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Trial registered on ANZCTR
Registration number
ACTRN12616000959471
Ethics application status
Approved
Date submitted
15/07/2016
Date registered
21/07/2016
Date last updated
7/07/2020
Date data sharing statement initially provided
4/06/2019
Type of registration
Prospectively registered
Titles & IDs
Public title
A multicentre study of the dose concentration response of febuxostat in patients with chronic gout.
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Scientific title
A multicentre, prospective, open-label, pharmacokinetic pharmacodynamic (PKPD) study of febuxostat in patients with chronic gout.
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Secondary ID [1]
289688
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Nil.
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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:
Gout
299489
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Condition category
Condition code
Musculoskeletal
299473
299473
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0
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Other muscular and skeletal disorders
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Inflammatory and Immune System
299521
299521
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0
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Other inflammatory or immune system disorders
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
This study aims at exploring a) the dose-concentrations-response relationships of febuxostat in patients with chronic gout b) the influence of renal function on the plasma concentrations of febuxostat and response of urate to febuxostat.
A number of blood samples (up to 4 blood samples per dose level) will be collected at least one week after the initiation and/or dose adjustment for the determination of the plasma concentrations of febuxostat and urate. In this open-label observational study, the dose of febuxostat, dose adjustment, duration of administration and the target treatment serum urate are judged by the treating rheumatologist as part of usual management of gout. Some data will be collected including; baseline and steady-state treatment concentrations of serum urate and creatinine, age, sex, height, weight, medical history and current co-morbidities and concomitant therapies (including change in co-therapies during enrollment). Some information pertaining to gout (duration of gout, frequency of gout attacks and past gout treatments, if any) will also be collected.
Patients will be asked to complete The ARMS (Adherence to Refills and Medications Scale) questionnaire in order to assess their general adherence behaviour. A ‘Febuxostat adherence Questionnaire’ will also be completed before each blood collection in order to capture the extent of adherence to treatment with febuxostat over the week prior to collecting a blood sample. Patients will also be offered a participant's diary to monitor their adherence to febuxostat.
Patients will be followed up for up to 6 months from recruitment. After the follow up period ends, patients with chronic gout will continue to take febuxostat to maintain their serum urate concentrations below the target concentrations, as part of their chronic gout management, treating doctors will continue following up patients as per usual care.
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Intervention code [1]
295311
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Treatment: Drugs
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Comparator / control treatment
No control group.
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Control group
Uncontrolled
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Outcomes
Primary outcome [1]
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The PD parameter to be assessed is the change in serum urate concentrations.
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Assessment method [1]
298952
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Timepoint [1]
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Baseline serum urate (not during an acute attack) and change in serum urate post treatment (at least 1 week after the initiation and/or dose change).
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Secondary outcome [1]
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The pharmacokinetic parameters to be assessed include; the plasma area under the concentration time curve, apparent clearance, and peak and trough concentrations of febuxostat. The relationship of an individual’s pharmacokinetic parameters with the reduction in serum urate concentrations will be explored and reported as mathematical equations.
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Assessment method [1]
325758
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Timepoint [1]
325758
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Up to 4 blood samples (10 mL each) will be collected at least one week after intervention commencement and/or dose adjustment.
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Eligibility
Key inclusion criteria
Patients for whom febuxostat is, or has been, clinically indicated for the treatment of chronic gout.
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
1) Any patient with a past history of febuxostat hypersensitivity.
2) Patients taking xanthine oxidoreductase substrates such as mercaptopurine/azathioprine or theophylline (no studies to substantiate the combination with febuxostat).*
3) Women lactating, pregnant or of childbearing potential who are not willing to avoid becoming pregnant during the study.
4) Patients with a history of a psychological illness or condition such as to interfere with the patient's ability to understand the requirements of the study.
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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)
Non applicable.
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Non applicable.
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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
Single group
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Other design features
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Phase
Phase 4
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Type of endpoint/s
Pharmacokinetics / pharmacodynamics
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Statistical methods / analysis
There is no established method for calculating a sample size for PKPD open-label studies. A sample size of up to 120 patients was chosen on the basis of previous studies of similar medicines and to provide sufficient data to assess the dose-concentration-response relationship of febuxostat in patients with gout.
A population pharmacokinetic model for febuxostat will be developed using existing data from the literature. This model, together with plasma concentrations determined in our study, will be used to estimate individual pharmacokinetic parameters of febuxostat (PK analysis) for each patient with gout. The relationships of the pharmacokinetic parameters, notably the plasma area under the concentration time curve, apparent clearance, and peak and trough concentrations will be correlated with the reduction in plasma urate. The influence of renal function (creatinine clearance) on the pharmacokinetics or response to febuxostat will be examined. The significance of other patient characteristics (e.g. body weight, sex and age) will also be investigated. The febuxostat dose-concentration-response relationships will be fitted using modelling techniques. The clinical relevance of the results will be examined and reported.
