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

Systemic Inflammatory Response Syndrome (SIRS) Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01624246
• Other study ID #: CXL-PK-04
• Status: Completed
• Phase: Phase 1
• First received: June 14, 2012
• Last updated: April 6, 2017
• Start date: May 2012
• Est. completion date: March 2013

Study information

• Verified date: April 2017
• Source: Forest Laboratories
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: March 2013
• Est. primary completion date: March 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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 ß-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

Related Conditions & MeSH terms

• Augmented Renal Clearance (ARC)
• Systemic Inflammatory Response Syndrome
• Systemic Inflammatory Response Syndrome (SIRS)

Intervention

Drug:
• Ceftaroline fosamil/Avibactam (CXL)
IV infusion of CXL (combination of ceftaroline fosamil [600 mg] plus avibactam [600 mg]) infused over 60 (± 5) minutes.

Locations

Country	Name	City	State
Australia	Investigational Site	Herston	Queensland
Australia	Investigational Site	Southport	Queensland
United States	Investigational Site	Chicago	Illinois
United States	Investigational Site	Cleveland	Ohio
United States	Investigational Site	Columbus	Ohio
United States	Investigational Site	Dayton	Ohio
United States	Investigational Site	Duluth	Minnesota
United States	Investigational Site	Fresno	California
United States	Investigational Site	Gainesville	Florida
United States	Investigational Site	Hartford	Connecticut
United States	Investigational Site	Houston	Texas
United States	Investigational Site	Los Angeles	California
United States	Investigational Site	Maywood	Illinois
United States	Investigational Site	Miami	Florida
United States	Investigational Site	Neptune	New Jersey
United States	Investigational Site	Omaha	Nebraska
United States	Investigational Site	Peoria	Illinois
United States	Investigational Site	San Diego	California
United States	Investigational Site	Stanford	California
United States	Investigational Site	Washington	District of Columbia
United States	Investigational Site	Winston Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Forest Laboratories

Countries where clinical trial is conducted

United States,  Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plasma Pharmacokinetic Parameters of Ceftaroline and Avibactam: Area under the plasma concentration versus time curve, Cmax, Tmax, T½, , CL, Vz, and Vss.	The following PK parameters, if calculable, will be determined for ceftaroline, ceftaroline fosamil, ceftaroline M-1, and avibactam: area under the plasma concentration versus time curve, Cmax, time of maximum plasma drug concentration (Tmax), T½, apparent total body clearance of drug from plasma (CL), apparent volume of distribution during the terminal phase (Vz), and Vss.	Up to 3 days
Secondary	Safety and Tolerability of a Single Dose of IV Ceftaroline fosamil and Avibactam.	Adverse events will be summarized. Vital signs (pulse, blood pressure, respiratory rate, temperature), oxygen saturation and concomitant medications will be summarized. Complete blood count (CBC) and comprehensive metabolic panel results will be summarized.	24-36 hours after last study procedure