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

NCT01664065 | Completed Phase 1

• 1 other identifier: D3720C00012
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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

Conditions

Renal Disease

Keywords

Patient Safety; Tolerability; Pharmacokinetics

Outcome Measures

Primary Outcomes (3)

• 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.

  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)

  pre-dose, 20, 40, 60, 65, 75, 90 min, 2.25, 3.25 , 4.25, 5.25, 8, 12, 24, 36, 48 h

• 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.

  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)

  pre-dose, 20, 40, 60, 65, 75, 90 min, 2.25, 3.25 , 4.25, 5.25, 8, 12, 24, 36, 48 h

• Pharmacokinetics of Ceftaroline after intravenous infusion of Ceftaroline fosamil in patients with end stage renal diseaseand to characterise the clearance of Ceftaroline.

  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

  pre-dose, 20, 40, 60, 65, 75, 90 min, 2.25, 3.25 , 4.25, 5.25, 8, 12, 24, 36, 48 h

Secondary Outcomes (5)

• Safety and tolerability in terms of adverse events, laboratory data, physical examinations, ECG and vital signs.

  Screening up to 10 days after discharge from study site.

• 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.

  pre-dose, 20, 40, 60, 65, 75, 90 min, 2.25, 3.25 , 4.25, 5.25, 8, 12, 24, 36, 48 h

• 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.

  pre-dose, 20, 40, 60, 65, 75, 90 min, 2.25, 3.25 , 4.25, 5.25, 8, 12, 24, 36, 48 h

• 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.

  pre-dose, 20, 40, 60, 65, 75, 90 min, 2.25, 3.25 , 4.25, 5.25, 8, 12, 24, 36, 48 h

• 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.

  pre-dose, 20, 40, 60, 65, 75, 90 min, 2.25, 3.25 , 4.25, 5.25, 8, 12, 24, 36, 48 h

Study Arms (2)

AZ drug: A

EXPERIMENTAL

200 mg Ceftaroline fosamil 1h infusion

Drug: 200 mg Ceftaroline fosamil

AZ drug: B

EXPERIMENTAL

600 mg Ceftaroline fosamil 1h infusion

Drug: 600 mg Ceftaroline fosamil

Interventions

200 mg Ceftaroline fosamil DRUG

1 h infusion

AZ drug: A

600 mg Ceftaroline fosamil DRUG

1 h infusion

AZ drug: B

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Pfizer: lead

Study Sites (1)

Research Site

London, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 26545441 BACKGROUND

• Das S, Li J, Iaconis J, Zhou D, Stone GG, Yan JL, Melnick D. Ceftaroline fosamil doses and breakpoints for Staphylococcus aureus in complicated skin and soft tissue infections. J Antimicrob Chemother. 2019 Feb 1;74(2):425-431. doi: 10.1093/jac/dky439.

  PMID: 30380060 DERIVED

Related Links

• D3720C00012\_SCR\_Synopsis
• D3720C00012 revised csp REDACTED 13Aug2014

MeSH Terms

Conditions

Kidney Diseases

Interventions

Ceftaroline

Condition Hierarchy (Ancestors)

Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Cephalosporins; beta-Lactams; Lactams; Amides; Organic Chemicals; Thiazines; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• David Melnick, MD

  AstraZeneca Pharmaceuticals;C2C-716 1800 Concord PikePO. Box 15437Wilmington De 19850-5437

  STUDY DIRECTOR

• Arpeat Kaviya, MBChB, MRCP

  Quintiles Drug Research Unit at Guy's Hospital 6 Newcomen St

  PRINCIPAL INVESTIGATOR

• Mirjana Kujacic, MD

  AstraZeneca Research and Development SE-431 83 Mölndal

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 10, 2012
• First Posted: August 14, 2012
• Study Start: February 1, 2013
• Primary Completion: November 1, 2013
• Study Completion: November 1, 2013
• Last Updated: September 5, 2017

Record last verified: 2017-09

Locations

GB (1)