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

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

Detailed Description
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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).

Official Title
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A Phase 1, Multicenter, Open-label, Single-dose Study to Assess the Pharmacokinetics of Ceftaroline Fosamil/Avibactam in Adults With Augmented Renal Clearance

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

Intervention / Treatment
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* Drug: Ceftaroline fosamil/Avibactam (CXL)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ceftaroline fosamil/Avibactam<br> | Drug: Ceftaroline fosamil/Avibactam (CXL)<br>* IV infusion of CXL (combination of ceftaroline fosamil [600 mg] plus avibactam [600 mg]) infused over 60 (± 5) minutes.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |