A Study to Assess Safety, Tolerability and Pharmacokinetics of Ceftaroline in Healthy Subjects

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01612507
First received: June 4, 2012
Last updated: November 21, 2012
Last verified: November 2012
  Purpose

The purpose of this study is to assess the safety, tolerability, and pharmacokinetics of different dose regimens of Ceftaroline


Condition Intervention Phase
Healthy Volunteers
Drug: 600 mg Ceftaroline fosamil
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Basic Science
Official Title: A Phase I, Single Centre, Randomised, Double-blind, Placebo-controlled Parallel Group Study to Assess the Safety, Tolerability, and Pharmacokinetics of Ceftaroline After Different Intravenous Dose Regimens of Ceftaroline Fosamil to Healthy Subjects

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Safety and tolerability in terms of adverse events, laboratory data, vital signs following single and multiple dose regimens of ceftaroline fosamil compared to placebo [ Time Frame: Screening up to 19 days after first dose ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 24-hour plasma pharmacokinetic profile in terms of (see description) for ceftaroline following single dose administration of ceftaroline fosamil 600 mg (every 12 h) 1 h infusion [ Time Frame: Day 1, 4 and 8: Pre-dose, 20 min, 40 min, 55 min, 65 min, 75 min, 90 min, 120 min, 3 h, 4 h, 6 h, 8 h, 12 h, 18 h 24 h Day 6:predose ] [ Designated as safety issue: No ]
    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 concentrations [AUC(0-t)]; area under the plasma concentration-time curve from zero to 12 hours after the start of the infusion [AUC(0-12), apparent terminal rate constant (λz), terminal half life (t1/2λz,h).

  • 24-hour plasma pharmacokinetic profile in terms of (see description) for ceftaroline following multiple dose administration of ceftaroline fosamil 600 mg (every 12 h) 1 h infusion [ Time Frame: Day 1, 4 and 8: Pre-dose, 20 min, 40 min, 55 min, 65 min, 75 min, 90 min, 120 min, 3 h, 4 h, 6 h, 8 h, 12 h, 18 h 24 h,Day 6:predose ] [ Designated as safety issue: No ]
    Maximum plasma concentration at steady state during dosing interval (Css,max), time to maximum concentration at steady state during dosing interval (tss,max), minimum plasma concentration at steady state during dosing interval (Css,min), area under the plasma concentration time curve from zero to time of the last quantifiable concentrations [AUC(0-t)], area under the plasma concentration-time curve from zero to the end of the dosing interval (AUCτ); average plasma concentration during the dosing interval (Css,av), fluctuation index (FI, %)

  • 24-hour plasma pharmacokinetic profile in terms of (see description) for ceftaroline following single dose administration of ceftaroline fosamil 600 mg (every 8 h) 2 h infusion [ Time Frame: Day 1, 4 and 8: Pre-dose, 30 min, 60 min, 90 min, 115 min, 125 min, 2 h 15 min, 2.5 h, 3 h, 4 h, 6 h, 8 h, 12 h, 18 h 24 h,Day 6:predose ] [ Designated as safety issue: No ]
    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 concentrations [AUC(0-t)]; area under the plasma concentration-time curve from zero to 8 hours after the start of the infusion [AUC(0-8), apparent terminal rate constant (λz), terminal half life (t1/2λz,h).

  • 24 hour plasma pharmacokinetic profile in terms of (see description) for ceftaroline following multiple dose administration of ceftaroline fosamil 600 mg (every 8 h) 2 h infusion [ Time Frame: Day 1,4 and 8: Pre-dose, 30 min, 60 min, 90 min, 115 min, 125 min, 2 h 15 min, 2.5 h, 3 h, 4 h, 6 h, 8 h, 12 h, 18 h 24 h,Day 6:predose ] [ Designated as safety issue: No ]
    Maximum plasma concentration at steady state during dosing interval (Css,max), time to maximum concentration at steady state during dosing interval (tss,max), minimum plasma concentration at steady state during dosing interval (Css,min), area under the plasma concentration time curve from zero to time of the last quantifiable concentrations [AUC(0-t)], area under the plasma concentration-time curve from zero to the end of the dosing interval (AUCτ); average plasma concentration during the dosing interval (Css,av), fluctuation index (FI, %)

  • Urine pharmacokinetic parameters in terms of (see description) for ceftaroline following single dose administration of ceftaroline fosamil 600 mg (every 12 h) 1 h infusion [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    Amount of analyte excreted in the urine (Ae) during each interval and cumulatively, fraction of dose excreted into urine (fe,%) during each interval and cumulatively, total fraction of dose excreted in urine for all analytes combined (fe,total¬,%), and renal clearance (CLR).

  • Urine pharmacokinetic parameters in terms of (see description) for ceftaroline following multiple dose administration of ceftaroline fosamil 600 mg (every 12 h) 1 h infusion [ Time Frame: Day 8 ] [ Designated as safety issue: No ]
    Amount of analyte excreted in the urine (Ae,ss, mg) during each interval and cumulatively up to the end of the dosing interval, fraction of dose excreted into urine (fe,ss,%) during each interval and cumulatively up to the end of the dosing interval, total fraction of dose excreted in urine for all analytes combined (fe,ss,total ,%), and renal clearance (CLR,ss, L/h).

  • 24-hour plasma pharmacokinetic profile in terms of (see description) for ceftaroline fosamil following single dose administration of ceftaroline fosamil 600 mg (every 12 h) 1 h infusion [ Time Frame: Day 1, 4 and 8: Pre-dose, 20 min, 40 min, 55 min, 65 min, 75 min, 90 min, 120 min, 3 h, 4 h, 6 h, 8 h, 12 h, 18 h 24 h,Day 6:predose ] [ Designated as safety issue: No ]
    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 concentrations [AUC(0-t)]; area under the plasma concentration-time curve from zero to 12 hours after the start of the infusion [AUC(0-12), apparent terminal rate constant (λz), terminal half life (t1/2λz,h).

  • 24-hour plasma pharmacokinetic profile in terms of (see description) for ceftaroline fosamil following multiple dose administration of ceftaroline fosamil 600 mg (every 12 h) 1 h infusion [ Time Frame: Day 1, 4 and 8: Pre-dose, 20 min, 40 min, 55 min, 65 min, 75 min, 90 min, 120 min, 3 h, 4 h, 6 h, 8 h, 12 h, 18 h 24 h,Day 6:predose ] [ Designated as safety issue: No ]
    Maximum plasma concentration at steady state during dosing interval (Css,max), time to maximum concentration at steady state during dosing interval (tss,max), minimum plasma concentration at steady state during dosing interval (Css,min), area under the plasma concentration time curve from zero to time of the last quantifiable concentrations [AUC(0-t)], area under the plasma concentration-time curve from zero to the end of the dosing interval (AUCτ); average plasma concentration during the dosing interval (Css,av), fluctuation index (FI, %)

  • 24-hour plasma pharmacokinetic profile in terms of (see description) for ceftaroline fosamil following single dose administration of ceftaroline fosamil 600 mg (every 8 h) 2 h infusion [ Time Frame: Day 1, 4 and 8: Pre-dose, 30 min, 60 min, 90 min, 115 min, 125 min, 2 h 15 min, 2.5 h, 3 h, 4 h, 6 h, 8 h, 12 h, 18 h 24 h,Day 6:predose ] [ Designated as safety issue: No ]
    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 concentrations [AUC(0-t)]; area under the plasma concentration-time curve from zero to 8 hours after the start of the infusion [AUC(0-8), apparent terminal rate constant (λz), terminal half life (t1/2λz,h).

  • 24-hour plasma pharmacokinetic profile in terms of (see description) for ceftaroline fosamil following multiple dose administration of ceftaroline fosamil 600 mg (every 8 h) 2 h infusion [ Time Frame: Day 1, 4 and 8: Pre-dose, 30 min, 60 min, 90 min, 115 min, 125 min, 2 h 15 min, 2.5 h, 3 h, 4 h, 6 h, 8 h, 12 h, 18 h 24 h,Day 6:predose ] [ Designated as safety issue: No ]
    Maximum plasma concentration at steady state during dosing interval (Css,max), time to maximum concentration at steady state during dosing interval (tss,max), minimum plasma concentration at steady state during dosing interval (Css,min), area under the plasma concentration time curve from zero to time of the last quantifiable concentrations [AUC(0-t)], area under the plasma concentration-time curve from zero to the end of the dosing interval (AUCτ); average plasma concentration during the dosing interval (Css,av), fluctuation index (FI, %)

  • 24-hour plasma pharmacokinetic profile in terms of (see description) for ceftaroline M-1 following single dose administration of ceftaroline fosamil 600 mg (every 12 h) 1 h infusion [ Time Frame: Day 1, 4 and 8: Pre-dose, 20 min, 40 min, 55 min, 65 min, 75 min, 90 min, 120 min, 3 h, 4 h, 6 h, 8 h, 12 h, 18 h 24 h,Day 6:predose ] [ Designated as safety issue: No ]
    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 concentrations [AUC(0-t)]; area under the plasma concentration-time curve from zero to 12 hours after the start of the infusion [AUC(0-12), apparent terminal rate constant (λz), terminal half life (t1/2λz,h).

  • 24-hour plasma pharmacokinetic profile in terms of (see description) for ceftaroline M-1 following multiple dose administration of ceftaroline fosamil 600 mg (every 12 h) 1 h infusion [ Time Frame: Day 1, 4 and 8: Pre-dose, 20 min, 40 min, 55 min, 65 min, 75 min, 90 min, 120 min, 3 h, 4 h, 6 h, 8 h, 12 h, 18 h 24 h,Day 6:predose ] [ Designated as safety issue: No ]
    Maximum plasma concentration at steady state during dosing interval (Css,max), time to maximum concentration at steady state during dosing interval (tss,max), minimum plasma concentration at steady state during dosing interval (Css,min), area under the plasma concentration time curve from zero to time of the last quantifiable concentrations [AUC(0-t)], area under the plasma concentration-time curve from zero to the end of the dosing interval (AUCτ); average plasma concentration during the dosing interval (Css,av), fluctuation index (FI,%)

  • 24-hour plasma pharmacokinetic profile in terms of (see description) for ceftaroline M-1 following single dose administration of ceftaroline fosamil 600 mg (every 8 h) 2 h infusion [ Time Frame: Day 1, 4 and 8: Pre-dose, 30 min, 60 min, 90 min, 115 min, 125 min, 2 h 15 min, 2.5 h, 3 h, 4 h, 6 h, 8 h, 12 h, 18 h 24 h,Day 6:predose ] [ Designated as safety issue: No ]
    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 concentrations [AUC(0-t)]; area under the plasma concentration-time curve from zero to 8 hours after the start of the infusion [AUC(0-8), apparent terminal rate constant (λz), terminal half life (t1/2λz,h).

  • 24-hour plasma pharmacokinetic profile in terms of (see description) for ceftaroline M-1 following multiple dose administration of ceftaroline fosamil 600 mg (every 8 h) 2 h infusion [ Time Frame: Day 1, 4 and 8: Pre-dose, 30 min, 60 min, 90 min, 115 min, 125 min, 2 h 15 min, 2.5 h, 3 h, 4 h, 6 h, 8 h, 12 h, 18 h 24 h,Day 6:predose ] [ Designated as safety issue: No ]
    Maximum plasma concentration at steady state during dosing interval (Css,max), time to maximum concentration at steady state during dosing interval (tss,max), minimum plasma concentration at steady state during dosing interval (Css,min), area under the plasma concentration time curve from zero to time of the last quantifiable concentrations [AUC(0-t)], area under the plasma concentration-time curve from zero to the end of the dosing interval (AUCτ); average plasma concentration during the dosing interval (Css,av), fluctuation index (FI, %)

  • Urine pharmacokinetic parameters in terms of (see description) for ceftaroline fosamil following single dose administration of ceftaroline fosamil 600 mg (every 12 h) 1 h infusion [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    Amount of analyte excreted in the urine (Ae) during each interval and cumulatively, fraction of dose excreted into urine (fe,%) during each interval and cumulatively, total fraction of dose excreted in urine for all analytes combined (fe,total¬,%), and renal clearance (CL R).

  • Urine pharmacokinetic parameters in terms of (see description) for ceftaroline fosamil following multiple dose administration of ceftaroline fosamil 600 mg (every 12 h) 1 h infusion [ Time Frame: Day 8 ] [ Designated as safety issue: No ]
    Amount of analyte excreted in the urine (Ae,ss, mg) during each interval and cumulatively up to the end of the dosing interval, fraction of dose excreted into urine (fe,ss,%) during each interval and cumulatively up to the end of the dosing interval, total fraction of dose excreted in urine for all analytes combined (fe,ss,total ,%), and renal clearance (CLR,ss, L/h).

  • Urine pharmacokinetic parameters in terms of (see description) for ceftaroline fosamil following single dose administration of ceftaroline fosamil 600 mg (every 8 h) 2 h infusion [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    Amount of analyte excreted in the urine (Ae) during each interval and cumulatively, fraction of dose excreted into urine (fe,%) during each interval and cumulatively, total fraction of dose excreted in urine for all analytes combined (fe,total¬,%), and renal clearance (CLR).

  • Urine pharmacokinetic parameters in terms of (see description) for ceftaroline fosamil following multiple dose administration of ceftaroline fosamil 600 mg (every 8 h) 2 h infusion [ Time Frame: Day 8 ] [ Designated as safety issue: No ]
    Amount of analyte excreted in the urine (Ae,ss, mg) during each interval and cumulatively up to the end of the dosing interval, fraction of dose excreted into urine (fe,ss,%) during each interval and cumulatively up to the end of the dosing interval, total fraction of dose excreted in urine for all analytes combined (fe,ss,total ,%), and renal clearance (CLR,ss, L/h).

  • Urine pharmacokinetic parameters in terms of (see description) for ceftaroline M- 1 following single dose administration of ceftaroline fosamil 600 mg (every 12 h) 1 h infusion [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    Amount of analyte excreted in the urine (Ae) during each interval and cumulatively, fraction of dose excreted into urine (fe,%) during each interval and cumulatively, total fraction of dose excreted in urine for all analytes combined (fe,total¬,%), and renal clearance (CLR).

  • Urine pharmacokinetic parameters in terms of (see description) for ceftaroline M- 1 following multiple dose administration of ceftaroline fosamil 600 mg (every 12 h) 1 h infusion [ Time Frame: Day 8 ] [ Designated as safety issue: No ]
    Amount of analyte excreted in the urine (Ae,ss, mg) during each interval and cumulatively up to the end of the dosing interval, fraction of dose excreted into urine (fe,ss,%) during each interval and cumulatively up to the end of the dosing interval, total fraction of dose excreted in urine for all analytes combined (fe,ss,total ,%), and renal clearance (CLR,ss, L/h).

  • Urine pharmacokinetic parameters in terms of (see description) for ceftaroline M- 1 following single dose administration of ceftaroline fosamil 600 mg (every 8 h) 2 h infusion [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    Amount of analyte excreted in the urine (Ae) during each interval and cumulatively, fraction of dose excreted into urine (fe,%) during each interval and cumulatively, total fraction of dose excreted in urine for all analytes combined (fe,total¬,%), and renal clearance (CLR).

  • Urine pharmacokinetic parameters in terms of (see description) for ceftaroline M- 1 following multiple dose administration of ceftaroline fosamil 600 mg (every 8 h) 2 h infusion [ Time Frame: Day 8 ] [ Designated as safety issue: No ]
    Amount of analyte excreted in the urine (Ae,ss, mg) during each interval and cumulatively up to the end of the dosing interval, fraction of dose excreted into urine (fe,ss,%) during each interval and cumulatively up to the end of the dosing interval, total fraction of dose excreted in urine for all analytes combined (fe,ss,total ,%), and renal clearance (CLR,ss, L/h).

  • Urine pharmacokinetic parameters in terms of (see description) for ceftaroline following single dose administration of ceftaroline fosamil 600 mg (every 8 h) 2 h infusion [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    Amount of analyte excreted in the urine (Ae) during each interval and cumulatively, fraction of dose excreted into urine (fe,%) during each interval and cumulatively, total fraction of dose excreted in urine for all analytes combined (fe,total¬,%), and renal clearance (CLR).

  • Urine pharmacokinetic parameters in terms of (see description) for ceftaroline following multiple dose administration of ceftaroline fosamil 600 mg (every 8 h) 2 h infusion [ Time Frame: Day 8 ] [ Designated as safety issue: No ]
    amount of analyte excreted in the urine (Ae,ss, mg) during each interval and cumulatively up to the end of the dosing interval, fraction of dose excreted into urine (fe,ss,%) during each interval and cumulatively up to the end of the dosing interval, total fraction of dose excreted in urine for all analytes combined (fe,ss,total ,%), and renal clearance (CLR,ss, L/h).

  • 24-hour plasma pharmacokinetic profile in terms of (see description) for ceftaroline following single dose administration of ceftaroline fosamil 600 mg (every 12 h) 1 h infusion [ Time Frame: Day 1, 4 and 8: Pre-dose, 20 min, 40 min, 55 min, 65 min, 75 min, 90 min, 120 min, 3 h, 4 h, 6 h, 8 h, 12 h, 18 h 24 h Day 6:predose ] [ Designated as safety issue: No ]
    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), and volume of distribution at steady state (Vss for ceftaroline fosamil, apparent Vss for ceftaroline).

  • 24-hour plasma pharmacokinetic profile in terms of (see description) for ceftaroline following multiple dose administration of ceftaroline fosamil 600 mg (every 12 h) 1 h infusion [ Time Frame: Day 1, 4 and 8: Pre-dose, 20 min, 40 min, 55 min, 65 min, 75 min, 90 min, 120 min, 3 h, 4 h, 6 h, 8 h, 12 h, 18 h 24 h,Day 6:predose ] [ Designated as safety issue: No ]
    Apparent terminal rate constant (λz), terminal half-life (t½λz, h), accumulation ratio based on Cmax [Rac(Cmax)], accumulation ratio based on AUC [Rac(AUC)], and linearity factor.Mean residence time (MRT), plasma clearance at steady state (CLss for ceftaroline fosamil, apparent CLss for ceftaroline), volume of distribution based on the terminal phase (Vz for ceftaroline fosamil, apparent Vz for ceftaroline), and volume of distribution at steady state (Vss for ceftaroline fosamil, apparent Vss for ceftaroline).

  • 24-hour plasma pharmacokinetic profile in terms of (see description) for ceftaroline following single dose administration of ceftaroline fosamil 600 mg (every 8 h) 2 h infusion [ Time Frame: Day 1, 4 and 8: Pre-dose, 30 min, 60 min, 90 min, 115 min, 125 min, 2 h 15 min, 2.5 h, 3 h, 4 h, 6 h, 8 h, 12 h, 18 h 24 h,Day 6:predose ] [ Designated as safety issue: No ]
    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), and volume of distribution at steady state (Vss for ceftaroline fosamil, apparent Vss for ceftaroline).

  • 24 hour plasma pharmacokinetic profile in terms of (see description) for ceftaroline following multiple dose administration of ceftaroline fosamil 600 mg (every 8 h) 2 h infusion [ Time Frame: Day 1,4 and 8: Pre-dose, 30 min, 60 min, 90 min, 115 min, 125 min, 2 h 15 min, 2.5 h, 3 h, 4 h, 6 h, 8 h, 12 h, 18 h 24 h,Day 6:predose ] [ Designated as safety issue: No ]
    Apparent terminal rate constant (λz), terminal half-life (t½λz, h), accumulation ratio based on Cmax [Rac(Cmax)], accumulation ratio based on AUC [Rac(AUC)], and linearity factor. Mean residence time (MRT), plasma clearance at steady state (CLss for ceftaroline fosamil, apparent CLss for ceftaroline), volume of distribution based on the terminal phase (Vz for ceftaroline fosamil, apparent Vz for ceftaroline), and volume of distribution at steady state (Vss for ceftaroline fosamil, apparent Vss for ceftaroline).

  • 24-hour plasma pharmacokinetic profile in terms of (see description) for ceftaroline fosamil following single dose administration of ceftaroline fosamil 600 mg (every 12 h) 1 h infusion [ Time Frame: Day 1, 4 and 8: Pre-dose, 20 min, 40 min, 55 min, 65 min, 75 min, 90 min, 120 min, 3 h, 4 h, 6 h, 8 h, 12 h, 18 h 24 h,Day 6:predose ] [ Designated as safety issue: No ]
    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), and volume of distribution at steady state (Vss for ceftaroline fosamil, apparent Vss for ceftaroline).

  • 24-hour plasma pharmacokinetic profile in terms of (see description) for ceftaroline fosamil following multiple dose administration of ceftaroline fosamil 600 mg (every 12 h) 1 h infusion [ Time Frame: Day 1, 4 and 8: Pre-dose, 20 min, 40 min, 55 min, 65 min, 75 min, 90 min, 120 min, 3 h, 4 h, 6 h, 8 h, 12 h, 18 h 24 h,Day 6:predose ] [ Designated as safety issue: No ]
    Apparent terminal rate constant (λz), terminal half-life (t½λz, h), accumulation ratio based on Cmax [Rac(Cmax)], accumulation ratio based on AUC [Rac(AUC)], and linearity factor.Mean residence time (MRT), plasma clearance at steady state (CLss for ceftaroline fosamil, apparent CLss for ceftaroline), volume of distribution based on the terminal phase (Vz for ceftaroline fosamil, apparent Vz for ceftaroline), and volume of distribution at steady state (Vss for ceftaroline fosamil, apparent Vss for ceftaroline).

  • 24-hour plasma pharmacokinetic profile in terms of (see description) for ceftaroline fosamil following single dose administration of ceftaroline fosamil 600 mg (every 8 h) 2 h infusion [ Time Frame: Day 1, 4 and 8: Pre-dose, 30 min, 60 min, 90 min, 115 min, 125 min, 2 h 15 min, 2.5 h, 3 h, 4 h, 6 h, 8 h, 12 h, 18 h 24 h,Day 6:predose ] [ Designated as safety issue: No ]
    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), and volume of distribution at steady state (Vss for ceftaroline fosamil, apparent Vss for ceftaroline).

  • 24-hour plasma pharmacokinetic profile in terms of (see description) for ceftaroline fosamil following multiple dose administration of ceftaroline fosamil 600 mg (every 8 h) 2 h infusion [ Time Frame: Day 1, 4 and 8: Pre-dose, 30 min, 60 min, 90 min, 115 min, 125 min, 2 h 15 min, 2.5 h, 3 h, 4 h, 6 h, 8 h, 12 h, 18 h 24 h,Day 6:predose ] [ Designated as safety issue: No ]
    Apparent terminal rate constant (λz), terminal half-life (t½λz, h), accumulation ratio based on Cmax [Rac(Cmax)], accumulation ratio based on AUC [Rac(AUC)], and linearity factor. Mean residence time (MRT), plasma clearance at steady state (CLss for ceftaroline fosamil, apparent CLss for ceftaroline), volume of distribution based on the terminal phase (Vz for ceftaroline fosamil, apparent Vz for ceftaroline), and volume of distribution at steady state (Vss for ceftaroline fosamil, apparent Vss for ceftaroline).

  • 24-hour plasma pharmacokinetic profile in terms of (see description) for ceftaroline M-1 following multiple dose administration of ceftaroline fosamil 600 mg (every 12 h) 1 h infusion [ Time Frame: Day 1, 4 and 8: Pre-dose, 20 min, 40 min, 55 min, 65 min, 75 min, 90 min, 120 min, 3 h, 4 h, 6 h, 8 h, 12 h, 18 h 24 h,Day 6:predose ] [ Designated as safety issue: No ]
    Apparent terminal rate constant (λz), terminal half-life (t½λz, h), accumulation ratio based on Cmax [Rac(Cmax)], accumulation ratio based on AUC [Rac(AUC)], and linearity factor.

  • 24-hour plasma pharmacokinetic profile in terms of (see description) for ceftaroline M-1 following multiple dose administration of ceftaroline fosamil 600 mg (every 8 h) 2 h infusion [ Time Frame: Day 1, 4 and 8: Pre-dose, 30 min, 60 min, 90 min, 115 min, 125 min, 2 h 15 min, 2.5 h, 3 h, 4 h, 6 h, 8 h, 12 h, 18 h 24 h,Day 6:predose ] [ Designated as safety issue: No ]
    Apparent terminal rate constant (λz), terminal half-life (t½λz, h), accumulation ratio based on Cmax [Rac(Cmax)], accumulation ratio based on AUC [Rac(AUC)], and linearity factor.


Enrollment: 41
Study Start Date: July 2012
Study Completion Date: November 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A
600 mg Ceftaroline fosamil 1 h infusion
Drug: 600 mg Ceftaroline fosamil
1 h infusion
Experimental: B
Placebo 1 h infusion
Drug: Placebo
1 h infusion
Experimental: C
600 mg Ceftaroline fosamil 2 h infusion
Drug: 600 mg Ceftaroline fosamil
2 h infusion
Experimental: D
Placebo 2 h infusion
Drug: Placebo
2 h infusion

Detailed Description:

A Phase I, Single Centre, Randomised, Double-blind, Placebo-controlled Parallel Group Study to Assess the Safety, Tolerability, and Pharmacokinetics of Ceftaroline after Different Intravenous Dose Regimens of Ceftaroline Fosamil to Healthy Subjects

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Provision of signed and dated, written informed consent prior to any study specific procedures including the optional safety biomarker analysis
  • Healthy male and female subjects aged 18 to 55 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 1 month 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 30 kg/m2 and weigh at least 50 kg and no more than 100 kg

Exclusion Criteria:

  • Has received another new chemical entity (defined as a compound which has not been approved for marketing) or has participated in any other clinical study that included drug treatment within 3 months of the first administration of investigational drug
  • 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
  • Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody, and human immunodeficiency virus (HIV)
  • History or presence of gastrointestinal, hepatic, or renal disease or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs
  • Any clinically significant abnormalities in the physical examination, 12-lead ECG, or vital signs, as judged by the Investigator
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01612507

Locations
United Kingdom
Research site
London, United Kingdom
Sponsors and Collaborators
AstraZeneca
Investigators
Study Director: David Melnick, MD AstraZeneca PharmaceuticalsC2C-7161800 Concord PikePO. Box 15437Wilmington De 19850-5437
Principal Investigator: Elizabeth Tranter, MBCHB MRCP Hammersmith Medicines Cumberland Avenue London NW10 7EW UK
Study Chair: Mirjana Kujacic, MD AstraZeneca Research and DevelopmentSE-431 83 MolndalSweden
  More Information

No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01612507     History of Changes
Other Study ID Numbers: D3720C00010
Study First Received: June 4, 2012
Last Updated: November 21, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by AstraZeneca:
Phase 1
healthy volunteers
Parallel Group Study
ceftaroline fosamil different doses
safety
Cmax
tmax
AUC

ClinicalTrials.gov processed this record on September 11, 2014