Efficacy and Safety of Extended Release and Immediate Release Febuxostat in Participants With Gout

• Sponsor: Takeda (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02139046
• Collaborator: (none)
• Enrollment: 1,790
• Locations: 192
• Arms: 5
• Duration (Months): 19
• Patients Per Site: 9.3
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of febuxostat 40 mg extended release (XR) and 80 mg XR in comparison with febuxostat 40 mg immediate release (IR) and 80 mg IR, respectively, in participants with gout.

Condition or Disease	Intervention/Treatment	Phase
Gout	Drug: Febuxostat IR; Drug: Febuxostat XR; Drug: Febuxostat placebo; Drug: Colchicine; Drug: Naproxen; Drug: Lansoprazole	Phase 3

Detailed Description

The drug being tested in this study is called febuxostat. Febuxostat is being tested to decrease and maintain serum urate in people who have gout. This study will look at serum urate levels in people who take febuxostat extended release (XR) capsules compared to febuxostat immediate release (IR) capsules and placebo.

The study will enroll approximately 1750 patients. Participants will be randomly assigned (by chance) to one of the five treatment groups-which will remain undisclosed to the patient and study doctor during the study (unless there is an urgent medical need):

• Febuxostat 40 mg XR

• Febuxostat 80 mg XR

• Febuxostat 40 mg IR

• Febuxostat 80 mg IR

• Placebo (dummy inactive pill) - this is a tablet that looks like the study drug but has no active ingredient.

All participants will be asked to take one capsule at the same time each day throughout the study, and will be asked to call an interactive voice response system any time they are having a gout flare up. In addition to study medication, participants will also take 0.6 mg of colchicine every day or every other day, or naproxen 250 mg twice a day and lansoprazole 15 mg once a day to prevent gout flare ups.

This multi-centre trial will be conducted in the United States. The overall time to participate in this study is up to approximately 4 months and participants will make up to 7 visits to the clinic.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1790 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Randomized, Double Blind, Multicenter, Placebo Controlled Study to Evaluate the Efficacy and Safety of Febuxostat 40 mg XR, 80 mg XR, 40 mg IR and 80 mg IR in Subjects With Gout
• Study Start Date: Apr 1, 2014
• Actual Primary Completion Date: Nov 1, 2015
• Actual Study Completion Date: Nov 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Febuxostat IR 40 mg Febuxostat Immediate Release (IR) 40 mg over-encapsulated tablet, orally, once daily, and colchicine 0.6 mg tablet, orally, every day (for participants with estimated glomerular filtration rate (eGFR) ≥ 60 mL/min) or every other day (if eGFR ≥ 15 - ≤ 59 mL/min), or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.	Drug: Febuxostat IR; Febuxostat IR over-encapsulated tablets; Other Names: Uloric ; Drug: Colchicine; Colchicine tablets; Drug: Naproxen; Naproxen tablets; Drug: Lansoprazole; Lansoprazole capsules
Active Comparator: Febuxostat IR 80 mg Febuxostat IR 80 mg over-encapsulated tablet, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.	Drug: Febuxostat IR; Febuxostat IR over-encapsulated tablets; Other Names: Uloric ; Drug: Colchicine; Colchicine tablets; Drug: Naproxen; Naproxen tablets; Drug: Lansoprazole; Lansoprazole capsules
Experimental: Febuxostat XR 40 mg Febuxostat Extended Release (XR) 40 mg over-encapsulated capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.	Drug: Febuxostat XR; Febuxostat XR over-encapsulated capsules; Other Names: Uloric ; Drug: Colchicine; Colchicine tablets; Drug: Naproxen; Naproxen tablets; Drug: Lansoprazole; Lansoprazole capsules
Experimental: Febuxostat XR 80 mg Febuxostat XR 80 mg over-encapsulated capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.	Drug: Febuxostat XR; Febuxostat XR over-encapsulated capsules; Other Names: Uloric ; Drug: Colchicine; Colchicine tablets; Drug: Naproxen; Naproxen tablets; Drug: Lansoprazole; Lansoprazole capsules
Placebo Comparator: Placebo Febuxostat placebo-matching capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.	Drug: Febuxostat placebo; Febuxostat placebo-matching capsules; Drug: Colchicine; Colchicine tablets; Drug: Naproxen; Naproxen tablets; Drug: Lansoprazole; Lansoprazole capsules

