Clinical trial NCT01624246: Pharmacokinetic Study of Ceftaroline Fosamil/Avibactam in Adults With Augmented Renal Clearance
Official title: A Phase 1, Multicenter, Open-label, Single-dose Study to Assess the Pharmacokinetics of Ceftaroline Fosamil/Avibactam in Adults With Augmented Renal Clearance
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Augmented Renal Clearance (ARC)
Systemic Inflammatory Response Syndrome (SIRS)
Lead sponsor: Forest Laboratories
Sponsor class: INDUSTRY
First posted: 2012-06-20
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To evaluate the pharmacokinetic (PK) profiles of ceftaroline and avibactam in adults with augmented renal clearance (ARC).

Detailed description: To evaluate the single-dose pharmacokinetic (PK) profiles of ceftaroline and avibactam following intravenous (IV) administration of ceftaroline fosamil/avibactam ("CXL") in adults with augmented renal clearance (ARC).

Eligibility criteria: Inclusion Criteria:

* Male or female adults ≥ 18 and ≤ 55 years old
* Augmented renal clearance, defined as:

  * Estimated CrCl ≥ 115 mL/min (calculated using modified Cockcroft-Gault, before the measured 8-hour urine collection)
  * Measured CrCl ≥ 140 mL/min (from an 8-hour urine collection)
* Hospitalized and diagnosed with SIRS, defined by at least 2 of the following:

  * Temperature (oral, rectal, tympanic, or core) \> 38.5°C or \< 35.0°C
  * Heart rate \> 90 beats/min
  * Respiratory rate \> 20 breaths/min or PaCO2 \< 32 mmHg
  * Leukocytosis (\> 12,000 white blood cells \[WBC\]/mm3), leukopenia (\< 4000 WBC/mm3), or bandemia (\> 10% immature neutrophils \[bands\] regardless of total peripheral WBC)
* Requires indwelling urinary bladder catheter per standard of care (through the end of the 8-hour urine collection)

Exclusion Criteria:

* History of any known hypersensitivity or allergic reaction to cephalosporins or any β-lactam antimicrobial (eg, penicillins)
* History of chronic kidney disease, hemodialysis, or peritoneal dialysis; or history of acute renal replacement therapy (eg, hemodialysis, hemofiltration) associated with current illness
* Suspected rhabdomyolysis or creatine kinase \> 10,000 U/L
* Significant anemia defined as hemoglobin \< 9 g/dL or hematocrit \< 27%
* Transfusion of packed red blood cells (PRBC) or whole blood within 24 hours of study drug infusion or anticipated need for a transfusion before the last PK blood sample is collected
* If female, currently pregnant or breastfeeding

Primary outcomes:
measure: Plasma Pharmacokinetic Parameters of Ceftaroline and Avibactam: Area under the plasma concentration versus time curve, Cmax, Tmax, T½, , CL, Vz, and Vss.
timeFrame: Up to 3 days
Secondary outcomes:
measure: Safety and Tolerability of a Single Dose of IV Ceftaroline fosamil and Avibactam.
timeFrame: 24-36 hours after last study procedure
Other outcomes:
Locations:
city: Fresno
country: United States
facility: Investigational Site
state: California
city: Los Angeles
country: United States
facility: Investigational Site
state: California
city: San Diego
country: United States
facility: Investigational Site
state: California
city: Stanford
country: United States
facility: Investigational Site
state: California
city: Hartford
country: United States
facility: Investigational Site
state: Connecticut
city: Washington
country: United States
facility: Investigational Site
state: District of Columbia
city: Gainesville
country: United States
facility: Investigational Site
state: Florida
city: Miami
country: United States
facility: Investigational Site
state: Florida
city: Chicago
country: United States
facility: Investigational Site
state: Illinois
city: Maywood
country: United States
facility: Investigational Site
state: Illinois
city: Peoria
country: United States
facility: Investigational Site
state: Illinois
city: Duluth
country: United States
facility: Investigational Site
state: Minnesota
city: Omaha
country: United States
facility: Investigational Site
state: Nebraska
city: Neptune
country: United States
facility: Investigational Site
state: New Jersey
city: Winston Salem
country: United States
facility: Investigational Site
state: North Carolina
city: Cleveland
country: United States
facility: Investigational Site
state: Ohio
city: Columbus
country: United States
facility: Investigational Site
state: Ohio
city: Dayton
country: United States
facility: Investigational Site
state: Ohio
city: Houston
country: United States
facility: Investigational Site
state: Texas
city: Herston
country: Australia
facility: Investigational Site
state: Queensland
city: Southport
country: Australia
facility: Investigational Site
state: Queensland
Study officials:
affiliation: Forest Laboratories
name: Medical Monitor
role: STUDY_DIRECTOR
References:
citation: Li J, Lovern M, Green ML, Chiu J, Zhou D, Comisar C, Xiong Y, Hing J, MacPherson M, Wright JG, Riccobene T, Carrothers TJ, Das S. Ceftazidime-Avibactam Population Pharmacokinetic Modeling and Pharmacodynamic Target Attainment Across Adult Indications and Patient Subgroups. Clin Transl Sci. 2019 Mar;12(2):151-163. doi: 10.1111/cts.12585. Epub 2018 Sep 28.