Febuxostat Versus Allopurinol Control Trial in Subjects With Gout

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the safety and efficacy of febuxostat, once daily (QD), versus allopurinol in subjects with gout.

Detailed Description
-----------------
This was a randomized, controlled, double-blind study of 52 weeks duration. Subjects receiving prior urate-lowering therapy underwent a 2-week washout period prior to randomization. Subjects were then randomized to one of three treatment groups: febuxostat 80 milligram (mg), febuxostat 120 mg, or allopurinol 300 mg. Naproxen (250 mg twice daily) or colchicine (0.6 mg once daily) was provided for prophylaxis of acute gout flares during the washout period and the first 8 weeks of double-blind treatment.

Official Title
-----------------
A Phase 3, Randomized, Multicenter Study Comparing the Safety and Efficacy of Oral Febuxostat Versus Allopurinol in Subjects With Gout

Conditions
-----------------
Gout

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Meeting the preliminary criteria of the American Rheumatism Association for the classification of the acute arthritis of primary gout. Serum uric acid ≥ 8.0 milligrams per deciliter (mg/dL) at Baseline Exclusion Criteria: Serum creatinine >1.5 mg/dL Calculated creatinine clearance of <50 milliliters per minutes (mL/min) Pregnancy or lactation; Concurrent therapy with urate lowering agents, azathioprine, 6-mercaptopurine, thiazide diuretics, or medications containing aspirin (>325 mg) or other salicylates; Body Mass Index (BMI) >50 kilogram per meter²(kg/m²); A history of xanthinuria, active liver disease, or hepatic dysfunction; A history of alcohol abuse or intake of 14 or more alcohol-containing drinks/week.

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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 52 weeks.<br>* Other names: Uloric;|
| Experimental: Febuxostat 120 mg QD<br> | Drug: Febuxostat<br>* Febuxostat 120 mg, orally, once daily for up to 52 weeks.<br>* Other names: Uloric;|
| Active Comparator: Allopurinol 300 mg QD<br> | Drug: Allopurinol<br>* Allopurinol 300 mg, capsules, orally, once daily for up to 52 weeks.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects With the Last 3 Serum Urate Levels <6.0 Milligrams 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 (up to 52 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects With Serum Urate <6.0 mg/dL at Week 28 Visit | 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 With Serum Urate <6.0 mg/dL at Week 52 Visit | Serum urate values were obtained at the Week 52 visit. The percentage of subjects whose serum urate was <6.0 mg/dL at the Week 52 visit was summarized. | Week 52 | 
| Percentage of Subjects With Serum Urate <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. The timing of the final visit may have differed for each subject. | Final Visit (up to 52 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 Week 52. | Serum urate values were obtained at the Week 52 visit. The percent change in serum urate was calculated as [(week 52 - baseline levels/baseline)]*100 and summarized. | Baseline and Week 52 | 
| Percent Change From Baseline in Serum Urate Levels at Final Visit | The percent change in serum urate from baseline to the Final visit was calculated as [(Final Visit - baseline levels/baseline)]*100 and summarized. The Final visit was the last visit with a serum urate value. The timing of the final visit may have differed for each subject. | Baseline and Final Visit (up to 52 weeks) | 
| Percent Change From Baseline in Tophus Size at Week 28, as Determined by Physical Measurement, in Subjects With a Palpable Primary Tophus at Screening. | 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 From Baseline in Tophus Size at Week 52, as Determined by Physical Measurement, in Subjects With a Palpable Primary Tophus at Screening. | The percent change from baseline in primary tophus size as determined by physical measurement was calculated as [(Week 52 - 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 52 visit, the size was assumed to be zero. | Baseline and Week 52 | 
| Percent Change From Baseline in Tophus Size at Final Visit, as Determined by Physical Measurement, in Subjects With a Palpable Primary Tophus at Screening. | 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 52 weeks) | 
| Change From Baseline in Total Number of Tophi at Week 28 in Subjects With Palpable Tophi at Screening. | The 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 no longer palpable at the Week 28 visit, the total count was assumed to be zero. | Baseline and Week 28 | 
| Change From Baseline in Total Number of Tophi at Week 52 in Subjects With Palpable Tophi at Screening. | The change from baseline at Week 52 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 no longer palpable at the Week 52 visit, the total count was assumed to be zero. | Baseline and Week 52 | 
| Change From Baseline in Total Number of Tophi at Final Visit in Subjects With Palpable Tophi at Screening. | Change in number of tophi/subject calculated for the subset of subjects with palpable tophi at 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. | Baseline and Final Visit (up to 52 weeks) | 
| Percentage of Subjects Requiring Treatment for Gout Flares Between Weeks 8 and 52. | The percentage of subjects requiring treatment for a gout flare between Weeks 8 and 52 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 52 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
uric Acid, xanthine oxidase, tophi, Drug Therapy