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Serum Urate <5.0 mg/dL at Month 3 [Month 3]

Secondary Outcome Measures

1. Percentage of Participants With at Least One Gout Flare Requiring Treatment [Baseline to Month 3]

   A participant was considered to have a gout flare if the following criteria were met: Participant-reported acute particular pain typical of a gout attack that was deemed by participant and/or investigator to require treatment and was treated with colchicine, nonsteroidal anti-inflammatory drugs (NSAIDs) or steroids, Participant experienced at least 3 or more of: 1) Joint swelling, 2) Redness, 3) Tenderness, 4) Pain, Participant experienced at least one or more of: 1) Rapid onset of pain, 2) Decreased range of motion, 3) Joint warmth, 4) Other symptoms similar to a prior gout flare.

2. Percentage of Participants With Serum Urate <6.0 mg/dL at Month 3 [Month 3]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.

2. The participant or, when applicable, the participant's legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedure.

3. Has a history or presence of gout defined as having one or more of the American

Rheumatism Association (ARA) criteria for the diagnosis of gout:

1. A tophus proven to contain urate crystals by chemical or polarized light microscopic means, AND/OR;

2. Characteristic urate crystals in the joint fluid, AND/OR;

3. History of at least 6 of the following clinical, laboratory, and x-ray phenomena:

1. more than one attack of acute arthritis, ii. maximum inflammation developed within 1 day, iii. monoarticular arthritis, iv. redness observed over joints, v. first metatarsophalangeal joint painful or swollen, vi. unilateral first metatarsophalangeal joint attack, vii. unilateral tarsal joint attack, viii. tophus (proven or suspected),

1. Hyperuricemia, x. asymmetric swelling within a joint on x-ray, xi. subcortical cysts without erosions on x-ray; xii. joint fluid culture negative for organisms during attack.

1. Is male or female at least 18 years of age, inclusive.

2. A female participant of childbearing potential who is sexually active with a nonsterilized male partner agrees to use routinely adequate contraception from signing of informed consent throughout the duration of the study.

3. Have a serum urate (sUA) level ≥8.0 mg/dL at the Day -4 Visit or at the retest visit.

4. Has an estimated Glomerular Filtration Rate (eGRF) ≥15 mL/min using the Modification of Diet in Renal Disease (MDRD) formula at the Screening visit (Day -21 for participants on urate lowering therapy (ULT) and Day -4 for participants not on ULT) or at the retest visit.

5. Has at least one gout flare within 12 months prior to Screening visit.

Exclusion Criteria:

1. Has received any investigational compound within 30 days prior to Screening.

2. Is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in conduct of this study (eg, spouse, parent, child, sibling) or may consent under duress.

3. Is breastfeeding or pregnant.

4. Has secondary hyperuricemia (eg, due to myeloproliferative disorder).

5. Has a history of xanthinuria.

6. Has received ULT (ie, allopurinol, probenecid, etc.) within 20 days prior to Day 1/Randomization Visit.

7. Has a known hypersensitivity to febuxostat or any components of their formulation; has a known hypersensitivity to naproxen, any other nonsteroidal anti-inflammatory drug (NSAID), aspirin, lansoprazole, colchicine or any components in their formulation.

8. Has active peptic ulcer disease.

9. Has a history of cancer (other than basal cell carcinoma of the skin) within 5 years prior to the Screening Visit.

10. Has alanine aminotransferase (ALT) and aspartate aminotransferase (AST) values >2 x the upper limit of normal (ULN).

11. Has rheumatoid arthritis which requires treatment.

12. Has a significant medical condition and/or conditions that would interfere with the treatment, safety, or compliance with the protocol.

13. Has experienced a myocardial infarction (MI), stroke, hospitalized unstable angina, cardiac or cerebrovascular revascularization procedure or hospitalized transient ischemic attack (TIA) - except in participants who have severe renal impairment.

14. Participants with severe renal impairment had a MI or stroke within 90 days prior to initial screening visit or has a MI or stroke during the screening period prior to Day 1/Randomization Visit.

