Febuxostat Versus Allopurinol Control Trial in Subjects With Gout - Study Results

Study Type:	Interventional
Study Design:	Randomized, Double Blind (Subject, Investigator, Outcomes Assessor), Active Control, Parallel Assignment
Condition:	Gout
Interventions:	Drug: Febuxostat Drug: Allopurinol

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Subjects were enrolled at 112 investigative sites, 106 in the United States and 6 in Canada, from 11 July 2002 to 20 February 2004.

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.

	Febuxostat 80 mg QD	Febuxostat 120 mg QD	Allopurinol 300 mg QD
STARTED	256	251	253
COMPLETED	168	153	187
NOT COMPLETED	88	98	66
Lost to Follow-up	25	18	21
Adverse Event	16	23	8
Gout Flare	10	28	9
Personal Reason(s)	19	13	13
Other	11	14	14
Protocol Violation	7	2	1

	Febuxostat 80 mg QD	Febuxostat 120 mg QD	Allopurinol 300 mg QD	Total
Number of Participants [units: participants]	256	251	253	760
Age, Customized [units: subjects]
<45 years	75	71	84	230
45 years to <65 years	140	133	125	398
≥65 years	41	47	44	132
Age [units: years] Mean ± Standard Deviation	51.8 ± 11.69	52.0 ± 12.12	51.6 ± 12.63	51.8 ± 12.13
Gender [units: subjects]
Female	13	8	10	31
Male	243	243	243	729
Body Mass Index [units: subjects]
<18.5 kilogram per meter² (kg/m²)	0	0	0	0
18.5 kg/m² to <25 kg/m²	15	12	7	34
25 kg/m² to <30 kg/m²	75	87	89	251
≥30 kg/m²	166	152	154	472
missing	0	0	3	3
Calculated Creatinine Clearance^[1] [units: subjects]
<50 milliliters per minute (mL/min)	13	8	13	34
50 mL/min to <80 mL/min	77	90	68	235
80 mL/min to <120 mL/min	138	130	140	408
≥120 mL/min	28	23	29	80
missing	0	0	3	3
Presence of Primary Palpable Tophus [units: subjects]
Yes	52	53	46	151
No, but other tophi present	1	2	3	6
No and no other tophi present	203	196	204	603
Race/Ethnicity [units: subjects]
White	193	199	195	587
Black or African American	24	20	18	62
Hispanic	22	17	19	58
Asian	10	9	6	25
Other	7	6	15	28

[1]	Calculated creatinine clearance based on the Cockcroft-Gault equation using ideal body weight.

Measure Type	Primary
Measure Title	Percentage of Subjects With the Last 3 Serum Urate Levels <6.0 Milligrams 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 (up to 52 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 intent-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.

Reporting Groups

	Description
Febuxostat 80 mg QD	Febuxostat 80 mg, orally, once daily for up to 52 weeks.
Febuxostat 120 mg QD	Febuxostat 120 mg, orally, once daily for up to 52 weeks.
Allopurinol 300 mg QD	Allopurinol 300 mg, orally, once daily for up to 52 weeks.

Measured Values

	Febuxostat 80 mg QD	Febuxostat 120 mg QD	Allopurinol 300 mg QD
Number of Participants Analyzed [units: participants]	255	250	251
Percentage of Subjects With the Last 3 Serum Urate Levels <6.0 Milligrams Per Deciliter (mg/dL) [units: Percentage of subjects]	53	62	21

Statistical Analysis 1 for Percentage of Subjects With the Last 3 Serum Urate Levels <6.0 Milligrams Per Deciliter (mg/dL)

Groups ^[1]	Febuxostat 80 mg QD vs. Allopurinol 300 mg QD
Non-Inferiority/Equivalence Test ^[2]	Yes
Difference in percentage ^[3]	32
97.5% Confidence Interval	( 23.1 to 41.3 )

[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 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 2 for Percentage of Subjects With the Last 3 Serum Urate Levels <6.0 Milligrams Per Deciliter (mg/dL)

Groups ^[1]	Febuxostat 120 mg QD vs. Allopurinol 300 mg QD
Non-Inferiority/Equivalence Test ^[2]	Yes
Difference in percentage ^[3]	41
97.5% Confidence Interval	( 31.5 to 49.5 )

[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 3 for Percentage of Subjects With the Last 3 Serum Urate Levels <6.0 Milligrams Per Deciliter (mg/dL)

Groups ^[1]	Febuxostat 80 mg QD vs. Allopurinol 300 mg QD
Method ^[2]	Fisher Exact
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:
	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 for multiple comparisons.

Statistical Analysis 4 for Percentage of Subjects With the Last 3 Serum Urate Levels <6.0 Milligrams Per Deciliter (mg/dL)

Groups ^[1]	Febuxostat 120 mg QD vs. Allopurinol 300 mg QD
Method ^[2]	Fisher Exact
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:
	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 for multiple comparisons.

Statistical Analysis 5 for Percentage of Subjects With the Last 3 Serum Urate Levels <6.0 Milligrams Per Deciliter (mg/dL)

Groups ^[1]	Febuxostat 80 mg QD vs. Febuxostat 120 mg QD
Method ^[2]	Fisher Exact
P Value ^[3]	0.072

[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.

Measure Type	Secondary
Measure Title	Percentage of Subjects With Serum Urate <6.0 mg/dL at Week 28 Visit
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 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 52 weeks.
Febuxostat 120 mg QD	Febuxostat 120 mg, orally, once daily for up to 52 weeks.
Allopurinol 300 mg QD	Allopurinol 300 mg, orally, once daily for up to 52 weeks.

Measured Values

	Febuxostat 80 mg QD	Febuxostat 120 mg QD	Allopurinol 300 mg QD
Number of Participants Analyzed [units: participants]	186	159	199
Percentage of Subjects With Serum Urate <6.0 mg/dL at Week 28 Visit [units: Percentage of subjects]	72	82	42

Statistical Analysis 1 for Percentage of Subjects With Serum Urate <6.0 mg/dL at Week 28 Visit

Groups ^[1]	Febuxostat 80 mg QD vs. Allopurinol 300 mg QD
Method ^[2]	Fisher Exact
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:
	Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 2 for Percentage of Subjects With Serum Urate <6.0 mg/dL at Week 28 Visit

Groups ^[1]	Febuxostat 120 mg QD vs. Allopurinol 300 mg QD
Method ^[2]	Fisher Exact
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:
	Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 3 for Percentage of Subjects With Serum Urate <6.0 mg/dL at Week 28 Visit

Groups ^[1]	Febuxostat 80 mg QD vs. Febuxostat 120 mg QD
Method ^[2]	Fisher Exact
P Value ^[3]	0.031

[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.

Measure Type	Secondary
Measure Title	Percentage of Subjects With Serum Urate <6.0 mg/dL at Week 52 Visit
Measure Description	Serum urate values were obtained at the Week 52 visit. The percentage of subjects whose serum urate was <6.0 mg/dL at the Week 52 visit was summarized.
Time Frame	Week 52
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 52 weeks.
Febuxostat 120 mg QD	Febuxostat 120 mg, orally, once daily for up to 52 weeks.
Allopurinol 300 mg QD	Allopurinol 300 mg, orally, once daily for up to 52 weeks.

Measured Values

	Febuxostat 80 mg QD	Febuxostat 120 mg QD	Allopurinol 300 mg QD
Number of Participants Analyzed [units: participants]	159	145	178
Percentage of Subjects With Serum Urate <6.0 mg/dL at Week 52 Visit [units: Percentage of subjects]	81	82	39

Statistical Analysis 1 for Percentage of Subjects With Serum Urate <6.0 mg/dL at Week 52 Visit

Groups ^[1]	Febuxostat 80 mg QD vs. Allopurinol 300 mg QD
Method ^[2]	Fisher Exact
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:
	Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 2 for Percentage of Subjects With Serum Urate <6.0 mg/dL at Week 52 Visit

Groups ^[1]	Febuxostat 120 mg QD vs. Allopurinol 300 mg QD
Method ^[2]	Fisher Exact
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:
	Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 3 for Percentage of Subjects With Serum Urate <6.0 mg/dL at Week 52 Visit

Groups ^[1]	Febuxostat 80 mg QD vs. Febuxostat 120 mg QD
Method ^[2]	Fisher Exact
P Value ^[3]	0.883

[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.

Measure Type	Secondary
Measure Title	Percentage of Subjects With Serum Urate <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. The timing of the final visit may have differed for each subject.
Time Frame	Final Visit (up to 52 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 52 weeks.
Febuxostat 120 mg QD	Febuxostat 120 mg, orally, once daily for up to 52 weeks.
Allopurinol 300 mg QD	Allopurinol 300 mg, orally, once daily for up to 52 weeks.

Measured Values

	Febuxostat 80 mg QD	Febuxostat 120 mg QD	Allopurinol 300 mg QD
Number of Participants Analyzed [units: participants]	249	242	242
Percentage of Subjects With Serum Urate <6.0 mg/dL at Final Visit [units: Percentage of subjects]	74	80	36

Statistical Analysis 1 for Percentage of Subjects With Serum Urate <6.0 mg/dL at Final Visit

Groups ^[1]	Febuxostat 80 mg QD vs. Allopurinol 300 mg QD
Method ^[2]	Fisher Exact
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:
	Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 2 for Percentage of Subjects With Serum Urate <6.0 mg/dL at Final Visit

Groups ^[1]	Febuxostat 120 mg QD vs. Allopurinol 300 mg QD
Method ^[2]	Fisher Exact
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:
	Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 3 for Percentage of Subjects With Serum Urate <6.0 mg/dL at Final Visit

Groups ^[1]	Febuxostat 80 mg QD vs. Febuxostat 120 mg QD
Method ^[2]	Fisher Exact
P Value ^[3]	0.164

[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.

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 52 weeks.
Febuxostat 120 mg QD	Febuxostat 120 mg, orally, once daily for up to 52 weeks.
Allopurinol 300 mg QD	Allopurinol 300 mg, orally, once daily for up to 52 weeks.

Measured Values

	Febuxostat 80 mg QD	Febuxostat 120 mg QD	Allopurinol 300 mg QD
Number of Participants Analyzed [units: participants]	186	159	199
Percent Change From Baseline in Serum Urate Levels at Week 28. [units: percent change from baseline] Mean ± Standard Deviation	-46.3 ± 15.76	-53.5 ± 18.20	-34.8 ± 12.92

Statistical Analysis 1 for Percent Change From Baseline in Serum Urate Levels at Week 28.

Groups ^[1]	Febuxostat 80 mg QD vs. Allopurinol 300 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 one-way ANOVA model with treatment as a factor. Statistical significance was determined at the 0.05 level without adjustment 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. Allopurinol 300 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 one-way ANOVA model with treatment as a factor. Statistical significance was determined at the 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 3 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 one-way ANOVA model with treatment as a factor. Statistical significance was determined at the 0.05 level without adjustment for multiple comparisons.

Measure Type	Secondary
Measure Title	Percent Change From Baseline in Serum Urate Levels at Week 52.
Measure Description	Serum urate values were obtained at the Week 52 visit. The percent change in serum urate was calculated as [(week 52 - baseline levels/baseline)]*100 and summarized.
Time Frame	Baseline and Week 52
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 52 weeks.
Febuxostat 120 mg QD	Febuxostat 120 mg, orally, once daily for up to 52 weeks.
Allopurinol 300 mg QD	Allopurinol 300 mg, orally, once daily for up to 52 weeks.

