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Long-Term Safety of Febuxostat in Subjects With Gout. (FOCUS)

Primary Purpose

Gout

Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Febuxostat
Febuxostat
Febuxostat
Sponsored by
Takeda
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Gout focused on measuring Uric acid, xanthine oxidase, tophi, Drug Therapy

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Hyperuricemia (serum uric acid ≥8.0 mg/dL upon entering parent study TMX-00-004). Must meet American College of Rheumatology criteria for gout. Must have adequate renal function (serum creatinine <1.5 mg/dL). Must have completed four weeks of double-blind dosing in Study TMX-00-004. Must not have experienced any serious study drug-related Adverse Events in Study TMX 00-004. Females of childbearing potential who are sexually active must agree to use adequate contraception, and can neither be pregnant nor lactating from Screening throughout the duration of the study. Exclusion Criteria: History of xanthinuria Alcohol consumption >14/week Has a History of significant concomitant illness Has active liver disease. Has a body mass index greater than 50 kg/m2 Any other significant medical condition that would interfere with the treatment, safety or compliance with the protocol, as defined by the investigator.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm Type

    Experimental

    Experimental

    Experimental

    Arm Label

    1

    2

    3

    Arm Description

    Outcomes

    Primary Outcome Measures

    Percentage of Subjects Whose Serum Urate Level Decreases to or is Maintained at <6.0 mg/dL at Month 6 Visit.
    Serum urate values were obtained at the Month 6 visit. The percentage of subjects whose serum urate was <6.0 mg/dL at the Month 6 visit was summarized.
    Percentage of Subjects Whose Serum Urate Level Decreases to or is Maintained at <6.0 mg/dL at Month 12 Visit.
    Serum urate values were obtained at the Month 12 visit. The percentage of subjects whose serum urate was <6.0 mg/dL at the Month 12 visit was summarized.
    Percentage of Subjects Whose Serum Urate Level Decreases to or is Maintained at <6.0 mg/dL at Month 18 Visit.
    Serum urate values were obtained at the Month 18 visit. The percentage of subjects whose serum urate was <6.0 mg/dL at the Month 18 visit was summarized.
    Percentage of Subjects Whose Serum Urate Level Decreases to or is Maintained at <6.0 mg/dL at Month 24 Visit.
    Serum urate values were obtained at the Month 24 visit. The percentage of subjects whose serum urate was <6.0 mg/dL at the Month 24 visit was summarized.
    Percentage of Subjects Whose Serum Urate Level Decreases to or is Maintained at <6.0 mg/dL at Month 36 Visit.
    Serum urate values were obtained at the Month 36 visit. The percentage of subjects whose serum urate was <6.0 mg/dL at the Month 36 visit was summarized.
    Percentage of Subjects Whose Serum Urate Level Decreases to or is Maintained at <6.0 mg/dL at Month 48 Visit.
    Serum urate values were obtained at the Month 48 visit. The percentage of subjects whose serum urate was <6.0 mg/dL at the Month 48 visit was summarized.
    Percentage of Subjects Whose Serum Urate Level Decreases to or is Maintained at <6.0 mg/dL at Month 60 Visit.
    Serum urate values were obtained at the Month 60 visit. The percentage of subjects whose serum urate was <6.0 mg/dL at the Month 60 visit was summarized.
    Percentage of Subjects Whose Serum Urate Level Decreases to or is Maintained at <6.0 mg/dL at Final Visit.
    The percentage of subjects whose serum urate was <6.0 mg/dL at the final visit was summarized. The final visit was the last visit at which a serum urate value was collected.

