A Study to Assess the Pharmacokinetics of Ceftaroline in End Stage Renal Disease Patients and Matched Healthy Subjects

Study Description

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Brief Summary:

The purpose of this study is to assess the safety, tolerability and pharmacokinetics of Ceftaroline in a group of patients with renal disease and matching healthy subjects with normal renal function

Condition or disease	Intervention/treatment	Phase
Renal Disease	Drug: 200 mg Ceftaroline fosamil; Drug: 600 mg Ceftaroline fosamil	Phase 1

Detailed Description:

An Open-label, Nonrandomised, Phase I Study to Assess the Pharmacokinetics of Ceftaroline After Intravenous Administration of aSingle Dose of Ceftaroline Fosamil (200 mg) to Patients with End-stage Renal Disease Undergoing Haemodialysis when Compared to a Single Dose of Ceftaroline Fosamil (600 mg)

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	15 participants
Allocation:	Non-Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Basic Science
Official Title:	An Open-label, Nonrandomised, Phase I Study to Assess the Pharmacokinetics of Ceftaroline After Intravenous Administration of aSingle Dose of Ceftaroline Fosamil (200 mg) to Patients With End-stage Renal Disease Undergoing Haemodialysis When Compared to a Single Dose of Ceftaroline Fosamil (600 mg)
Study Start Date :	February 2013
Actual Primary Completion Date :	November 2013
Actual Study Completion Date :	November 2013

Arms and Interventions

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Arm	Intervention/treatment
Experimental: AZ drug: A; 200 mg Ceftaroline fosamil 1h infusion	Drug: 200 mg Ceftaroline fosamil; 1 h infusion
Experimental: AZ drug: B; 600 mg Ceftaroline fosamil 1h infusion	Drug: 600 mg Ceftaroline fosamil; 1 h infusion

Outcome Measures

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Primary Outcome Measures :

1. Pharmacokinetics of Ceftaroline after intravenous infusion of Ceftaroline Fosamil in patients with end-stage renal disease and a matched control population with normal renal function to characterise the clearance of Ceftaroline. [ Time Frame: pre-dose, 20, 40, 60, 65, 75, 90 min, 2.25, 3.25 , 4.25, 5.25, 8, 12, 24, 36, 48 h ]
   Group 1 (patient group/period 1 and 2); Group 2 (control group - healthy). Maximum plasma concentration (Cmax), time to maximum concentration (tmax), area under the plasma concentration-time curve from zero to infinity (AUC), area under the plasma concentration-time curve from zero to time of the last quantifiable concentration (AUC(0-t)), area under the plasma concentration-time curve from zero to 12 hours after the start of the infusion (AUC(0-12)), terminal rate constant (λz), terminal half-life (t1/2λz),dose normalised Cmax, dose-normalised AUC, dose-normalised AUC(0-t), and dose-normalised AUC(0-12)
2. Pharmacokinetics of Ceftaroline after intravenous infusion of Ceftaroline fosamil in patients with end-stage renal disease and a matched control population with normal renal function to characterise the clearance of Ceftaroline. [ Time Frame: pre-dose, 20, 40, 60, 65, 75, 90 min, 2.25, 3.25 , 4.25, 5.25, 8, 12, 24, 36, 48 h ]
   Group 1 (patient group/period 1 and 2);Group 2 (control group - healthy). Mean residence time (MRT), total body clearance of drug from plasma (CL for ceftaroline fosamil, apparent CL for ceftaroline), volume of distribution based on the terminal phase (Vz for ceftaroline fosamil, apparent Vz for ceftaroline), volume of distribution at steady-state (Vss for ceftaroline fosamil, apparent Vss for ceftaroline)
3. Pharmacokinetics of Ceftaroline after intravenous infusion of Ceftaroline fosamil in patients with end stage renal diseaseand to characterise the clearance of Ceftaroline. [ Time Frame: pre-dose, 20, 40, 60, 65, 75, 90 min, 2.25, 3.25 , 4.25, 5.25, 8, 12, 24, 36, 48 h ]
   Group 1 (patient group/period 2). Area under the plasma concentration -time curve from 75 min to 5.25 hr after the start of the infusion (AUC(1-5)), amount of drug extracted unchanged into the dialysate (AD) during each 1-hour interval, cumulatively, and overall (AD(1-5)) for the entire haemodialysis session (time: 75 min to 5.25 hr after the start of infusion); percent of dose recovered in dialysate (fD,%) during each 1-hour interval, cumulatively, and overall (fD(1-5),%) for the entire haemodialysis session (time: 75 min to 5.25 hr after the start of infusion), extraction coefficient (E) at each time point during haemodialysis

Secondary Outcome Measures :