15. Participant consumes >14 alcoholic beverages/week. Has a history of alcoholism or illicit drug abuse within 5 years.

16. Has participated in another investigational study within the 30 days prior to the Screening Visit.

17. Has a known history of infection with hepatitis B, hepatitis C, or human immunodeficiency virus.

18. Is required to take excluded medications.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Binghamton	Alabama	United States
2		Birmingham	Alabama	United States
3		Huntsville	Alabama	United States
4		Gilbert	Arizona	United States
5		Glendale	Arizona	United States
6		Phoenix	Arizona	United States
7		Tucson	Arizona	United States
8		Fayetteville	Arkansas	United States
9		Little Rock	Arkansas	United States
10		Searcy	Arkansas	United States
11		Bellflower	California	United States
12		Carmichael	California	United States
13		Costa Mesa	California	United States
14		Covina	California	United States
15		El Cajon	California	United States
16		Encinitas	California	United States
17		Encino	California	United States
18		Escondido	California	United States
19		Gold River	California	United States
20		Irvine	California	United States
21		Lancaster	California	United States
22		Lomita	California	United States
23		Long Beach	California	United States
24		Los Angeles	California	United States
25		Monterey Park	California	United States
26		Murrieta	California	United States
27		North Hollywood	California	United States
28		Norwalk	California	United States
29		Paramount	California	United States
30		Rancho Cucamonga	California	United States
31		Riverside	California	United States
32		Roseville	California	United States
33		Sacramento	California	United States
34		San Diego	California	United States
35		San Jose	California	United States
36		San Ramon	California	United States
37		Santa Clarita	California	United States
38		Tustin	California	United States
39		Upland	California	United States
40		Arvada	Colorado	United States
41		Westminster	Colorado	United States
42		Wheat Ridge	Colorado	United States
43		Lewes	Delaware	United States
44		Boynton Beach	Florida	United States
45		Brandon	Florida	United States
46		Clearwater	Florida	United States
47		Coral Gables	Florida	United States
48		Coral Springs	Florida	United States
49		Daytona Beach	Florida	United States
50		Deland	Florida	United States
51		Doral	Florida	United States
52		Edgewater	Florida	United States
53		Fort Lauderdale	Florida	United States
54		Fort Meyers	Florida	United States
55		Fort Myers	Florida	United States
56		Hialeah	Florida	United States
57		Hollywood	Florida	United States
58		Homestead	Florida	United States
59		Jacksonville	Florida	United States
60		Jupiter	Florida	United States
61		Miami	Florida	United States
62		North Bay Village	Florida	United States
63		Orlando	Florida	United States
64		Pembroke Pines	Florida	United States
65		Pinellas Park	Florida	United States
66		Plant City	Florida	United States
67		Port Charlotte	Florida	United States
68		Sanford	Florida	United States
69		Tallahassee	Florida	United States
70		Tampa	Florida	United States
71		Winter Haven	Florida	United States
72		Atlanta	Georgia	United States
73		Augusta	Georgia	United States
74		Columbus	Georgia	United States
75		Dunwoody	Georgia	United States
76		Fort Valley	Georgia	United States
77		Marietta	Georgia	United States
78		Newnan	Georgia	United States
79		Norcross	Georgia	United States
80		Roswell	Georgia	United States
81		Savannah	Georgia	United States
82		Suwanee	Georgia	United States
83		Honolulu	Hawaii	United States
84		Meridian	Idaho	United States
85		Gurnee	Illinois	United States
86		Avon	Indiana	United States
87		Brownsburg	Indiana	United States
88		Newburgh	Indiana	United States
89		Augusta	Kansas	United States
90		Wichita	Kansas	United States
91		Crestview Hills	Kentucky	United States
92		Elizabethtown	Kentucky	United States