Measured Values

	Febuxostat 80 mg QD	Febuxostat 120 mg QD	Allopurinol 300 mg QD
Number of Participants Analyzed [units: participants]	159	145	178
Percent Change From Baseline in Serum Urate Levels at Week 52. [units: percent change from baseline] Mean ± Standard Deviation	-47.7 ± 17.50	-53.0 ± 19.31	-34.8 ± 13.56

Statistical Analysis 1 for Percent Change From Baseline in Serum Urate Levels at Week 52.

Groups ^[1]	Febuxostat 80 mg QD vs. Allopurinol 300 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 one-way ANOVA model with treatment as a factor. Statistical significance was determined at the 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 2 for Percent Change From Baseline in Serum Urate Levels at Week 52.

Groups ^[1]	Febuxostat 120 mg QD vs. Allopurinol 300 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 one-way ANOVA model with treatment as a factor. Statistical significance was determined at the 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 3 for Percent Change From Baseline in Serum Urate Levels at Week 52.

Groups ^[1]	Febuxostat 80 mg QD vs. Febuxostat 120 mg QD
Method ^[2]	ANOVA
P Value ^[3]	0.006

[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 one-way ANOVA model with treatment as a factor. Statistical significance was determined at the 0.05 level without adjustment for multiple comparisons.

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 calculated as [(Final Visit - baseline levels/baseline)]*100 and summarized. The Final visit was the last visit with a serum urate value. The timing of the final visit may have differed for each subject.
Time Frame	Baseline and Final Visit (up to 52 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 52 weeks.
Febuxostat 120 mg QD	Febuxostat 120 mg, orally, once daily for up to 52 weeks.
Allopurinol 300 mg QD	Allopurinol 300 mg, orally, once daily for up to 52 weeks.

Measured Values

	Febuxostat 80 mg QD	Febuxostat 120 mg QD	Allopurinol 300 mg QD
Number of Participants Analyzed [units: participants]	249	242	242
Percent Change From Baseline in Serum Urate Levels at Final Visit [units: percent change from baseline] Mean ± Standard Deviation	-44.7 ± 19.10	-51.5 ± 19.91	-33.0 ± 15.33

Statistical Analysis 1 for Percent Change From Baseline in Serum Urate Levels at Final Visit

Groups ^[1]	Febuxostat 80 mg QD vs. Allopurinol 300 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 one-way ANOVA model with treatment as a factor. Statistical significance was determined at the 0.05 level without adjustment 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. Allopurinol 300 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 one-way ANOVA model with treatment as a factor. Statistical significance was determined at the 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 3 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 one-way ANOVA model with treatment as a factor. Statistical significance was determined at the 0.05 level without adjustment for multiple comparisons.

Measure Type	Secondary
Measure Title	Percent Change From Baseline in Tophus Size at Week 28, as Determined by Physical Measurement, in Subjects With a Palpable Primary Tophus at Screening.
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, had a baseline serum urate ≥8.0 mg/dL, and 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 52 weeks.
Febuxostat 120 mg QD	Febuxostat 120 mg, orally, once daily for up to 52 weeks.
Allopurinol 300 mg QD	Allopurinol 300 mg, orally, once daily for up to 52 weeks.

Measured Values

	Febuxostat 80 mg QD	Febuxostat 120 mg QD	Allopurinol 300 mg QD
Number of Participants Analyzed [units: participants]	36	28	33
Percent Change From Baseline in Tophus Size at Week 28, as Determined by Physical Measurement, in Subjects With a Palpable Primary Tophus at Screening. [units: percent change from baseline] Median ( Inter-Quartile Range )	-29.5 ( -66.0 to 4.1 )	-49.5 ( -80.0 to -34.9 )	-28.6 ( -54.9 to 0.0 )

Statistical Analysis 1 for Percent Change From Baseline in Tophus Size at Week 28, as Determined by Physical Measurement, in Subjects With a Palpable Primary Tophus at Screening.

Groups ^[1]	Febuxostat 80 mg QD vs. Allopurinol 300 mg QD
Method ^[2]	Wilcoxon (Mann-Whitney)
P Value ^[3]	>0.999

[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 the Wilcoxon rank-sum test. Statistical significance was determined at the 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 2 for Percent Change From Baseline in Tophus Size at Week 28, as Determined by Physical Measurement, in Subjects With a Palpable Primary Tophus at Screening.

