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

This study has been completed.
Sponsor:
Information provided by:
Takeda
ClinicalTrials.gov Identifier:
NCT00175019
First received: September 12, 2005
Last updated: July 22, 2010
Last verified: July 2010

September 12, 2005
July 22, 2010
July 2003
February 2007   (final data collection date for primary outcome measure)
  • Percentage of Subjects Whose Serum Urate Level Decreases to < 6.0 mg/dL at Month 1. [ Time Frame: Month 1 ] [ Designated as safety issue: No ]
    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. [ Time Frame: Month 12 ] [ Designated as safety issue: No ]
    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. [ Time Frame: Month 24 ] [ Designated as safety issue: No ]
    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. [ Time Frame: Month 36 ] [ Designated as safety issue: No ]
    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. [ Time Frame: Last Visit on treatment (up to 40 months). ] [ Designated as safety issue: No ]
    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.
The proportion of subjects whose serum urate level decreases to < 6.0 mg/dL.
Complete list of historical versions of study NCT00175019 on ClinicalTrials.gov Archive Site
  • Percent Change in Serum Urate Levels From Baseline to the Last Visit on Treatment. [ Time Frame: Last Visit on treatment (up to 40 months). ] [ Designated as safety issue: No ]
    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. [ Time Frame: Month 12 ] [ Designated as safety issue: No ]
    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. [ Time Frame: Month 24 ] [ Designated as safety issue: No ]
    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. [ Time Frame: Month 36 ] [ Designated as safety issue: No ]
    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. [ Time Frame: Final Visit (up to 40 months). ] [ Designated as safety issue: No ]
    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. [ Time Frame: Final Visit (up to 40 months). ] [ Designated as safety issue: No ]
    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. [ Time Frame: Month 12 ] [ Designated as safety issue: No ]
    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. [ Time Frame: After Month 12 to Final Visit ] [ Designated as safety issue: No ]
    The percentage of subjects requiring treatment for gout flare after the first 12 months of final stable treatment was summarized.
The percent reduction in serum urate levels from baseline,change in size and number of tophi, percent of subjects requiring treatment for gout flare.
Not Provided
Not Provided
 
Allopurinol Versus Febuxostat in Subjects Completing the Phase 3 Trials C02-009 or C02-010
A Phase 3, Open-Label, Randomized, Allopurinol-Controlled Study to Assess the Long-Term Safety of Oral Febuxostat in Subjects With Gout

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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Gout
  • Drug: Febuxostat
    Febuxostat 80 mg, tablets, orally, once daily.
    Other Names:
    • TMX-67
    • Tei-6720
    • Uloric
  • Drug: Febuxostat
    Febuxostat 120 mg, tablets, orally, once daily.
    Other Names:
    • TMX-67
    • Tei-6720
    • Uloric
  • Drug: Allopurinol
    Allopurinol 100 mg or 300 mg, tablets, orally, once daily.
    Other Name: Zyloprim
  • Experimental: Febuxostat 80 mg QD
    Intervention: Drug: Febuxostat
  • Experimental: Febuxostat 120 mg QD
    Intervention: Drug: Febuxostat
  • Active Comparator: Allopurinol QD
    Intervention: Drug: Allopurinol
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. Epub 2009 Mar 13.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
1086
February 2007
February 2007   (final data collection date for primary outcome measure)

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.
Both
18 Years to 85 Years
No
Contact information is only displayed when the study is recruiting subjects
Not Provided
 
NCT00175019
C02-021, U1111-1113-9814
No
Sr. VP, Clinical Science, Takeda Global Research & Development Center, Inc.
Takeda
Not Provided
Study Chair: Medical Director Takeda
Takeda
July 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP