Population Pharmacokinetics and Safety of Intravenous Ceftolozane/Tazobactam in Adult Cystic Fibrosis Patients
Condition: Cystic Fibrosis; Cystic Fibrosis Pulmonary Exacerbation; Pseudomonas Aeruginosa Infection
MeSH terms: Pseudomonas Infections; Cystic Fibrosis; Pulmonary Fibrosis; Fibrosis
Intervention: Ceftolozane/Tazobactam
Intervention description: 1 hour intravenous infusion
Intervention MeSH terms: Tazobactam; Ceftolozane; Ceftolozane, tazobactam drug combination
Phase: Phase 4
Study type: Interventional
Primary purpose: Other
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 21.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        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