Ceftaroline China Pharmacokinetics Study (CeftarolineChi)

A Phase I, Single Center, Open Label, Two Groups Study to Assess the Safety and Pharmacokinetics of Ceftaroline in Healthy Chinese Volunteers Following Single and Multiple Administration of 600 mg Ceftaroline Fosamil as 60-minute Intravenous Infusion Every 12 Hours and as 120-minute Intravenous Infusion Every 8 Hours

The purpose of this study is to evaluate the pharmacokinetics, safety and tolerability of ceftaroline in Chinese healthy subjects following single and multiple intravenous doses.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Ceftaroline; Drug: Ceftaroline

Detailed Description

A Phase I, Single Center and Open Label Study to Assess the Safety and Pharmacokinetics of Ceftaroline in Healthy Chinese Volunteers Following Single and Multiple Administration of 600 mg Ceftaroline Fosamil as 60-minute Intravenous Infusion Every 12 hours and as 120-minute Intravenous Infusion Every 8 hours.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing, China

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Provision of informed consent prior to any study specific procedures.
• Are healthy male or female Chinese volunteers aged between 18 and 45 inclusive.
• Have a Body Mass Index (BMI) between (and including) 19 and 24 kg/m2 and weigh at least 50 kg.
• Be willing to communicate with the investigator and comply with all study procedures.

Exclusion Criteria:

• Creatine clearance <80 mL/min as calculated by the Cockcroft Gault equation
• History of any hypersensitivity or allergic reaction to any β-lactam antimicrobial.
• Symptoms of any clinically significant illness within 2 weeks of screening.
• Use of any other investigational compound or participation in another clinical trial within 2 months prior to Visit 2.
• Blood donation with 3 months of screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Ceftaroline q12h; Ceftaroline 600mg q12h	Drug: Ceftaroline; 60-minute single intravenous dose of 600 mg of Ceftaroline on Days 1 and 8; 60-minute intravenous dose of 600 mg of Ceftaroline twice per day on Days 3-7.; Drug: Ceftaroline; Single intravenous dose on Days 1 and 9. Intravenous three times per day on Days 2-8.
EXPERIMENTAL: Ceftaroline q8h; ceftaroline 600mg q8h	Drug: Ceftaroline; 60-minute single intravenous dose of 600 mg of Ceftaroline on Days 1 and 8; 60-minute intravenous dose of 600 mg of Ceftaroline twice per day on Days 3-7.; Drug: Ceftaroline; Single intravenous dose on Days 1 and 9. Intravenous three times per day on Days 2-8.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area under the concentration curve of Ceftaroline over the time (AUC).	Group1: Samples taken on Day 8:Pre-dose, 20 min, 40 min, 55 min, 65 min, 75 min, 1.5 hr, 2 hr, 3 hr ,4 hr, 6hr , 8 hr, 12 hr, 18 hr, 24 hr, 36 hr and 48 hr after the start of infusion of the study drug.
Area under the concentration curve of Ceftaroline over the time (AUC).	Group2: Day3 and Day 5 through 8: pre-dose; Day 4: Pre-dose, 60 min, 90 min, 115 min, 125 min, 2 hr15min, 2.5hr, 3 hr ,4hr, 6hr, 8 hr after the start of infusion of the study drug.
Area under the concentration curve of Ceftaroline over the time (AUC).	Group 2: Day 9: Pre-dose, 60 min, 90 min, 115 min, 125 min, 2 hr15min, 2.5hr, 3 hr ,4 hr, 6hr, 8 hr,12hr,18hr,24hr after the start of infusion of the study drug.
Maximum plasma concentration (Cmax) of Ceftaroline.	Group1: Samples taken on Day 8:Pre-dose, 20 min, 40 min, 55 min, 65 min, 75 min, 1.5 hr, 2 hr, 3 hr ,4 hr, 6hr , 8 hr, 12 hr, 18 hr, 24 hr, 36 hr and 48 hr after the start of infusion of the study drug.
Maximum plasma concentration (Cmax) of Ceftaroline.	Group2:Days 2 through 7: Pre-dose Day 8: Pre-dose, 60 min,90 min,115 min,125 min,2 hr15min,2.5hr,3 hr,4 hr,6hr, 8 hr,12hr,18hr,24hr after the start of infusion of the study drug
Area under the concentration curve of Ceftaroline over the time (AUC)	Group1: Samples taken on Day 1:Pre-dose, 20 min, 40 min, 55 min, 65 min, 75 min, 1.5 hr, 2 hr, 3 hr ,4 hr, 6hr , 8 hr, 12 hr, 18 hr, 24 hr, 36 hr and 48 hr after the start of infusion of the study drug.
Area under the concentration curve of Ceftaroline over the time (AUC)	Group2: Samples taken on Day 1:Pre-dose, 60 min, 90 min, 115 min, 125 min, 2 hr15min, 2.5hr, 3 hr ,4 hr, 6hr , 8 hr, 12 hr, 18 hr, 24 hr after the start of infusion of the study drug.
Maximum plasma concentration (Cmax) of Ceftaroline	Group1: Samples taken on Day 1:Pre-dose, 20 min, 40 min, 55 min, 65 min, 75 min, 1.5 hr, 2 hr, 3 hr ,4 hr, 6hr , 8 hr, 12 hr, 18 hr, 24 hr, 36 hr and 48 hr after the start of infusion of the study drug.
Maximum plasma concentration (Cmax) of Ceftaroline	Group2: Samples taken on Day 1:Pre-dose, 60 min, 90 min, 115 min, 125 min, 2 hr15min, 2.5hr, 3 hr ,4 hr, 6hr , 8 hr, 12 hr, 18 hr, 24 hr after the start of infusion of the study drug.

