Clinical trial NCT05314764: Cefiderocol Pharmacokinetics in Adult Patients With Cystic Fibrosis
Official title: Population Pharmacokinetics of Cefiderocol During Acute Pulmonary Exacerbations in Adult Patients With Cystic Fibrosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Cystic Fibrosis
Pneumonia, Bacterial
Lead sponsor: Hartford Hospital
Sponsor class: OTHER
Collaborators: name: Shionogi Inc.
name: Keystone Bioanalytical, Inc.
name: Indiana University Health Methodist Hospital
name: University of Pittsburgh Medical Center
name: University of Texas
First posted: 2022-04-06
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Open-label, descriptive, pharmacokinetic study
Primary purpose: OTHER

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.

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)

Primary outcomes:
measure: Clearance
timeFrame: 0, 1.5, 3, 3.25, 4, 5, 6, and 8 hours after the final dose
measure: Volume of Distribution
timeFrame: 0, 1.5, 3, 3.25, 4, 5, 6, and 8 hours after the final dose
Secondary outcomes:
measure: Probability of Target Attainment at 4 mcg/mL
timeFrame: 24 hours
Other outcomes:
Locations:
city: Hartford
country: United States
facility: Hartford Hospital
state: Connecticut
city: Indianapolis
country: United States
facility: IU Health University Hospital
state: Indiana
city: Pittsburgh
country: United States
facility: UPMC Presbyterian Hospital
state: Pennsylvania
city: Dallas
country: United States
facility: UT Southwestern Clements University Hospital
state: Texas
Study officials:
affiliation: Hartford Hospital
name: Joseph L Kuti, PharmD
role: PRINCIPAL_INVESTIGATOR
References: