Cefiderocol Pharmacokinetics in Adult Patients With Cystic Fibrosis

Sponsor
Hartford Hospital (Other)
Overall Status
Recruiting
CT.gov ID
NCT05314764
Collaborator
Shionogi Inc. (Industry), Keystone Bioanalytical, Inc. (Other), Indiana University Health Methodist Hospital (Other), University of Pittsburgh Medical Center (Other), University of Texas (Other)
12
4
1
12
3
0.3

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 4

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
12 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Intervention Model Description:
Open-label, descriptive, pharmacokinetic studyOpen-label, descriptive, pharmacokinetic study
Masking:
None (Open Label)
Primary Purpose:
Other
Official Title:
Population Pharmacokinetics of Cefiderocol During Acute Pulmonary Exacerbations in Adult Patients With Cystic Fibrosis
Actual Study Start Date :
Jun 1, 2022
Anticipated Primary Completion Date :
May 1, 2023
Anticipated Study Completion Date :
Jun 1, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: 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.

Drug: Cefiderocol
Patients will receive intravenous cefiderocol every 6 to 8 hours for 4 to 6 doses.
Other Names:
  • Fetroja
  • Outcome Measures

    Primary Outcome Measures

    1. Clearance [0, 1.5, 3, 3.25, 4, 5, 6, and 8 hours after the final dose]

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

    2. Volume of Distribution [0, 1.5, 3, 3.25, 4, 5, 6, and 8 hours after the final dose]

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

    Secondary Outcome Measures

    1. Probability of Target Attainment at 4 mcg/mL [24 hours]

      This simulated outcome indicates the likelihood that cefiderocol will retain drug concentrations above the MIC for >/= 75% of the dosing interval at an MIC of 4 mcg/ml when administered as a 2g every 8 hour dose infused over 3 hour in patients up to a creatinine clearance of 120 ml/min. This analysis is conducted via a Monte Carlo simulation using the population pharmacokinetic parameter estimates and dispersion from the 12 participants who contributed pharmacokinetic data to the study

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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)

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Hartford Hospital Hartford Connecticut United States 06106
    2 IU Health University Hospital Indianapolis Indiana United States 46202
    3 UPMC Presbyterian Hospital Pittsburgh Pennsylvania United States 15213
    4 UT Southwestern Clements University Hospital Dallas Texas United States 75390

    Sponsors and Collaborators

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

    Investigators

    • Principal Investigator: Joseph L Kuti, PharmD, Hartford Hospital

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Joseph L. Kuti, PharmD, Associate Director, CAIRD, Hartford Hospital
    ClinicalTrials.gov Identifier:
    NCT05314764
    Other Study ID Numbers:
    • HHC-2022-0078
    First Posted:
    Apr 6, 2022
    Last Update Posted:
    Jun 3, 2022
    Last Verified:
    Jun 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Jun 3, 2022