Pharmacokinetic Study of Ceftaroline Fosamil/Avibactam in Adults With Augmented Renal Clearance

Forest Laboratories

Status and phase: Completed; Phase 1

Conditions: Systemic Inflammatory Response Syndrome (SIRS); Augmented Renal Clearance (ARC)

Treatments: Drug: Ceftaroline fosamil/Avibactam (CXL)

Study type: Interventional

Funder types: Industry

Identifiers

NCT01624246

CXL-PK-04

Details and patient eligibility

About

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

Full 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).

Enrollment: 12 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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12 participants in 1 patient group

Ceftaroline fosamil/Avibactam

Experimental group

Treatment:

Drug: Ceftaroline fosamil/Avibactam (CXL)