Cefiderocol Pharmacokinetics in Adult Patients With Cystic Fibrosis

Cystic Fibrosis Clinical Trial

Official title:

Population Pharmacokinetics of Cefiderocol During Acute Pulmonary Exacerbations in Adult Patients With Cystic Fibrosis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05314764
• Other study ID #: HHC-2022-0078
• Status: Recruiting
• Phase: Phase 4
• Start date: June 1, 2022
• Est. completion date: June 2023

Study information

• Verified date: December 2022
• Source: Hartford Hospital
• Contact: Joseph L Kuti, PharmD
• Phone: 860-972-3612
• Email: joseph.kuti[@]hhchealth.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 12
• Est. completion date: June 2023
• Est. primary completion date: May 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 ß-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)

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis
• Pneumonia, Bacterial

Intervention

Drug:
• Cefiderocol
Patients will receive intravenous cefiderocol every 6 to 8 hours for 4 to 6 doses.

Locations

Country	Name	City	State
United States	UT Southwestern Clements University Hospital	Dallas	Texas
United States	Hartford Hospital	Hartford	Connecticut
United States	IU Health University Hospital	Indianapolis	Indiana
United States	UPMC Presbyterian Hospital	Pittsburgh	Pennsylvania

Sponsors (6)

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

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Probability of Target Attainment at 4 mcg/mL	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	24 hours