Groups ^[1]	Febuxostat 120 mg QD vs. Allopurinol 300 mg QD
Method ^[2]	Wilcoxon (Mann-Whitney)
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:
	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 the Wilcoxon rank-sum test. Statistical significance was determined at the 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 3 for Percent Change From Baseline in Tophus Size at Week 28, as Determined by Physical Measurement, in Subjects With a Palpable Primary Tophus at Screening.

Groups ^[1]	Febuxostat 80 mg QD vs. Febuxostat 120 mg QD
Method ^[2]	Wilcoxon (Mann-Whitney)
P Value ^[3]	0.024

[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 the Wilcoxon rank-sum test. Statistical significance was determined at the 0.05 level without adjustment for multiple comparisons.

Measure Type	Secondary
Measure Title	Percent Change From Baseline in Tophus Size at Week 52, as Determined by Physical Measurement, in Subjects With a Palpable Primary Tophus at Screening.
Measure Description	The percent change from baseline in primary tophus size as determined by physical measurement was calculated as [(Week 52 - baseline sizes)/baseline]*100 for the subset of subjects with a primary palpable tophus at the Screening Visit. If the primary tophus was no longer palpable at the Week 52 visit, the size was assumed to be zero.
Time Frame	Baseline and Week 52
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 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 52 weeks.
Febuxostat 120 mg QD	Febuxostat 120 mg, orally, once daily for up to 52 weeks.
Allopurinol 300 mg QD	Allopurinol 300 mg, orally, once daily for up to 52 weeks.

Measured Values

	Febuxostat 80 mg QD	Febuxostat 120 mg QD	Allopurinol 300 mg QD
Number of Participants Analyzed [units: participants]	32	26	30
Percent Change From Baseline in Tophus Size at Week 52, as Determined by Physical Measurement, in Subjects With a Palpable Primary Tophus at Screening. [units: percent change from baseline] Median ( Inter-Quartile Range )	-83.4 ( -100 to -15.6 )	-65.5 ( -85.5 to -38.9 )	-49.7 ( -96.0 to 0.0 )

Statistical Analysis 1 for Percent Change From Baseline in Tophus Size at Week 52, as Determined by Physical Measurement, in Subjects With a Palpable Primary Tophus at Screening.

Groups ^[1]	Febuxostat 80 mg QD vs. Allopurinol 300 mg QD
Method ^[2]	Wilcoxon (Mann-Whitney)
P Value ^[3]	0.083

[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 the Wilcoxon rank-sum test. Statistical significance was determined at the 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 2 for Percent Change From Baseline in Tophus Size at Week 52, as Determined by Physical Measurement, in Subjects With a Palpable Primary Tophus at Screening.

Groups ^[1]	Febuxostat 120 mg QD vs. Allopurinol 300 mg QD
Method ^[2]	Wilcoxon (Mann-Whitney)
P Value ^[3]	0.164

[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 the Wilcoxon rank-sum test. Statistical significance was determined at the 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 3 for Percent Change From Baseline in Tophus Size at Week 52, as Determined by Physical Measurement, in Subjects With a Palpable Primary Tophus at Screening.

Groups ^[1]	Febuxostat 80 mg QD vs. Febuxostat 120 mg QD
Method ^[2]	Wilcoxon (Mann-Whitney)
P Value ^[3]	0.619

[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 the Wilcoxon rank-sum test. Statistical significance was determined at the 0.05 level without adjustment for multiple comparisons.

Measure Type	Secondary
Measure Title	Percent Change From Baseline in Tophus Size at Final Visit, as Determined by Physical Measurement, in Subjects With a Palpable Primary Tophus at Screening.
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 52 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 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 52 weeks.
Febuxostat 120 mg QD	Febuxostat 120 mg, orally, once daily for up to 52 weeks.
Allopurinol 300 mg QD	Allopurinol 300 mg, orally, once daily for up to 52 weeks.

