Population Pharmacokinetics and Safety of Intravenous Ceftolozane/Tazobactam in Adult Cystic Fibrosis Patients



Status:Completed
Conditions:Pulmonary, Pulmonary
Therapuetic Areas:Pulmonary / Respiratory Diseases
Healthy:No
Age Range:18 - Any
Updated:4/17/2018
Start Date:September 2015
End Date:October 2016

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A Prospective, Multicenter, Open-Label Study to Assess Population Pharmacokinetics and Safety of Intravenous Ceftolozane/Tazobactam in Adult Cystic Fibrosis Patients Admitted With Acute Pulmonary Exacerbation

There is established evidence that adult patients with Cystic Fibrosis (CF) may have altered
antibiotic pharmacokinetics compared with non-CF patients. Ceftolozane/Tazobactam is a newly
approved broad spectrum intravenous antibiotic, which has potent in vitro activity against
multidrug resistant Pseudomonas aeruginosa, the most common pathogen implicated in CF
pulmonary exacerbations. This study will determine the pharmacokinetics and tolerability of
ceftolozane/tazobactam in 20 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 ceftolozane/tazobactam 3 grams every 8 hours. Blood will
be sampled after the final dose to determine concentrations and pharmacokinetics of
ceftolozane and tazobactam. Safety and tolerability will be assessed throughout the 3 day
study.

Participants will receive 4-6 doses of ceftolozane/tazobactam 3 grams every 8 hours, in
addition to standard intravenous antibiotic therapy selected by the site. Just prior and then
after the final dose, a total of six blood samples will be collected to measure ceftolozane
and tazobactam 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 39% of the dosing interval. These data will be utilized to
determine an optimized dosing regimen for adults with CF.

Inclusion Criteria:

1. Age 18 years or older

2. Documented diagnosis of CF

3. Acute pulmonary exacerbation as the primary reason for admission to the hospital with
requirement to receive systemic antibiotic treatment

4. If female, subjects must be non-pregnant and non-lactating. Females can be either not
of a child-bearing potential or if of a child-bearing potential, on acceptable modes
of birth control such as abstinence from sexual intercourse, oral/parenteral
contraceptives, or barrier method

Exclusion Criteria:

1. 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)

2. Prior (within 24 hours of first dose of study drug) or concomitant receipt of
piperacillin/tazobactam or probenecid

3. History of lung transplant

4. Moderate to severe renal dysfunction defined as a creatinine clearance < 50 mL/min (as
calculated by the Cockcroft-Gault equation using actual body weight) or requirement
for continuous renal replacement therapy or hemodialysis

5. A hemoglobin less than 8 gm/dl at baseline

6. Any rapidly-progressing disease or immediately life-threatening illness (defined as
imminent death within 48 hours in the opinion of the investigator)

7. Any condition or circumstance that, in the opinion of the investigator, would
compromise the safety of the patient or the quality of study data

8. Planned or prior participation in any other interventional drug study within 30 days
We found this trial at
4
sites
Indianapolis, Indiana 46202
Principal Investigator: Rebecca Pettit, PharmD
Phone: 317-948-9362
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Philadelphia, Pennsylvania 19134
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Chapel Hill, North Carolina
Principal Investigator: Marianne Muhlebach, MD
Phone: 919-966-1055
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80 Seymour St
Hartford, Connecticut 6102
(860) 545-5000
Principal Investigator: Joseph L Kuti, PharmD
Phone: 860-972-3612
The Hartford Hospital Hartford Hospital is the major teaching hospital affiliated with the University of...
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