93		Lexington	Kentucky	United States
94		Louisville	Kentucky	United States
95		Owensboro	Kentucky	United States
96		Paducah	Kentucky	United States
97		Baker	Louisiana	United States
98		Lafayette	Louisiana	United States
99		Mandeville	Louisiana	United States
100		Metairie	Louisiana	United States
101		Biddeford	Maine	United States
102		Columbia	Maryland	United States
103		Frederick	Maryland	United States
104		Oxon Hill	Maryland	United States
105		Brockton	Massachusetts	United States
106		Fall River	Massachusetts	United States
107		Buckley	Michigan	United States
108		Detroit	Michigan	United States
109		Kalamazoo	Michigan	United States
110		Biloxi	Mississippi	United States
111		Olive Branch	Mississippi	United States
112		Hazelwood	Missouri	United States
113		Washington	Missouri	United States
114		Billings	Montana	United States
115		Missoula	Montana	United States
116		Bellevue	Nebraska	United States
117		Lincoln	Nebraska	United States
118		Omaha	Nebraska	United States
119		Las Vegas	Nevada	United States
120		Reno	Nevada	United States
121		Lodi	New Jersey	United States
122		Teaneck	New Jersey	United States
123		Albuquerque	New Mexico	United States
124		Brooklyn	New York	United States
125		Endwell	New York	United States
126		Manhasset	New York	United States
127		Columbiana	North Carolina	United States
128		Greensboro	North Carolina	United States
129		Greenville	North Carolina	United States
130		Hickory	North Carolina	United States
131		Raleigh	North Carolina	United States
132		Salisbury	North Carolina	United States
133		Wilmington	North Carolina	United States
134		Fargo	North Dakota	United States
135		Chagrin Falls	Ohio	United States
136		Cincinnati	Ohio	United States
137		Cleveland	Ohio	United States
138		Lyndhurst	Ohio	United States
139		Mentor	Ohio	United States
140		Perrysburg	Ohio	United States
141		Toledo	Ohio	United States
142		Wadsworth	Ohio	United States
143		Willoughby Hills	Ohio	United States
144		Oklahoma City	Oklahoma	United States
145		Tulsa	Oklahoma	United States
146		Portland	Oregon	United States
147		Altoona	Pennsylvania	United States
148		Duncansville	Pennsylvania	United States
149		Harleysville	Pennsylvania	United States
150		Lansdale	Pennsylvania	United States
151		McMurray	Pennsylvania	United States
152		Media	Pennsylvania	United States
153		Philadelphia	Pennsylvania	United States
154		Pittsburgh	Pennsylvania	United States
155		Uniontown	Pennsylvania	United States
156		Wyomissing	Pennsylvania	United States
157		Charleston	South Carolina	United States
158		Columbia	South Carolina	United States
159		Greer	South Carolina	United States
160		Mount Pleasant	South Carolina	United States
161		Rapid City	South Dakota	United States
162		Bristol	Tennessee	United States
163		Collierville	Tennessee	United States
164		Jackson	Tennessee	United States
165		Memphis	Tennessee	United States
166		Arlington	Texas	United States
167		Austin	Texas	United States
168		Bellaire	Texas	United States
169		Carrollton	Texas	United States
170		Corpus Christi	Texas	United States
171		Houston	Texas	United States
172		Humble	Texas	United States
173		Plano	Texas	United States
174		San Antonio	Texas	United States
175		Sugar Land	Texas	United States
176		The Woodlands	Texas	United States
177		Bountiful	Utah	United States
178		Salt Lake City City	Utah	United States
179		West Jordan	Utah	United States
180		Alexandria	Virginia	United States
181		Arlington	Virginia	United States
182		Burke	Virginia	United States
183		Charlottesville	Virginia	United States
184		Danville	Virginia	United States
185		Midlothian	Virginia	United States
186		Newport News	Virginia	United States
187		Norfolk	Virginia	United States
188		Richmond	Virginia	United States
189		Sterling	Virginia	United States
190		Spokane	Washington	United States
191		Clarksburg	West Virginia	United States
192		Milwaukee	Wisconsin	United States

