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Study Results
Related Studies
Phase 3, Febuxostat, Allopurinol and Placebo-Controlled Study in Gout Subjects. (APEX)
This study has been completed.
Study NCT00174915   Information provided by Takeda Global Research & Development Center, Inc.
First Received: September 9, 2005   Last Updated: August 13, 2009   History of Changes
Study Type: Interventional
Study Design: Randomized, Double Blind (Subject, Investigator, Outcomes Assessor), Active Control, Parallel Assignment
Condition: Gout
Interventions: Drug: Febuxostat
Drug: Allopurinol
Drug: Placebo

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Subjects were enrolled at 167 investigative sites in the United States from 21 February 2003 to 07 April 2004.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Subjects currently receiving urate-lowering therapy discontinued those urate-lowering therapies and initiated prophylactic medications before enrollment in once daily (QD) treatment groups.

Reporting Groups
  Description
Febuxostat 80 mg QD Febuxostat 80 mg, orally, once daily for up to 28 weeks.
Febuxostat 120 mg QD Febuxostat 120 mg, orally, once daily for up to 28 weeks.
Febuxostat 240 mg QD Febuxostat 240 mg, orally, once daily for up to 28 weeks.
Allopurinol QD 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.
Placebo QD Placebo, orally, once daily for up to 28 weeks.

Participant Flow:   Overall Study
  Febuxostat 80 mg QD Febuxostat 120 mg QD Febuxostat 240 mg QD Allopurinol QD Placebo QD
STARTED   267     269     134     268     134  
COMPLETED   174     200     86     211     101  
NOT COMPLETED   93     69     48     57     33  
      Lost to Follow-up               19                 17                 9                 17                 10  
      Adverse Event               18                 16                 11                 18                 5  
      Personal Reason(s)               16                 16                 9                 9                 9  
      Other               15                 8                 6                 5                 3  
      Gout Flare               13                 6                 8                 1                 0  
      Protocol Violation               6                 3                 3                 6                 3  
      Therapeutic Failure               6                 3                 2                 1                 3  



  Baseline Characteristics
  Hide Baseline Characteristics

Reporting Groups
  Description
Febuxostat 80 mg QD Febuxostat 80 mg, orally, once daily for up to 28 weeks.
Febuxostat 120 mg QD Febuxostat 120 mg, orally, once daily for up to 28 weeks.
Febuxostat 240 mg QD Febuxostat 240 mg, orally, once daily for up to 28 weeks.
Allopurinol QD 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.
Placebo QD Placebo, orally, once daily for up to 28 weeks.

Baseline Measures
  Febuxostat 80 mg QD Febuxostat 120 mg QD Febuxostat 240 mg QD Allopurinol QD Placebo QD Total
Number of Participants  
[units: participants]
 		267 269 134 268 134 1072
Age, Customized  
[units: subjects]
 		           
<45 years 82 79 33 82 36 312
45 years to <65 years 146 154 71 147 79 597
≥65 years 39 36 30 39 19 163
Age  
[units: years]
Mean ± Standard Deviation 		50.6 ± 12.24 51.2 ± 11.57 54.3 ± 12.83 51.8 ± 12.25 51.5 ± 12.18 51.6 ± 12.17
Gender  
[units: subjects]
 		           
Female 16 13 8 19 11 67
Male 251 256 126 249 123 1005
Race/Ethnicity, Customized  
[units: subjects]
 		           
White 200 214 107 206 108 835
Black or African American 38 27 13 33 9 120
Hispanic 13 16 8 17 10 64
Asian 8 8 1 6 3 26
Other 8 4 5 6 4 27
Body Mass Index  
[units: subjects]
 		           
<18.5 kilogram per meter² (kg/m²) 0 0 0 0 0 0
18.5 kg/m² to <25 kg/m² 10 11 9 15 16 61
25 kg/m² to <30 kg/m² 85 81 42 91 48 347
≥30 kg/m² 172 176 83 161 70 662
missing 0 1 0 1 0 2
Presence of a Primary PalpableTophus  
[units: subjects]
 		           
Yes 48 53 25 64 29 219
No, but other tophi present 0 3 1 1 1 6
No, and no other tophi present 219 213 108 203 104 847
Serum Creatinine  
[units: subjects]
 		           
≤1.5 milligram per deciliter (mg/dL) 258 258 129 258 129 1032
>1.5 mg/dL 9 11 5 10 5 40



  Outcome Measures
  Hide All Outcome Measures

1.  Primary:   Percentage of Subjects Whose Last Three Serum Urate Levels Are <6.0 Milligram Per Deciliter (mg/dL).   [ Last 3 visits (any last 3 visits up to week 28) ]

Measure Type Primary
Measure Title Percentage of Subjects Whose Last Three Serum Urate Levels Are <6.0 Milligram Per Deciliter (mg/dL).
Measure Description 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.
Time Frame Last 3 visits (any last 3 visits up to week 28)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Analysis was performed on all randomized subjects who took at least 1 dose of study drug and had a baseline serum urate ≥8.0 mg/dL. If subject prematurely discontinued from study before at least 3 serum urate levels were obtained, subject was considered a nonresponder; if at least 3 serum urate were obtained postbaseline, those 3 visits were used.

Reporting Groups
  Description
Febuxostat 80 mg QD Febuxostat 80 mg, orally, once daily for up to 28 weeks.
Febuxostat 120 mg QD Febuxostat 120 mg, orally, once daily for up to 28 weeks.
Febuxostat 240 mg QD Febuxostat 240 mg, orally, once daily for up to 28 weeks.
Allopurinol QD 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.
Placebo QD Placebo, orally, once daily for up to 28 weeks.

Measured Values
  Febuxostat 80 mg QD Febuxostat 120 mg QD Febuxostat 240 mg QD Allopurinol QD Placebo QD
Number of Participants Analyzed
[units: participants] 		262 269 134 268 134
Percentage of Subjects Whose Last Three Serum Urate Levels Are <6.0 Milligram Per Deciliter (mg/dL).
[units: Percentage of subjects]
 		48 65 69 22 0


Statistical Analysis 1 for Percentage of Subjects Whose Last Three Serum Urate Levels Are <6.0 Milligram Per Deciliter (mg/dL).
Groups [1] Febuxostat 80 mg QD vs. Placebo QD
Method [2] Cochran-Mantel-Haenszel
P Value [3] <0.001
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL versus [v.] >1.5 mg/dL).
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  The overall 0.05 level of significance for the multiple comparisons of each febuxostat dose to placebo was controlled using Hochberg's method. The p-value was statistically significant.

Statistical Analysis 2 for Percentage of Subjects Whose Last Three Serum Urate Levels Are <6.0 Milligram Per Deciliter (mg/dL).
Groups [1] Febuxostat 120 mg QD vs. Placebo QD
Method [2] Cochran-Mantel-Haenszel
P Value [3] <0.001
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  The overall 0.05 level of significance for the multiple comparisons of each febuxostat dose to placebo was controlled using Hochberg's method. The p-value was statistically significant.

Statistical Analysis 3 for Percentage of Subjects Whose Last Three Serum Urate Levels Are <6.0 Milligram Per Deciliter (mg/dL).
Groups [1] Febuxostat 240 mg QD vs. Placebo QD
Method [2] Cochran-Mantel-Haenszel
P Value [3] <0.001
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  The overall 0.05 level of significance for the multiple comparisons of each febuxostat dose to placebo was controlled using Hochberg's method. The p-value was statistically significant.

Statistical Analysis 4 for Percentage of Subjects Whose Last Three Serum Urate Levels Are <6.0 Milligram Per Deciliter (mg/dL).
Groups [1] Febuxostat 80 mg QD vs. Allopurinol QD
Non-Inferiority/Equivalence Test [2] Yes
Difference in percentage [3] 25.7
97.5% Confidence Interval ( 16.7 to 34.7 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  Non-inferiority of febuxostat 80 mg to allopurinol was declared if the value of the lower bound of the 97.5% confidence interval is > -10%.
[3] Other relevant estimation information:
  No text entered.

Statistical Analysis 5 for Percentage of Subjects Whose Last Three Serum Urate Levels Are <6.0 Milligram Per Deciliter (mg/dL).
Groups [1] Febuxostat 120 mg QD vs. Allopurinol QD
Non-Inferiority/Equivalence Test [2] Yes
Difference in percentage [3] 42.7
97.5% Confidence Interval ( 34.0 to 51.3 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  Non-inferiority of febuxostat 120 mg to allopurinol was declared if the value of the lower bound of the 97.5% confidence interval is > -10%.
[3] Other relevant estimation information:
  No text entered.

Statistical Analysis 6 for Percentage of Subjects Whose Last Three Serum Urate Levels Are <6.0 Milligram Per Deciliter (mg/dL).
Groups [1] Febuxostat 80 mg QD vs. Allopurinol QD
Method [2] Cochran-Mantel-Haenszel
P Value [3] <0.001
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Comparisons of each febuxostat dose to allopurinol were adjusted to control the overall 0.05 level of significance for superiority by using Hochberg's method. The p-value was statistically significant.

Statistical Analysis 7 for Percentage of Subjects Whose Last Three Serum Urate Levels Are <6.0 Milligram Per Deciliter (mg/dL).
Groups [1] Febuxostat 120 mg QD vs. Allopurinol QD
Method [2] Cochran-Mantel-Haenszel
P Value [3] <0.001
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Comparisons of each febuxostat dose to allopurinol were adjusted to control the overall 0.05 level of significance for superiority by using Hochberg's method. The p-value was statistically significant.

Statistical Analysis 8 for Percentage of Subjects Whose Last Three Serum Urate Levels Are <6.0 Milligram Per Deciliter (mg/dL).
Groups [1] Febuxostat 80 mg QD vs. Febuxostat 120 mg QD
Method [2] Cochran-Mantel-Haenszel
P Value [3] <0.001
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 9 for Percentage of Subjects Whose Last Three Serum Urate Levels Are <6.0 Milligram Per Deciliter (mg/dL).
Groups [1] Febuxostat 240 mg QD vs. Allopurinol QD
Method [2] Cochran-Mantel-Haenszel
P Value [3] <0.001
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 10 for Percentage of Subjects Whose Last Three Serum Urate Levels Are <6.0 Milligram Per Deciliter (mg/dL).
Groups [1] Febuxostat 80 mg QD vs. Febuxostat 240 mg QD
Method [2] Cochran-Mantel-Haenszel
P Value [3] <0.001
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 11 for Percentage of Subjects Whose Last Three Serum Urate Levels Are <6.0 Milligram Per Deciliter (mg/dL).
Groups [1] Febuxostat 120 mg QD vs. Febuxostat 240 mg QD
Method [2] Cochran-Mantel-Haenszel
P Value [3] 0.479
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 12 for Percentage of Subjects Whose Last Three Serum Urate Levels Are <6.0 Milligram Per Deciliter (mg/dL).
Groups [1] Allopurinol QD vs. Placebo QD
Method [2] Cochran-Mantel-Haenszel
P Value [3] <0.001
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.



2.  Secondary:   Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Week 28   [ Week 28 ]

Measure Type Secondary
Measure Title Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Week 28
Measure Description 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.
Time Frame Week 28  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Analysis was performed on intend to treat (ITT) subjects, which were defined as all randomized subjects who took at least 1 dose of study drug and who had a baseline serum urate ≥8.0 mg/dL. Missing data were not imputed.

Reporting Groups
  Description
Febuxostat 80 mg QD Febuxostat 80 mg, orally, once daily for up to 28 weeks.
Febuxostat 120 mg QD Febuxostat 120 mg, orally, once daily for up to 28 weeks.
Febuxostat 240 mg QD Febuxostat 240 mg, orally, once daily for up to 28 weeks.
Allopurinol QD 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.
Placebo QD Placebo, orally, once daily for up to 28 weeks.

Measured Values
  Febuxostat 80 mg QD Febuxostat 120 mg QD Febuxostat 240 mg QD Allopurinol QD Placebo QD
Number of Participants Analyzed
[units: participants] 		161 188 83 208 99
Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Week 28
[units: Percentage of subjects]
 		76 87 94 41 1


Statistical Analysis 1 for Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Week 28
Groups [1] Febuxostat 80 mg QD vs. Placebo QD
Method [2] Cochran-Mantel-Haenszel
P Value [3] <0.001
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 2 for Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Week 28
Groups [1] Febuxostat 120 mg QD vs. Placebo QD
Method [2] Cochran-Mantel-Haenszel
P Value [3] <0.001
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 3 for Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Week 28
Groups [1] Febuxostat 240 mg QD vs. Placebo QD
Method [2] Cochran-Mantel-Haenszel
P Value [3] <0.001
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 4 for Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Week 28
Groups [1] Febuxostat 80 mg QD vs. Allopurinol QD
Method [2] Cochran-Mantel-Haenszel
P Value [3] <0.001
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 5 for Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Week 28
Groups [1] Febuxostat 120 mg QD vs. Allopurinol QD
Method [2] Cochran-Mantel-Haenszel
P Value [3] <0.001
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 6 for Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Week 28
Groups [1] Febuxostat 240 mg QD vs. Allopurinol QD
Method [2] Cochran-Mantel-Haenszel
P Value [3] <0.001
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 7 for Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Week 28
Groups [1] Febuxostat 80 mg QD vs. Febuxostat 120 mg QD
Method [2] Cochran-Mantel-Haenszel
P Value [3] 0.011
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 8 for Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Week 28
Groups [1] Febuxostat 80 mg QD vs. Febuxostat 240 mg QD
Method [2] Cochran-Mantel-Haenszel
P Value [3] <0.001
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 9 for Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Week 28
Groups [1] Febuxostat 120 mg QD vs. Febuxostat 240 mg QD
Method [2] Cochran-Mantel-Haenszel
P Value [3] 0.091
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 10 for Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Week 28
Groups [1] Allopurinol QD vs. Placebo QD
Method [2] Cochran-Mantel-Haenszel
P Value [3] <0.001
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.



3.  Secondary:   Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Final Visit   [ Final Visit (up to 28 weeks). ]

Measure Type Secondary
Measure Title Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Final Visit
Measure Description 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.
Time Frame Final Visit (up to 28 weeks).  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Analysis was performed on the ITT subjects, which were defined as all randomized subjects who took at least 1 dose of study drug and who had a baseline serum urate ≥8.0 mg/dL. Missing data were not imputed.

Reporting Groups
  Description
Febuxostat 80 mg QD Febuxostat 80 mg, orally, once daily for up to 28 weeks.
Febuxostat 120 mg QD Febuxostat 120 mg, orally, once daily for up to 28 weeks.
Febuxostat 240 mg QD Febuxostat 240 mg, orally, once daily for up to 28 weeks.
Allopurinol QD 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.
Placebo QD Placebo, orally, once daily for up to 28 weeks.

Measured Values
  Febuxostat 80 mg QD Febuxostat 120 mg QD Febuxostat 240 mg QD Allopurinol QD Placebo QD
Number of Participants Analyzed
[units: participants] 		253 265 126 263 127
Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Final Visit
[units: Percentage of subjects]
 		72 79 92 39 1


Statistical Analysis 1 for Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Final Visit
Groups [1] Febuxostat 80 mg QD vs. Placebo QD
Method [2] Cochran-Mantel-Haenszel
P Value [3] <0.001
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 2 for Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Final Visit
Groups [1] Febuxostat 120 mg QD vs. Placebo QD
Method [2] Cochran-Mantel-Haenszel
P Value [3] <0.001
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 3 for Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Final Visit
Groups [1] Febuxostat 240 mg QD vs. Placebo QD
Method [2] Cochran-Mantel-Haenszel
P Value [3] <0.001
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 4 for Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Final Visit
Groups [1] Febuxostat 80 mg QD vs. Allopurinol QD
Method [2] Cochran-Mantel-Haenszel
P Value [3] <0.001
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 5 for Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Final Visit
Groups [1] Febuxostat 120 mg QD vs. Allopurinol QD
Method [2] Cochran-Mantel-Haenszel
P Value [3] <0.001
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 6 for Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Final Visit
Groups [1] Febuxostat 240 mg QD vs. Allopurinol QD
Method [2] Cochran-Mantel-Haenszel
P Value [3] <0.001
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 7 for Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Final Visit
Groups [1] Febuxostat 80 mg QD vs. Febuxostat 120 mg QD
Method [2] Cochran-Mantel-Haenszel
P Value [3] 0.074
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 8 for Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Final Visit
Groups [1] Febuxostat 80 mg QD vs. Febuxostat 240 mg QD
Method [2] Cochran-Mantel-Haenszel
P Value [3] <0.001
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 9 for Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Final Visit
Groups [1] Febuxostat 120 mg QD vs. Febuxostat 240 mg QD
Method [2] Cochran-Mantel-Haenszel
P Value [3] 0.001
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 10 for Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Final Visit
Groups [1] Allopurinol QD vs. Placebo QD
Method [2] Cochran-Mantel-Haenszel
P Value [3] <0.001
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.



4.  Secondary:   Percent Change From Baseline in Serum Urate Levels at Week 28.   [ Baseline and Week 28 ]

Measure Type Secondary
Measure Title Percent Change From Baseline in Serum Urate Levels at Week 28.
Measure Description 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.
Time Frame Baseline and Week 28  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Analysis was performed on the ITT subjects, which were defined as all randomized subjects. who took at least 1 dose of study drug and who had a baseline serum urate ≥8.0 mg/dL. Missing data were not imputed.

Reporting Groups
  Description
Febuxostat 80 mg QD Febuxostat 80 mg, orally, once daily for up to 28 weeks.
Febuxostat 120 mg QD Febuxostat 120 mg, orally, once daily for up to 28 weeks.
Febuxostat 240 mg QD Febuxostat 240 mg, orally, once daily for up to 28 weeks.
Allopurinol QD 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.
Placebo QD Placebo, orally, once daily for up to 28 weeks.

Measured Values
  Febuxostat 80 mg QD Febuxostat 120 mg QD Febuxostat 240 mg QD Allopurinol QD Placebo QD
Number of Participants Analyzed
[units: participants] 		161 188 83 208 99
Percent Change From Baseline in Serum Urate Levels at Week 28.
[units: Percent change]
Mean ± Standard Deviation 		-47.6 ± 15.86 -54.9 ± 14.97 -67.8 ± 18.18 -34.4 ± 14.21 -3.6 ± 13.85


Statistical Analysis 1 for Percent Change From Baseline in Serum Urate Levels at Week 28.
Groups [1] Febuxostat 80 mg QD vs. Placebo QD
Method [2] ANOVA
P Value [3] <0.001
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  P-values for pairwise comparisons are from contrast within the framework of the ANOVA model with treatment and baseline renal function as factors. Statistical significance was determined at the 0.05 level without adjustments for multiple comparisons.

Statistical Analysis 2 for Percent Change From Baseline in Serum Urate Levels at Week 28.
Groups [1] Febuxostat 120 mg QD vs. Placebo QD
Method [2] ANOVA
P Value [3] <0.001
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  P-values for pairwise comparisons are from contrast within the framework of the ANOVA model with treatment and baseline renal function as factors. Statistical significance was determined at the 0.05 level without adjustments for multiple comparisons.

Statistical Analysis 3 for Percent Change From Baseline in Serum Urate Levels at Week 28.
Groups [1] Febuxostat 240 mg QD vs. Placebo QD
Method [2] ANOVA
P Value [3] <0.001
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  P-values for pairwise comparisons are from contrast within the framework of the ANOVA model with treatment and baseline renal function as factors. Statistical significance was determined at the 0.05 level without adjustments for multiple comparisons.

Statistical Analysis 4 for Percent Change From Baseline in Serum Urate Levels at Week 28.
Groups [1] Febuxostat 80 mg QD vs. Allopurinol QD
Method [2] ANOVA
P Value [3] <0.001
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  P-values for pairwise comparisons are from contrast within the framework of the ANOVA model with treatment and baseline renal function as factors. Statistical significance was determined at the 0.05 level without adjustments for multiple comparisons.

Statistical Analysis 5 for Percent Change From Baseline in Serum Urate Levels at Week 28.
Groups [1] Febuxostat 120 mg QD vs. Allopurinol QD
Method [2] ANOVA
P Value [3] <0.001
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  P-values for pairwise comparisons are from contrast within the framework of the ANOVA model with treatment and baseline renal function as factors. Statistical significance was determined at the 0.05 level without adjustments for multiple comparisons.

Statistical Analysis 6 for Percent Change From Baseline in Serum Urate Levels at Week 28.
Groups [1] Febuxostat 240 mg QD vs. Allopurinol QD
Method [2] ANOVA
P Value [3] <0.001
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  P-values for pairwise comparisons are from contrast within the framework of the ANOVA model with treatment and baseline renal function as factors. Statistical significance was determined at the 0.05 level without adjustments for multiple comparisons.

Statistical Analysis 7 for Percent Change From Baseline in Serum Urate Levels at Week 28.
Groups [1] Febuxostat 80 mg QD vs. Febuxostat 120 mg QD
Method [2] ANOVA
P Value [3] <0.001
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  P-values for pairwise comparisons are from contrast within the framework of the ANOVA model with treatment and baseline renal function as factors. Statistical significance was determined at the 0.05 level without adjustments for multiple comparisons.

Statistical Analysis 8 for Percent Change From Baseline in Serum Urate Levels at Week 28.
Groups [1] Febuxostat 80 mg QD vs. Febuxostat 240 mg QD
Method [2] ANOVA
P Value [3] <0.001
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  P-values for pairwise comparisons are from contrast within the framework of the ANOVA model with treatment and baseline renal function as factors. Statistical significance was determined at the 0.05 level without adjustments for multiple comparisons.

Statistical Analysis 9 for Percent Change From Baseline in Serum Urate Levels at Week 28.
Groups [1] Febuxostat 120 mg QD vs. Febuxostat 240 mg QD
Method [2] ANOVA
P Value [3] <0.001
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  P-values for pairwise comparisons are from contrast within the framework of the ANOVA model with treatment and baseline renal function as factors. Statistical significance was determined at the 0.05 level without adjustments for multiple comparisons.

Statistical Analysis 10 for Percent Change From Baseline in Serum Urate Levels at Week 28.
Groups [1] Allopurinol QD vs. Placebo QD
Method [2] ANOVA
P Value [3] <0.001
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  P-values for pairwise comparisons are from contrast within the framework of the ANOVA model with treatment and baseline renal function as factors. Statistical significance was determined at the 0.05 level without adjustments for multiple comparisons.



5.  Secondary:   Percent Change From Baseline in Serum Urate Levels at Final Visit   [ Baseline and Final Visit (up to 28 weeks) ]

Measure Type Secondary
Measure Title Percent Change From Baseline in Serum Urate Levels at Final Visit
Measure Description 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.
Time Frame Baseline and Final Visit (up to 28 weeks)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Analysis was performed on the ITT subjects, which were defined as all randomized subjects. who took at least 1 dose of study drug and who had a baseline serum urate ≥8.0 mg/dL. Missing data were not imputed.

Reporting Groups
  Description
Febuxostat 80 mg QD Febuxostat 80 mg, orally, once daily for up to 28 weeks.
Febuxostat 120 mg QD Febuxostat 120 mg, orally, once daily for up to 28 weeks.
Febuxostat 240 mg QD Febuxostat 240 mg, orally, once daily for up to 28 weeks.
Allopurinol QD 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.
Placebo QD Placebo, orally, once daily for up to 28 weeks.

Measured Values
  Febuxostat 80 mg QD Febuxostat 120 mg QD Febuxostat 240 mg QD Allopurinol QD Placebo QD
Number of Participants Analyzed
[units: participants] 		253 265 126 263 127
Percent Change From Baseline in Serum Urate Levels at Final Visit
[units: Percent change]
Mean ± Standard Deviation 		-45.2 ± 18.16 -51.9 ± 17.99 -66.3 ± 20.62 -33.7 ± 14.75 -3.0 ± 13.28


Statistical Analysis 1 for Percent Change From Baseline in Serum Urate Levels at Final Visit
Groups [1] Febuxostat 80 mg QD vs. Placebo QD
Method [2] ANOVA
P Value [3] <0.001
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  P-values for pairwise comparisons are from contrast within the framework of the ANOVA model with treatment and baseline renal function as factors. Statistical significance was determined at the 0.05 level without adjustments for multiple comparisons.

Statistical Analysis 2 for Percent Change From Baseline in Serum Urate Levels at Final Visit
Groups [1] Febuxostat 120 mg QD vs. Placebo QD
Method [2] ANOVA
P Value [3] <0.001
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  P-values for pairwise comparisons are from contrast within the framework of the ANOVA model with treatment and baseline renal function as factors. Statistical significance was determined at the 0.05 level without adjustments for multiple comparisons.

Statistical Analysis 3 for Percent Change From Baseline in Serum Urate Levels at Final Visit
Groups [1] Febuxostat 240 mg QD vs. Placebo QD
Method [2] ANOVA
P Value [3] <0.001
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  P-values for pairwise comparisons are from contrast within the framework of the ANOVA model with treatment and baseline renal function as factors. Statistical significance was determined at the 0.05 level without adjustments for multiple comparisons.

Statistical Analysis 4 for Percent Change From Baseline in Serum Urate Levels at Final Visit
Groups [1] Febuxostat 80 mg QD vs. Allopurinol QD
Method [2] ANOVA
P Value [3] <0.001
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  P-values for pairwise comparisons are from contrast within the framework of the ANOVA model with treatment and baseline renal function as factors. Statistical significance was determined at the 0.05 level without adjustments for multiple comparisons.

Statistical Analysis 5 for Percent Change From Baseline in Serum Urate Levels at Final Visit
Groups [1] Febuxostat 120 mg QD vs. Allopurinol QD
Method [2] ANOVA
P Value [3] <0.001
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  P-values for pairwise comparisons are from contrast within the framework of the ANOVA model with treatment and baseline renal function as factors. Statistical significance was determined at the 0.05 level without adjustments for multiple comparisons.

Statistical Analysis 6 for Percent Change From Baseline in Serum Urate Levels at Final Visit
Groups [1] Febuxostat 240 mg QD vs. Allopurinol QD
Method [2] ANOVA
P Value [3] <0.001
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  P-values for pairwise comparisons are from contrast within the framework of the ANOVA model with treatment and baseline renal function as factors. Statistical significance was determined at the 0.05 level without adjustments for multiple comparisons.

Statistical Analysis 7 for Percent Change From Baseline in Serum Urate Levels at Final Visit
Groups [1] Febuxostat 80 mg QD vs. Febuxostat 120 mg QD
Method [2] ANOVA
P Value [3] <0.001
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  P-values for pairwise comparisons are from contrast within the framework of the ANOVA model with treatment and baseline renal function as factors. Statistical significance was determined at the 0.05 level without adjustments for multiple comparisons.

Statistical Analysis 8 for Percent Change From Baseline in Serum Urate Levels at Final Visit
Groups [1] Febuxostat 80 mg QD vs. Febuxostat 240 mg QD
Method [2] ANOVA
P Value [3] <0.001
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  P-values for pairwise comparisons are from contrast within the framework of the ANOVA model with treatment and baseline renal function as factors. Statistical significance was determined at the 0.05 level without adjustments for multiple comparisons.

Statistical Analysis 9 for Percent Change From Baseline in Serum Urate Levels at Final Visit
Groups [1] Febuxostat 120 mg QD vs. Febuxostat 240 mg QD
Method [2] ANOVA
P Value [3] <0.001
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  P-values for pairwise comparisons are from contrast within the framework of the ANOVA model with treatment and baseline renal function as factors. Statistical significance was determined at the 0.05 level without adjustments for multiple comparisons.

Statistical Analysis 10 for Percent Change From Baseline in Serum Urate Levels at Final Visit
Groups [1] Allopurinol QD vs. Placebo QD
Method [2] ANOVA
P Value [3] <0.001
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  P-values for pairwise comparisons are from contrast within the framework of the ANOVA model with treatment and baseline renal function as factors. Statistical significance was determined at the 0.05 level without adjustments for multiple comparisons.



6.  Secondary:   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.   [ Baseline and Week 28 ]

Measure Type Secondary
Measure Title 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.
Measure Description 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.
Time Frame Baseline and Week 28  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Analysis was performed on the ITT subjects, which were defined as all randomized subjects who took at least 1 dose of study drug, who had a baseline serum urate ≥8.0 mg/dL, and who had a palpable primary tophus measured at baseline. Missing data were not imputed.

Reporting Groups
  Description
Febuxostat 80 mg QD Febuxostat 80 mg, orally, once daily for up to 28 weeks.
Febuxostat 120 mg QD Febuxostat 120 mg, orally, once daily for up to 28 weeks.
Febuxostat 240 mg QD Febuxostat 240 mg, orally, once daily for up to 28 weeks.
Allopurinol QD 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.
Placebo QD Placebo, orally, once daily for up to 28 weeks.

Measured Values
  Febuxostat 80 mg QD Febuxostat 120 mg QD Febuxostat 240 mg QD Allopurinol QD Placebo QD
Number of Participants Analyzed
[units: participants] 		26 35 14 46 21
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.
[units: percent change from baseline]
Median ( Inter-Quartile Range ) 		-45.6
( -85.9 to 3.0 )		 -54.2
( -100.0 to -16.7 )		 -53.2
( -77.8 to -22.1 )		 -31.5
( -95.0 to 5.6 )		 -52.0
( -62.5 to -21.4 )


Statistical Analysis 1 for 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.
Groups [1] Febuxostat 80 mg QD vs. Placebo QD
Method [2] Wilcoxon (Mann-Whitney)
P Value [3] 0.789
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 2 for 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.
Groups [1] Febuxostat 120 mg QD vs. Placebo QD
Method [2] Wilcoxon (Mann-Whitney)
P Value [3] 0.320
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 3 for 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.
Groups [1] Febuxostat 240 mg QD vs. Placebo QD
Method [2] Wilcoxon (Mann-Whitney)
P Value [3] 0.381
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 4 for 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.
Groups [1] Febuxostat 80 mg QD vs. Allopurinol QD
Method [2] Wilcoxon (Mann-Whitney)
P Value [3] 0.809
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 5 for 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.
Groups [1] Febuxostat 120 mg QD vs. Allopurinol QD
Method [2] Wilcoxon (Mann-Whitney)
P Value [3] 0.154
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 6 for 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.
Groups [1] Febuxostat 240 mg QD vs. Allopurinol QD
Method [2] Wilcoxon (Mann-Whitney)
P Value [3] 0.247
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 7 for 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.
Groups [1] Febuxostat 80 mg QD vs. Febuxostat 120 mg QD
Method [2] Wilcoxon (Mann-Whitney)
P Value [3] 0.415
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 8 for 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.
Groups [1] Febuxostat 80 mg QD vs. Febuxostat 240 mg QD
Method [2] Wilcoxon (Mann-Whitney)
P Value [3] 0.649
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at the 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 9 for 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.
Groups [1] Febuxostat 120 mg QD vs. Febuxostat 240 mg QD
Method [2] Wilcoxon (Mann-Whitney)
P Value [3] 0.807
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 10 for 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.
Groups [1] Allopurinol QD vs. Placebo QD
Method [2] Wilcoxon (Mann-Whitney)
P Value [3] 0.844
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.



7.  Secondary:   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.   [ Baseline and Final Visit (up to 28 weeks) ]

Measure Type Secondary
Measure Title 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.
Measure Description 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.
Time Frame Baseline and Final Visit (up to 28 weeks)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Analysis was performed on the ITT subjects, which were defined as all randomized subjects who took at least 1 dose of study drug, who had a baseline serum urate ≥8.0 mg/dL, and who had a palpable primary tophus measured at baseline. Missing data were not imputed.

Reporting Groups
  Description
Febuxostat 80 mg QD Febuxostat 80 mg, orally, once daily for up to 28 weeks.
Febuxostat 120 mg QD Febuxostat 120 mg, orally, once daily for up to 28 weeks.
Febuxostat 240 mg QD Febuxostat 240 mg, orally, once daily for up to 28 weeks.
Allopurinol QD 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.
Placebo QD Placebo, orally, once daily for up to 28 weeks.

Measured Values
  Febuxostat 80 mg QD Febuxostat 120 mg QD Febuxostat 240 mg QD Allopurinol QD Placebo QD
Number of Participants Analyzed
[units: participants] 		42 50 24 61 26
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.
[units: percent change from baseline]
Median ( Inter-Quartile Range ) 		-33.8
( -85.4 to 0.0 )		 -42.4
( -90.3 to 0.0 )		 -47.0
( -80.0 to -13.8 )		 -22.6
( -66.7 to 0 )		 -40.3
( -62.5 to -16.7 )


Statistical Analysis 1 for 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.
Groups [1] Febuxostat 80 mg QD vs. Placebo QD
Method [2] Wilcoxon (Mann-Whitney)
P Value [3] 0.699
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 2 for 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.
Groups [1] Febuxostat 120 mg QD vs. Placebo QD
Method [2] Wilcoxon (Mann-Whitney)
P Value [3] 0.822
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 3 for 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.
Groups [1] Febuxostat 240 mg QD vs. Placebo QD
Method [2] Wilcoxon (Mann-Whitney)
P Value [3] 0.579
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 4 for 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.
Groups [1] Febuxostat 80 mg QD vs. Allopurinol QD
Method [2] Wilcoxon (Mann-Whitney)
P Value [3] 0.679
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 5 for 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.
Groups [1] Febuxostat 120 mg QD vs. Allopurinol QD
Method [2] Wilcoxon (Mann-Whitney)
P Value [3] 0.278
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 6 for 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.
Groups [1] Febuxostat 240 mg QD vs. Allopurinol QD
Method [2] Wilcoxon (Mann-Whitney)
P Value [3] 0.104
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 7 for 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.
Groups [1] Febuxostat 80 mg QD vs. Febuxostat 120 mg QD
Method [2] Wilcoxon (Mann-Whitney)
P Value [3] 0.560
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 8 for 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.
Groups [1] Febuxostat 80 mg QD vs. Febuxostat 240 mg QD
Method [2] Wilcoxon (Mann-Whitney)
P Value [3] 0.309
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 9 for 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.
Groups [1] Febuxostat 120 mg QD vs. Febuxostat 240 mg QD
Method [2] Wilcoxon (Mann-Whitney)
P Value [3] 0.759
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 10 for 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.
Groups [1] Allopurinol QD vs. Placebo QD
Method [2] Wilcoxon (Mann-Whitney)
P Value [3] 0.385
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.



8.  Secondary:   Change in the Total Number of Tophi at Week 28 in the Subset of Subjects With Palpable Tophi at the Screening Visit.   [ Baseline and Week 28 ]

Measure Type Secondary
Measure Title Change in the Total Number of Tophi at Week 28 in the Subset of Subjects With Palpable Tophi at the Screening Visit.
Measure Description 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.
Time Frame Baseline and Week 28  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Analysis was performed on the ITT subjects, which were defined as all randomized subjects who took at least 1 dose of study drug,had a baseline serum urate ≥8.0 mg/dL, and had palpable tophi at the screening visit. Missing data were not imputed.

Reporting Groups
  Description
Febuxostat 80 mg QD Febuxostat 80 mg, orally, once daily for up to 28 weeks.
Febuxostat 120 mg QD Febuxostat 120 mg, orally, once daily for up to 28 weeks.
Febuxostat 240 mg QD Febuxostat 240 mg, orally, once daily for up to 28 weeks.
Allopurinol QD 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.
Placebo QD Placebo, orally, once daily for up to 28 weeks.

Measured Values
  Febuxostat 80 mg QD Febuxostat 120 mg QD Febuxostat 240 mg QD Allopurinol QD Placebo QD
Number of Participants Analyzed
[units: participants] 		28 38 16 47 22
Change in the Total Number of Tophi at Week 28 in the Subset of Subjects With Palpable Tophi at the Screening Visit.
[units: number of tophi]
Median ( Inter-Quartile Range ) 		0.0
( -0.5 to 0.0 )		 0.0
( -2.0 to 0.0 )		 0.0
( -1.0 to 0.0 )		 0.0
( -1.0 to 0.0 )		 0.0
( 0.0 to 0.0 )


Statistical Analysis 1 for Change in the Total Number of Tophi at Week 28 in the Subset of Subjects With Palpable Tophi at the Screening Visit.
Groups [1] Febuxostat 80 mg QD vs. Placebo QD
Method [2] Wilcoxon (Mann-Whitney)
P Value [3] 0.949
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 2 for Change in the Total Number of Tophi at Week 28 in the Subset of Subjects With Palpable Tophi at the Screening Visit.
Groups [1] Febuxostat 120 mg QD vs. Placebo QD
Method [2] Wilcoxon (Mann-Whitney)
P Value [3] 0.050
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 3 for Change in the Total Number of Tophi at Week 28 in the Subset of Subjects With Palpable Tophi at the Screening Visit.
Groups [1] Febuxostat 240 mg QD vs. Placebo QD
Method [2] Wilcoxon (Mann-Whitney)
P Value [3] 0.577
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 4 for Change in the Total Number of Tophi at Week 28 in the Subset of Subjects With Palpable Tophi at the Screening Visit.
Groups [1] Febuxostat 80 mg QD vs. Allopurinol QD
Method [2] Wilcoxon (Mann-Whitney)
P Value [3] 0.598
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 5 for Change in the Total Number of Tophi at Week 28 in the Subset of Subjects With Palpable Tophi at the Screening Visit.
Groups [1] Febuxostat 120 mg QD vs. Allopurinol QD
Method [2] Wilcoxon (Mann-Whitney)
P Value [3] 0.062
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 6 for Change in the Total Number of Tophi at Week 28 in the Subset of Subjects With Palpable Tophi at the Screening Visit.
Groups [1] Febuxostat 240 mg QD vs. Allopurinol QD
Method [2] Wilcoxon (Mann-Whitney)
P Value [3] 0.969
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 7 for Change in the Total Number of Tophi at Week 28 in the Subset of Subjects With Palpable Tophi at the Screening Visit.
Groups [1] Febuxostat 80 mg QD vs. Febuxostat 120 mg QD
Method [2] Wilcoxon (Mann-Whitney)
P Value [3] 0.056
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 8 for Change in the Total Number of Tophi at Week 28 in the Subset of Subjects With Palpable Tophi at the Screening Visit.
Groups [1] Febuxostat 80 mg QD vs. Febuxostat 240 mg QD
Method [2] Wilcoxon (Mann-Whitney)
P Value [3] 0.659
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 9 for Change in the Total Number of Tophi at Week 28 in the Subset of Subjects With Palpable Tophi at the Screening Visit.
Groups [1] Febuxostat 120 mg QD vs. Febuxostat 240 mg QD
Method [2] Wilcoxon (Mann-Whitney)
P Value [3] 0.197
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 10 for Change in the Total Number of Tophi at Week 28 in the Subset of Subjects With Palpable Tophi at the Screening Visit.
Groups [1] Allopurinol QD vs. Placebo QD
Method [2] Wilcoxon (Mann-Whitney)
P Value [3] 0.521
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.



9.  Secondary:   Change in the Total Number of Tophi at Final Visit in the Subset of Subjects With Palpable Tophi at the Screening Visit   [ Final Visit (up to 28 weeks) ]

Measure Type Secondary
Measure Title Change in the Total Number of Tophi at Final Visit in the Subset of Subjects With Palpable Tophi at the Screening Visit
Measure Description 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.
Time Frame Final Visit (up to 28 weeks)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Analysis was performed on the ITT subjects, which were defined as all randomized subjects who took at least 1 dose of study drug,had a baseline serum urate ≥8.0 mg/dL, and had palpable tophi at the screening visit. Missing data were not imputed.

Reporting Groups
  Description
Febuxostat 80 mg QD Febuxostat 80 mg, orally, once daily for up to 28 weeks.
Febuxostat 120 mg QD Febuxostat 120 mg, orally, once daily for up to 28 weeks.
Febuxostat 240 mg QD Febuxostat 240 mg, orally, once daily for up to 28 weeks.
Allopurinol QD 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.
Placebo QD Placebo, orally, once daily for up to 28 weeks.

Measured Values
  Febuxostat 80 mg QD Febuxostat 120 mg QD Febuxostat 240 mg QD Allopurinol QD Placebo QD
Number of Participants Analyzed
[units: participants] 		42 53 25 62 27
Change in the Total Number of Tophi at Final Visit in the Subset of Subjects With Palpable Tophi at the Screening Visit
[units: number of tophi]
Median ( Inter-Quartile Range ) 		0.0
( 0.0 to 0.0 )		 0.0
( -1.0 to 0.0 )		 0.0
( -1.0 to 0.0 )		 0.0
( 0.0 to 0.0 )		 0.0
( 0.0 to 0.0 )


Statistical Analysis 1 for Change in the Total Number of Tophi at Final Visit in the Subset of Subjects With Palpable Tophi at the Screening Visit
Groups [1] Febuxostat 80 mg QD vs. Placebo QD
Method [2] Wilcoxon (Mann-Whitney)
P Value [3] 0.683
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 2 for Change in the Total Number of Tophi at Final Visit in the Subset of Subjects With Palpable Tophi at the Screening Visit
Groups [1] Febuxostat 120 mg QD vs. Placebo QD
Method [2] Wilcoxon (Mann-Whitney)
P Value [3] 0.078
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 3 for Change in the Total Number of Tophi at Final Visit in the Subset of Subjects With Palpable Tophi at the Screening Visit
Groups [1] Febuxostat 240 mg QD vs. Placebo QD
Method [2] Wilcoxon (Mann-Whitney)
P Value [3] 0.442
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 4 for Change in the Total Number of Tophi at Final Visit in the Subset of Subjects With Palpable Tophi at the Screening Visit
Groups [1] Febuxostat 80 mg QD vs. Allopurinol QD
Method [2] Wilcoxon (Mann-Whitney)
P Value [3] 0.990
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 5 for Change in the Total Number of Tophi at Final Visit in the Subset of Subjects With Palpable Tophi at the Screening Visit
Groups [1] Febuxostat 120 mg QD vs. Allopurinol QD
Method [2] Wilcoxon (Mann-Whitney)
P Value [3] 0.077
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 6 for Change in the Total Number of Tophi at Final Visit in the Subset of Subjects With Palpable Tophi at the Screening Visit
Groups [1] Febuxostat 240 mg QD vs. Allopurinol QD
Method [2] Wilcoxon (Mann-Whitney)
P Value [3] 0.662
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 7 for Change in the Total Number of Tophi at Final Visit in the Subset of Subjects With Palpable Tophi at the Screening Visit
Groups [1] Febuxostat 80 mg QD vs. Febuxostat 120 mg QD
Method [2] Wilcoxon (Mann-Whitney)
P Value [3] 0.139
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 8 for Change in the Total Number of Tophi at Final Visit in the Subset of Subjects With Palpable Tophi at the Screening Visit
Groups [1] Febuxostat 80 mg QD vs. Febuxostat 240 mg QD
Method [2] Wilcoxon (Mann-Whitney)
P Value [3] 0.705
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 9 for Change in the Total Number of Tophi at Final Visit in the Subset of Subjects With Palpable Tophi at the Screening Visit
Groups [1] Febuxostat 120 mg QD vs. Febuxostat 240 mg QD
Method [2] Wilcoxon (Mann-Whitney)
P Value [3] 0.337
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 10 for Change in the Total Number of Tophi at Final Visit in the Subset of Subjects With Palpable Tophi at the Screening Visit
Groups [1] Allopurinol QD vs. Placebo QD
Method [2] Wilcoxon (Mann-Whitney)
P Value [3] 0.643
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.



10.  Secondary:   Percentage of Subjects Requiring Treatment for a Gout Flare Between Weeks 8 and 28 of the Double-Blind Treatment Period.   [ Weeks 8 through 28 ]

Measure Type Secondary
Measure Title Percentage of Subjects Requiring Treatment for a Gout Flare Between Weeks 8 and 28 of the Double-Blind Treatment Period.
Measure Description 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.
Time Frame Weeks 8 through 28  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Analysis was performed on the ITT subjects who had at least one dose of study drug between Weeks 8 and 28.

Reporting Groups
  Description
Febuxostat 80 mg QD Febuxostat 80 mg, orally, once daily for up to 28 weeks.
Febuxostat 120 mg QD Febuxostat 120 mg, orally, once daily for up to 28 weeks.
Febuxostat 240 mg QD Febuxostat 240 mg, orally, once daily for up to 28 weeks.
Allopurinol QD 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.
Placebo QD Placebo, orally, once daily for up to 28 weeks.

Measured Values
  Febuxostat 80 mg QD Febuxostat 120 mg QD Febuxostat 240 mg QD Allopurinol QD Placebo QD
Number of Participants Analyzed
[units: participants] 		223 240 106 237 119
Percentage of Subjects Requiring Treatment for a Gout Flare Between Weeks 8 and 28 of the Double-Blind Treatment Period.
[units: percentage of subjects]
 		55 54 57 46 52


Statistical Analysis 1 for Percentage of Subjects Requiring Treatment for a Gout Flare Between Weeks 8 and 28 of the Double-Blind Treatment Period.
Groups [1] Febuxostat 80 mg QD vs. Placebo QD
Method [2] Cochran-Mantel-Haenszel
P Value [3] 0.645
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 2 for Percentage of Subjects Requiring Treatment for a Gout Flare Between Weeks 8 and 28 of the Double-Blind Treatment Period.
Groups [1] Febuxostat 120 mg QD vs. Placebo QD
Method [2] Cochran-Mantel-Haenszel
P Value [3] 0.756
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 3 for Percentage of Subjects Requiring Treatment for a Gout Flare Between Weeks 8 and 28 of the Double-Blind Treatment Period.
Groups [1] Febuxostat 240 mg QD vs. Placebo QD
Method [2] Cochran-Mantel-Haenszel
P Value [3] 0.428
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 4 for Percentage of Subjects Requiring Treatment for a Gout Flare Between Weeks 8 and 28 of the Double-Blind Treatment Period.
Groups [1] Febuxostat 80 mg QD vs. Allopurinol QD
Method [2] Cochran-Mantel-Haenszel
P Value [3] 0.076
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL)
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons..

Statistical Analysis 5 for Percentage of Subjects Requiring Treatment for a Gout Flare Between Weeks 8 and 28 of the Double-Blind Treatment Period.
Groups [1] Febuxostat 120 mg QD vs. Allopurinol QD
Method [2] Cochran-Mantel-Haenszel
P Value [3] 0.106
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 6 for Percentage of Subjects Requiring Treatment for a Gout Flare Between Weeks 8 and 28 of the Double-Blind Treatment Period.
Groups [1] Febuxostat 240 mg QD vs. Allopurinol QD
Method [2] Cochran-Mantel-Haenszel
P Value [3] 0.069
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 7 for Percentage of Subjects Requiring Treatment for a Gout Flare Between Weeks 8 and 28 of the Double-Blind Treatment Period.
Groups [1] Febuxostat 80 mg QD vs. Febuxostat 120 mg QD
Method [2] Cochran-Mantel-Haenszel
P Value [3] 0.837
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 8 for Percentage of Subjects Requiring Treatment for a Gout Flare Between Weeks 8 and 28 of the Double-Blind Treatment Period.
Groups [1] Febuxostat 80 mg QD vs. Febuxostat 240 mg QD
Method [2] Cochran-Mantel-Haenszel
P Value [3] 0.749
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 9 for Percentage of Subjects Requiring Treatment for a Gout Flare Between Weeks 8 and 28 of the Double-Blind Treatment Period.
Groups [1] Febuxostat 120 mg QD vs. Febuxostat 240 mg QD
Method [2] Cochran-Mantel-Haenszel
P Value [3] 0.581
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 10 for Percentage of Subjects Requiring Treatment for a Gout Flare Between Weeks 8 and 28 of the Double-Blind Treatment Period.
Groups [1] Allopurinol QD vs. Placebo QD
Method [2] Cochran-Mantel-Haenszel
P Value [3] 0.311
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  The Cochran-Mantel-Haenszel test was stratified by baseline renal function (serum creatinine ≤1.5 mg/dL v. >1.5 mg/dL).
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.




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  Other Adverse Events
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.  


Results Point of Contact:  
Name/Title: Sr. VP, Clinical Science
Organization: Takeda Global Research & Development Center, Inc.
phone: 800-778-2860
e-mail: clinicaltrialregistry@tpna.com


Publications of Results:
Schumacher HR Jr, Becker MA, Wortmann RL, Macdonald PA, Hunt B, Streit J, Lademacher C, Joseph-Ridge N. Effects of febuxostat versus allopurinol and placebo in reducing serum urate in subjects with hyperuricemia and gout: A 28-week, phase III, randomized, double-blind, parallel-group trial. Arthritis Rheum. 2008 Nov 15;59(11):1540-8.
Becker MA, MacDonald PA, Hunt BJ, Lademacher C, Joseph-Ridge N. Determinants of the clinical outcomes of gout during the first year of urate-lowering therapy. Nucleosides Nucleotides Nucleic Acids. 2008 Jun;27(6):585-91.


Responsible Party: Takeda Global Research & Development Center, Inc. ( Senior Vice President, Clinical Science )
Study ID Numbers: C02-009
Study First Received: September 9, 2005
Results First Received: March 12, 2009
Last Updated: August 13, 2009
ClinicalTrials.gov Identifier: NCT00174915     History of Changes
Health Authority: United States: Food and Drug Administration





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