1. Safety and tolerability in terms of adverse events, laboratory data, physical examinations, ECG and vital signs. [ Time Frame: Screening up to 10 days after discharge from study site. ]
2. Pharmacokinetics of Ceftaroline M-1 after intravenous infusion of Ceftaroline fosamil in patients with end-stage renal disease and a matched control population with normal renal function to characterise the clearance of Ceftaroline. [ Time Frame: pre-dose, 20, 40, 60, 65, 75, 90 min, 2.25, 3.25 , 4.25, 5.25, 8, 12, 24, 36, 48 h ]
   Group 1 (patient group/period 1 and 2); Group 2 (control group - healthy). Maximum plasma concentration (Cmax), time to maximum concentration (tmax), area under the plasma concentration-time curve from zero to infinity (AUC), area under the plasma concentration-time curve from zero to time of the last quantifiable concentration (AUC(0-t)), area under the plasma concentration-time curve from zero to 12 hours after the start of the infusion (AUC(0-12)), terminal rate constant (λz), terminal half-life (t1/2λz),dose normalised Cmax, dose-normalised AUC, dose-normalised AUC(0-t), and dose-normalised AUC(0-12)
3. Pharmacokinetics of Ceftaroline M-1 after intravenous infusion of Ceftaroline fosamil in patients with end stage renal disease and to characterise the clearance of Ceftaroline. [ Time Frame: pre-dose, 20, 40, 60, 65, 75, 90 min, 2.25, 3.25 , 4.25, 5.25, 8, 12, 24, 36, 48 h ]
   Group 1 (patient group/period 2). Area under the plasma concentration -time curve from 75 min to 5.25 hr after the start of the infusion (AUC(1-5)), amount of drug extracted unchanged into the dialysate (AD) during each 1-hour interval, cumulatively, and overall (AD(1-5)) for the entire haemodialysis session (time: 75 min to 5.25 hr after the start of infusion); percent of dose recovered in dialysate (fD,%) during each 1-hour interval, cumulatively, and overall (fD(1-5),%) for the entire haemodialysis session (time: 75 min to 5.25 hr after the start of infusion), extraction coefficient (E) at each time point during haemodialysis
4. Pharmacokinetics of Ceftaroline fosamil after intravenous infusion of Ceftaroline fosamil in patients with end-stage renal disease and a matched control population with normal renal function to characterise the clearance of Ceftaroline. [ Time Frame: pre-dose, 20, 40, 60, 65, 75, 90 min, 2.25, 3.25 , 4.25, 5.25, 8, 12, 24, 36, 48 h ]
   Group 1 (patient group/period 1 and 2); Group 2 (control group - healthy). Maximum plasma concentration (Cmax), time to maximum concentration (tmax), area under the plasma concentration-time curve from zero to infinity (AUC), area under the plasma concentration-time curve from zero to time of the last quantifiable concentration (AUC(0-t)), area under the plasma concentration-time curve from zero to 12 hours after the start of the infusion (AUC(0-12)), terminal rate constant (λz), terminal half-life (t1/2λz),dose normalised Cmax, dose-normalised AUC, dose-normalised AUC(0-t), and dose-normalised AUC(0-12)
5. Pharmacokinetics of Ceftaroline fosamil after intravenous infusion of Ceftaroline fosamil in patients with end-stage renal disease and a matched control population with normal renal function to characterise the clearance of Ceftaroline. [ Time Frame: pre-dose, 20, 40, 60, 65, 75, 90 min, 2.25, 3.25 , 4.25, 5.25, 8, 12, 24, 36, 48 h ]
   Group 1 (patient group/period 1 and 2);Group 2 (control group - healthy). Mean residence time (MRT), total body clearance of drug from plasma (CL for ceftaroline fosamil, apparent CL for ceftaroline), volume of distribution based on the terminal phase (Vz for ceftaroline fosamil, apparent Vz for ceftaroline), volume of distribution at steady-state (Vss for ceftaroline fosamil, apparent Vss for ceftaroline).

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 75 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion criteria:

• Provision of signed and dated, written informed consent prior to any study specific procedures
• Male and female subjects aged 18 to 75 years (inclusive) with suitable veins for cannulation or repeated venipuncture
• Women of childbearing potential must have a negative pregnancy test, be non-lactating, and be using a highly effective form of birth control for 3 months prior to enrollment, during the study, and for 3 months after completion of all study-related proceed
• Have a body mass index (BMI) between 18 and 35 kg/m2 and weigh at between 50 and 110 kg
• Haematocrit level higher than 30% at screening and baseline for each treatment period

Exclusion criteria:

• History or presence of gastrointestinal, hepatic, or any other condition known to interfere with the absorption, distribution, metabolism, or excretion of drugs
• Any clinically significant abnormalities in clinical chemistry, haematology, or urinalysis results, as judged by the investigator
• Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG that may interfere with the interpretation of QTc interval changes
• History of any clinically significant disease or disorder which, in the opinion of the investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study
• Receiving any dialysis treatment other than intermittent haemodialysis

Contacts and Locations

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Locations

United Kingdom
Research Site
London, United Kingdom

Sponsors and Collaborators

Pfizer

Investigators

Study Director:	David Melnick, MD	AstraZeneca Pharmaceuticals;C2C-716 1800 Concord PikePO. Box 15437Wilmington De 19850-5437
Principal Investigator:	Arpeat Kaviya, MBChB, MRCP	Quintiles Drug Research Unit at Guy's Hospital 6 Newcomen St
Study Chair:	Mirjana Kujacic, MD	AstraZeneca Research and Development SE-431 83 Mölndal

More Information

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Additional Information:

D3720C00012_SCR_Synopsis 

D3720C00012 revised csp REDACTED 13Aug2014 

Publications:

Sunzel M, Learoyd M, Li J, Li Y, Ngo N, Edeki T. An open-label, non-randomised, phase 1, single-dose study to assess the pharmacokinetics of ceftaroline in patients with end-stage renal disease requiring intermittent haemodialysis. Int J Antimicrob Agents. 2015 Dec;46(6):682-8. doi: 10.1016/j.ijantimicag.2015.09.009. Epub 2015 Oct 22.

Responsible Party:	Pfizer
ClinicalTrials.gov Identifier:	NCT01664065 History of Changes
Other Study ID Numbers:	D3720C00012
First Posted:	August 14, 2012
Last Update Posted:	September 5, 2017
Last Verified:	September 2017

Keywords provided by Pfizer:

Patient Safety; Tolerability; Pharmacokinetics

Additional relevant MeSH terms:

Kidney Diseases; Kidney Failure, Chronic; Urologic Diseases; Renal Insufficiency, Chronic	Renal Insufficiency; Cephalosporins; Anti-Bacterial Agents; Anti-Infective Agents