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Allopurinol Versus Febuxostat in Subjects Completing the Phase 3 Trials C02-009 or C02-010 (EXCEL)

Primary Purpose

Gout

Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Febuxostat
Febuxostat
Allopurinol
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, hyperuricemia, tophi, Drug Therapy

Eligibility Criteria

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

Inclusion Criteria: Is receiving thiazide diuretic therapy (only to subjects randomized to or receiving febuxostat). Has a serum urate level less than 8.0 mg/dL and is not taking uric acid-lowering therapy (other than allopurinol or febuxostat). Has participated in a clinical study in which febuxostat was administered. Is completing Phase 3 Studies C02-009 or C02-010. Must not have experienced any serious study drug-related adverse events in the previous study. 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: Has had any other significant medical condition as defined by the investigator that would interfere with the treatment, safety, or compliance with the protocol. Is intolerant of allopurinol.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm Type

    Experimental

    Experimental

    Active Comparator

    Arm Label

    Febuxostat 80 mg QD

    Febuxostat 120 mg QD

    Allopurinol QD

    Arm Description

    Outcomes

    Primary Outcome Measures

    Percentage of Subjects Whose Serum Urate Level Decreases to < 6.0 mg/dL at Month 1.
    Serum urate values were obtained at the Month 1 visit. The percentage of subjects whose serum urate was <6.0 mg/dL at the Month 1 visit was summarized.
    Percentage of Subjects Whose Serum Urate Level Decreases to < 6.0 mg/dL at Month 12.
    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 < 6.0 mg/dL at Month 24.
    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 < 6.0 mg/dL at Month 36.
    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 < 6.0 mg/dL at Last Visit on Treatment.
    The percentage of subjects whose serum urate was <6.0 mg/dL at the last visit on treatment was summarized. The last visit on treatment was the last visit at which a serum urate value was collected prior to any changes in drug and/or dose from the initial treatment assignment.

    Secondary Outcome Measures

    Percent Change in Serum Urate Levels From Baseline to the Last Visit on Treatment.
    The percent change in serum urate from baseline to the last visit on treatment was summarized. The last visit on treatment was the last visit at which a serum urate value was collected prior to any changes in drug and/or dose from the initial treatment assignment.
    Percent Change From Baseline in Primary Tophus Size at Month 12 for Subjects With Palpable Tophi Measured at Baseline.
    The area of the primary tophus was calculated based on the length and width of the tophus measured at the Month 12 visit. The percent change from baseline in primary tophus size to the Month 12 visit was summarized.
    Percent Change From Baseline in Primary Tophus Size at Month 24 for Subjects With Palpable Tophi Measured at Baseline.
    The area of the primary tophus was calculated based on the length and width of the tophus measured at baseline and Month 24 visit. The percent change from baseline in primary tophus size to the Month 24 visit was summarized.
    Percent Change From Baseline in Primary Tophus Size at Month 36 for Subjects With Palpable Tophi Measured at Baseline.
    The area of the primary tophus was calculated based on the length and width of the tophus measured at baseline and Month 36 visit. The percent change from baseline in primary tophus size to the Month 36 visit was summarized.
    Percent Change From Baseline in Primary Tophus Size at Final Visit for Subjects With Palpable Tophi Measured at Baseline.
    The area of the primary tophus was calculated based on the length and width of the tophus measured at baseline and final visit. The percent change from baseline in primary tophus size to the final visit was summarized.
    Percent Change From Baseline in the Total Number of Tophi for Subjects With Palpable Tophi at Final Visit.
    The number of tophi were counted at baseline and final visits. The percent change from baseline in the number of tophi to the final visit was summarized.
    Percentage of Subjects Requiring Treatment for Gout Flare up to Month 12.
    The percentage of subjects requiring treatment for gout flare during the first twelve months of final stable treatment was summarized.
    Percentage of Subjects Requiring Treatment for Gout Flare After Month 12.
    The percentage of subjects requiring treatment for gout flare after the first 12 months of final stable treatment was summarized.

    Full Information

    First Posted
    September 12, 2005
    Last Updated
    July 22, 2010
    Sponsor
    Takeda
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00175019
    Brief Title
    Allopurinol Versus Febuxostat in Subjects Completing the Phase 3 Trials C02-009 or C02-010
    Acronym
    EXCEL
    Official Title
    A Phase 3, Open-Label, Randomized, Allopurinol-Controlled Study to Assess the Long-Term Safety of Oral Febuxostat in Subjects With Gout
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    July 2010
    Overall Recruitment Status
    Completed
    Study Start Date
    July 2003 (undefined)
    Primary Completion Date
    February 2007 (Actual)
    Study Completion Date
    February 2007 (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 determine the long-term safety of febuxostat, once daily (QD), compared to allopurinol in reducing serum urate 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 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 insufficient) 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 partially of uric acid crystals. Management of gout requires chronic treatment aimed at lowering serum urate levels 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 the management of hyperuricemia in patients with gout. This study was originally designed and initiated having all subjects initially assigned to 80 mg febuxostat provided as an 80 mg tablet, to be administered orally. Subjects could be titrated to 120 mg, provided as one 40 and 80 mg tablet, between Months 2 and 6, if their serum uric acid rose > 6.0 mg/dL; the dose could be down-titrated to 80 mg if the serum uric acid decreased to < 3.0 mg/dL. The protocol was amended to add a comparator arm, and to have subjects randomized to 80 or 120 mg febuxostat or allopurinol (100 or 300 mg, dependent on renal function). The information below reflects the treatments following the implementation of the revised protocol.

