FACT: Febuxostat Versus Allopurinol Control Trial in Subjects With Gout

• Sponsor: Takeda (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00102440
• Collaborator: (none)
• Enrollment: 760
• Arms: 3
• Duration (Months): 19.1

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Gout	Drug: Febuxostat; Drug: Febuxostat; Drug: Allopurinol	Phase 3

Detailed Description

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 760 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Randomized, Multicenter Study Comparing the Safety and Efficacy of Oral Febuxostat Versus Allopurinol in Subjects With Gout
• Study Start Date: Jul 1, 2002
• Actual Primary Completion Date: Feb 1, 2004
• Actual Study Completion Date: Feb 1, 2004

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Febuxostat 80 mg QD	Drug: Febuxostat; Febuxostat 80 mg, orally, once daily for up to 52 weeks.; Other Names: TMX-67 Tei-6720 Uloric
Experimental: Febuxostat 120 mg QD	Drug: Febuxostat; Febuxostat 120 mg, orally, once daily for up to 52 weeks.; Other Names: TMX-67 Tei-6720 Uloric
Active Comparator: Allopurinol 300 mg QD	Drug: Allopurinol; Allopurinol 300 mg, capsules, orally, once daily for up to 52 weeks.

Outcome Measures

Primary Outcome Measures

1. Percentage of Subjects With the Last 3 Serum Urate Levels <6.0 Milligrams Per Deciliter (mg/dL) [Last 3 Visits (up to 52 weeks)]

   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.

Secondary Outcome Measures

1. Percentage of Subjects With Serum Urate <6.0 mg/dL at Week 28 Visit [Week 28]

   Serum urate values were obtained at the Week 28 visit. The percentage of subjects whose serum urate was <6.0 mg/dL at the Week 28 visit was summarized.

2. Percentage of Subjects With Serum Urate <6.0 mg/dL at Week 52 Visit [Week 52]

   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.

3. Percentage of Subjects With Serum Urate <6.0 mg/dL at Final Visit [Final Visit (up to 52 weeks)]

   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.

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

   Serum urate values were obtained at the Week 28 visit. The percent change in serum urate was calculated as [(week 28 - baseline levels/baseline)]*100 and summarized.

5. Percent Change From Baseline in Serum Urate Levels at Week 52. [Baseline and Week 52]

   Serum urate values were obtained at the Week 52 visit. The percent change in serum urate was calculated as [(week 52 - baseline levels/baseline)]*100 and summarized.

6. Percent Change From Baseline in Serum Urate Levels at Final Visit [Baseline and Final Visit (up to 52 weeks)]

   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.

7. Percent Change From Baseline in Tophus Size at Week 28, as Determined by Physical Measurement, in Subjects With a Palpable Primary Tophus at Screening. [Baseline and Week 28]

   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.

8. Percent Change From Baseline in Tophus Size at Week 52, as Determined by Physical Measurement, in Subjects With a Palpable Primary Tophus at Screening. [Baseline and Week 52]

   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.

9. Percent Change From Baseline in Tophus Size at Final Visit, as Determined by Physical Measurement, in Subjects With a Palpable Primary Tophus at Screening. [Baseline and Final Visit (up to 52 weeks)]

   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.

10. Change From Baseline in Total Number of Tophi at Week 28 in Subjects With Palpable Tophi at Screening. [Baseline and Week 28]

    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.

11. Change From Baseline in Total Number of Tophi at Week 52 in Subjects With Palpable Tophi at Screening. [Baseline and Week 52]

    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.

12. Change From Baseline in Total Number of Tophi at Final Visit in Subjects With Palpable Tophi at Screening. [Baseline and Final Visit (up to 52 weeks)]

    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.

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

    The percentage of subjects requiring treatment for a gout flare between Weeks 8 and 52 of the double-blind treatment period was summarized. A subject who reported more than 1 gout flare during this period was counted only once.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Meeting the preliminary criteria of the American Rheumatism Association for the classification of the acute arthritis of primary gout.

• Serum uric acid ≥ 8.0 milligrams per deciliter (mg/dL) at Baseline

Exclusion Criteria:

• Serum creatinine >1.5 mg/dL

• Calculated creatinine clearance of <50 milliliters per minutes (mL/min)

• Pregnancy or lactation;

• Concurrent therapy with urate lowering agents, azathioprine, 6-mercaptopurine, thiazide diuretics, or medications containing aspirin (>325 mg) or other salicylates;

• Body Mass Index (BMI) >50 kilogram per meter²(kg/m²);

• A history of xanthinuria, active liver disease, or hepatic dysfunction;

• A history of alcohol abuse or intake of 14 or more alcohol-containing drinks/week.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Takeda

Investigators

• Study Director: Medical Director, Takeda

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• American College of Rheumatology
• Uloric Package Insert

Publications

None provided.

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT00102440
• Other Study ID Numbers: C02-010; U1111-1114-0184
• First Posted: Jan 31, 2005
• Last Update Posted: Feb 2, 2012
• Last Verified: Jan 1, 2012

• Keywords provided by Takeda: uric Acid; xanthine oxidase; tophi; Drug Therapy
• Additional relevant MeSH terms: Gout; Allopurinol; Febuxostat

Study Results

Participant Flow

Recruitment Details	Subjects were enrolled at 112 investigative sites, 106 in the United States and 6 in Canada, from 11 July 2002 to 20 February 2004.
Pre-assignment Detail	Subjects currently receiving urate-lowering therapy discontinued those urate-lowering therapies and initiated prophylactic medications before enrollment in once daily (QD) treatment groups.

Arm/Group Title	Febuxostat 80 mg QD	Febuxostat 120 mg QD	Allopurinol 300 mg QD
Arm/Group Description	Febuxostat 80 mg, orally, once daily for up to 52 weeks.	Febuxostat 120 mg, orally, once daily for up to 52 weeks.	Allopurinol 300 mg, orally, once daily for up to 52 weeks.
Period Title: Overall Study
STARTED	256	251	253
COMPLETED	168	153	187
NOT COMPLETED	88	98	66

Baseline Characteristics

Arm/Group Title	Febuxostat 80 mg QD	Febuxostat 120 mg QD	Allopurinol 300 mg QD	Total
Arm/Group Description	Febuxostat 80 mg, orally, once daily for up to 52 weeks.	Febuxostat 120 mg, orally, once daily for up to 52 weeks.	Allopurinol 300 mg, orally, once daily for up to 52 weeks.	Total of all reporting groups
Overall Participants	256	251	253	760
Age, Customized (subjects) [Number]
<45 years	75	71	84	230
45 years to <65 years	140	133	125	398
≥65 years	41	47	44	132
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	51.8 (11.69)	52.0 (12.12)	51.6 (12.63)	51.8 (12.13)
Sex: Female, Male (Count of Participants)
Female	13 5.1%	8 3.2%	10 4%	31 4.1%
Male	243 94.9%	243 96.8%	243 96%	729 95.9%
Body Mass Index (subjects) [Number]
<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 (subjects) [Number]
<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 (subjects) [Number]
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 (subjects) [Number]
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

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Febuxostat 80 mg QD	Febuxostat 120 mg QD	Allopurinol 300 mg QD
Arm/Group Description	Febuxostat 80 mg, orally, once daily for up to 52 weeks.	Febuxostat 120 mg, orally, once daily for up to 52 weeks.	Allopurinol 300 mg, orally, once daily for up to 52 weeks.
Measure Participants	255	250	251
Number [Percentage of subjects]	53	62	21

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Febuxostat 80 mg QD, Allopurinol 300 mg QD
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	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%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in percentage
	Estimated Value	32
	Confidence Interval	() 97.5%; 23.1 to 41.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Febuxostat 120 mg QD, Allopurinol 300 mg QD
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	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%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in percentage
	Estimated Value	41
	Confidence Interval	() 97.5%; 31.5 to 49.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Febuxostat 80 mg QD, Allopurinol 300 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	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.
	Method	Fisher Exact
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Febuxostat 120 mg QD, Allopurinol 300 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	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.
	Method	Fisher Exact
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Febuxostat 80 mg QD, Febuxostat 120 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.072
	Comments	Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
	Method	Fisher Exact
	Comments

2. Secondary Outcome

Title	Percentage of Subjects With Serum Urate <6.0 mg/dL at Week 28 Visit
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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Febuxostat 80 mg QD	Febuxostat 120 mg QD	Allopurinol 300 mg QD
Arm/Group Description	Febuxostat 80 mg, orally, once daily for up to 52 weeks.	Febuxostat 120 mg, orally, once daily for up to 52 weeks.	Allopurinol 300 mg, orally, once daily for up to 52 weeks.
Measure Participants	186	159	199
Number [Percentage of subjects]	72	82	42

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Febuxostat 80 mg QD, Allopurinol 300 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Febuxostat 120 mg QD, Allopurinol 300 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
	Method	Fisher Exact
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Febuxostat 80 mg QD, Febuxostat 120 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.031
	Comments	Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
	Method	Fisher Exact
	Comments

3. Secondary Outcome

Title	Percentage of Subjects With Serum Urate <6.0 mg/dL at Week 52 Visit
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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Febuxostat 80 mg QD	Febuxostat 120 mg QD	Allopurinol 300 mg QD
Arm/Group Description	Febuxostat 80 mg, orally, once daily for up to 52 weeks.	Febuxostat 120 mg, orally, once daily for up to 52 weeks.	Allopurinol 300 mg, orally, once daily for up to 52 weeks.
Measure Participants	159	145	178
Number [Percentage of subjects]	81	82	39

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Febuxostat 80 mg QD, Allopurinol 300 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Febuxostat 120 mg QD, Allopurinol 300 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
	Method	Fisher Exact
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Febuxostat 80 mg QD, Febuxostat 120 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.883
	Comments	Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
	Method	Fisher Exact
	Comments

4. Secondary Outcome

Title	Percentage of Subjects With Serum Urate <6.0 mg/dL at Final Visit
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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Febuxostat 80 mg QD	Febuxostat 120 mg QD	Allopurinol 300 mg QD
Arm/Group Description	Febuxostat 80 mg, orally, once daily for up to 52 weeks.	Febuxostat 120 mg, orally, once daily for up to 52 weeks.	Allopurinol 300 mg, orally, once daily for up to 52 weeks.
Measure Participants	249	242	242
Number [Percentage of subjects]	74	80	36

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Febuxostat 80 mg QD, Allopurinol 300 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Febuxostat 120 mg QD, Allopurinol 300 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
	Method	Fisher Exact
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Febuxostat 80 mg QD, Febuxostat 120 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.164
	Comments	Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
	Method	Fisher Exact
	Comments

5. Secondary Outcome

Title	Percent Change From Baseline in Serum Urate Levels at Week 28.
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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Febuxostat 80 mg QD	Febuxostat 120 mg QD	Allopurinol 300 mg QD
Arm/Group Description	Febuxostat 80 mg, orally, once daily for up to 52 weeks.	Febuxostat 120 mg, orally, once daily for up to 52 weeks.	Allopurinol 300 mg, orally, once daily for up to 52 weeks.
Measure Participants	186	159	199
Mean (Standard Deviation) [percent change from baseline]	-46.3 (15.76)	-53.5 (18.20)	-34.8 (12.92)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Febuxostat 80 mg QD, Allopurinol 300 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	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.
	Method	ANOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Febuxostat 120 mg QD, Allopurinol 300 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	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.
	Method	ANOVA
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Febuxostat 80 mg QD, Febuxostat 120 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	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.
	Method	ANOVA
	Comments

6. Secondary Outcome

Title	Percent Change From Baseline in Serum Urate Levels at Week 52.
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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Febuxostat 80 mg QD	Febuxostat 120 mg QD	Allopurinol 300 mg QD
Arm/Group Description	Febuxostat 80 mg, orally, once daily for up to 52 weeks.	Febuxostat 120 mg, orally, once daily for up to 52 weeks.	Allopurinol 300 mg, orally, once daily for up to 52 weeks.
Measure Participants	159	145	178
Mean (Standard Deviation) [percent change from baseline]	-47.7 (17.50)	-53.0 (19.31)	-34.8 (13.56)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Febuxostat 80 mg QD, Allopurinol 300 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	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.
	Method	ANOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Febuxostat 120 mg QD, Allopurinol 300 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	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.
	Method	ANOVA
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Febuxostat 80 mg QD, Febuxostat 120 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.006
	Comments	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.
	Method	ANOVA
	Comments

7. Secondary Outcome

Title	Percent Change From Baseline in Serum Urate Levels at Final Visit
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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Febuxostat 80 mg QD	Febuxostat 120 mg QD	Allopurinol 300 mg QD
Arm/Group Description	Febuxostat 80 mg, orally, once daily for up to 52 weeks.	Febuxostat 120 mg, orally, once daily for up to 52 weeks.	Allopurinol 300 mg, orally, once daily for up to 52 weeks.
Measure Participants	249	242	242
Mean (Standard Deviation) [percent change from baseline]	-44.7 (19.10)	-51.5 (19.91)	-33.0 (15.33)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Febuxostat 80 mg QD, Allopurinol 300 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	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.
	Method	ANOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Febuxostat 120 mg QD, Allopurinol 300 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	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.
	Method	ANOVA
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Febuxostat 80 mg QD, Febuxostat 120 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	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.
	Method	ANOVA
	Comments

8. Secondary Outcome

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.
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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Febuxostat 80 mg QD	Febuxostat 120 mg QD	Allopurinol 300 mg QD
Arm/Group Description	Febuxostat 80 mg, orally, once daily for up to 52 weeks.	Febuxostat 120 mg, orally, once daily for up to 52 weeks.	Allopurinol 300 mg, orally, once daily for up to 52 weeks.
Measure Participants	36	28	33
Median (Inter-Quartile Range) [percent change from baseline]	-29.5	-49.5	-28.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Febuxostat 80 mg QD, Allopurinol 300 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	>0.999
	Comments	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.
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Febuxostat 120 mg QD, Allopurinol 300 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.011
	Comments	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.
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Febuxostat 80 mg QD, Febuxostat 120 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.024
	Comments	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.
	Method	Wilcoxon (Mann-Whitney)
	Comments

9. Secondary Outcome

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.
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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Febuxostat 80 mg QD	Febuxostat 120 mg QD	Allopurinol 300 mg QD
Arm/Group Description	Febuxostat 80 mg, orally, once daily for up to 52 weeks.	Febuxostat 120 mg, orally, once daily for up to 52 weeks.	Allopurinol 300 mg, orally, once daily for up to 52 weeks.
Measure Participants	32	26	30
Median (Inter-Quartile Range) [percent change from baseline]	-83.4	-65.5	-49.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Febuxostat 80 mg QD, Allopurinol 300 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.083
	Comments	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.
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Febuxostat 120 mg QD, Allopurinol 300 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.164
	Comments	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.
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Febuxostat 80 mg QD, Febuxostat 120 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.619
	Comments	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.
	Method	Wilcoxon (Mann-Whitney)
	Comments

10. Secondary Outcome

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.
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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Febuxostat 80 mg QD	Febuxostat 120 mg QD	Allopurinol 300 mg QD
Arm/Group Description	Febuxostat 80 mg, orally, once daily for up to 52 weeks.	Febuxostat 120 mg, orally, once daily for up to 52 weeks.	Allopurinol 300 mg, orally, once daily for up to 52 weeks.
Measure Participants	50	51	44
Median (Inter-Quartile Range) [percent change from baseline]	-51.7	-43.8	-39.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Febuxostat 80 mg QD, Allopurinol 300 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.080
	Comments	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.
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Febuxostat 120 mg QD, Allopurinol 300 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.372
	Comments	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.
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Febuxostat 80 mg QD, Febuxostat 120 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.246
	Comments	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.
	Method	Wilcoxon (Mann-Whitney)
	Comments

11. Secondary Outcome

Title	Change From Baseline in Total Number of Tophi at Week 28 in Subjects With Palpable Tophi at Screening.
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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Febuxostat 80 mg QD	Febuxostat 120 mg QD	Allopurinol 300 mg QD
Arm/Group Description	Febuxostat 80 mg, orally, once daily for up to 52 weeks.	Febuxostat 120 mg, orally, once daily for up to 52 weeks.	Allopurinol 300 mg, orally, once daily for up to 52 weeks.
Measure Participants	38	30	37
Median (Inter-Quartile Range) [number of tophi]	0.0	0.0	0.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Febuxostat 80 mg QD, Allopurinol 300 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.674
	Comments	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.
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Febuxostat 120 mg QD, Allopurinol 300 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.320
	Comments	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.
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Febuxostat 80 mg QD, Febuxostat 120 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.411
	Comments	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.
	Method	Wilcoxon (Mann-Whitney)
	Comments

12. Secondary Outcome

Title	Change From Baseline in Total Number of Tophi at Week 52 in Subjects With Palpable Tophi at Screening.
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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Febuxostat 80 mg QD	Febuxostat 120 mg QD	Allopurinol 300 mg QD
Arm/Group Description	Febuxostat 80 mg, orally, once daily for up to 52 weeks.	Febuxostat 120 mg, orally, once daily for up to 52 weeks.	Allopurinol 300 mg, orally, once daily for up to 52 weeks.
Measure Participants	33	28	35
Median (Inter-Quartile Range) [number of tophi]	0.0	-1.0	0.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Febuxostat 80 mg QD, Allopurinol 300 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.507
	Comments	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.
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Febuxostat 120 mg QD, Allopurinol 300 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.188
	Comments	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.
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Febuxostat 80 mg QD, Febuxostat 120 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.362
	Comments	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.
	Method	Wilcoxon (Mann-Whitney)
	Comments

13. Secondary Outcome

Title	Change From Baseline in Total Number of Tophi at Final Visit in Subjects With Palpable Tophi at Screening.
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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Febuxostat 80 mg QD	Febuxostat 120 mg QD	Allopurinol 300 mg QD
Arm/Group Description	Febuxostat 80 mg, orally, once daily for up to 52 weeks.	Febuxostat 120 mg, orally, once daily for up to 52 weeks.	Allopurinol 300 mg, orally, once daily for up to 52 weeks.
Measure Participants	52	53	47
Median (Inter-Quartile Range) [number of tophi]	0.0	0.0	0.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Febuxostat 80 mg QD, Allopurinol 300 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.657
	Comments	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.
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Febuxostat 120 mg QD, Allopurinol 300 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.444
	Comments	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.
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Febuxostat 80 mg QD, Febuxostat 120 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.719
	Comments	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.
	Method	Wilcoxon (Mann-Whitney)
	Comments

14. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Analysis was performed on the ITT subjects who had at least one dose of study drug between Weeks 8 and 52.

Arm/Group Title	Febuxostat 80 mg QD	Febuxostat 120 mg QD	Allopurinol 300 mg QD
Arm/Group Description	Febuxostat 80 mg, orally, once daily for up to 52 weeks.	Febuxostat 120 mg, orally, once daily for up to 52 weeks.	Allopurinol 300 mg, orally, once daily for up to 52 weeks.
Measure Participants	228	215	234
Number [percentage of subjects]	64	70	64

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Febuxostat 80 mg QD, Allopurinol 300 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	>0.999
	Comments	Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Febuxostat 120 mg QD, Allopurinol 300 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.229
	Comments	Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
	Method	Fisher Exact
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Febuxostat 80 mg QD, Febuxostat 120 mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.266
	Comments	Statistical significance was determined at 0.05 level without adjustment for multiple comparisons.
	Method	Fisher Exact
	Comments

