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Trial registered on ANZCTR
Registration number
ACTRN12617001046392
Ethics application status
Approved
Date submitted
15/07/2017
Date registered
18/07/2017
Date last updated
18/07/2017
Type of registration
Retrospectively registered
Titles & IDs
Public title
Effect of food on oral flucloxacillin pharmacokinetics and pharmacodynamics in healthy volunteers
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Scientific title
Effect of food on oral flucloxacillin pharmacokinetics and pharmacodynamics in healthy volunteers
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Secondary ID [1]
292437
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None
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Skin infection
304043
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Condition category
Condition code
Infection
303368
303368
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0
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Other infectious diseases
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Volunteers received flucloxacillin 1000 mg orally on an empty stomach or after a standardized high-fat high-calorie breakfast (per FDA recommendations for bioequivalence studies ie. equating to ~968 kcal of energy, 38 g of protein, 65 g of fat and 58 g of carbohydrate) after an 8 hour overnight fast (free access to water during this time) on two study days separated by a 7-day 'washout period'.
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Intervention code [1]
298615
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Treatment: Drugs
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Comparator / control treatment
Flucloxacillin 1000 mg orally, administered in the fasting state (current recommended practice).
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Control group
Active
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Outcomes
Primary outcome [1]
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.Total flucloxacillin plasma concentrations were measured using a published LC-MS/MS method.
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Assessment method [1]
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Timepoint [1]
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Blood samples were taken at 0, 0.5, 1.5, 2, 3, 4, 6, 8 and 12 hours post dose for determination of total and free flucloxacillin plasma concentrations
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Primary outcome [2]
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Free flucloxacillin concentrations measured using a published LC-MS/MS method.
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Assessment method [2]
302771
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Timepoint [2]
302771
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Blood samples were taken at 0, 0.5, 1.5, 2, 3, 4, 6, 8 and 12 hours post dose for determination of total and free flucloxacillin plasma concentrations
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Secondary outcome [1]
336916
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Flucloxacillin concentrations in urine were measured using LC-MS/MS.
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Assessment method [1]
336916
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Timepoint [1]
336916
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Urine was collected from 0 - 12 hours post-dose to determine the total flucloxacillin urinary excretion.
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Eligibility
Key inclusion criteria
Healthy volunteers
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Minimum age
18
Years
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Maximum age
40
Years
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Sex
Both males and females
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Can healthy volunteers participate?
Yes
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Key exclusion criteria
Food intolerance, pregnancy, chronic illness, renal impairment (creatinine clearance < 80 mL/min by Cockcroft-Gault formula), liver dysfunction, malabsorption or known intolerance of flucloxacillin. Volunteers were excluded from the study if they took any regular medications (other than a hormonal oral contraceptive pill) or were intolerant of fasting for up to 10 hours.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Non-randomised trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
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Other design features
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Phase
Phase 3
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Type of endpoint/s
Pharmacokinetics / pharmacodynamics
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Statistical methods / analysis
The number of volunteers chosen was standard for a PK/PD study of this type (n=12). Treatment arms were compared for common PK parameters and for the free concentrations achieved for 30%, 50% and 70% of the usual dose intervals. Statistical analysis was undertaken using Graphpad Prism (student t-test and bioequivalence testing if no difference was identified). Modelling was undertaken using Monolix to predict steady-state pharmacokinetics. The probability of target attainment (PTAs) for each arm were plotted against a range of MICs of common skin-infecting bacteria
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Recruitment
Recruitment status
Completed
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Date of first participant enrolment
Anticipated
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Actual
1/03/2014
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Date of last participant enrolment
Anticipated
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Actual
3/04/2014
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Date of last data collection
Anticipated
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Actual
12/04/2014
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Sample size
Target
12
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Accrual to date
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Final
12
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Recruitment outside Australia
Country [1]
9058
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New Zealand
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State/province [1]
9058
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Funding & Sponsors
Funding source category [1]
296997
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Charities/Societies/Foundations
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Name [1]
296997
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New Zealand Pharmacy & Education Research Foundation
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Address [1]
296997
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Po Box 11640
Manners Street
Wellington 6142
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Country [1]
296997
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New Zealand
