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

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

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

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: 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

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

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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)]	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
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	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)	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
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	Baseline is defined as - Screening up.	From baseline to 14 days after first dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Baseline is defnied as - Screening up	From baseline to 14 days after first dose
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	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)]	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
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	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)	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
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	Baseline is defined as- Screening up.	From baseline to 14 days after first dose)

Collaborators and Investigators

• Sponsor: Pfizer
• 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 MolndalSweden

Publications and helpful links

General Publications

• Edeki T, Kujacic M, Broadhurst H, Li J, Sunzel M. Safety, local tolerability and pharmacokinetics of ceftaroline fosamil administered in a reduced infusion volume. Br J Clin Pharmacol. 2014 Dec;78(6):1291-7. doi: 10.1111/bcp.12465.

Helpful Links

• Related Info
• CSR-D3720C00015.pdf
• Clinical Study Protocol Redacted

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (Actual): September 1, 2012
• Study Completion (Actual): September 1, 2012

Study Registration Dates

• First Submitted: April 5, 2012
• First Submitted That Met QC Criteria: April 13, 2012
• First Posted (Estimate): April 16, 2012

Study Record Updates

• Last Update Posted (Actual): September 5, 2017
• Last Update Submitted That Met QC Criteria: September 1, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: Phase 1; tmax; healthy volunteers; AUC; Cmax; ceftaroline fosamil; cross-over study; various infusion volumes; local tolerability
• Additional Relevant MeSH Terms: Anti-Infective Agents; Anti-Bacterial Agents; Ceftaroline fosamil; Cephalosporins
• Other Study ID Numbers: D3720C00015