Adverse Events

Arm/Group Title	Febuxostat 80 mg QD		Febuxostat 120 mg QD		Allopurinol 300 mg QD
Arm/Group Description	Febuxostat 80 mg, orally, once daily for up to 52 weeks.		Febuxostat 120 mg, orally, once daily for up to 52 weeks.		Allopurinol 300 mg, orally, once daily for up to 52 weeks.
All Cause Mortality
	Febuxostat 80 mg QD		Febuxostat 120 mg QD		Allopurinol 300 mg QD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Febuxostat 80 mg QD		Febuxostat 120 mg QD		Allopurinol 300 mg QD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/256 (3.9%)		19/251 (7.6%)		18/253 (7.1%)
Cardiac disorders
Cardiac Disorders not elsewhere classified (NEC)	0/256 (0%)		0/251 (0%)		1/253 (0.4%)
Coronary Artery Disorders NEC	0/256 (0%)		0/251 (0%)		4/253 (1.6%)
Heart Failures NEC	3/256 (1.2%)		1/251 (0.4%)		0/253 (0%)
Ischaemic Coronary Artery Disorders NEC	3/256 (1.2%)		2/251 (0.8%)		2/253 (0.8%)
Rate and Rhythm Disorders NEC	0/256 (0%)		0/251 (0%)		1/253 (0.4%)
Supraventricular Arrhythmias	1/256 (0.4%)		1/251 (0.4%)		0/253 (0%)
Ventricular Arrhythmias and Cardiac Arrest	0/256 (0%)		2/251 (0.8%)		1/253 (0.4%)
Gastrointestinal disorders
Acute and Chronic Pancreatitis	0/256 (0%)		1/251 (0.4%)		0/253 (0%)
Gastrointestinal Fistulae	0/256 (0%)		0/251 (0%)		1/253 (0.4%)
Gastrointestinal Ulcers and Perforation, Site Unspecified	0/256 (0%)		0/251 (0%)		1/253 (0.4%)
Intestinal Haemorrhages	0/256 (0%)		1/251 (0.4%)		0/253 (0%)
Intestinal Ulcers and Perforation NEC	0/256 (0%)		1/251 (0.4%)		0/253 (0%)
Peritoneal and Retroperitoneal Haemorrhages	1/256 (0.4%)		0/251 (0%)		0/253 (0%)
Umbilical Hernias	0/256 (0%)		0/251 (0%)		1/253 (0.4%)
General disorders
Febrile Disorders	0/256 (0%)		1/251 (0.4%)		0/253 (0%)
Immune system disorders
Allergies to Food, Food Additives, Drugs and Other Chemicals	1/256 (0.4%)		0/251 (0%)		0/253 (0%)
Infections and infestations
Abdominal and Gastrointestinal Infections	0/256 (0%)		1/251 (0.4%)		2/253 (0.8%)
Infections NEC	1/256 (0.4%)		0/251 (0%)		0/253 (0%)
Lower Respiratory Tract and Lung Infections	0/256 (0%)		1/251 (0.4%)		0/253 (0%)
Skin Structures and Soft Tissue Infections	0/256 (0%)		1/251 (0.4%)		0/253 (0%)
Staphylococcal Infections	0/256 (0%)		0/251 (0%)		1/253 (0.4%)
Urinary Tract Infections	0/256 (0%)		1/251 (0.4%)		0/253 (0%)
Viral Infections NEC	0/256 (0%)		1/251 (0.4%)		0/253 (0%)
Injury, poisoning and procedural complications
Chest and Lung Injuries NEC	1/256 (0.4%)		0/251 (0%)		0/253 (0%)
Non-Site Specific Injuries NEC	1/256 (0.4%)		0/251 (0%)		0/253 (0%)
Site Specific Injuries NEC	1/256 (0.4%)		0/251 (0%)		0/253 (0%)
Investigations
Coagulation and Bleeding Analyses	1/256 (0.4%)		0/251 (0%)		0/253 (0%)
Musculoskeletal and connective tissue disorders
Joint Related Signs and Symptoms	1/256 (0.4%)		0/251 (0%)		0/253 (0%)
Musculoskeletal and Connective Tissue Signs and Symptoms NEC	0/256 (0%)		0/251 (0%)		1/253 (0.4%)
Osteoarthropathies	0/256 (0%)		0/251 (0%)		1/253 (0.4%)
Spine and Neck Deformities	1/256 (0.4%)		0/251 (0%)		0/253 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colonic Neoplasms Malignant	0/256 (0%)		1/251 (0.4%)		0/253 (0%)
Prostatic Neoplasms Malignant	0/256 (0%)		1/251 (0.4%)		0/253 (0%)