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Primary sponsor type
Hospital
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Name
Canterbury District Health Board (Christchurch Hospital campus)
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Address
PO Box 4170
Christchurch 8140
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Country
New Zealand
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Secondary sponsor category [1]
296002
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University
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Name [1]
296002
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University of Otago, Christchurch
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Address [1]
296002
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Private Bag 4345
Christchurch 8140
New Zealand
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Country [1]
296002
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New Zealand
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Ethics approval
Ethics application status
Approved
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Ethics committee name [1]
298193
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Northern B Health & Disability Ethics Committee
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Ethics committee address [1]
298193
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Ministry of Health
Health and Disability Ethics Committees
PO Box 5013
Wellington 6140
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Ethics committee country [1]
298193
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New Zealand
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Date submitted for ethics approval [1]
298193
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23/12/2013
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Approval date [1]
298193
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21/02/2014
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Ethics approval number [1]
298193
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12/NTB/56
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Summary
Brief summary
Flucloxacillin is usually recommended to be given on an empty stomach, because food reduces and delays peak concentrations. It is now known that for penicillins, the time the free (unbound) concentrations are above the minimum inhibitory concentrations is more important for bacterial kill than peak concentrations. In this study, the effects of food on flucloxacillin PK-PD were assess using a modern assay to accurately quantify free flucloxacillin concentrations. Total and free flucloxacillin concentrations were measured for 12 hours after a single oral dose of flucloxacillin 1000 mg, after a standardized breakfast and in a fasting state separated by a week's washout.
Pharmacokinetics and pharmacodynamics were compared in the fed and fasting states.
Food reduced the total and free flucloxacillin area under the curve by about 20%, and the peak by about 50%, and increased the time to reach peak concentrations by approximately 2-fold. These changes did not importantly impact on parameters such as free time above MIC and probability of target attainment suggesting that flucloxacillin can be taken with food without compromising efficacy in most cases.
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Trial website
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Trial related presentations / publications
This work has been included in a presentation at the New Zealand Hospital Pharmacists Association in Christchurch, New Zealand (November 2013). This has been published in the conference handbook (not official conference proceedings) i.e. SJ Gardiner 'Preserving our Licence to Kill - three years in the life of an antimicrobial stewardship pharmacist', New Zealand Hospital Pharmacists Association, Christchurch, New Zealand 2016.
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Public notes
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Contacts
Principal investigator
Name
76286
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Dr Sharon Gardiner
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Address
76286
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C/- Infectious Diseases
Christchurch Hospital
PO Box 4710
Christchurch 8140
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Country
76286
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New Zealand
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Phone
76286
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+6433640084
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Fax
76286
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Email
76286
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[email protected]
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Contact person for public queries
Name
76287
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Dr Sharon Gardiner
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Address
76287
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C/0 Infectious Diseases
Po Box 4710
Christchurch 8140
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Country
76287
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New Zealand
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Phone
76287
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+6433640084
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Fax
76287
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Email
76287
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[email protected]
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Contact person for scientific queries
Name
76288
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Dr Sharon Gardiner
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Address
76288
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C/- Infectious Diseases
Christchurch Hospital
PO Box 4710
Christchurch
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Country
76288
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New Zealand
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Phone
76288
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+6433640084
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Fax
76288
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Email
76288
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[email protected]
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No information has been provided regarding IPD availability
What supporting documents are/will be available?
No Supporting Document Provided
Results publications and other study-related documents
Documents added manually
No documents have been uploaded by study researchers.
Documents added automatically
Source
Title
Year of Publication
DOI
Embase
Total flucloxacillin plasma concentrations poorly reflect unbound concentrations in hospitalized patients with Staphylococcus aureus bacteraemia.
2018
https://dx.doi.org/10.1111/bcp.13673
N.B. These documents automatically identified may not have been verified by the study sponsor.
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