Measured Values

	Febuxostat 80 mg QD	Febuxostat 120 mg QD	Allopurinol 300 mg QD
Number of Participants Analyzed [units: participants]	50	51	44
Percent Change From Baseline in Tophus Size at Final Visit, as Determined by Physical Measurement, in Subjects With a Palpable Primary Tophus at Screening. [units: percent change from baseline] Median ( Inter-Quartile Range )	-51.7 ( -100 to -8.3 )	-43.8 ( -83.0 to 0.0 )	-39.6 ( -65.0 to 1.5 )

Statistical Analysis 1 for Percent Change From Baseline in Tophus Size at Final Visit, as Determined by Physical Measurement, in Subjects With a Palpable Primary Tophus at Screening.

Groups ^[1]	Febuxostat 80 mg QD vs. Allopurinol 300 mg QD
Method ^[2]	Wilcoxon (Mann-Whitney)
P Value ^[3]	0.080

[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 the Wilcoxon rank-sum test. Statistical significance was determined at the 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 2 for Percent Change From Baseline in Tophus Size at Final Visit, as Determined by Physical Measurement, in Subjects With a Palpable Primary Tophus at Screening.

Groups ^[1]	Febuxostat 120 mg QD vs. Allopurinol 300 mg QD
Method ^[2]	Wilcoxon (Mann-Whitney)
P Value ^[3]	0.372

[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 the Wilcoxon rank-sum test. Statistical significance was determined at the 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 3 for Percent Change From Baseline in Tophus Size at Final Visit, as Determined by Physical Measurement, in Subjects With a Palpable Primary Tophus at Screening.

Groups ^[1]	Febuxostat 80 mg QD vs. Febuxostat 120 mg QD
Method ^[2]	Wilcoxon (Mann-Whitney)
P Value ^[3]	0.246

[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 the Wilcoxon rank-sum test. Statistical significance was determined at the 0.05 level without adjustment for multiple comparisons.

Measure Type	Secondary
Measure Title	Change From Baseline in Total Number of Tophi at Week 28 in Subjects With Palpable Tophi at Screening.
Measure Description	The change from baseline at Week 28 in the total number of tophi per subject was calculated for the subset of subjects with palpable tophi at the Screening Visit. If the tophi were no longer palpable at the Week 28 visit, the total count was assumed to be zero.
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 baseline. Missing data were not imputed.

Reporting Groups

	Description
Febuxostat 80 mg QD	Febuxostat 80 mg, orally, once daily for up to 52 weeks.
Febuxostat 120 mg QD	Febuxostat 120 mg, orally, once daily for up to 52 weeks.
Allopurinol 300 mg QD	Allopurinol 300 mg, orally, once daily for up to 52 weeks.

Measured Values

	Febuxostat 80 mg QD	Febuxostat 120 mg QD	Allopurinol 300 mg QD
Number of Participants Analyzed [units: participants]	38	30	37
Change From Baseline in Total Number of Tophi at Week 28 in Subjects With Palpable Tophi at Screening. [units: number of tophi] Median ( Inter-Quartile Range )	0.0 ( 0.0 to 0.0 )	0.0 ( -1.0 to 0.0 )	0.0 ( 0.0 to 0.0 )

Statistical Analysis 1 for Change From Baseline in Total Number of Tophi at Week 28 in Subjects With Palpable Tophi at Screening.

Groups ^[1]	Febuxostat 80 mg QD vs. Allopurinol 300 mg QD
Method ^[2]	Wilcoxon (Mann-Whitney)
P Value ^[3]	0.674

[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 the Wilcoxon rank-sum test. Statistical significance was determined at the 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 2 for Change From Baseline in Total Number of Tophi at Week 28 in Subjects With Palpable Tophi at Screening.

Groups ^[1]	Febuxostat 120 mg QD vs. Allopurinol 300 mg 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:
	P-values for pairwise comparisons are from the Wilcoxon rank-sum test. Statistical significance was determined at the 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 3 for Change From Baseline in Total Number of Tophi at Week 28 in Subjects With Palpable Tophi at Screening.

