Clinical trial NCT01612507: A Study to Assess Safety, Tolerability and Pharmacokinetics of Ceftaroline in Healthy Subjects
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Phase 1
healthy volunteers
Parallel Group Study
ceftaroline fosamil different doses
safety
Cmax
tmax
AUC
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2012-06-05
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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

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 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

Primary outcomes:
measure: Safety and tolerability in terms of adverse events, laboratory data, vital signs following single and multiple dose regimens of ceftaroline fosamil compared to placebo
timeFrame: Screening up to 19 days after first dose
Secondary outcomes:
measure: 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
timeFrame: 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
measure: 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
timeFrame: 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
measure: 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
timeFrame: 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
measure: 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
timeFrame: 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
measure: 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
timeFrame: Day 1
measure: 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
timeFrame: Day 8
measure: 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
timeFrame: 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
measure: 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
timeFrame: 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
measure: 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
timeFrame: 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
measure: 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
timeFrame: 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
measure: 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
timeFrame: 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
measure: 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
timeFrame: 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
measure: 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
timeFrame: 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
measure: 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
timeFrame: 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
measure: 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
timeFrame: Day 1
measure: 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
timeFrame: Day 8
measure: 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
timeFrame: Day 1
measure: 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
timeFrame: Day 8
measure: 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
timeFrame: Day 1
measure: 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
timeFrame: Day 8
measure: 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
timeFrame: Day 1
measure: 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
timeFrame: Day 8
measure: 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
timeFrame: Day 1
measure: 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
timeFrame: Day 8
measure: 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
timeFrame: 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
measure: 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
timeFrame: 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
measure: 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
timeFrame: 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
measure: 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
timeFrame: 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
measure: 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
timeFrame: 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
measure: 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
timeFrame: 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
measure: 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
timeFrame: 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
measure: 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
timeFrame: 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
measure: 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
timeFrame: 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
measure: 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
timeFrame: 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
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Research site
Study officials:
affiliation: AstraZeneca PharmaceuticalsC2C-7161800 Concord PikePO. Box 15437Wilmington De 19850-5437
name: David Melnick, MD
role: STUDY_DIRECTOR
affiliation: Hammersmith Medicines Cumberland Avenue London NW10 7EW UK
name: Elizabeth Tranter, MBCHB MRCP
role: PRINCIPAL_INVESTIGATOR
affiliation: AstraZeneca Research and DevelopmentSE-431 83 MolndalSweden
name: Mirjana Kujacic, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.