-last	The area under the plasma concentration-time curve from time zero to the time of the last measurable concentration (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.
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)	Blood samples for PK analysis were obtained pre-dose, and at 2, 4, 6, 8, and 12 hours after the start of dosing.

Collaborators and Investigators

• Sponsor: Basilea Pharmaceutica
• Investigators: Study Director: Marc Engelhardt, MD, Basilea Pharmaceutica

Publications and helpful links

General Publications

• Rubino CM, Polak M, Schropf S, Munch HG, Smits A, Cossey V, Tomasik T, Kwinta P, Snariene R, Liubsys A, Gardovska D, Hornik CD, Bosheva M, Ruehle C, Litherland K, Hamed K. Pharmacokinetics and Safety of Ceftobiprole in Pediatric Patients. Pediatr Infect Dis J. 2021 Nov 1;40(11):997-1003. doi: 10.1097/INF.0000000000003296.

Study record dates

Study Major Dates

• Study Start (Actual): November 22, 2016
• Primary Completion (Actual): February 25, 2020
• Study Completion (Actual): February 25, 2020

Study Registration Dates

• First Submitted: August 5, 2015
• First Submitted That Met QC Criteria: August 17, 2015
• First Posted (Estimated): August 19, 2015

Study Record Updates

• Last Update Posted (Actual): June 5, 2023
• Last Update Submitted That Met QC Criteria: May 9, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections and Mycoses; Bacterial Infections; Anti-Infective Agents; Anti-Bacterial Agents; Ceftobiprole; Ceftobiprole medocaril; Cephalosporins
• Other Study ID Numbers: BPR-PIP-001; 2013-004614-18 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No