Cefiderocol Pharmacokinetics in Adult Patients With Cystic Fibrosis

NCT05314764 | Completed Phase 4 FDA Drug

• 1 other identifier: HHC-2022-0078
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 4

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.

Conditions

Cystic Fibrosis; Pneumonia, Bacterial

Outcome Measures

Primary Outcomes (2)

• Clearance

  This outcome determines the clearance of cefiderocol over the dosing interval.

  0, 1.5, 3, 3.25, 4, 5, 6, and 8 hours after the final dose

• Volume of Distribution

  This outcome determines the volume of distribution of cefiderocol over the dosing interval.

  0, 1.5, 3, 3.25, 4, 5, 6, and 8 hours after the final dose

Secondary Outcomes (1)

• Probability of Target Attainment at 4 mcg/mL

  24 hours

Study Arms (1)

Cefiderocol

EXPERIMENTAL

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.

Drug: Cefiderocol

Interventions

Cefiderocol DRUG

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

Also known as: Fetroja

Cefiderocol

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Hartford Hospital: lead
• Shionogi Inc.: collaborator
• Keystone Bioanalytical, Inc.: collaborator
• Indiana University Health Methodist Hospital: collaborator
• University of Pittsburgh Medical Center: collaborator
• University of Texas: collaborator

Study Sites (4)

Hartford Hospital

Hartford, Connecticut, 06106, United States

Location

IU Health University Hospital

Indianapolis, Indiana, 46202, United States

Location

UPMC Presbyterian Hospital

Pittsburgh, Pennsylvania, 15213, United States

Location

UT Southwestern Clements University Hospital

Dallas, Texas, 75390, United States

Location

MeSH Terms

Conditions

Cystic Fibrosis; Pneumonia, Bacterial

Interventions

Cefiderocol

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Pneumonia; Respiratory Tract Infections

Intervention Hierarchy (Ancestors)

Cephalosporins; beta-Lactams; Lactams; Amides; Organic Chemicals; Thiazines; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Joseph L Kuti, PharmD

  Hartford Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Director, CAIRD

Model Details: Open-label, descriptive, pharmacokinetic study

Study Record Dates

• First Submitted: March 29, 2022
• First Posted: April 6, 2022
• Study Start: June 1, 2022
• Primary Completion: June 1, 2024
• Study Completion: December 11, 2024
• Last Updated: December 16, 2024

Record last verified: 2024-12

Locations

US (4)