FOCUS: Long-Term Safety of Febuxostat in Subjects With Gout.

• Sponsor: Takeda (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00174941
• Collaborator: (none)
• Enrollment: 116
• Arms: 3
• Duration (Months): 69

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the long-term safety of febuxostat, once daily (QD), in maintaining serum urate levels within clinically acceptable levels in subjects with gout.

Condition or Disease	Intervention/Treatment	Phase
Gout	Drug: Febuxostat; Drug: Febuxostat; Drug: Febuxostat	Phase 2

Detailed Description

Uric acid is the end product of purine degradation in humans. Hyperuricemia, a urate concentration in serum exceeding the limit of urate solubility (approximately 7.0 milligrams per deciliter [mg/dL]), is a common biochemical abnormality. Aberrations in any of the multiple mechanisms involved in the production and/or excretion of uric acid may increase serum urate concentrations, with persistent hyperuricemia as a marker for extracellular fluid monosodium urate supersaturation. As such, hyperuricemia is a necessary (but often not sufficient) risk factor for monosodium urate crystal deposition in tissues and is the fundamental pathophysiological process underlying the clinical manifestations of gout, which is a chronic disease characterized by urate crystal formation and deposition in joints and bones. Gout may progress from episodic attacks of acute inflammatory arthritis to a disabling chronic disorder characterized by deforming arthropathy; destructive deposits of urate crystals (tophi) in bones, joints, and other organs; structural and functional renal impairment due to interstitial urate crystal deposition; and urinary tract stones composed entirely or in part of uric acid crystals. Management of gout requires chronic treatment aimed at lowering serum urate into a subsaturating range (usually <6.0 mg/dL) in which crystal formation and deposition are prevented or reversed.

Febuxostat (TMX-67) is a non-purine selective xanthine oxidase inhibitor being developed as an orally administered agent for management of hyperuricemia in patients with gout.

Subjects who want to participate in this study will have successfully completed study TMX-00-004 (NCT00174967).

All participants will initially receive an 80 mg dose. Dose titrations will occur in order to obtain and maintain clinically acceptable serum urate levels.

Study Design

• Study Type: Interventional
• Actual Enrollment: 116 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II, Open-Label Study, to Assess the Long-Term Safety of Oral TMX-67 in Subjects With Gout
• Study Start Date: Mar 1, 2001
• Actual Primary Completion Date: Dec 1, 2006
• Actual Study Completion Date: Dec 1, 2006

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	Drug: Febuxostat; Febuxostat 40 mg, tablets, orally, once daily, based on serum urate level.; Other Names: TMX-67 Tei-6720 Uloric
Experimental: 2	Drug: Febuxostat; Febuxostat 80 mg, tablets, orally, once daily, based on serum urate level.; Other Names: TMX-67 Tei-6720 Uloric
Experimental: 3	Drug: Febuxostat; Febuxostat 120 mg, tablets, orally, once daily, based on serum urate level.; Other Names: TMX-67 Tei-6720 Uloric

Outcome Measures

Primary Outcome Measures

1. Percentage of Subjects Whose Serum Urate Level Decreases to or is Maintained at <6.0 mg/dL at Month 6 Visit. [Month 6]

   Serum urate values were obtained at the Month 6 visit. The percentage of subjects whose serum urate was <6.0 mg/dL at the Month 6 visit was summarized.

2. Percentage of Subjects Whose Serum Urate Level Decreases to or is Maintained at <6.0 mg/dL at Month 12 Visit. [Month 12]

   Serum urate values were obtained at the Month 12 visit. The percentage of subjects whose serum urate was <6.0 mg/dL at the Month 12 visit was summarized.

3. Percentage of Subjects Whose Serum Urate Level Decreases to or is Maintained at <6.0 mg/dL at Month 18 Visit. [Month 18]

   Serum urate values were obtained at the Month 18 visit. The percentage of subjects whose serum urate was <6.0 mg/dL at the Month 18 visit was summarized.

4. Percentage of Subjects Whose Serum Urate Level Decreases to or is Maintained at <6.0 mg/dL at Month 24 Visit. [Month 24]

   Serum urate values were obtained at the Month 24 visit. The percentage of subjects whose serum urate was <6.0 mg/dL at the Month 24 visit was summarized.

5. Percentage of Subjects Whose Serum Urate Level Decreases to or is Maintained at <6.0 mg/dL at Month 36 Visit. [Month 36]

   Serum urate values were obtained at the Month 36 visit. The percentage of subjects whose serum urate was <6.0 mg/dL at the Month 36 visit was summarized.

