Phase 3, Febuxostat, Allopurinol and Placebo-Controlled Study in Gout Subjects.

Study Overview
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Brief Summary
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The purpose of this study is to compare febuxostat, allopurinol and placebo, once daily (QD), in subjects with gout.

Detailed Description
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A Phase 3 Study comparing 80 mg, 120 mg or 240 mg of febuxostat, allopurinol (300 mg for those with normal renal function and 100 mg for those with impaired renal function) and placebo administered once daily in subjects with gout. Subjects will receive treatment for 28 weeks.

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

Conditions
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Gout

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Hyperuricemia (serum urate ≥8.0 mg/dL and gout by American Rheumatism Association Criteria Renal function defined as a serum creatinine level of < 2.0 mg/dL and creatinine clearance of > 20 milliliters per minute (mL/min) by Cockroft and Gault formula. Exclusion Criteria: History of xanthinuria Intolerance to allopurinol Presence of renal calculi, Alcohol intake of ≥ 14 drinks/week Clinically significant medical condition

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 80 mg QD<br> | Drug: Febuxostat<br>* Febuxostat 80 mg, orally, once daily for up to 28 weeks.<br>* Other names: Uloric;|
| Experimental: Febuxostat 120 mg QD<br> | Drug: Febuxostat<br>* Febuxostat 120 mg, orally, once daily for up to 28 weeks.<br>* Other names: Uloric;|
| Experimental: Febuxostat 240 mg QD<br> | Drug: Febuxostat<br>* Febuxostat 240 mg, orally, once daily for up to 28 weeks.<br>* Other names: Uloric;|
| Active Comparator: Allopurinol QD<br> | Drug: Allopurinol<br>* Allopurinol, orally, once daily for up to 28 weeks. Dose of allopurinol received was based on renal status. Subjects with serum creatinine ≤1.5 mg/dL received 300 mg once daily; subjects with serum creatinine >1.5 mg/dL and ≤2.0 mg/dL received 100 mg once daily.<br>|
| Placebo Comparator: Placebo QD<br> | Drug: Placebo<br>* Placebo, orally, once daily for up to 28 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects Whose Last Three Serum Urate Levels Are <6.0 Milligram Per Deciliter (mg/dL). | Each subject's serum urate at the last 3 visits determined the subject's response for the primary efficacy variable. A subject who prematurely discontinued without least 3 postbaseline serum urate levels was considered a nonresponder; if at least 3 serum urate were obtained postbaseline, those 3 visits were used. The last 3 visits used may have differed for each subject. | Last 3 visits (any last 3 visits up to week 28) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Week 28 | Serum urate values were obtained at the Week 28 visit. The percentage of subjects whose serum urate was <6.0 mg/dL at the Week 28 visit was summarized. | Week 28 | 
| Percentage of Subjects Whose Serum Urate Levels Are <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 and may have differed by subject. | Final Visit (up to 28 weeks). | 
| Percent Change From Baseline in Serum Urate Levels at Week 28. | Serum urate values were obtained at the Week 28 visit. The percent change in serum urate was calculated as [(Week 28 - baseline levels)/baseline]*100 and summarized. | Baseline and Week 28 | 
| 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 percent change in serum urate was calculated as [(Final visit - baseline levels)/baseline]*100. The final visit was the last visit at which a serum urate value was collected. The timing of the final visit may have differed for each subject. | Baseline and Final Visit (up to 28 weeks) | 
| Percent Change in Primary Tophus Size at Week 28, as Determined by Physical Measurement in the Subset of Subjects With Palpable Tophi at the Screening Visit. | The percent change from baseline in primary tophus size as determined by physical measurement was calculated as [(Week 28 - baseline sizes)/baseline]*100 for the subset of subjects with a primary palpable tophus at the Screening Visit. If the primary tophus was no longer palpable at the Week 28 visit, the size was assumed to be zero. | Baseline and Week 28 | 
| Percent Change in Primary Tophus Size at Final Visit, as Determined by Physical Measurement in the Subset of Subjects With Palpable Tophi at the Screening Visit. | Percent change in primary tophus size was calculated as [(Final Visit - baseline sizes)/baseline]*100 for the subset of subjects with a primary palpable tophus at Screening. If tophus was not palpable at Final visit, the size was assumed to be 0. The timing of the final visit may have differed for each subject. | Baseline and Final Visit (up to 28 weeks) | 
| Change in the Total Number of Tophi at Week 28 in the Subset of Subjects With Palpable Tophi at the Screening Visit. | Change from baseline at Week 28 in the total number of tophi per subject was calculated for the subset of subjects with palpable tophi at the Screening Visit. If the tophi were not palpable at the Week 28 visit, the total count was assumed to be 0. | Baseline and Week 28 | 
| Change in the Total Number of Tophi at Final Visit in the Subset of Subjects With Palpable Tophi at the Screening Visit | Change in number of tophi/subject was calculated for the subset of subjects with palpable tophi at the Screening. If the tophi were not palpable at the Final Visit, total count was assumed to be 0. The timing of the final visit may have differed for each subject. | Final Visit (up to 28 weeks) | 
| Percentage of Subjects Requiring Treatment for a Gout Flare Between Weeks 8 and 28 of the Double-Blind Treatment Period. | Percentage of subjects requiring treatment for a gout flare between Weeks 8 and 28 of the double-blind treatment period was summarized. A subject who reported more than 1 gout flare during this period was counted only once. | Weeks 8 through 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Uric Acid, gout, xanthine oxidase, febuxostat, tophi