Sponsors and Collaborators

• Takeda

Investigators

• Study Director: Medical Director Clinical Science, Takeda

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT02139046
• Other Study ID Numbers: FEB-XR_301; U1111-1152-4040
• First Posted: May 15, 2014
• Last Update Posted: Nov 3, 2016
• Last Verified: Sep 1, 2016

• Keywords provided by Takeda: Drug therapy
• Additional relevant MeSH terms: Gout; Naproxen; Colchicine; Febuxostat; Lansoprazole; Dexlansoprazole

Study Results

Participant Flow

Recruitment Details	Participants took part in the study at 217 investigative sites in the United States from 18 April 2014 to 18 November 2015.
Pre-assignment Detail	Participants with a diagnosis of gout were enrolled equally in 1 of 5 treatment groups: once a day placebo, febuxostat 40 mg extended release (XR), febuxostat 80 mg XR, febuxostat 40 mg immediate release (IR) or febuxostat 80 mg IR.

Arm/Group Title	Placebo	Febuxostat IR 40 mg	Febuxostat XR 40 mg	Febuxostat IR 80 mg	Febuxostat XR 80 mg
Arm/Group Description	Febuxostat placebo-matching capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.	Febuxostat Immediate Release (IR) 40 mg over-encapsulated tablet, orally, once daily, and colchicine 0.6 mg tablet, orally, every day (for participants with estimated glomerular filtration rate (eGFR) ≥ 60 mL/min) or every other day (if eGFR ≥ 15 - ≤ 59 mL/min), or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.	Febuxostat Extended Release (XR) 40 mg over-encapsulated capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.	Febuxostat IR 80 mg over-encapsulated tablet, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.	Febuxostat XR 80 mg over-encapsulated capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.
Period Title: Overall Study
STARTED	358	359	357	358	358
Safety Analysis Set	356	358	355	357	357
Full Analysis Set	357	357	355	357	357
COMPLETED	296	305	298	290	301
NOT COMPLETED	62	54	59	68	57

Baseline Characteristics

Arm/Group Title	Placebo	Febuxostat IR 40 mg	Febuxostat XR 40 mg	Febuxostat IR 80 mg	Febuxostat XR 80 mg	Total
Arm/Group Description	Febuxostat placebo-matching capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.	Febuxostat Immediate Release (IR) 40 mg over-encapsulated tablet, orally, once daily, and colchicine 0.6 mg tablet, orally, every day (for participants with estimated glomerular filtration rate (eGFR) ≥ 60 mL/min) or every other day (if eGFR ≥ 15 - ≤ 59 mL/min), or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.	Febuxostat Extended Release (XR) 40 mg over-encapsulated capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.	Febuxostat IR 80 mg over-encapsulated tablet, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.	Febuxostat XR 80 mg over-encapsulated capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.	Total of all reporting groups
Overall Participants	357	357	355	357	357	1783
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.4 (11.55)	55.5 (11.07)	55.1 (12.68)	54.9 (11.32)	55.4 (11.93)	55.1 (11.71)
Age, Customized (participants) [Number]
< 45 years	71 19.9%	58 16.2%	74 20.8%	68 19%	61 17.1%	332 18.6%
45 to < 65 years	223 62.5%	225 63%	193 54.4%	219 61.3%	222 62.2%	1082 60.7%
>= 65 years	63 17.6%	74 20.7%	88 24.8%	70 19.6%	74 20.7%	369 20.7%
Age, Customized (participants) [Number]
18 to < 65 years	294 82.4%	283 79.3%	267 75.2%	287 80.4%	283 79.3%	1414 79.3%
65 to < 85 years	60 16.8%	73 20.4%	86 24.2%	69 19.3%	73 20.4%	361 20.2%
>= 85 years	3 0.8%	1 0.3%	2 0.6%	1 0.3%	1 0.3%	8 0.4%
Sex: Female, Male (Count of Participants)
Female	41 11.5%	46 12.9%	43 12.1%	42 11.8%	34 9.5%	206 11.6%
Male	316 88.5%	311 87.1%	312 87.9%	315 88.2%	323 90.5%	1577 88.4%
Race/Ethnicity, Customized (participants) [Number]
American Indian or Alaska Native	1 0.3%	2 0.6%	0 0%	1 0.3%	3 0.8%	7 0.4%
Asian	23 6.4%	19 5.3%	22 6.2%	23 6.4%	25 7%	112 6.3%
Black or African American	94 26.3%	89 24.9%	100 28.2%	98 27.5%	93 26.1%	474 26.6%
Native Hawaiian or Other Pacific Islander	3 0.8%	5 1.4%	4 1.1%	3 0.8%	5 1.4%	20 1.1%
White	231 64.7%	235 65.8%	226 63.7%	230 64.4%	225 63%	1147 64.3%
Other: Multi-Racial	5 1.4%	7 2%	3 0.8%	2 0.6%	6 1.7%	23 1.3%
Race/Ethnicity, Customized (participants) [Number]
Hispanic or Latino	53 14.8%	51 14.3%	61 17.2%	49 13.7%	52 14.6%	266 14.9%
Not Hispanic or Latino	304 85.2%	306 85.7%	294 82.8%	308 86.3%	305 85.4%	1517 85.1%
Region of Enrollment (participants) [Number]
United States	357 100%	357 100%	355 100%	357 100%	357 100%	1783 100%
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	175.2 (9.95)	174.8 (10.46)	174.4 (10.45)	174.3 (9.42)	175.3 (9.50)	174.8 (9.96)
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	106.83 (25.285)	104.65 (24.157)	104.71 (27.995)	102.16 (22.832)	104.64 (23.033)	104.60 (24.745)
Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	34.88 (8.276)	34.32 (8.014)	34.29 (8.141)	33.68 (7.477)	34.08 (7.205)	34.25 (7.834)
Smoking History (participants) [Number]
Never Smoked	191 53.5%	190 53.2%	185 52.1%	190 53.2%	205 57.4%	961 53.9%
Current Smoker	58 16.2%	56 15.7%	60 16.9%	65 18.2%	47 13.2%	286 16%
Ex-Smoker	108 30.3%	111 31.1%	110 31%	102 28.6%	105 29.4%	536 30.1%
Alcohol Classification (participants) [Number]
Never Drank	81 22.7%	92 25.8%	85 23.9%	68 19%	74 20.7%	400 22.4%
Current Drinker	234 65.5%	204 57.1%	218 61.4%	234 65.5%	232 65%	1122 62.9%
Ex-Drinker	42 11.8%	61 17.1%	52 14.6%	55 15.4%	51 14.3%	261 14.6%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Serum Urate <5.0 mg/dL at Month 3
Time Frame	Month 3

