Cefiderocol Pharmacokinetics in Adult Patients With Cystic Fibrosis

NCT ID: NCT05314764

Last Updated: 2024-12-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-06-01
• Study Completion Date: 2024-12-11

Brief 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.

Detailed Description

Participants will receive 4-6 doses of cefiderocol 2 grams every 6-8 hours, in addition to standard intravenous antibiotic therapy selected by the site. Just prior and then after the final dose, a total of nine blood samples will be collected to measure cefiderocol concentrations. Data will be fit to a population pharmacokinetic model. The final model will be utilized in a Monte Carlo simulation to determine the probability of several different dosing regimens retaining concentrations above the minimum inhibitory concentration (MIC) for at least 75% of the dosing interval. These data will be utilized to determine an optimized dosing regimen for adults with CF.

Conditions

Cystic Fibrosis; Pneumonia, Bacterial

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Cefiderocol

Participants will receive intravenous cefiderocol at a dosing regimen consistent with the current prescribing information and according estimated renal function. Each dose will be infused over 3 hours.

Group Type: EXPERIMENTAL

Cefiderocol

Intervention Type: DRUG

Patients will receive intravenous cefiderocol every 6 to 8 hours for 4 to 6 doses.

Interventions

Cefiderocol

Patients will receive intravenous cefiderocol every 6 to 8 hours for 4 to 6 doses.

Intervention Type: DRUG

Other Intervention Names

Fetroja

Eligibility 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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shionogi Inc.

INDUSTRY

Sponsor Role: collaborator

Keystone Bioanalytical, Inc.

UNKNOWN

Sponsor Role: collaborator

Indiana University Health Methodist Hospital

OTHER

Sponsor Role: collaborator

University of Pittsburgh Medical Center

OTHER

Sponsor Role: collaborator

University of Texas

OTHER

Sponsor Role: collaborator

Hartford Hospital

OTHER

Sponsor Role: lead

Responsible Party

Joseph L. Kuti, PharmD

Associate Director, CAIRD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Joseph L Kuti, PharmD

Role: PRINCIPAL_INVESTIGATOR

Hartford Hospital

Locations

Hartford Hospital

Hartford, Connecticut, United States

IU Health University Hospital

Indianapolis, Indiana, United States

UPMC Presbyterian Hospital

Pittsburgh, Pennsylvania, United States

UT Southwestern Clements University Hospital

Dallas, Texas, United States

Countries

United States

Other Identifiers

HHC-2022-0078

Identifier Type: -

Identifier Source: org_study_id