Clinical trial NCT01664065: A Study to Assess the Pharmacokinetics of Ceftaroline in End Stage Renal Disease Patients and Matched Healthy Subjects
Official title: An Open-label, Nonrandomised, Phase I Study to Assess the Pharmacokinetics of Ceftaroline After Intravenous Administration of aSingle Dose of Ceftaroline Fosamil (200 mg) to Patients With End-stage Renal Disease Undergoing Haemodialysis When Compared to a Single Dose of Ceftaroline Fosamil (600 mg)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Renal Disease
Keywords: Patient Safety
Tolerability
Pharmacokinetics
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2012-08-14
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this study is to assess the safety, tolerability and pharmacokinetics of Ceftaroline in a group of patients with renal disease and matching healthy subjects with normal renal function

Detailed description: An Open-label, Nonrandomised, Phase I Study to Assess the Pharmacokinetics of Ceftaroline After Intravenous Administration of aSingle Dose of Ceftaroline Fosamil (200 mg) to Patients with End-stage Renal Disease Undergoing Haemodialysis when Compared to a Single Dose of Ceftaroline Fosamil (600 mg)

Eligibility criteria: Inclusion criteria:

* Provision of signed and dated, written informed consent prior to any study specific procedures
* Male and female subjects aged 18 to 75 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 3 months 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 35 kg/m2 and weigh at between 50 and 110 kg
* Haematocrit level higher than 30% at screening and baseline for each treatment period

Exclusion criteria:

* History or presence of gastrointestinal, hepatic, or any other condition known to interfere with the absorption, distribution, metabolism, or excretion of drugs
* Any clinically significant abnormalities in clinical chemistry, haematology, or urinalysis results, as judged by the investigator
* Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG that may interfere with the interpretation of QTc interval changes
* 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
* Receiving any dialysis treatment other than intermittent haemodialysis

Primary outcomes:
measure: Pharmacokinetics of Ceftaroline after intravenous infusion of Ceftaroline Fosamil in patients with end-stage renal disease and a matched control population with normal renal function to characterise the clearance of Ceftaroline.
timeFrame: pre-dose, 20, 40, 60, 65, 75, 90 min, 2.25, 3.25 , 4.25, 5.25, 8, 12, 24, 36, 48 h
measure: Pharmacokinetics of Ceftaroline after intravenous infusion of Ceftaroline fosamil in patients with end-stage renal disease and a matched control population with normal renal function to characterise the clearance of Ceftaroline.
timeFrame: pre-dose, 20, 40, 60, 65, 75, 90 min, 2.25, 3.25 , 4.25, 5.25, 8, 12, 24, 36, 48 h
measure: Pharmacokinetics of Ceftaroline after intravenous infusion of Ceftaroline fosamil in patients with end stage renal diseaseand to characterise the clearance of Ceftaroline.
timeFrame: pre-dose, 20, 40, 60, 65, 75, 90 min, 2.25, 3.25 , 4.25, 5.25, 8, 12, 24, 36, 48 h
Secondary outcomes:
measure: Safety and tolerability in terms of adverse events, laboratory data, physical examinations, ECG and vital signs.
timeFrame: Screening up to 10 days after discharge from study site.
measure: Pharmacokinetics of Ceftaroline M-1 after intravenous infusion of Ceftaroline fosamil in patients with end-stage renal disease and a matched control population with normal renal function to characterise the clearance of Ceftaroline.
timeFrame: pre-dose, 20, 40, 60, 65, 75, 90 min, 2.25, 3.25 , 4.25, 5.25, 8, 12, 24, 36, 48 h
measure: Pharmacokinetics of Ceftaroline M-1 after intravenous infusion of Ceftaroline fosamil in patients with end stage renal disease and to characterise the clearance of Ceftaroline.
timeFrame: pre-dose, 20, 40, 60, 65, 75, 90 min, 2.25, 3.25 , 4.25, 5.25, 8, 12, 24, 36, 48 h
measure: Pharmacokinetics of Ceftaroline fosamil after intravenous infusion of Ceftaroline fosamil in patients with end-stage renal disease and a matched control population with normal renal function to characterise the clearance of Ceftaroline.
timeFrame: pre-dose, 20, 40, 60, 65, 75, 90 min, 2.25, 3.25 , 4.25, 5.25, 8, 12, 24, 36, 48 h
measure: Pharmacokinetics of Ceftaroline fosamil after intravenous infusion of Ceftaroline fosamil in patients with end-stage renal disease and a matched control population with normal renal function to characterise the clearance of Ceftaroline.
timeFrame: pre-dose, 20, 40, 60, 65, 75, 90 min, 2.25, 3.25 , 4.25, 5.25, 8, 12, 24, 36, 48 h
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Research Site
Study officials:
affiliation: AstraZeneca Pharmaceuticals;C2C-716 1800 Concord PikePO. Box 15437Wilmington De 19850-5437
name: David Melnick, MD
role: STUDY_DIRECTOR
affiliation: Quintiles Drug Research Unit at Guy's Hospital 6 Newcomen St
name: Arpeat Kaviya, MBChB, MRCP
role: PRINCIPAL_INVESTIGATOR
affiliation: AstraZeneca Research and Development SE-431 83 Mölndal
name: Mirjana Kujacic, MD
role: STUDY_CHAIR
References:
citation: Sunzel M, Learoyd M, Li J, Li Y, Ngo N, Edeki T. An open-label, non-randomised, phase 1, single-dose study to assess the pharmacokinetics of ceftaroline in patients with end-stage renal disease requiring intermittent haemodialysis. Int J Antimicrob Agents. 2015 Dec;46(6):682-8. doi: 10.1016/j.ijantimicag.2015.09.009. Epub 2015 Oct 22.
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.