6. Percentage of Subjects Whose Serum Urate Level Decreases to or is Maintained at <6.0 mg/dL at Month 48 Visit. [Month 48]

   Serum urate values were obtained at the Month 48 visit. The percentage of subjects whose serum urate was <6.0 mg/dL at the Month 48 visit was summarized.

7. Percentage of Subjects Whose Serum Urate Level Decreases to or is Maintained at <6.0 mg/dL at Month 60 Visit. [Month 60]

   Serum urate values were obtained at the Month 60 visit. The percentage of subjects whose serum urate was <6.0 mg/dL at the Month 60 visit was summarized.

8. Percentage of Subjects Whose Serum Urate Level Decreases to or is Maintained at <6.0 mg/dL at Final Visit. [Last Visit on treatment (up to 66 months).]

   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.

Secondary Outcome Measures

1. Percent Change in Serum Urate Levels From Baseline at Month 6 Visit. [Baseline and Month 6]

   Serum urate values were obtained at the Month 6 visit. The percent change in serum urate from baseline to the Month 6 visit was summarized.

2. Percent Change in Serum Urate Levels From Baseline at Month 12 Visit. [Baseline and Month 12]

   Serum urate values were obtained at the Month 12 visit. The percent change in serum urate from baseline to the Month 12 visit was summarized.

3. Percent Change in Serum Urate Levels From Baseline at Month 18 Visit. [Baseline and Month 18]

   Serum urate values were obtained at the Month 18 visit. The percent change in serum urate from baseline to the Month 18 visit was summarized.

4. Percent Change in Serum Urate Levels From Baseline at Month 24 Visit. [Baseline and Month 24]

   Serum urate values were obtained at the Month 24 visit. The percent change in serum urate from baseline to the Month 24 visit was summarized.

5. Percent Change in Serum Urate Levels From Baseline at Month 36 Visit. [Baseline and Month 36]

   Serum urate values were obtained at the Month 36 visit. The percent change in serum urate from baseline to the Month 36 visit was summarized.

6. Percent Change in Serum Urate Levels From Baseline at Month 48 Visit. [Baseline and Month 48]

   Serum urate values were obtained at the Month 48 visit. The percent change in serum urate from baseline to the Month 48 visit was summarized.

7. Percent Change in Serum Urate Levels From Baseline at Month 60 Visit. [Baseline and Month 60]

   The secondary outcome was the mean percent change from baseline to Month 60 visit as assessed by serum urate levels collected at baseline and at the Month 60 visit by dose at observation.

8. Percent Change in Serum Urate Levels From Baseline at Final Visit. [Baseline and Last Visit on treatment (up to 66 months).]

   The percent change in serum urate from baseline to the final visit was summarized. The final visit was the last visit at which a serum urate value was collected.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Hyperuricemia (serum uric acid ≥8.0 mg/dL upon entering parent study TMX-00-004).

• Must meet American College of Rheumatology criteria for gout.

• Must have adequate renal function (serum creatinine <1.5 mg/dL).

• Must have completed four weeks of double-blind dosing in Study TMX-00-004.

• Must not have experienced any serious study drug-related Adverse Events in Study TMX 00-004.

• Females of childbearing potential who are sexually active must agree to use adequate contraception, and can neither be pregnant nor lactating from Screening throughout the duration of the study.

Exclusion Criteria:

• History of xanthinuria

• Alcohol consumption >14/week

• Has a History of significant concomitant illness

• Has active liver disease.

• Has a body mass index greater than 50 kg/m2

• Any other significant medical condition that would interfere with the treatment, safety or compliance with the protocol, as defined by the investigator.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Takeda

Investigators

• Study Chair: Medical Director, Takeda

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Uloric Package Insert

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00174941
• Other Study ID Numbers: TMX-01-005; U1111-1114-2039
• First Posted: Sep 15, 2005
• Last Update Posted: Jan 27, 2011
• Last Verified: Jan 1, 2011

• Keywords provided by , ,: Uric acid; xanthine oxidase; tophi; Drug Therapy
• Additional relevant MeSH terms: Gout; Febuxostat

Study Results

Participant Flow

Recruitment Details	Subjects were enrolled at 23 investigational sites in the United States from 21 March 2001 to 29 December 2006
Pre-assignment Detail	Subjects were to have completed 4 weeks of double-blind dosing in Study TMX-00-004 (NCT00174967) before enrollment in once daily (QD) treatment groups. Dose titrations will occur in order to obtain and maintain clinically acceptable serum urate levels.

