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

NCT01577589 | Completed Phase 1

• 1 other identifier: D3720C00015
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Healthy

Keywords

Phase 1; healthy volunteers; cross-over study; ceftaroline fosamil; various infusion volumes; local tolerability; Cmax; tmax; AUC

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (4)

• 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

  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

  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

  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

  From baseline to 14 days after first dose)

Study Arms (6)

A

EXPERIMENTAL

600 mg ceftaroline fosamil in 50 ml infusion volume

Drug: 600 mg ceftaroline fosamil in 50 ml infusion volume

B

PLACEBO COMPARATOR

Placebo in 50 ml infusion volume

Drug: Placebo in 50 ml infusion volume

C

EXPERIMENTAL

600 ceftaroline fosamil in 250 ml infusion volume

Drug: 600 ceftaroline fosamil in 250 ml infusion volume

D

PLACEBO COMPARATOR

Placebo in 250 ml infusion volume

Drug: Placebo in 250 ml infusion volume

E

EXPERIMENTAL

600 mg ceftaroline in 100 ml infusion volume

Drug: 600 mg ceftaroline in 100 ml infusion volume

F

PLACEBO COMPARATOR

Placebo in 100 ml infusion volume

Drug: Placebo in 100 ml infusion volume

Interventions

600 mg ceftaroline fosamil in 50 ml infusion volume DRUG

IV infusion

A

Placebo in 50 ml infusion volume DRUG

IV infusion

B

600 ceftaroline fosamil in 250 ml infusion volume DRUG

IV infusion

C

Placebo in 250 ml infusion volume DRUG

IV infusion

D

600 mg ceftaroline in 100 ml infusion volume DRUG

IV infusion

E

Placebo in 100 ml infusion volume DRUG

IV infusion

F

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 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Pfizer: lead

Study Sites (1)

Research site

London, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 25041494 DERIVED

Related Links

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

MeSH Terms

Interventions

Ceftaroline

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 PharmaceuticalsC2C-7161800 Concord PikePO. Box 15437Wilmington De 19850-5437

  STUDY DIRECTOR

• Elizabeth Tranter, MBCHB MRCP

  Hammersmith Medicines Research Cumberland Avenue London NW10 EW UK

  PRINCIPAL INVESTIGATOR

• Mirjana Kujacic, MD

  AstraZeneca Research and DevelopmentSE-431 83 MölndalSweden

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 5, 2012
• First Posted: April 16, 2012
• Study Start: April 1, 2012
• Primary Completion: September 1, 2012
• Study Completion: September 1, 2012
• Last Updated: September 5, 2017

Record last verified: 2017-09

Locations

GB (1)