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

Primary Purpose

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

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Ceftaroline fosamil/Avibactam (CXL)
Sponsored by
Forest Laboratories
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Augmented Renal Clearance (ARC)

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesDoes not accept 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

Sites / Locations

  • Investigational Site
  • Investigational Site
  • Investigational Site
  • Investigational Site
  • Investigational Site
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  • Investigational Site
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  • Investigational Site
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  • Investigational Site
  • Investigational Site
  • Investigational Site
  • Investigational Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Ceftaroline fosamil/Avibactam

Arm Description

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Full Information

First Posted
June 14, 2012
Last Updated
April 6, 2017
Sponsor
Forest Laboratories
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1. Study Identification

Unique Protocol Identification Number
NCT01624246
Brief Title
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

2. Study Status

Record Verification Date
April 2017
Overall Recruitment Status
Completed
Study Start Date
May 2012 (undefined)
Primary Completion Date
March 2013 (Actual)
Study Completion Date
March 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Forest Laboratories

4. Oversight

Data Monitoring Committee
No

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Augmented Renal Clearance (ARC), Systemic Inflammatory Response Syndrome (SIRS)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Ceftaroline fosamil/Avibactam
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Ceftaroline fosamil/Avibactam (CXL)
Intervention Description
IV infusion of CXL (combination of ceftaroline fosamil [600 mg] plus avibactam [600 mg]) infused over 60 (± 5) minutes.
Primary Outcome Measure Information:
Title
Plasma Pharmacokinetic Parameters of Ceftaroline and Avibactam: Area under the plasma concentration versus time curve, Cmax, Tmax, T½, , CL, Vz, and Vss.
Description
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.
Time Frame
Up to 3 days
Secondary Outcome Measure Information:
Title
Safety and Tolerability of a Single Dose of IV Ceftaroline fosamil and Avibactam.
Description
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.
Time Frame
24-36 hours after last study procedure

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Monitor
Organizational Affiliation
Forest Laboratories
Official's Role
Study Director
Facility Information:
Facility Name
Investigational Site
City
Fresno
State/Province
California
ZIP/Postal Code
93711
Country
United States
Facility Name
Investigational Site
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
Investigational Site
City
San Diego
State/Province
California
ZIP/Postal Code
92123
Country
United States
Facility Name
Investigational Site
City
Stanford
State/Province
California
ZIP/Postal Code
94605
Country
United States
Facility Name
Investigational Site
City
Hartford
State/Province
Connecticut
ZIP/Postal Code
06102
Country
United States
Facility Name
Investigational Site
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Facility Name
Investigational Site
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Facility Name
Investigational Site
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Investigational Site
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Investigational Site
City
Maywood
State/Province
Illinois
ZIP/Postal Code
60153
Country
United States
Facility Name
Investigational Site
City
Peoria
State/Province
Illinois
ZIP/Postal Code
61606
Country
United States
Facility Name
Investigational Site
City
Duluth
State/Province
Minnesota
ZIP/Postal Code
55805
Country
United States
Facility Name
Investigational Site
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68131
Country
United States
Facility Name
Investigational Site
City
Neptune
State/Province
New Jersey
ZIP/Postal Code
07753
Country
United States
Facility Name
Investigational Site
City
Winston Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
Facility Name
Investigational Site
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Investigational Site
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Investigational Site
City
Dayton
State/Province
Ohio
ZIP/Postal Code
45409
Country
United States
Facility Name
Investigational Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77401
Country
United States
Facility Name
Investigational Site
City
Herston
State/Province
Queensland
ZIP/Postal Code
4029
Country
Australia
Facility Name
Investigational Site
City
Southport
State/Province
Queensland
ZIP/Postal Code
4215
Country
Australia

12. IPD Sharing Statement

Citations:
PubMed Identifier
30221827
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.
Results Reference
derived

Learn more about this trial

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

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