Groups ^[1]	Febuxostat 80 mg QD vs. Febuxostat 120 mg QD
Method ^[2]	Wilcoxon (Mann-Whitney)
P Value ^[3]	0.411

[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 the Wilcoxon rank-sum test. Statistical significance was determined at the 0.05 level without adjustment for multiple comparisons.

Measure Type	Secondary
Measure Title	Change From Baseline in Total Number of Tophi at Week 52 in Subjects With Palpable Tophi at Screening.
Measure Description	The change from baseline at Week 52 in the total number of tophi per subject was calculated for the subset of subjects with palpable tophi at the Screening Visit. If the tophi were no longer palpable at the Week 52 visit, the total count was assumed to be zero.
Time Frame	Baseline and Week 52
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 baseline. Missing data were not imputed.

Reporting Groups

	Description
Febuxostat 80 mg QD	Febuxostat 80 mg, orally, once daily for up to 52 weeks.
Febuxostat 120 mg QD	Febuxostat 120 mg, orally, once daily for up to 52 weeks.
Allopurinol 300 mg QD	Allopurinol 300 mg, orally, once daily for up to 52 weeks.

Measured Values

	Febuxostat 80 mg QD	Febuxostat 120 mg QD	Allopurinol 300 mg QD
Number of Participants Analyzed [units: participants]	33	28	35
Change From Baseline in Total Number of Tophi at Week 52 in Subjects With Palpable Tophi at Screening. [units: number of tophi] Median ( Inter-Quartile Range )	0.0 ( -1.0 to 0.0 )	-1.0 ( -1.0 to 0.0 )	0.0 ( -1.0 to 0.0 )

Statistical Analysis 1 for Change From Baseline in Total Number of Tophi at Week 52 in Subjects With Palpable Tophi at Screening.

Groups ^[1]	Febuxostat 80 mg QD vs. Allopurinol 300 mg QD
Method ^[2]	Wilcoxon (Mann-Whitney)
P Value ^[3]	0.507

[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 the Wilcoxon rank-sum test. Statistical significance was determined at the 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 2 for Change From Baseline in Total Number of Tophi at Week 52 in Subjects With Palpable Tophi at Screening.

Groups ^[1]	Febuxostat 120 mg QD vs. Allopurinol 300 mg QD
Method ^[2]	Wilcoxon (Mann-Whitney)
P Value ^[3]	0.188

[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 the Wilcoxon rank-sum test. Statistical significance was determined at the 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 3 for Change From Baseline in Total Number of Tophi at Week 52 in Subjects With Palpable Tophi at Screening.

Groups ^[1]	Febuxostat 80 mg QD vs. Febuxostat 120 mg QD
Method ^[2]	Wilcoxon (Mann-Whitney)
P Value ^[3]	0.362

[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 the Wilcoxon rank-sum test. Statistical significance was determined at the 0.05 level without adjustment for multiple comparisons.

Measure Type	Secondary
Measure Title	Change From Baseline in Total Number of Tophi at Final Visit in Subjects With Palpable Tophi at Screening.
Measure Description	Change in number of tophi/subject calculated for the subset of subjects with palpable tophi at Screening. If the tophi were not palpable at the Final Visit, total count was assumed to be 0. The timing of the final visit may have differed for each subject.
Time Frame	Baseline and Final Visit (up to 52 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 baseline. Missing data were not imputed.

Reporting Groups

	Description
Febuxostat 80 mg QD	Febuxostat 80 mg, orally, once daily for up to 52 weeks.
Febuxostat 120 mg QD	Febuxostat 120 mg, orally, once daily for up to 52 weeks.
Allopurinol 300 mg QD	Allopurinol 300 mg, orally, once daily for up to 52 weeks.

