Cefiderocol Pharmacokinetics in Adult Patients With Cystic Fibrosis

• Status: Not yet recruiting
• Trial end date: 2023-06-01
• Target enrollment: 0
• Participant gender: All

Summary

There is established evidence that adult patients with Cystic Fibrosis (CF) may have altered antibiotic pharmacokinetics compared with non-CF patients. Cefiderocol is a newly approved broad spectrum intravenous siderophore cephalosporin antibiotic, which has potent in vitro activity against multidrug resistant Pseudomonas aeruginosa, Burkholderia cepacia complex, Achromobacter species, and Stenotrophomonas maltophilia, all pathogens implicated in CF pulmonary exacerbations. This study will determine the pharmacokinetics and tolerability of cefiderocol in 12 adult CF patients admitted for a pulmonary exacerbation at one of 4 participating hospitals in the US. Patients will remain on standard of care IV antibiotics and receive 4-6 doses of cefiderocol 2 grams infused over 3 hours every 6-8 hours, depending on kidney function. Blood will be sampled after the final dose to determine concentrations and pharmacokinetics of cefiderocol. Safety and tolerability will be assessed throughout the 2 day study.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Hartford Hospital
• Collaborators: Indiana University Health Methodist Hospital; Keystone Bioanalytical, Inc.; Shionogi Inc.; University of Pittsburgh Medical Center; University of Texas

Criteria

Inclusion Criteria:

• Documented diagnosis of CF

• Acute pulmonary exacerbation as the primary reason for admission to the hospital with requirement to receive systemic antibiotic treatment

Exclusion Criteria:

• Females that are pregnant and/or breastfeeding

• History of any moderate or severe hypersensitivity or allergic reaction to any β-lactam antibiotic (a history of mild rash to a cephalosporin followed by uneventful re-exposure is not a contraindication)

• History of a lung transplant at any time in the past or any other organ transplantation (e.g., liver) within the last 6 months

• Moderate to severe renal dysfunction defined as a creatinine clearance < 60 mL/min (as calculated by the Cockcroft-Gault equation using actual body weight) or requirement for continuous renal replacement therapy or hemodialysis

• A hemoglobin less than 8 gm/dL at baseline

• Any rapidly-progressing disease or immediately life-threatening illness (defined as imminent death within 48 hours in the opinion of the investigator)