Efficacy and Safety of Oral Febuxostat in Participants With Gout

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Gout

Intervention / Treatment
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* Drug: Febuxostat
* Drug: Febuxostat
* Drug: Allopurinol


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Febuxostat 40 mg QD<br> | Drug: Febuxostat<br>* Febuxostat 40 mg, capsules, orally, once daily for up to 6 months.<br>* Other names: Uloric;|
| Experimental: Febuxostat 80 mg QD<br> | Drug: Febuxostat<br>* Febuxostat 80 mg, capsules, orally, once daily for up to 6 months.<br>* Other names: Uloric;|
| Active Comparator: Allopurinol 200 mg or 300 mg QD<br>(dependent on renal function) | Drug: Allopurinol<br>* 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.<br>* Other names: Zyloprim;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects Whose Serum Urate Level is <6.0 Milligrams Per Deciliter (mg/dL) at the Final Visit. | The percentage of subjects whose serum urate level 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. | Last Visit on treatment (up to 6 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Renal Impairment Subjects Whose Final Visit Serum Urate Level is <6.0 mg/dl | The percentage of subjects with mild-to-moderate renal impairment 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. | Last Visit on treatment (up to 6 months) | 
| Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Month 2 Visit. | Serum urate values were obtained at the Month 2 visit. The percentage of subjects whose serum urate was <6.0 mg/dL at the Month 2 visit was summarized. | Month 2 | 
| Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Month 4 Visit. | Serum urate values were obtained at the Month 4 visit. The percentage of subjects whose serum urate was <6.0 mg/dL at the Month 4 visit was summarized. | Month 4 | 
| Percentage of Subjects Whose Serum Urate Levels Are <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. | Month 6 | 
| Percentage of Subjects Whose Serum Urate Levels Are <5.0 mg/dL at Month 2 Visit. | Serum urate values were obtained at the Month 2 visit. The percentage of subjects whose serum urate was <5.0 mg/dL at the Month 2 visit was summarized. | Month 2 | 
| Percentage of Subjects Whose Serum Urate Levels Are <5.0 mg/dL at Month 4 Visit. | Serum urate values were obtained at the Month 4 visit. The percentage of subjects whose serum urate was <5.0 mg/dL at the Month 4 visit was summarized. | Month 4 | 
| Percentage of Subjects Whose Serum Urate Levels Are <5.0 mg/dL at Month 6 Visit. | Serum urate values were obtained at the Month 6 visit. The percentage of subjects whose serum urate was <5.0 mg/dL at the Month 6 visit was summarized. | Month 6 | 
| Percentage of Subjects Whose Serum Urate Levels Are <5.0 mg/dL at Final Visit. | The percentage of subjects whose serum urate level was <5.0 mg/dL at the Final Visit was summarized. The Final Visit was the last visit at which a serum urate values was collected. | Last Visit on treatment (up to 6 months) | 
| Percentage of Subjects Whose Serum Urate Levels Are <4.0 mg/dL at Month 2 Visit | Serum urate values were obtained at the Month 2 visit. The percentage of subjects whose serum urate was <4.0 mg/dL at the Month 2 visit was summarized. | Month 2 | 
| Percentage of Subjects Whose Serum Urate Levels Are <4.0 mg/dL at Month 4 Visit | Serum urate values were obtained at the Month 4 visit. The percentage of subjects whose serum urate was <4.0 mg/dL at the Month 4 visit was summarized. | Month 4 | 
| Percentage of Subjects Whose Serum Urate Levels Are <4.0 mg/dL at Month 6 Visit | Serum urate values were obtained at the Month 6 visit. The percentage of subjects whose serum urate was <4.0 mg/dL at the Month 6 visit was summarized. | Month 6 | 
| Percentage of Subjects Whose Serum Urate Levels Are <4.0 mg/dL at Final Visit | The percentage of subjects whose serum urate level was <4.0 mg/dL at the Final Visit was summarized. The Final Visit was the last visit at which a serum urate values was collected. | Last Visit on treatment (up to 6 months) | 
| Mean Percent Change From Baseline in Serum Urate Levels at Month 2 Visit. | Serum urate values were obtained at the Month 2 visit. The percent change in serum urate from baseline to the Month 2 visit was summarized. | Baseline and Month 2 | 
| Mean Percent Change From Baseline in Serum Urate Levels at Month 4 Visit | Serum urate values were obtained at the Month 4 visit. The percent change in serum urate from baseline to the Month 4 visit was summarized. | Baseline and Month 4 | 
| Mean Percent Change From Baseline in Serum Urate Levels 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. | Baseline and Month 6 | 
| Mean Percent Change From Baseline in Serum Urate Levels 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. | Baseline and Last Visit on treatment (up to 6 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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tophi, hyperuricemia, uric acid, Drug Therapy