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) included all participants who were randomized and received at least 1 dose of double-blind study medication. Participants who discontinued double-blind study drug prior to the Month 3 visit were considered treatment failures, i.e. to have serum urate ≥ 5.0 mg/dL.

Arm/Group Title	Placebo	Febuxostat IR 40 mg	Febuxostat XR 40 mg	Febuxostat IR 80 mg	Febuxostat XR 80 mg
Arm/Group Description	Febuxostat placebo-matching capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.	Febuxostat Immediate Release (IR) 40 mg over-encapsulated tablet, orally, once daily, and colchicine 0.6 mg tablet, orally, every day (for participants with estimated glomerular filtration rate (eGFR) ≥ 60 mL/min) or every other day (if eGFR ≥ 15 - ≤ 59 mL/min), or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.	Febuxostat Extended Release (XR) 40 mg over-encapsulated capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.	Febuxostat IR 80 mg over-encapsulated tablet, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.	Febuxostat XR 80 mg over-encapsulated capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.
Measure Participants	357	357	355	357	357
Number [percentage of participants]	0.3 0.1%	15.7 4.4%	25.9 7.3%	42.6 11.9%	50.1 14%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Febuxostat XR 40 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	To adjust for multiple comparisons, a closed testing strategy was used. Febuxostat XR 40 and 80 mg were tested separately versus placebo and the corresponding febuxostat IR group at a Bonferroni-corrected significance level of 0.025.
	Method	Z-test
	Comments	Point estimates, confidence intervals, and p-values are presented using the Cui, Hung, and Wang (CHW) Z-test which accounts for the interim analysis.
Method of Estimation	Estimation Parameter	Difference in Proportions
	Estimated Value	25.6
	Confidence Interval	(2-Sided) 95%; 20.4 to 30.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Febuxostat XR 80 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	To adjust for multiple comparisons, a closed testing strategy was used. Febuxostat XR 40 and 80 mg were tested separately versus placebo and the corresponding febuxostat IR group at a Bonferroni-corrected significance level of 0.025.
	Method	Z-test
	Comments	Point estimates, confidence intervals, and p-values are presented using the CHW Z-test which accounts for the interim analysis.
Method of Estimation	Estimation Parameter	Difference in Proportions
	Estimated Value	49.8
	Confidence Interval	(2-Sided) 95%; 43.9 to 55.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Febuxostat IR 40 mg, Febuxostat XR 40 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments	To adjust for multiple comparisons, a closed testing strategy was used. Febuxostat XR 40 and 80 mg were tested separately versus placebo and the corresponding febuxostat IR group at a Bonferroni-corrected significance level of 0.025.
	Method	Z-test
	Comments	Point estimates, confidence intervals, and p-values are presented using the CHW Z-test which accounts for the interim analysis.
Method of Estimation	Estimation Parameter	Difference in Proportions
	Estimated Value	10.2
	Confidence Interval	(2-Sided) 95%; 3.5 to 17.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Febuxostat IR 80 mg, Febuxostat XR 80 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.043
	Comments	To adjust for multiple comparisons, a closed testing strategy was used. Febuxostat XR 40 and 80 mg were tested separately versus placebo and the corresponding febuxostat IR group at a Bonferroni-corrected significance level of 0.025.
	Method	Z-test
	Comments	Point estimates, confidence intervals, and p-values are presented using the CHW Z-test which accounts for the interim analysis.
Method of Estimation	Estimation Parameter	Difference in Proportions
	Estimated Value	7.5
	Confidence Interval	(2-Sided) 95%; -0.8 to 15.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percentage of Participants With at Least One Gout Flare Requiring Treatment
Description	A participant was considered to have a gout flare if the following criteria were met: Participant-reported acute particular pain typical of a gout attack that was deemed by participant and/or investigator to require treatment and was treated with colchicine, nonsteroidal anti-inflammatory drugs (NSAIDs) or steroids, Participant experienced at least 3 or more of: 1) Joint swelling, 2) Redness, 3) Tenderness, 4) Pain, Participant experienced at least one or more of: 1) Rapid onset of pain, 2) Decreased range of motion, 3) Joint warmth, 4) Other symptoms similar to a prior gout flare.
Time Frame	Baseline to Month 3