Arm/Group Title	Febuxostat 40 mg QD	Febuxostat 80 mg QD	Febuxostat 120 mg QD	Total Febuxostat
Arm/Group Description	Febuxostat 40 mg, orally, once daily, based on serum urate level.	Febuxostat 80 mg, orally, once daily, based on serum urate level.	Febuxostat 120 mg, orally, once daily, based on serum urate level.
Period Title: Overall Study
STARTED	8	79	29	116
COMPLETED	6	41	11	58
NOT COMPLETED	2	38	18	58

Baseline Characteristics

Arm/Group Title	Febuxostat 40 mg QD	Febuxostat 80 mg QD	Febuxostat 120 mg QD	Total
Arm/Group Description	Febuxostat 40 mg orally, once daily, based on serum urate level.	Febuxostat 80 mg, orally, once daily, based on serum urate level	Febuxostat 120 mg, orally, once daily, based on serum urate level	Total of all reporting groups
Overall Participants	8	79	29	116
Age, Customized (Subjects) [Number]
<45 years	2	20	9	31
45 to <65 years	4	40	15	59
≥65 years	2	19	5	26
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.5 (11.44)	53.9 (12.85)	51.3 (13.01)	53.3 (12.74)
Sex: Female, Male (Count of Participants)
Female	0 0%	9 11.4%	2 6.9%	11.0 9.5%
Male	8 100%	70 88.6%	27 93.1%	105.0 90.5%
History of Kidney Stone (Subjects) [Number]
Yes	0	11	3	14
No	8	68	26	102
Presence of Tophus (Subjects) [Number]
Yes	1	13	12	26
No	7	66	17	90
Race/Ethnicity (Subjects) [Number]
Asian	0	0	2	2
Black or African American	1	5	3	9
White	7	71	21	99
Hispanic	0	2	1	3
Other	0	1	2	3
Renal Function (Subjects) [Number]
Normal	3	33	12	48
Impaired	5	46	17	68
Urine Uric Acid (Subjects) [Number]
Underexcretor	5	62	21	88
Overproducer	3	16	7	26
Missing	0	1	1	2
Body Mass Index (kiligram per meter² (kg/m²)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kiligram per meter² (kg/m²)]	28.4 (2.78)	32.9 (5.28)	33.9 (6.82)	32.9 (5.69)
Serum Urate (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	9.58 (1.18)	9.48 (1.04)	10.23 (1.74)	9.7 (1.30)

Outcome Measures

1. Primary Outcome

Title	Percentage of Subjects Whose Serum Urate Level Decreases to or is Maintained at <6.0 mg/dL at Month 6 Visit.
Description	Serum urate values were obtained at the Month 6 visit. The percentage of subjects whose serum urate was <6.0 mg/dL at the Month 6 visit was summarized.
Time Frame	Month 6

Outcome Measure Data

Analysis Population Description

Subjects with a serum urate value at the Month 6 visit were included in the analysis. Results were summarized by the dose the subject was receiving at the Month 6 visit. Subjects must have been receiving that dose for at least 14 days prior to the visit.

Arm/Group Title	Febuxostat 40 mg QD	Febuxostat 80 mg QD	Febuxostat 120 mg QD	Total Febuxostat
Arm/Group Description	Febuxostat 40 mg, orally, once daily, based on serum urate level.	Febuxostat 80 mg, orally, once daily, based on serum urate level.	Febuxostat 120 mg, orally, once daily, based on serum urate level.
Measure Participants	10	58	17	85
Number [percentage of subjects]	50	93	65	82

2. Secondary Outcome

Title	Percent Change in Serum Urate Levels From Baseline at Month 6 Visit.
Description	Serum urate values were obtained at the Month 6 visit. The percent change in serum urate from baseline to the Month 6 visit was summarized.
Time Frame	Baseline and Month 6

Outcome Measure Data

Analysis Population Description

Subjects with a serum urate value at the Month 6 visit were included in the analysis. Results were summarized by the dose the subject was receiving at the Month 6 visit. Subjects must have been receiving that dose for at least 14 days prior to the visit.

Arm/Group Title	Febuxostat 40 mg QD	Febuxostat 80 mg QD	Febuxostat 120 mg QD	Total Febuxostat
Arm/Group Description	Febuxostat 40 mg, orally, once daily, based on serum urate level.	Febuxostat 80 mg, orally, once daily, based on serum urate level.	Febuxostat 120 mg, orally, once daily, based on serum urate level.
Measure Participants	10	58	17	85
Mean (Standard Deviation) [percent change from baseline]	-35.9 (9.55)	-50.6 (9.84)	-47.6 (19.6)	-48.3 (13.07)

3. Primary Outcome

Title	Percentage of Subjects Whose Serum Urate Level Decreases to or is Maintained at <6.0 mg/dL at Month 12 Visit.
Description	Serum urate values were obtained at the Month 12 visit. The percentage of subjects whose serum urate was <6.0 mg/dL at the Month 12 visit was summarized.
Time Frame	Month 12

Outcome Measure Data

Analysis Population Description

Subjects with a serum urate value at the Month 12 visit were included in the analysis. Results were summarized by the dose the subject was receiving at the Month 12 visit. Subjects must have been receiving that dose for at least 14 days prior to the visit.