Testicular Neoplasms Malignant	0/256 (0%)		0/251 (0%)		1/253 (0.4%)
Nervous system disorders
Central Nervous System Vascular Disorders NEC	0/256 (0%)		1/251 (0.4%)		0/253 (0%)
Central nervous system Hemorrhages & Cerebrovascular Accidents	0/256 (0%)		1/251 (0.4%)		0/253 (0%)
Cervical Spinal Cord and Nerve Root Disorders	0/256 (0%)		1/251 (0.4%)		0/253 (0%)
Disturbances in Consciousness NEC	0/256 (0%)		1/251 (0.4%)		1/253 (0.4%)
Encephalopathies NEC	0/256 (0%)		1/251 (0.4%)		0/253 (0%)
Renal and urinary disorders
Renal Failure and Impairment	2/256 (0.8%)		0/251 (0%)		0/253 (0%)
Renal Lithiasis	0/256 (0%)		0/251 (0%)		1/253 (0.4%)
Respiratory, thoracic and mediastinal disorders
Bronchospasm and Obstruction	1/256 (0.4%)		0/251 (0%)		0/253 (0%)
Pneumothorax and Pleural Effusions NEC	1/256 (0.4%)		0/251 (0%)		0/253 (0%)
Pulmonary Thrombotic and Embolic Conditions	0/256 (0%)		1/251 (0.4%)		0/253 (0%)
Respiratory Failures (Excluding [Excl] Neonatal)	1/256 (0.4%)		1/251 (0.4%)		0/253 (0%)
Vascular disorders
Peripheral Embolism and Thrombosis	0/256 (0%)		1/251 (0.4%)		0/253 (0%)
Other (Not Including Serious) Adverse Events
	Febuxostat 80 mg QD		Febuxostat 120 mg QD		Allopurinol 300 mg QD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	164/256 (64.1%)		145/251 (57.8%)		167/253 (66%)
Gastrointestinal disorders
Diarrhoea (Excl Infective)	27/256 (10.5%)		25/251 (10%)		16/253 (6.3%)
Nausea and Vomiting Symptoms	19/256 (7.4%)		13/251 (5.2%)		8/253 (3.2%)
General disorders
Oedema NEC	18/256 (7%)		8/251 (3.2%)		8/253 (3.2%)
Infections and infestations
Influenza Viral Infections	12/256 (4.7%)		13/251 (5.2%)		12/253 (4.7%)
Lower Respiratory Tract and Lung Infections	13/256 (5.1%)		7/251 (2.8%)		8/253 (3.2%)
Upper Respiratory Tract Infections	77/256 (30.1%)		53/251 (21.1%)		72/253 (28.5%)
Injury, poisoning and procedural complications
Limb Injuries NEC (Including [Incl] Traumatic Amputation)	12/256 (4.7%)		10/251 (4%)		11/253 (4.3%)
Non-Site Specific Injuries NEC	11/256 (4.3%)		10/251 (4%)		12/253 (4.7%)
Investigations
Liver Function Analyses	13/256 (5.1%)		16/251 (6.4%)		12/253 (4.7%)
Musculoskeletal and connective tissue disorders
Joint Related Signs and Symptoms	39/256 (15.2%)		32/251 (12.7%)		37/253 (14.6%)
Musculoskeletal and Connective Tissue Signs and Symptoms NEC	35/256 (13.7%)		38/251 (15.1%)		37/253 (14.6%)
Nervous system disorders
Headache NEC	23/256 (9%)		23/251 (9.2%)		22/253 (8.7%)
Neurological Signs and Symptoms NEC	17/256 (6.6%)		9/251 (3.6%)		7/253 (2.8%)
Respiratory, thoracic and mediastinal disorders
Upper Respiratory Tract Signs and Symptoms	13/256 (5.1%)		10/251 (4%)		17/253 (6.7%)
Vascular disorders
Vascular Hypertensive Disorders NEC	7/256 (2.7%)		10/251 (4%)		14/253 (5.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

No publication related to study results will be published prior to publication of a multi-center report submitted for publication within 18 months after conclusion or termination of a study. Results publications will be submitted to sponsor for review 60 days in advance of publication. Sponsor can require removal of confidential information unrelated to study results. Sponsor can embargo a proposed publication for another 60 days to preserve intellectual property.