    Secondary Outcome Measures

    Percent Change in Serum Urate Levels From Baseline at Month 6 Visit.
    Serum urate values were obtained at the Month 6 visit. The percent change in serum urate from baseline to the Month 6 visit was summarized.
    Percent Change in Serum Urate Levels From Baseline at Month 12 Visit.
    Serum urate values were obtained at the Month 12 visit. The percent change in serum urate from baseline to the Month 12 visit was summarized.
    Percent Change in Serum Urate Levels From Baseline at Month 18 Visit.
    Serum urate values were obtained at the Month 18 visit. The percent change in serum urate from baseline to the Month 18 visit was summarized.
    Percent Change in Serum Urate Levels From Baseline at Month 24 Visit.
    Serum urate values were obtained at the Month 24 visit. The percent change in serum urate from baseline to the Month 24 visit was summarized.
    Percent Change in Serum Urate Levels From Baseline at Month 36 Visit.
    Serum urate values were obtained at the Month 36 visit. The percent change in serum urate from baseline to the Month 36 visit was summarized.
    Percent Change in Serum Urate Levels From Baseline at Month 48 Visit.
    Serum urate values were obtained at the Month 48 visit. The percent change in serum urate from baseline to the Month 48 visit was summarized.
    Percent Change in Serum Urate Levels From Baseline at Month 60 Visit.
    The secondary outcome was the mean percent change from baseline to Month 60 visit as assessed by serum urate levels collected at baseline and at the Month 60 visit by dose at observation.
    Percent Change in Serum Urate Levels From Baseline at Final Visit.
    The percent change in serum urate from baseline to the final visit was summarized. The final visit was the last visit at which a serum urate value was collected.

    Full Information

    First Posted
    September 12, 2005
    Last Updated
    January 25, 2011
    Sponsor
    Takeda
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00174941
    Brief Title
    Long-Term Safety of Febuxostat in Subjects With Gout.
    Acronym
    FOCUS
    Official Title
    Phase II, Open-Label Study, to Assess the Long-Term Safety of Oral TMX-67 in Subjects With Gout
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    January 2011
    Overall Recruitment Status
    Completed
    Study Start Date
    March 2001 (undefined)
    Primary Completion Date
    December 2006 (Actual)
    Study Completion Date
    December 2006 (Actual)

    3. Sponsor/Collaborators

    Name of the Sponsor
    Takeda

    4. Oversight

    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    The purpose of this study is to evaluate the long-term safety of febuxostat, once daily (QD), in maintaining serum urate levels within clinically acceptable levels in subjects with gout.
    Detailed Description
    Uric acid is the end product of purine degradation in humans. Hyperuricemia, a urate concentration in serum exceeding the limit of urate solubility (approximately 7.0 milligrams per deciliter [mg/dL]), is a common biochemical abnormality. Aberrations in any of the multiple mechanisms involved in the production and/or excretion of uric acid may increase serum urate concentrations, with persistent hyperuricemia as a marker for extracellular fluid monosodium urate supersaturation. As such, hyperuricemia is a necessary (but often not sufficient) risk factor for monosodium urate crystal deposition in tissues and is the fundamental pathophysiological process underlying the clinical manifestations of gout, which is a chronic disease characterized by urate crystal formation and deposition in joints and bones. Gout may progress from episodic attacks of acute inflammatory arthritis to a disabling chronic disorder characterized by deforming arthropathy; destructive deposits of urate crystals (tophi) in bones, joints, and other organs; structural and functional renal impairment due to interstitial urate crystal deposition; and urinary tract stones composed entirely or in part of uric acid crystals. Management of gout requires chronic treatment aimed at lowering serum urate into a subsaturating range (usually <6.0 mg/dL) in which crystal formation and deposition are prevented or reversed. Febuxostat (TMX-67) is a non-purine selective xanthine oxidase inhibitor being developed as an orally administered agent for management of hyperuricemia in patients with gout. Subjects who want to participate in this study will have successfully completed study TMX-00-004 (NCT00174967). All participants will initially receive an 80 mg dose. Dose titrations will occur in order to obtain and maintain clinically acceptable serum urate levels.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Gout
    Keywords
    Uric acid, xanthine oxidase, tophi, Drug Therapy