Arm/Group Title	Febuxostat 40 mg QD	Febuxostat 80 mg QD	Febuxostat 120 mg QD	Total Febuxostat
Arm/Group Description	Febuxostat 40 mg, orally, once daily, based on serum urate level.	Febuxostat 80 mg, orally, once daily, based on serum urate level.	Febuxostat 120 mg, orally, once daily, based on serum urate level.
Measure Participants	7	55	18	80
Number [percentage of subjects]	57	85	67	79

4. Primary Outcome

Title	Percentage of Subjects Whose Serum Urate Level Decreases to or is Maintained at <6.0 mg/dL at Month 18 Visit.
Description	Serum urate values were obtained at the Month 18 visit. The percentage of subjects whose serum urate was <6.0 mg/dL at the Month 18 visit was summarized.
Time Frame	Month 18

Outcome Measure Data

Analysis Population Description

Subjects with a serum urate value at the Month 18 visit were included in the analysis. Results were summarized by the dose the subject was receiving at the Month 18 visit. Subjects must have been receiving that dose for at least 14 days prior to the visit.

Arm/Group Title	Febuxostat 40 mg QD	Febuxostat 80 mg QD	Febuxostat 120 mg QD	Total Febuxostat
Arm/Group Description	Febuxostat 40 mg, orally, once daily, based on serum urate level.	Febuxostat 80 mg, orally, once daily, based on serum urate level.	Febuxostat 120 mg, orally, once daily, based on serum urate level.
Measure Participants	8	50	14	72
Number [percentage of subjects]	50	82	57	74

5. Primary Outcome

Title	Percentage of Subjects Whose Serum Urate Level Decreases to or is Maintained at <6.0 mg/dL at Month 24 Visit.
Description	Serum urate values were obtained at the Month 24 visit. The percentage of subjects whose serum urate was <6.0 mg/dL at the Month 24 visit was summarized.
Time Frame	Month 24

Outcome Measure Data

Analysis Population Description

Subjects with a serum urate value at the Month 24 visit were included in the analysis. Results were summarized by the dose the subject was receiving at the Month 24 visit. Subjects must have been receiving that dose for at least 14 days prior to the visit.

Arm/Group Title	Febuxostat 40 mg QD	Febuxostat 80 mg QD	Febuxostat 120 mg QD	Total Febuxostat
Arm/Group Description	Febuxostat 40 mg, orally, once daily, based on serum urate level.	Febuxostat 80 mg, orally, once daily, based on serum urate level.	Febuxostat 120 mg, orally, once daily, based on serum urate level.
Measure Participants	8	49	13	70
Number [percentage of subjects]	63	76	92	77

6. Primary Outcome

Title	Percentage of Subjects Whose Serum Urate Level Decreases to or is Maintained at <6.0 mg/dL at Month 36 Visit.
Description	Serum urate values were obtained at the Month 36 visit. The percentage of subjects whose serum urate was <6.0 mg/dL at the Month 36 visit was summarized.
Time Frame	Month 36

Outcome Measure Data

Analysis Population Description

Subjects with a serum urate value at the Month 36 visit were included in the analysis. Results were summarized by the dose the subject was receiving at the Month 36 visit. Subjects must have been receiving that dose for at least 14 days prior to the visit.

Arm/Group Title	Febuxostat 40 mg QD	Febuxostat 80 mg QD	Febuxostat 120 mg QD	Total Febuxostat
Arm/Group Description	Febuxostat 40 mg, orally, once daily, based on serum urate level.	Febuxostat 80 mg, orally, once daily, based on serum urate level.	Febuxostat 120 mg, orally, once daily, based on serum urate level.
Measure Participants	6	45	13	64
Number [percentage of subjects]	67	84	92	84

7. Primary Outcome

Title	Percentage of Subjects Whose Serum Urate Level Decreases to or is Maintained at <6.0 mg/dL at Month 48 Visit.
Description	Serum urate values were obtained at the Month 48 visit. The percentage of subjects whose serum urate was <6.0 mg/dL at the Month 48 visit was summarized.
Time Frame	Month 48

Outcome Measure Data

Analysis Population Description

Subjects with a serum urate value at the Month 48 visit were included in the analysis. Results were summarized by the dose the subject was receiving at the Month 48 visit. Subjects must have been receiving that dose for at least 14 days prior to the visit.

Arm/Group Title	Febuxostat 40 mg QD	Febuxostat 80 mg QD	Febuxostat 120 mg QD	Total Febuxostat
Arm/Group Description	Febuxostat 40 mg, orally, once daily, based on serum urate level.	Febuxostat 80 mg, orally, once daily, based on serum urate level.	Febuxostat 120 mg, orally, once daily, based on serum urate level.
Measure Participants	6	39	13	58
Number [percentage of subjects]	83	92	85	90

8. Primary Outcome

Title	Percentage of Subjects Whose Serum Urate Level Decreases to or is Maintained at <6.0 mg/dL at Month 60 Visit.
Description	Serum urate values were obtained at the Month 60 visit. The percentage of subjects whose serum urate was <6.0 mg/dL at the Month 60 visit was summarized.
Time Frame	Month 60

Outcome Measure Data

Analysis Population Description

Subjects with a serum urate value at the Month 60 visit were included in the analysis. Results were summarized by the dose the subject was receiving at the Month 60 visit. Subjects must have been receiving that dose for at least 14 days prior to the visit.

Arm/Group Title	Febuxostat 40 mg QD	Febuxostat 80 mg QD	Febuxostat 120 mg QD	Total Febuxostat
Arm/Group Description	Febuxostat 40 mg, orally, once daily, based on serum urate level.	Febuxostat 80 mg, orally, once daily, based on serum urate level.	Febuxostat 120 mg, orally, once daily, based on serum urate level.
Measure Participants	6	41	11	58
Number [percentage of subjects]	100	93	91	93

9. Primary Outcome

Title	Percentage of Subjects Whose Serum Urate Level Decreases to or is Maintained at <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.
Time Frame	Last Visit on treatment (up to 66 months).

Outcome Measure Data

Analysis Population Description

Two subjects who did not have any post-baseline Serum Urate Level measurements were excluded from this analysis. Results were summarized by the dose the subject was receiving at the time of the final visit. Subjects must have been receiving that dose for at least 14 days prior to the visit.

Arm/Group Title	Febuxostat 40 mg QD	Febuxostat 80 mg QD	Febuxostat 120 mg QD	Total Febuxostat
Arm/Group Description	Febuxostat 40 mg, orally, once daily, based on serum urate level.	Febuxostat 80 mg, orally, once daily, based on serum urate level.	Febuxostat 120 mg, orally, once daily, based on serum urate level.
Measure Participants	8	79	27	114
Number [percentage of subjects]	100	82	81	83

10. Secondary Outcome

Title	Percent Change in Serum Urate Levels From Baseline at Month 12 Visit.
Description	Serum urate values were obtained at the Month 12 visit. The percent change in serum urate from baseline to the Month 12 visit was summarized.
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

Subjects with a serum urate value at the Month 12 visit were included in the analysis. Results were summarized by the dose the subject was receiving at the Month 12 visit. Subjects must have been receiving that dose for at least 14 days prior to the visit.

Arm/Group Title	Febuxostat 40 mg QD	Febuxostat 80 mg QD	Febuxostat 120 mg QD	Total Febuxostat
Arm/Group Description	Febuxostat 40 mg, orally, once daily, based on serum urate level.	Febuxostat 80 mg, orally, once daily, based on serum urate level.	Febuxostat 120 mg, orally, once daily, based on serum urate level.
Measure Participants	7	55	18	80
Mean (Standard Deviation) [percentage of subjects]	-35.0 (13.16)	-49.7 (9.26)	-49.3 (15.77)	-48.3 (11.94)

11. Secondary Outcome

Title	Percent Change in Serum Urate Levels From Baseline at Month 18 Visit.
Description	Serum urate values were obtained at the Month 18 visit. The percent change in serum urate from baseline to the Month 18 visit was summarized.
Time Frame	Baseline and Month 18

Outcome Measure Data

Analysis Population Description

Subjects with a serum urate value at the Month 18 visit were included in the analysis. Results were summarized by the dose the subject was receiving at the Month 18 visit. Subjects must have been receiving that dose for at least 14 days prior to the visit.

Arm/Group Title	Febuxostat 40 mg QD	Febuxostat 80 mg QD	Febuxostat 120 mg QD	Total Febuxostat
Arm/Group Description	Febuxostat 40 mg, orally, once daily, based on serum urate level.	Febuxostat 80 mg, orally, once daily, based on serum urate level.	Febuxostat 120 mg, orally, once daily, based on serum urate level.
Measure Participants	8	50	14	72
Mean (Standard Deviation) [percent change from baseline]	-35.5 (16.35)	-48.7 (11.12)	-39.5 (19.36)	-45.4 (14.35)

12. Secondary Outcome

Title	Percent Change in Serum Urate Levels From Baseline at Month 24 Visit.
Description	Serum urate values were obtained at the Month 24 visit. The percent change in serum urate from baseline to the Month 24 visit was summarized.
Time Frame	Baseline and Month 24

Outcome Measure Data

Analysis Population Description

Subjects with a serum urate value at the Month 24 visit were included in the analysis. Results were summarized by the dose the subject was receiving at the Month 24 visit. Subjects must have been receiving that dose for at least 14 days prior to the visit.