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Recruitment
Recruitment status
Recruiting
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Date of first participant enrolment
Anticipated
15/08/2016
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Actual
13/09/2016
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Date of last participant enrolment
Anticipated
15/12/2020
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Actual
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Date of last data collection
Anticipated
15/03/2021
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Actual
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Sample size
Target
120
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Accrual to date
31
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Final
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Recruitment in Australia
Recruitment state(s)
NSW
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Recruitment hospital [1]
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Royal Prince Alfred Hospital - Camperdown
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Recruitment hospital [2]
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Campbelltown Hospital - Campbelltown
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Recruitment hospital [3]
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Camden Hospital - Camden
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Recruitment hospital [4]
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St Vincent's Private Hospital (Darlinghurst) - Darlinghurst
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Recruitment hospital [5]
8522
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St Vincent's Hospital (Darlinghurst) - Darlinghurst
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Recruitment postcode(s) [1]
13607
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2050 - Camperdown
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Recruitment postcode(s) [2]
13608
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2560 - Campbelltown
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Recruitment postcode(s) [3]
13609
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2570 - Camden
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Recruitment postcode(s) [4]
13610
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2010 - Darlinghurst
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Recruitment postcode(s) [5]
13611
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2217 - Kogarah
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Recruitment postcode(s) [6]
13612
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2134 - Burwood
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Recruitment postcode(s) [7]
13613
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2042 - Newtown
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Recruitment postcode(s) [8]
16615
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2228 - Miranda
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Funding & Sponsors
Funding source category [1]
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Charities/Societies/Foundations
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Name [1]
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Clinical Pharmacology Lexy Davies Trust Fund
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Address [1]
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390 Victoria St, Darlinghurst, Australia, NSW 2010.
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Country [1]
294070
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Australia
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Primary sponsor type
Hospital
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Name
St Vincent's Hospital
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Address
390 Victoria St, Darlingurst, Australia, NSW 2010.
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Country
Australia
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Secondary sponsor category [1]
292900
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None
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Name [1]
292900
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Address [1]
292900
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Country [1]
292900
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Ethics approval
Ethics application status
Approved
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Ethics committee name [1]
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St Vincent's Hospital
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Ethics committee address [1]
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97-105 Boundary St, Darlinghurst, Australia, NSW 2010.
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Ethics committee country [1]
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Australia
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Date submitted for ethics approval [1]
295484
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28/01/2016
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Approval date [1]
295484
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15/03/2016
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Ethics approval number [1]
295484
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HREC/16/SVH/22
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Summary
Brief summary
The objectives of the study are:
1) Explore the dose-concentration-response relationship of febuxostat in patients with chronic gout.
2) Gain insights into optimisation of febuxostat therapy to achieve target plasma urate concentrations.
3) Understand inter-patient variations in the pharmacokinetic parameters of the drug and their impact on the serum urate concentration.
4) Explore factors that may affect the pharmacokinetics and/or the response of urate to febuxostat.
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Trial website
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Prof Richard O Day
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Address
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Department of Clinical Pharmacology and Toxicology,
Level 2 Xavier Building,
St Vincent's Hospital,
390 Victoria St,
Darlinghurst, Australia, NSW 2010.
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Country
67446
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Australia
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Phone
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+61, 2, 8382 2331
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Fax
67446
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+61, 2, 8382 2724
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Email
67446
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[email protected]
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Contact person for public queries
Name
67447
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Dr Bishoy Kamel
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Address
67447
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Department of Clinical Pharmacology and Toxicology,
Level 2 Xavier Building,
St Vincent's Hospital,
390 Victoria St,
Darlinghurst, Australia, NSW 2010.
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Country
67447
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Australia
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Phone
67447
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+61, 2, 8382 2051
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Fax
67447
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+61, 2, 8382 2724
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Email
67447
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[email protected]
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Contact person for scientific queries
Name
67448
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Prof Richard O Day
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Address
67448
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Department of Clinical Pharmacology and Toxicology,
Level 2 Xavier Building,
St Vincent's Hospital,
390 Victoria St,
Darlinghurst, Australia, NSW 2010.
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Country
67448
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Australia
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Phone
67448
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+61, 2, 8382 2331
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Fax
67448
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+61, 2, 8382 2724
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Email
67448
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[email protected]
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Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
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No/undecided IPD sharing reason/comment
Although we are happy to share data we are unable to do so at present since we have not sought permission from the study participants and have not asked the HREC either.
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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
A multicentre open-label pharmacokineticpharmacodynamic (PKPD) study of febuxostat in patients with chronic gout.
2017
https://dx.doi.org/10.1111/imj.13426
Embase
Population pharmacokinetic modelling of febuxostat in healthy subjects and people with gout.
2022
https://dx.doi.org/10.1111/bcp.15462
N.B. These documents automatically identified may not have been verified by the study sponsor.
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