Measured Values

	Febuxostat 80 mg QD	Febuxostat 120 mg QD	Allopurinol 300 mg QD
Number of Participants Analyzed [units: participants]	52	53	47
Change From Baseline in Total Number of Tophi at Final Visit in Subjects With Palpable Tophi at Screening. [units: number of tophi] Median ( Inter-Quartile Range )	0.0 ( -1.0 to 0.0 )	0.0 ( -1.0 to 0.0 )	0.0 ( -1.0 to 0.0 )

Statistical Analysis 1 for Change From Baseline in Total Number of Tophi at Final Visit in Subjects With Palpable Tophi at Screening.

Groups ^[1]	Febuxostat 80 mg QD vs. Allopurinol 300 mg QD
Method ^[2]	Wilcoxon (Mann-Whitney)
P Value ^[3]	0.657

[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 the Wilcoxon rank-sum test. Statistical significance was determined at the 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 2 for Change From Baseline in Total Number of Tophi at Final Visit in Subjects With Palpable Tophi at Screening.

Groups ^[1]	Febuxostat 120 mg QD vs. Allopurinol 300 mg QD
Method ^[2]	Wilcoxon (Mann-Whitney)
P Value ^[3]	0.444

[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 the Wilcoxon rank-sum test. Statistical significance was determined at the 0.05 level without adjustment for multiple comparisons.

Statistical Analysis 3 for Change From Baseline in Total Number of Tophi at Final Visit in Subjects With Palpable Tophi at Screening.

Groups ^[1]	Febuxostat 80 mg QD vs. Febuxostat 120 mg QD
Method ^[2]	Wilcoxon (Mann-Whitney)
P Value ^[3]	0.719

[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 the Wilcoxon rank-sum test. Statistical significance was determined at the 0.05 level without adjustment for multiple comparisons.

Measure Type	Secondary
Measure Title	Percentage of Subjects Requiring Treatment for Gout Flares Between Weeks 8 and 52.
Measure Description	The percentage of subjects requiring treatment for a gout flare between Weeks 8 and 52 of the double-blind treatment period was summarized. A subject who reported more than 1 gout flare during this period was counted only once.
Time Frame	Weeks 8 through 52
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 52.

Reporting Groups

	Description
Febuxostat 80 mg QD	Febuxostat 80 mg, orally, once daily for up to 52 weeks.
Febuxostat 120 mg QD	Febuxostat 120 mg, orally, once daily for up to 52 weeks.
Allopurinol 300 mg QD	Allopurinol 300 mg, orally, once daily for up to 52 weeks.

Measured Values

	Febuxostat 80 mg QD	Febuxostat 120 mg QD	Allopurinol 300 mg QD
Number of Participants Analyzed [units: participants]	228	215	234
Percentage of Subjects Requiring Treatment for Gout Flares Between Weeks 8 and 52. [units: percentage of subjects]	64	70	64

Statistical Analysis 1 for Percentage of Subjects Requiring Treatment for Gout Flares Between Weeks 8 and 52.

Groups ^[1]	Febuxostat 80 mg QD vs. Allopurinol 300 mg QD
Method ^[2]	Fisher Exact
P Value ^[3]	>0.999

[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 Percentage of Subjects Requiring Treatment for Gout Flares Between Weeks 8 and 52.

Groups ^[1]	Febuxostat 120 mg QD vs. Allopurinol 300 mg QD
Method ^[2]	Fisher Exact
P Value ^[3]	0.229

[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 Percentage of Subjects Requiring Treatment for Gout Flares Between Weeks 8 and 52.

Groups ^[1]	Febuxostat 80 mg QD vs. Febuxostat 120 mg QD
Method ^[2]	Fisher Exact
P Value ^[3]	0.266

[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.

Responsible Party:	Takeda Global Research & Development Center, Inc. ( Sr. VP, Clinical Science )
Study ID Numbers:	C02-010
Study First Received:	January 29, 2005
Results First Received:	March 12, 2009
Last Updated:	August 17, 2009
ClinicalTrials.gov Identifier:	NCT00102440 History of Changes
Health Authority:	United States: Food and Drug Administration