Arm/Group Title	Febuxostat 40 mg QD	Febuxostat 80 mg QD	Febuxostat 120 mg QD	Total Febuxostat
Arm/Group Description	Febuxostat 40 mg, orally, once daily, based on serum urate level.	Febuxostat 80 mg, orally, once daily, based on serum urate level.	Febuxostat 120 mg, orally, once daily, based on serum urate level.
Measure Participants	8	49	13	70
Mean (Standard Deviation) [percent change from baseline]	-38.9 (19.41)	-46.7 (11.59)	-54.7 (12.02)	-47.3 (13.24)

13. Secondary Outcome

Title	Percent Change in Serum Urate Levels From Baseline at Month 36 Visit.
Description	Serum urate values were obtained at the Month 36 visit. The percent change in serum urate from baseline to the Month 36 visit was summarized.
Time Frame	Baseline and Month 36

Outcome Measure Data

Analysis Population Description

Subjects with a serum urate value at the Month 36 visit were included in the analysis. Results were summarized by the dose the subject was receiving at the Month 36 visit. Subjects must have been receiving that dose for at least 14 days prior to the visit.

Arm/Group Title	Febuxostat 40 mg QD	Febuxostat 80 mg QD	Febuxostat 120 mg QD	Total Febuxostat
Arm/Group Description	Febuxostat 40 mg, orally, once daily, based on serum urate level.	Febuxostat 80 mg, orally, once daily, based on serum urate level.	Febuxostat 120 mg, orally, once daily, based on serum urate level.
Measure Participants	6	45	13	64
Mean (Standard Deviation) [percent change from baseline]	-43.0 (9.14)	-46.9 (13.35)	-56.4 (13.76)	-48.4 (13.6)

14. Secondary Outcome

Title	Percent Change in Serum Urate Levels From Baseline at Month 48 Visit.
Description	Serum urate values were obtained at the Month 48 visit. The percent change in serum urate from baseline to the Month 48 visit was summarized.
Time Frame	Baseline and Month 48

Outcome Measure Data

Analysis Population Description

Subjects with a serum urate value at the Month 48 visit were included in the analysis. Results were summarized by the dose the subject was receiving at the Month 48 visit. Subjects must have been receiving that dose for at least 14 days prior to the visit.

Arm/Group Title	Febuxostat 40 mg QD	Febuxostat 80 mg QD	Febuxostat 120 mg QD	Total Febuxostat
Arm/Group Description	Febuxostat 40 mg, orally, once daily, based on serum urate level.	Febuxostat 80 mg, orally, once daily, based on serum urate level.	Febuxostat 120 mg, orally, once daily, based on serum urate level.
Measure Participants	6	39	13	58
Mean (Standard Deviation) [percent change from baseline]	-50.0 (4.16)	-50.3 (10.61)	-53.8 (16.41)	-51.1 (11.64)

15. Secondary Outcome

Title	Percent Change in Serum Urate Levels From Baseline at Month 60 Visit.
Description	The secondary outcome was the mean percent change from baseline to Month 60 visit as assessed by serum urate levels collected at baseline and at the Month 60 visit by dose at observation.
Time Frame	Baseline and Month 60

Outcome Measure Data

Analysis Population Description

Subjects with a serum urate value at the Month 60 visit were included in the analysis. Results were summarized by the dose the subject was receiving at the Month 60 visit. Subjects must have been receiving that dose for at least 14 days prior to the visit.

Arm/Group Title	Febuxostat 40 mg QD	Febuxostat 80 mg QD	Febuxostat 120 mg QD	Total Febuxostat
Arm/Group Description	Febuxostat 40 mg, orally, once daily, based on serum urate level.	Febuxostat 80 mg, orally, once daily, based on serum urate level.	Febuxostat 120 mg, orally, once daily, based on serum urate level.
Measure Participants	6	41	11	58
Mean (Standard Deviation) [percent change from baseline]	-45.5 (8.70)	-51.1 (13.21)	-59.0 (18.74)	-52.0 (14.32)

16. Secondary Outcome

Title	Percent Change in Serum Urate Levels From Baseline at Final Visit.
Description	The percent change in serum urate from baseline to the final visit was summarized. The final visit was the last visit at which a serum urate value was collected.
Time Frame	Baseline and Last Visit on treatment (up to 66 months).

