Efficacy and Safety of Oral Febuxostat in Participants With Gout

Official Title: “A Phase 3, Randomized, Multicenter, Double-Blind, Allopurinol-Controlled Study Assessing the Efficacy and Safety of Oral Febuxostat in Subjects With Gout.”

The purpose of this study is to compare the efficacy and safety of febuxostat, once Daily (QD), to allopurinol in subjects with hyperuricemia and gout.

Renal impairment is common in subjects with gout, with the prevalence ranging from 50% to 70%. This population represents an unmet medical need as uricosuric drugs are contraindicated in these patients, and the only available treatment, allopurinol, may have to be dose reduced to avoid overt side effects.

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.

Treatment duration will be 6 months.

Intervention(s) in this Clinical Trial

• Drug: Febuxostat
  • Febuxostat 40 mg, capsules, orally, once daily for up to 6 months.
• Drug: Febuxostat
  • Febuxostat 80 mg, capsules, orally, once daily for up to 6 months.
• Drug: Allopurinol
  • Allopurinol 200 mg or 300 mg, capsules, orally, once daily for up to 6 months. Dose is dependent on the subject's renal function. Subjects with normal renal function or mild renal impairment received 300 mg once daily; subjects with moderate renal impairment received 200 mg once daily.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Febuxostat 40 mg QD
• Experimental: Febuxostat 80 mg QD
• Active Comparator: Allopurinol 200 mg or 300 mg QD
  • (dependent on renal function)

Primary Measures

• Percentage of Subjects Whose Serum Urate Level is <6.0 Milligrams Per Deciliter (mg/dL) at the Final Visit.
  • Time Frame: Last Visit on treatment (up to 6 months)
    Safety Issue?: No

Secondary Measures

• Percentage of Renal Impairment Subjects Whose Final Visit Serum Urate Level is <6.0 mg/dl
  • Time Frame: Last Visit on treatment (up to 6 months)
    Safety Issue?: No
• Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Month 2 Visit.
  • Time Frame: Month 2
    Safety Issue?: No
• Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Month 4 Visit.
  • Time Frame: Month 4
    Safety Issue?: No
• Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Month 6 Visit.
  • Time Frame: Month 6
    Safety Issue?: No
• Percentage of Subjects Whose Serum Urate Levels Are <5.0 mg/dL at Month 2 Visit.
  • Time Frame: Month 2
    Safety Issue?: No
• Percentage of Subjects Whose Serum Urate Levels Are <5.0 mg/dL at Month 4 Visit.
  • Time Frame: Month 4
    Safety Issue?: No
• Percentage of Subjects Whose Serum Urate Levels Are <5.0 mg/dL at Month 6 Visit.
  • Time Frame: Month 6
    Safety Issue?: No
• Percentage of Subjects Whose Serum Urate Levels Are <5.0 mg/dL at Final Visit.
  • Time Frame: Last Visit on treatment (up to 6 months)
    Safety Issue?: No
• Percentage of Subjects Whose Serum Urate Levels Are <4.0 mg/dL at Month 2 Visit
  • Time Frame: Month 2
    Safety Issue?: No
• Percentage of Subjects Whose Serum Urate Levels Are <4.0 mg/dL at Month 4 Visit
  • Time Frame: Month 4
    Safety Issue?: No
• Percentage of Subjects Whose Serum Urate Levels Are <4.0 mg/dL at Month 6 Visit
  • Time Frame: Month 6
    Safety Issue?: No
• Percentage of Subjects Whose Serum Urate Levels Are <4.0 mg/dL at Final Visit
  • Time Frame: Last Visit on treatment (up to 6 months)
    Safety Issue?: No
• Mean Percent Change From Baseline in Serum Urate Levels at Month 2 Visit.
  • Time Frame: Baseline and Month 2
    Safety Issue?: No
• Mean Percent Change From Baseline in Serum Urate Levels at Month 4 Visit
  • Time Frame: Baseline and Month 4
    Safety Issue?: No
• Mean Percent Change From Baseline in Serum Urate Levels at Month 6 Visit.
  • Time Frame: Baseline and Month 6
    Safety Issue?: No
• Mean Percent Change From Baseline in Serum Urate Levels at Final Visit.
  • Time Frame: Baseline and Last Visit on treatment (up to 6 months)
    Safety Issue?: No

Inclusion Criteria:

• Has one or more of the American Rheumatism Association criteria for the diagnosis of gout.
• 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.
• Must have a serum urate level greater than or equal to 8.0 milligram per deciliter (mg/dL).

Exclusion Criteria:

• Have a severe, unstable, or life threatening medical condition that would likely prevent them from completing this study.
• Has a known body reaction to febuxostat, allopurinol, naproxen, any other non-steroidal anti-inflammatory drug (NSAID), aspirin, lansoprazole, colchicine, or any components in their formulation.
• History of xanthinuria.
• Alcohol consumption greater than 14/week.
• History of significant concomitant illness.
• Active liver or peptic ulcer disease.
• Has rheumatoid arthritis requiring treatment.
• Has estimated creatinine clearance less than 30 milliliter per minute (mL/min) calculated using the Cockcroft-Gault formula corrected for ideal body weight.
• Requires therapy with any other urate-lowering drug other than the study drug;
• long-term use of NSAIDs and COX-2 inhibitors; salicylates; thiazide diuretics;
• losartan; azathioprine; mercaptopurine; theophylline; intravenous (IV) colchicine;
• cyclosporine; cyclophosphamide; pyrazinamide; sulfamethoxazole;trimethoprim.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 85 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Takeda Global Research & Development Center, Inc. Industry

Overall Clinical Trial Officials and Contacts

Medical Director Study Chair Takeda Global Research & Development Center, Inc.  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00430248

Study ID Number: F-GT06-153

ClinicalTrials.gov Identifier: NCT00430248

Health Authority: United States: Food and Drug Administration

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