A 2-part Study to Assess Local Tolerability, Safety and Pharmacokinetics of Ceftaroline in Healthy Subjects

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01577589
First received: April 5, 2012
Last updated: July 9, 2014
Last verified: July 2014
  Purpose

The purpose of this study is to assess the safety, tolerability, and pharmacokinetics of Ceftaroline 600 mg when administered by varying infusion volumes.


Condition Intervention Phase
Healthy
Drug: 600 mg ceftaroline fosamil in 50 ml infusion volume
Drug: Placebo in 50 ml infusion volume
Drug: 600 ceftaroline fosamil in 250 ml infusion volume
Drug: Placebo in 250 ml infusion volume
Drug: 600 mg ceftaroline in 100 ml infusion volume
Drug: Placebo in 100 ml infusion volume
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Basic Science
Official Title: A Phase I, Single-center, 2-part, Randomized, 2-way Crossover Study to Assess the Local Tolerability and Safety (Multiple-dose) and to Assess the Pharmacokinetics, Safety, and Tolerability (Single-dose) of Ceftaroline in Healthy Subjects When Ceftaroline Fosamil is Diluted in Various Infusion Volume

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • 24-hour pharmacokinetic profile in terms of (see description) for ceftaroline following single-dose administration of ceftaroline fosamil 600 mg diluted in various infusion volumes [ Time Frame: Pre-dose, 20 min, 40 min, 60 min, 65 min, 75 min, 90 min, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 18 h, 24 h post-dose ] [ Designated as safety issue: No ]
    Maximum plasma concentration (Cmax) Time to maximum concentration (tmax) Area under the 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)]

  • 24-hour pharmacokinetic profile in terms of (see description)for ceftaroline following single-dose administration of ceftaroline fosamil 600 mg diluted in various infusion volumes [ Time Frame: Pre-dose, 20 min, 40 min, 60 min, 65 min, 75 min, 90 min, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 18 h, 24 h post-dose ] [ Designated as safety issue: No ]
    Apparent terminal elimination rate constant (Lz) Half-life associated with the terminal slope (t½Lz),mean residence time (MRT) Total body clearance of drug from plasma (CL) Volume of distribution based on the terminal phase(Vz) Volume of distribution at steady state (Vss) Cmax ratios of ceftaroline/ceftaroline fosamil and ceftaroline M-1/ceftaroline (RM/D,Cmax) AUC ratios of ceftaroline/ceftaroline fosamil and ceftaroline M-1/ceftaroline (RM/D,AUC)

  • Local tolerability in terms of adverse events including local infusion site tolerability for ceftaroline following ceftaroline 600 mg diluted in various infusion volumes every 12 hours for 72 hours [ Time Frame: From baseline to 14 days after first dose ] [ Designated as safety issue: Yes ]
    Baseline is defined as - Screening up.


Secondary Outcome Measures:
  • Safety profile in terms of vital signs, ECG, laboratory variables, physical examination for ceftaroline following ceftaroline 600 mg diluted in various infusion volumes every 12 hours for 72 hours [ Time Frame: From baseline to 14 days after first dose ] [ Designated as safety issue: Yes ]
    Baseline is defnied as - Screening up

  • 24-hour pharmacokinetic profile in terms of ( see description) for ceftaroline fosamil and ceftaroline M-1following single-dose administration of ceftaroline fosamil 600 mg diluted in various infusion volumes [ Time Frame: Pre-dose, 20 min, 40 min, 60 min, 65 min, 75 min, 90 min, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 18 h, 24 h post-dose ] [ Designated as safety issue: No ]
    Maximum plasma concentration (Cmax) Time to maximum concentration (tmax) Area under the 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)]

  • 24-hour pharmacokinetic profile in terms of ( see description) for ceftaroline fosamil and ceftaroline M-1following single-dose administration of ceftaroline fosamil 600 mg diluted in various infusion volumes [ Time Frame: Pre-dose, 20 min, 40 min, 60 min, 65 min, 75 min, 90 min, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 18 h, 24 h post-dose ] [ Designated as safety issue: No ]
    Apparent terminal elimination rate constant (Lz) Half-life associated with the terminal slope (t½Lz),mean residence time (MRT) Total body clearance of drug from plasma (CL) Volume of distribution based on the terminal phase(Vz) Volume of distribution at steady state (Vss) Cmax ratios of ceftaroline/ceftaroline fosamil and ceftaroline M-1/ceftaroline (RM/D,Cmax) AUC ratios of ceftaroline/ceftaroline fosamil and ceftaroline M-1/ceftaroline (RM/D,AUC)

  • Safety and tolerability profile in terms of adverse events, vital signs, ECG, laboratory variables, physical exam of ceftaroline following single-dose administration of ceftaroline fosamil 600 mg diluted in various infusion volumes [ Time Frame: From baseline to 14 days after first dose) ] [ Designated as safety issue: Yes ]
    Baseline is defined as- Screening up.


Enrollment: 34
Study Start Date: April 2012
Study Completion Date: September 2012
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A
600 mg ceftaroline fosamil in 50 ml infusion volume
Drug: 600 mg ceftaroline fosamil in 50 ml infusion volume
IV infusion
Placebo Comparator: B
Placebo in 50 ml infusion volume
Drug: Placebo in 50 ml infusion volume
IV infusion
Experimental: C
600 ceftaroline fosamil in 250 ml infusion volume
Drug: 600 ceftaroline fosamil in 250 ml infusion volume
IV infusion
Placebo Comparator: D
Placebo in 250 ml infusion volume
Drug: Placebo in 250 ml infusion volume
IV infusion
Experimental: E
600 mg ceftaroline in 100 ml infusion volume
Drug: 600 mg ceftaroline in 100 ml infusion volume
IV infusion
Placebo Comparator: F
Placebo in 100 ml infusion volume
Drug: Placebo in 100 ml infusion volume
IV infusion

Detailed Description:

A Phase I, Single-center, 2-part, Randomized, 2-way Crossover Study to Assess the Local Tolerability and Safety (Multiple-dose) and to Assess the Pharmacokinetics, Safety, and Tolerability (Single-dose) of Ceftaroline in Healthy Subjects when Ceftaroline Fosamil is Diluted in Various Infusion Volume

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Provision of informed consent prior to any study specific requirements
  • 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
  • Male volunteers must be willing to use barrier contraception from the first day of dosing until 3 months after the last dose of IP.
  • Have a body mass index (BMI) between 18 and 30 kg/m2, and weigh at least 50 kg
  • Healthy male and/or female volunteers between the ages of 18 to 75 years inclusive, with veins on the back of both hands and both forearms suitable for cannulation or repeated venipuncture.

Exclusion Criteria:

  • Use of any other investigational compound or participation in another clinical trial within 1 month prior to first administration of IP in this study
  • History of any clinically significant disease or disorder (e.g., neurological, haematological, psychiatric, gastrointestinal, hepatic, renal disease)
  • Positive serology result on screening for serum hepatitis B surface antigen, hepatitis C antibody (HCV), or human immunodeficiency virus (HIV)
  • History or presence of gastrointestinal, hepatic, or renal disease or any other condition known to interfere with the absorption, distribution, metabolism or excretion of drugs
  • Any clinically significant abnormalities in the physical examination, lab, 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: NCT01577589

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 Research Cumberland Avenue London NW10 EW UK
Study Chair: Mirjana Kujacic, MD AstraZeneca Research and DevelopmentSE-431 83 MölndalSweden
  More Information

Additional Information:
No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01577589     History of Changes
Other Study ID Numbers: D3720C00015
Study First Received: April 5, 2012
Last Updated: July 9, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by AstraZeneca:
Phase 1
healthy volunteers
cross-over study
ceftaroline fosamil
various infusion volumes
local tolerability
Cmax
tmax
AUC

ClinicalTrials.gov processed this record on August 19, 2014