Outcome Measure Data

Analysis Population Description

Two subjects who did not have any post-baseline Serum Urate Level measurements were excluded from this analysis. Results were summarized by the dose the subject was receiving at the time of the final visit. Subjects must have been receiving that dose for at least 14 days prior to the visit.

Arm/Group Title	Febuxostat 40 mg QD	Febuxostat 80 mg QD	Febuxostat 120 mg QD	Total Febuxostat
Arm/Group Description	Febuxostat 40 mg, orally, once daily, based on serum urate level.	Febuxostat 80 mg, orally, once daily, based on serum urate level.	Febuxostat 120 mg, orally, once daily, based on serum urate level.
Measure Participants	8	79	27	114
Mean (Standard Deviation) [percent change from baseline]	-49.2 (7.10)	-47.1 (16.42)	-50.7 (19.12)	-48.1 (16.61)

Adverse Events

Arm/Group Title	Febuxostat 40 mg QD		Febuxostat 80 mg QD		Febuxostat 120 mg QD		Febuxostat Total
Arm/Group Description	Febuxostat 40 mg taken orally, once daily, based on serum urate level.		Febuxostat 80 mg, taken orally, once daily, based on serum urate level		Febuxostat 120 mg, taken orally, once daily, based on serum urate level
All Cause Mortality
	Febuxostat 40 mg QD		Febuxostat 80 mg QD		Febuxostat 120 mg QD		Febuxostat Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Febuxostat 40 mg QD		Febuxostat 80 mg QD		Febuxostat 120 mg QD		Febuxostat Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/12 (25%)		14/116 (12.1%)		4/37 (10.8%)		21/116 (18.1%)
Cardiac disorders
Cardiac Conduction Disorders	0/12 (0%)		1/116 (0.9%)		0/37 (0%)		1/116 (0.9%)
Supraventricular Arrhythmias	0/12 (0%)		5/116 (4.3%)		0/37 (0%)		5/116 (4.3%)
Gastrointestinal disorders
Duodenal and Small Intestinal Stenosis and Obstruction	0/12 (0%)		1/116 (0.9%)		0/37 (0%)		1/116 (0.9%)
Gastrointestinal Ulcers and Perforation, Site Unspecified	0/12 (0%)		1/116 (0.9%)		0/37 (0%)		1/116 (0.9%)
Intestinal Ulcers & Perforation not elsewhere classified (NEC)	1/12 (8.3%)		0/116 (0%)		0/37 (0%)		1/116 (0.9%)
General disorders
Pain and Discomfort NEC	0/12 (0%)		1/116 (0.9%)		0/37 (0%)		1/116 (0.9%)
Hepatobiliary disorders
Cholecystitis and Cholelithiasis	1/12 (8.3%)		1/116 (0.9%)		0/37 (0%)		2/116 (1.7%)
Infections and infestations
Abdominal and Gastrointestinal Infections	0/12 (0%)		1/116 (0.9%)		0/37 (0%)		1/116 (0.9%)
Lower Respiratory Tract and Lung Infections	1/12 (8.3%)		1/116 (0.9%)		0/37 (0%)		2/116 (1.7%)
Sepsis, Bacteraemia, Viraemia, and Infections	0/12 (0%)		1/116 (0.9%)		0/37 (0%)		1/116 (0.9%)
Injury, poisoning and procedural complications
Cerebral Injuries NEC	0/12 (0%)		0/116 (0%)		1/37 (2.7%)		1/116 (0.9%)
Fractures and Dislocations NEC	0/12 (0%)		0/116 (0%)		1/37 (2.7%)		1/116 (0.9%)
Non-Site Specific Injuries NEC	0/12 (0%)		1/116 (0.9%)		0/37 (0%)		1/116 (0.9%)
Radiation Injuries	0/12 (0%)		1/116 (0.9%)		0/37 (0%)		1/116 (0.9%)
Musculoskeletal and connective tissue disorders
Intervertebral Disc Disorders	0/12 (0%)		0/116 (0%)		1/37 (2.7%)		1/116 (0.9%)
Joint Related Disorders NEC	0/12 (0%)		1/116 (0.9%)		0/37 (0%)		1/116 (0.9%)
Osteoarthropathies	0/12 (0%)		1/116 (0.9%)		1/37 (2.7%)		2/116 (1.7%)