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Non-Randomized
    Enrollment
    116 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    1
    Arm Type
    Experimental
    Arm Title
    2
    Arm Type
    Experimental
    Arm Title
    3
    Arm Type
    Experimental
    Intervention Type
    Drug
    Intervention Name(s)
    Febuxostat
    Other Intervention Name(s)
    TMX-67, Tei-6720, Uloric
    Intervention Description
    Febuxostat 40 mg, tablets, orally, once daily, based on serum urate level.
    Intervention Type
    Drug
    Intervention Name(s)
    Febuxostat
    Other Intervention Name(s)
    TMX-67, Tei-6720, Uloric
    Intervention Description
    Febuxostat 80 mg, tablets, orally, once daily, based on serum urate level.
    Intervention Type
    Drug
    Intervention Name(s)
    Febuxostat
    Other Intervention Name(s)
    TMX-67, Tei-6720, Uloric
    Intervention Description
    Febuxostat 120 mg, tablets, orally, once daily, based on serum urate level.
    Primary Outcome Measure Information:
    Title
    Percentage of Subjects Whose Serum Urate Level Decreases to or is Maintained at <6.0 mg/dL at Month 6 Visit.
    Description
    Serum urate values were obtained at the Month 6 visit. The percentage of subjects whose serum urate was <6.0 mg/dL at the Month 6 visit was summarized.
    Time Frame
    Month 6
    Title
    Percentage of Subjects Whose Serum Urate Level Decreases to or is Maintained at <6.0 mg/dL at Month 12 Visit.
    Description
    Serum urate values were obtained at the Month 12 visit. The percentage of subjects whose serum urate was <6.0 mg/dL at the Month 12 visit was summarized.
    Time Frame
    Month 12
    Title
    Percentage of Subjects Whose Serum Urate Level Decreases to or is Maintained at <6.0 mg/dL at Month 18 Visit.
    Description
    Serum urate values were obtained at the Month 18 visit. The percentage of subjects whose serum urate was <6.0 mg/dL at the Month 18 visit was summarized.
    Time Frame
    Month 18
    Title
    Percentage of Subjects Whose Serum Urate Level Decreases to or is Maintained at <6.0 mg/dL at Month 24 Visit.
    Description
    Serum urate values were obtained at the Month 24 visit. The percentage of subjects whose serum urate was <6.0 mg/dL at the Month 24 visit was summarized.
    Time Frame
    Month 24
    Title
    Percentage of Subjects Whose Serum Urate Level Decreases to or is Maintained at <6.0 mg/dL at Month 36 Visit.
    Description
    Serum urate values were obtained at the Month 36 visit. The percentage of subjects whose serum urate was <6.0 mg/dL at the Month 36 visit was summarized.
    Time Frame
    Month 36
    Title
    Percentage of Subjects Whose Serum Urate Level Decreases to or is Maintained at <6.0 mg/dL at Month 48 Visit.
    Description
    Serum urate values were obtained at the Month 48 visit. The percentage of subjects whose serum urate was <6.0 mg/dL at the Month 48 visit was summarized.
    Time Frame
    Month 48
    Title
    Percentage of Subjects Whose Serum Urate Level Decreases to or is Maintained at <6.0 mg/dL at Month 60 Visit.
    Description
    Serum urate values were obtained at the Month 60 visit. The percentage of subjects whose serum urate was <6.0 mg/dL at the Month 60 visit was summarized.
    Time Frame
    Month 60
    Title
    Percentage of Subjects Whose Serum Urate Level Decreases to or is Maintained at <6.0 mg/dL at Final Visit.
    Description
    The percentage of subjects whose serum urate was <6.0 mg/dL at the final visit was summarized. The final visit was the last visit at which a serum urate value was collected.
    Time Frame
    Last Visit on treatment (up to 66 months).
    Secondary Outcome Measure Information:
    Title
    Percent Change in Serum Urate Levels From Baseline at Month 6 Visit.
    Description
    Serum urate values were obtained at the Month 6 visit. The percent change in serum urate from baseline to the Month 6 visit was summarized.
    Time Frame
    Baseline and Month 6
    Title
    Percent Change in Serum Urate Levels From Baseline at Month 12 Visit.
    Description
    Serum urate values were obtained at the Month 12 visit. The percent change in serum urate from baseline to the Month 12 visit was summarized.
    Time Frame
    Baseline and Month 12
    Title
    Percent Change in Serum Urate Levels From Baseline at Month 18 Visit.
    Description
    Serum urate values were obtained at the Month 18 visit. The percent change in serum urate from baseline to the Month 18 visit was summarized.
    Time Frame
    Baseline and Month 18
    Title
    Percent Change in Serum Urate Levels From Baseline at Month 24 Visit.
    Description
    Serum urate values were obtained at the Month 24 visit. The percent change in serum urate from baseline to the Month 24 visit was summarized.
    Time Frame
    Baseline and Month 24
    Title
    Percent Change in Serum Urate Levels From Baseline at Month 36 Visit.
    Description
    Serum urate values were obtained at the Month 36 visit. The percent change in serum urate from baseline to the Month 36 visit was summarized.
    Time Frame
    Baseline and Month 36
    Title
    Percent Change in Serum Urate Levels From Baseline at Month 48 Visit.
    Description
    Serum urate values were obtained at the Month 48 visit. The percent change in serum urate from baseline to the Month 48 visit was summarized.
    Time Frame
    Baseline and Month 48
    Title
    Percent Change in Serum Urate Levels From Baseline at Month 60 Visit.
    Description
    The secondary outcome was the mean percent change from baseline to Month 60 visit as assessed by serum urate levels collected at baseline and at the Month 60 visit by dose at observation.
    Time Frame
    Baseline and Month 60
    Title
    Percent Change in Serum Urate Levels From Baseline at Final Visit.
    Description
    The percent change in serum urate from baseline to the final visit was summarized. The final visit was the last visit at which a serum urate value was collected.
    Time Frame
    Baseline and Last Visit on treatment (up to 66 months).

