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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.
Scientific title
A multicentre, prospective, open-label, pharmacokinetic pharmacodynamic (PKPD) study of febuxostat in patients with chronic gout.
Secondary ID [1] 289688 0
Nil.
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Gout 299489 0
Condition category
Condition code
Musculoskeletal 299473 299473 0 0
Other muscular and skeletal disorders
Inflammatory and Immune System 299521 299521 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
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.
Intervention code [1] 295311 0
Treatment: Drugs
Comparator / control treatment
No control group.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 298952 0
The PD parameter to be assessed is the change in serum urate concentrations.
Timepoint [1] 298952 0
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).

Secondary outcome [1] 325758 0
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.
Timepoint [1] 325758 0
Up to 4 blood samples (10 mL each) will be collected at least one week after intervention commencement and/or dose adjustment.

Eligibility
Key inclusion criteria
Patients for whom febuxostat is, or has been, clinically indicated for the treatment of chronic gout.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Non applicable.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Non applicable.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 4
Type of endpoint/s
Pharmacokinetics / pharmacodynamics
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.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
15/08/2016
Actual
13/09/2016
Date of last participant enrolment
Anticipated
15/12/2020
Actual
Date of last data collection
Anticipated
15/03/2021
Actual
Sample size
Target
120
Accrual to date
31
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 6176 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 6177 0
Campbelltown Hospital - Campbelltown
Recruitment hospital [3] 6178 0
Camden Hospital - Camden
Recruitment hospital [4] 6179 0
St Vincent's Private Hospital (Darlinghurst) - Darlinghurst
Recruitment hospital [5] 8522 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment postcode(s) [1] 13607 0
2050 - Camperdown
Recruitment postcode(s) [2] 13608 0
2560 - Campbelltown
Recruitment postcode(s) [3] 13609 0
2570 - Camden
Recruitment postcode(s) [4] 13610 0
2010 - Darlinghurst
Recruitment postcode(s) [5] 13611 0
2217 - Kogarah
Recruitment postcode(s) [6] 13612 0
2134 - Burwood
Recruitment postcode(s) [7] 13613 0
2042 - Newtown
Recruitment postcode(s) [8] 16615 0
2228 - Miranda

Funding & Sponsors
Funding source category [1] 294070 0
Charities/Societies/Foundations
Name [1] 294070 0
Clinical Pharmacology Lexy Davies Trust Fund
Country [1] 294070 0
Australia
Primary sponsor type
Hospital
Name
St Vincent's Hospital
Address
390 Victoria St, Darlingurst, Australia, NSW 2010.
Country
Australia
Secondary sponsor category [1] 292900 0
None
Name [1] 292900 0
Address [1] 292900 0
Country [1] 292900 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295484 0
St Vincent's Hospital
Ethics committee address [1] 295484 0
97-105 Boundary St, Darlinghurst, Australia, NSW 2010.
Ethics committee country [1] 295484 0
Australia
Date submitted for ethics approval [1] 295484 0
28/01/2016
Approval date [1] 295484 0
15/03/2016
Ethics approval number [1] 295484 0
HREC/16/SVH/22

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.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 67446 0
Prof Richard O Day
Address 67446 0
Department of Clinical Pharmacology and Toxicology,
Level 2 Xavier Building,
St Vincent's Hospital,
390 Victoria St,
Darlinghurst, Australia, NSW 2010.
Country 67446 0
Australia
Phone 67446 0
+61, 2, 8382 2331
Fax 67446 0
+61, 2, 8382 2724
Email 67446 0
[email protected]
Contact person for public queries
Name 67447 0
Bishoy Kamel
Address 67447 0
Department of Clinical Pharmacology and Toxicology,
Level 2 Xavier Building,
St Vincent's Hospital,
390 Victoria St,
Darlinghurst, Australia, NSW 2010.
Country 67447 0
Australia
Phone 67447 0
+61, 2, 8382 2051
Fax 67447 0
+61, 2, 8382 2724
Email 67447 0
[email protected]
Contact person for scientific queries
Name 67448 0
Richard O Day
Address 67448 0
Department of Clinical Pharmacology and Toxicology,
Level 2 Xavier Building,
St Vincent's Hospital,
390 Victoria St,
Darlinghurst, Australia, NSW 2010.
Country 67448 0
Australia
Phone 67448 0
+61, 2, 8382 2331
Fax 67448 0
+61, 2, 8382 2724
Email 67448 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
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.


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
SourceTitleYear of PublicationDOI
EmbaseA multicentre open-label pharmacokineticpharmacodynamic (PKPD) study of febuxostat in patients with chronic gout.2017https://dx.doi.org/10.1111/imj.13426
EmbasePopulation pharmacokinetic modelling of febuxostat in healthy subjects and people with gout.2022https://dx.doi.org/10.1111/bcp.15462
N.B. These documents automatically identified may not have been verified by the study sponsor.