Pathological Fractures and Complications	0/12 (0%)		1/116 (0.9%)		0/37 (0%)		1/116 (0.9%)
Spine and Neck Deformities	1/12 (8.3%)		0/116 (0%)		0/37 (0%)		1/116 (0.9%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lip and Oral Cavity Neoplasms Malignant	0/12 (0%)		1/116 (0.9%)		0/37 (0%)		1/116 (0.9%)
Prostatic Neoplasms Malignant	0/12 (0%)		1/116 (0.9%)		0/37 (0%)		1/116 (0.9%)
Respiratory Tract and Pleural Neoplasms Benign NEC	0/12 (0%)		1/116 (0.9%)		0/37 (0%)		1/116 (0.9%)
Skin Neoplasms Malignant & Unspecified (Excluding Melanoma)	0/12 (0%)		0/116 (0%)		1/37 (2.7%)		1/116 (0.9%)
Nervous system disorders
Alzheimer's Disease (Including Subtypes)	0/12 (0%)		1/116 (0.9%)		0/37 (0%)		1/116 (0.9%)
Central Nervous System Hemorrhages & Cerebrovascular Accidents	1/12 (8.3%)		0/116 (0%)		0/37 (0%)		1/116 (0.9%)
Psychiatric disorders
Depressive Disorders	1/12 (8.3%)		0/116 (0%)		0/37 (0%)		1/116 (0.9%)
Renal and urinary disorders
Bladder and Urethral Symptoms	1/12 (8.3%)		0/116 (0%)		0/37 (0%)		1/116 (0.9%)
Other (Not Including Serious) Adverse Events
	Febuxostat 40 mg QD		Febuxostat 80 mg QD		Febuxostat 120 mg QD		Febuxostat Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/12 (41.7%)		44/116 (37.9%)		9/37 (24.3%)		53/116 (45.7%)
Gastrointestinal disorders
Diarrhoea	0/12 (0%)		9/116 (7.8%)		1/37 (2.7%)		10/116 (8.6%)
Gastrointestinal Atonic and Hypomotility Disorders NEC	0/12 (0%)		5/116 (4.3%)		0/37 (0%)		5/116 (4.3%)
Gastrointestinal Signs and Symptoms	0/12 (0%)		3/116 (2.6%)		1/37 (2.7%)		3/116 (2.6%)
Nausea and Vomiting Symptoms	0/12 (0%)		2/116 (1.7%)		0/37 (0%)		2/116 (1.7%)
General disorders
Oedema NEC	0/12 (0%)		2/116 (1.7%)		0/37 (0%)		2/116 (1.7%)
Injury, poisoning and procedural complications
Skin Injuries NEC	0/12 (0%)		0/116 (0%)		1/37 (2.7%)		1/116 (0.9%)
Investigations
Liver Function Analyses	0/12 (0%)		4/116 (3.4%)		2/37 (5.4%)		6/116 (5.2%)
White Blood Cell Analyses	0/12 (0%)		3/116 (2.6%)		0/37 (0%)		3/116 (2.6%)
Triglyceride Analyses	0/12 (0%)		2/116 (1.7%)		0/37 (0%)		2/116 (1.7%)
Blood Amylase Increased	1/12 (8.3%)		0/116 (0%)		0/37 (0%)		1/116 (0.9%)
Weight Increased	0/12 (0%)		0/116 (0%)		1/37 (2.7%)		1/116 (0.9%)
Blood Thyroid Stimulating Hormone Increased	0/12 (0%)		0/116 (0%)		1/37 (2.7%)		1/116 (0.9%)
Metabolism and nutrition disorders
Hyperlipidaemias NEC	1/12 (8.3%)		3/116 (2.6%)		0/37 (0%)		4/116 (3.4%)
Musculoskeletal and connective tissue disorders
Muscle Related Signs and Symptoms NEC	0/12 (0%)		3/116 (2.6%)		0/37 (0%)		3/116 (2.6%)
Arthropathies	1/12 (8.3%)		1/116 (0.9%)		0/37 (0%)		2/116 (1.7%)
Joint Related Signs and Symptoms	0/12 (0%)		2/116 (1.7%)		0/37 (0%)		2/116 (1.7%)
Muscle Pains	0/12 (0%)		0/116 (0%)		2/37 (5.4%)		2/116 (1.7%)
Musculoskeletal and Connective Tissue Signs and Symptoms NEC	0/12 (0%)		2/116 (1.7%)		0/37 (0%)		2/116 (1.7%)
Nervous system disorders
Headaches NEC	0/12 (0%)		5/116 (4.3%)		0/37 (0%)		5/116 (4.3%)
Renal and urinary disorders
Renal Lithiasis	1/12 (8.3%)		2/116 (1.7%)		0/37 (0%)		3/116 (2.6%)
Skin and subcutaneous tissue disorders
Rashes, Eruptions and Exanthems	1/12 (8.3%)		2/116 (1.7%)		0/37 (0%)		3/116 (2.6%)

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.