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    85 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Hyperuricemia (serum uric acid ≥8.0 mg/dL upon entering parent study TMX-00-004). Must meet American College of Rheumatology criteria for gout. Must have adequate renal function (serum creatinine <1.5 mg/dL). Must have completed four weeks of double-blind dosing in Study TMX-00-004. Must not have experienced any serious study drug-related Adverse Events in Study TMX 00-004. Females of childbearing potential who are sexually active must agree to use adequate contraception, and can neither be pregnant nor lactating from Screening throughout the duration of the study. Exclusion Criteria: History of xanthinuria Alcohol consumption >14/week Has a History of significant concomitant illness Has active liver disease. Has a body mass index greater than 50 kg/m2 Any other significant medical condition that would interfere with the treatment, safety or compliance with the protocol, as defined by the investigator.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Medical Director
    Organizational Affiliation
    Takeda
    Official's Role
    Study Chair

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    16911575
    Citation
    Colwell HH, Hunt BJ, Pasta DJ, Palo WA, Mathias SD, Joseph-Ridge N. Gout Assessment Questionnaire: Initial results of reliability, validity and responsiveness. Int J Clin Pract. 2006 Oct;60(10):1210-7. doi: 10.1111/j.1742-1241.2006.01104.x. Epub 2006 Aug 15.
    Results Reference
    result
    PubMed Identifier
    19141576
    Citation
    Schumacher HR Jr, Becker MA, Lloyd E, MacDonald PA, Lademacher C. Febuxostat in the treatment of gout: 5-yr findings of the FOCUS efficacy and safety study. Rheumatology (Oxford). 2009 Feb;48(2):188-94. doi: 10.1093/rheumatology/ken457.
    Results Reference
    result
    PubMed Identifier
    21169856
    Citation
    Whelton A, Macdonald PA, Zhao L, Hunt B, Gunawardhana L. Renal function in gout: long-term treatment effects of febuxostat. J Clin Rheumatol. 2011 Jan;17(1):7-13. doi: 10.1097/RHU.0b013e318204aab4.
    Results Reference
    result
    Links:
    URL
    http://general.takedapharm.com/content/file.aspx?applicationcode=6C7C39D8-5D09-453B-BF30-696A4AB88E62&fileTypeCode=ULORICPI
    Description
    Uloric Package Insert

    Learn more about this trial

    Long-Term Safety of Febuxostat in Subjects With Gout.

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