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Cefiderocol Pharmacokinetics in Adult Patients With Cystic Fibrosis

Primary Purpose

Cystic Fibrosis, Pneumonia, Bacterial

Status

Recruiting

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Cefiderocol

About this trial

This is an interventional other trial for Cystic Fibrosis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

Hartford HospitalRecruiting
IU Health University HospitalRecruiting
UPMC Presbyterian HospitalRecruiting
UT Southwestern Clements University HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Cefiderocol

Arm Description

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.

Outcomes

Primary Outcome Measures

Clearance

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

Volume of Distribution

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

Secondary Outcome Measures

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

Full Information

NCT ID

NCT05314764

First Posted

March 29, 2022

Last Updated

December 22, 2022

Sponsor

Hartford Hospital

Collaborators

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

1. Study Identification

Unique Protocol Identification Number

NCT05314764

Brief Title

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

2. Study Status

Record Verification Date

December 2022

Overall Recruitment Status

Recruiting

Study Start Date

June 1, 2022 (Actual)

Primary Completion Date

May 2023 (Anticipated)

Study Completion Date

June 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Hartford Hospital

Collaborators

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

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cystic Fibrosis, Pneumonia, Bacterial

7. Study Design

Primary Purpose

Other

Study Phase

Phase 4

Interventional Study Model

Single Group Assignment

Model Description

Open-label, descriptive, pharmacokinetic study

Masking

None (Open Label)

Allocation

N/A

Enrollment

12 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Cefiderocol

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Cefiderocol

Other Intervention Name(s)

Fetroja

Intervention Description

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

Primary Outcome Measure Information:

Title

Clearance

Description

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

Time Frame

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

Title

Volume of Distribution

Description

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

Time Frame

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

Secondary Outcome Measure Information:

Title

Probability of Target Attainment at 4 mcg/mL

Description

Time Frame

24 hours

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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)

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Joseph L Kuti, PharmD

Phone

860-972-3612

joseph.kuti@hhchealth.org

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Joseph L Kuti, PharmD

Organizational Affiliation

Hartford Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Hartford Hospital

City

Hartford

State/Province

Connecticut

ZIP/Postal Code

06106

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Joseph L Kuti, PharmD

Phone

860-972-3612

joseph.kuti@hhchealth.org

First Name & Middle Initial & Last Name & Degree

Samuel Pope, MD

Facility Name

IU Health University Hospital

City

Indianapolis

State/Province

Indiana

ZIP/Postal Code

46202

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Colleen M Sakon, PharmD

Phone

317-962-9363

csakon@iuhealth.org

Facility Name

UPMC Presbyterian Hospital

City

Pittsburgh

State/Province

Pennsylvania

ZIP/Postal Code

15213

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Ryan Shields, PharmD

shieldsrk@upmc.edu

Facility Name

UT Southwestern Clements University Hospital

City

Dallas

State/Province

Texas

ZIP/Postal Code

75390

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Marguerite Monogue, PharmD

Marguerite.Monogue@UTSouthwestern.edu

12. IPD Sharing Statement

Learn more about this trial

Cefiderocol Pharmacokinetics in Adult Patients With Cystic Fibrosis

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