    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, hyperuricemia, tophi, Drug Therapy

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    1086 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Febuxostat 80 mg QD
    Arm Type
    Experimental
    Arm Title
    Febuxostat 120 mg QD
    Arm Type
    Experimental
    Arm Title
    Allopurinol QD
    Arm Type
    Active Comparator
    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.
    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.
    Intervention Type
    Drug
    Intervention Name(s)
    Allopurinol
    Other Intervention Name(s)
    Zyloprim
    Intervention Description
    Allopurinol 100 mg or 300 mg, tablets, orally, once daily.
    Primary Outcome Measure Information:
    Title
    Percentage of Subjects Whose Serum Urate Level Decreases to < 6.0 mg/dL at Month 1.
    Description
    Serum urate values were obtained at the Month 1 visit. The percentage of subjects whose serum urate was <6.0 mg/dL at the Month 1 visit was summarized.
    Time Frame
    Month 1
    Title
    Percentage of Subjects Whose Serum Urate Level Decreases to < 6.0 mg/dL at Month 12.
    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 < 6.0 mg/dL at Month 24.
    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 < 6.0 mg/dL at Month 36.
    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 < 6.0 mg/dL at Last Visit on Treatment.
    Description
    The percentage of subjects whose serum urate was <6.0 mg/dL at the last visit on treatment was summarized. The last visit on treatment was the last visit at which a serum urate value was collected prior to any changes in drug and/or dose from the initial treatment assignment.
    Time Frame
    Last Visit on treatment (up to 40 months).
    Secondary Outcome Measure Information:
    Title
    Percent Change in Serum Urate Levels From Baseline to the Last Visit on Treatment.
    Description
    The percent change in serum urate from baseline to the last visit on treatment was summarized. The last visit on treatment was the last visit at which a serum urate value was collected prior to any changes in drug and/or dose from the initial treatment assignment.
    Time Frame
    Last Visit on treatment (up to 40 months).
    Title
    Percent Change From Baseline in Primary Tophus Size at Month 12 for Subjects With Palpable Tophi Measured at Baseline.
    Description
    The area of the primary tophus was calculated based on the length and width of the tophus measured at the Month 12 visit. The percent change from baseline in primary tophus size to the Month 12 visit was summarized.
    Time Frame
    Month 12
    Title
    Percent Change From Baseline in Primary Tophus Size at Month 24 for Subjects With Palpable Tophi Measured at Baseline.
    Description
    The area of the primary tophus was calculated based on the length and width of the tophus measured at baseline and Month 24 visit. The percent change from baseline in primary tophus size to the Month 24 visit was summarized.
    Time Frame
    Month 24
    Title
    Percent Change From Baseline in Primary Tophus Size at Month 36 for Subjects With Palpable Tophi Measured at Baseline.
    Description
    The area of the primary tophus was calculated based on the length and width of the tophus measured at baseline and Month 36 visit. The percent change from baseline in primary tophus size to the Month 36 visit was summarized.
    Time Frame
    Month 36
    Title
    Percent Change From Baseline in Primary Tophus Size at Final Visit for Subjects With Palpable Tophi Measured at Baseline.
    Description
    The area of the primary tophus was calculated based on the length and width of the tophus measured at baseline and final visit. The percent change from baseline in primary tophus size to the final visit was summarized.
    Time Frame
    Final Visit (up to 40 months).
    Title
    Percent Change From Baseline in the Total Number of Tophi for Subjects With Palpable Tophi at Final Visit.
    Description
    The number of tophi were counted at baseline and final visits. The percent change from baseline in the number of tophi to the final visit was summarized.
    Time Frame
    Final Visit (up to 40 months).
    Title
    Percentage of Subjects Requiring Treatment for Gout Flare up to Month 12.
    Description
    The percentage of subjects requiring treatment for gout flare during the first twelve months of final stable treatment was summarized.
    Time Frame
    Month 12
    Title
    Percentage of Subjects Requiring Treatment for Gout Flare After Month 12.
    Description
    The percentage of subjects requiring treatment for gout flare after the first 12 months of final stable treatment was summarized.
    Time Frame
    After Month 12 to Final Visit

    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: Is receiving thiazide diuretic therapy (only to subjects randomized to or receiving febuxostat). Has a serum urate level less than 8.0 mg/dL and is not taking uric acid-lowering therapy (other than allopurinol or febuxostat). Has participated in a clinical study in which febuxostat was administered. Is completing Phase 3 Studies C02-009 or C02-010. Must not have experienced any serious study drug-related adverse events in the previous study. 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: Has had any other significant medical condition as defined by the investigator that would interfere with the treatment, safety, or compliance with the protocol. Is intolerant of allopurinol.
    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
    19286847
    Citation
    Becker MA, Schumacher HR, MacDonald PA, Lloyd E, Lademacher C. Clinical efficacy and safety of successful longterm urate lowering with febuxostat or allopurinol in subjects with gout. J Rheumatol. 2009 Jun;36(6):1273-82. doi: 10.3899/jrheum.080814. Epub 2009 Mar 13.
    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

    Allopurinol Versus Febuxostat in Subjects Completing the Phase 3 Trials C02-009 or C02-010

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