Secondary Outcome Measures

Outcome Measure	Time Frame
Area under the concentration curve of Ceftaroline metabolite (Ceftaroline M-1) over the time (AUC).	Group1: Samples taken on Day 1:Pre-dose, 20 min, 40 min, 55 min, 65 min, 75 min, 1.5 hr, 2 hr, 3 hr ,4 hr, 6hr , 8 hr, 12 hr, 18 hr, 24 hr, 36 hr and 48 hr after the start of infusion of the study drug.
Area under the concentration curve of Ceftaroline metabolite (Ceftaroline M-1) over the time (AUC).	Group2: Samples taken on Day 1:Pre-dose, 60 min, 90 min, 115 min, 125 min, 2 hr15min, 2.5hr, 3 hr ,4 hr, 6hr , 8 hr, 12 hr, 18 hr, 24 hr after the start of infusion of the study drug.
Maximum plasma concentration (Cmax) of Ceftaroline metabolite (Ceftaroline M-1)	Group1: Samples taken on Day 1:Pre-dose, 20 min, 40 min, 55 min, 65 min, 75 min, 1.5 hr, 2 hr, 3 hr ,4 hr, 6hr , 8 hr, 12 hr, 18 hr, 24 hr, 36 hr and 48 hr after the start of infusion of the study drug.
Maximum plasma concentration (Cmax) of Ceftaroline metabolite (Ceftaroline M-1)	Group2: Samples taken on Day 1:Pre-dose, 60 min, 90 min, 115 min, 125 min, 2 hr15min, 2.5hr, 3 hr ,4 hr, 6hr , 8 hr, 12 hr, 18 hr, 24 hr after the start of infusion of the study drug.
Area under the concentration curve of Ceftaroline metabolite (Ceftaroline M-1) over the time (AUC).	Group1: Samples taken on Day 8:Pre-dose, 20 min, 40 min, 55 min, 65 min, 75 min, 1.5 hr, 2 hr, 3 hr ,4 hr, 6hr , 8 hr, 12 hr, 18 hr, 24 hr, 36 hr and 48 hr after the start of infusion of the study drug.
Area under the concentration curve of Ceftaroline metabolite (Ceftaroline M-1) over the time (AUC).	Group2:Days 2 through 7:Pre-dose Day8: Pre-dose,60 min,90 min,115 min,125 min, 2 hr 15min,2.5hr,3 hr,4 hr,6hr,8 hr,12hr,18hr,24hr after the start of infusion of the study drug.
Maximum plasma concentration (Cmax) of Ceftaroline metabolite (Ceftaroline M-1)	Group1: Samples taken on Day 8:Pre-dose, 20 min, 40 min, 55 min, 65 min, 75 min, 1.5 hr, 2 hr, 3 hr ,4 hr, 6hr , 8 hr, 12 hr, 18 hr, 24 hr, 36 hr and 48 hr after the start of infusion of the study drug.
Number of patients with adverse events.	From baseline to day 10
Maximum plasma concentration (Cmax) of Ceftaroline metabolite (Ceftaroline M-1)	Group2: Day3 and Day 5 through 8: pre-dose; Day 4: Pre-dose, 60 min, 90 min, 115 min, 125 min, 2 hr 15min, 2.5hr, 3 hr ,4hr, 6hr, 8 hr after the start of infusion of the study drug.
Maximum plasma concentration (Cmax) of Ceftaroline metabolite (Ceftaroline M-1)	Group2: Day 9: Pre-dose, 60 min, 90 min, 115 min, 125 min, 2 hr15min, 2.5hr, 3 hr ,4 hr, 6hr, 8 hr, 12hr, 18hr, 24hr after the start of infusion of the study drug.
Area under the concentration curve of Ceftaroline fosamil over the time (AUC).	Group1: Samples taken on Day 1:Pre-dose, 20 min, 40 min, 55 min, 65 min, 75 min, 1.5 hr, 2 hr, 3 hr ,4 hr, 6hr , 8 hr, 12 hr, 18 hr, 24 hr, 36 hr and 48 hr after the start of infusion of the study drug.
Area under the concentration curve of Ceftaroline fosamil over the time (AUC).	Group2: Samples taken on Day 1:Pre-dose, 60 min, 90 min, 115 min, 125 min, 2 hr15min, 2.5hr, 3 hr ,4 hr, 6hr , 8 hr, 12 hr, 18 hr, 24 hr after the start of infusion of the study drug.
Maximum plasma concentration (Cmax) of Ceftaroline fosamil	Group1: Samples taken on Day 1:Pre-dose, 20 min, 40 min, 55 min, 65 min, 75 min, 1.5 hr, 2 hr, 3 hr ,4 hr, 6hr , 8 hr, 12 hr, 18 hr, 24 hr, 36 hr and 48 hr after the start of infusion of the study drug.
Maximum plasma concentration (Cmax) of Ceftaroline fosamil	Group2: Samples taken on Day 1:Pre-dose, 60 min, 90 min, 115 min, 125 min, 2 hr15min, 2.5hr, 3 hr ,4 hr, 6hr , 8 hr, 12 hr, 18 hr, 24 hr after the start of infusion of the study drug.
Area under the concentration curve of Ceftaroline fosamil over the time (AUC).	Group1: Samples taken on Day 8:Pre-dose, 20 min, 40 min, 55 min, 65 min, 75 min, 1.5 hr, 2 hr, 3 hr ,4 hr, 6hr , 8 hr, 12 hr, 18 hr, 24 hr, 36 hr and 48 hr after the start of infusion of the study drug.
Area under the concentration curve of Ceftaroline fosamil over the time (AUC).	Group2: Day3 and Day 5 through 8: pre-dose; Day 4: Pre-dose, 60 min, 90 min, 115 min, 125 min, 2 hr15min, 2.5hr, 3 hr ,4hr, 6hr, 8 hr after the start of infusion of the study drug.
Area under the concentration curve of Ceftaroline fosamil over the time (AUC).	Group2: Day 9: Pre-dose, 60 min, 90 min, 115 min, 125 min, 2 hr15min, 2.5hr, 3 hr ,4 hr, 6hr, 8 hr,12hr,18hr,24hr after the start of infusion of the study drug.
Maximum plasma concentration (Cmax) of Ceftaroline fosamil	Group1: Samples taken on Day 8:Pre-dose, 20 min, 40 min, 55 min, 65 min, 75 min, 1.5 hr, 2 hr, 3 hr ,4 hr, 6hr , 8 hr, 12 hr, 18 hr, 24 hr, 36 hr and 48 hr after the start of infusion of the study drug.
Maximum plasma concentration (Cmax) of Ceftaroline fosamil	Group2: Day3 and Day 5 through 8: pre-dose; Day 4: Pre-dose, 60 min, 90 min, 115 min, 125 min, 2 hr 15min, 2.5hr, 3 hr ,4hr, 6hr, 8 hr after the start of infusion of the study drug.
Maximum plasma concentration (Cmax) of Ceftaroline fosamil	Group2: Day 9: Pre-dose, 60 min, 90 min, 115 min, 125 min, 2 hr15min, 2.5hr, 3 hr ,4 hr, 6hr, 8 hr,12hr,18hr,24hr after the start of infusion of the study drug.

Collaborators and Investigators

• Sponsor: Pfizer
• Collaborators: Forest Laboratories
• Investigators: Study Director: David Melnick, AstraZeneca Pharmaceuticals-US

Publications and helpful links

General Publications

• 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.
• Li J, Das S, Zhou D, Al-Huniti N. Population Pharmacokinetic Modeling and Probability of Target Attainment Analyses in Asian Patients With Community-Acquired Pneumonia Treated With Ceftaroline Fosamil. Clin Pharmacol Drug Dev. 2019 Jul;8(5):682-694. doi: 10.1002/cpdd.673. Epub 2019 May 1.
• Yang L, Sunzel M, Xu P, Edeki T, Wilson D, Li J, Li H. Evaluation of the pharmacokinetics and safety of single and multiple ceftaroline fosamil infusions in healthy Chinese and Western subjects. Int J Clin Pharmacol Ther. 2015 Aug;53(8):681-91. doi: 10.5414/CP202343.

Helpful Links

• Related Info
• CSR-D3720C00005.pdf
• Revised_CSP_1_Redacted_12.03.14

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (ACTUAL): April 1, 2012
• Study Completion (ACTUAL): April 1, 2012

Study Registration Dates

• First Submitted: September 30, 2011
• First Submitted That Met QC Criteria: October 24, 2011
• First Posted (ESTIMATE): October 25, 2011

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: pharmacokinetics
• Additional Relevant MeSH Terms: Anti-Infective Agents; Anti-Bacterial Agents; Ceftaroline fosamil; Cephalosporins
• Other Study ID Numbers: D3720C00005