Outcome Measure Data

Analysis Population Description

FAS included all participants who were randomized and received at least 1 dose of double-blind study medication.

Arm/Group Title	Placebo	Febuxostat IR 40 mg	Febuxostat XR 40 mg	Febuxostat IR 80 mg	Febuxostat XR 80 mg
Arm/Group Description	Febuxostat placebo-matching capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.	Febuxostat Immediate Release (IR) 40 mg over-encapsulated tablet, orally, once daily, and colchicine 0.6 mg tablet, orally, every day (for participants with estimated glomerular filtration rate (eGFR) ≥ 60 mL/min) or every other day (if eGFR ≥ 15 - ≤ 59 mL/min), or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.	Febuxostat Extended Release (XR) 40 mg over-encapsulated capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.	Febuxostat IR 80 mg over-encapsulated tablet, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.	Febuxostat XR 80 mg over-encapsulated capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.
Measure Participants	357	357	355	357	357
Number [percentage of participants]	20.7 5.8%	21.0 5.9%	22.8 6.4%	27.2 7.6%	26.6 7.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Febuxostat XR 40 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.503
	Comments	To adjust for multiple comparisons, a closed testing strategy was used. Febuxostat XR 40 and 80 mg were tested separately versus placebo and the corresponding febuxostat IR group at a Bonferroni-corrected significance level of 0.025.
	Method	Z-test
	Comments	Point estimates, confidence intervals, and p-values are presented using the CHW Z-test which accounts for the interim analysis.
Method of Estimation	Estimation Parameter	Difference in Proportions
	Estimated Value	2.1
	Confidence Interval	(2-Sided) 95%; -4.9 to 9.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Febuxostat IR 80 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.064
	Comments	To adjust for multiple comparisons, a closed testing strategy was used. Febuxostat XR 40 and 80 mg were tested separately versus placebo and the corresponding febuxostat IR group at a Bonferroni-corrected significance level of 0.025.
	Method	Z-test
	Comments	Point estimates, confidence intervals, and p-values are presented using the CHW Z-test which accounts for the interim analysis.
Method of Estimation	Estimation Parameter	Difference in Proportions
	Estimated Value	5.9
	Confidence Interval	(2-Sided) 95%; -1.2 to 13.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Febuxostat IR 40 mg, Febuxostat XR 40 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.561
	Comments	To adjust for multiple comparisons, a closed testing strategy was used. Febuxostat XR 40 and 80 mg were tested separately versus placebo and the corresponding febuxostat IR group at a Bonferroni-corrected significance level of 0.025.
	Method	Z-test
	Comments	Point estimates, confidence intervals, and p-values are presented using the CHW Z-test which accounts for the interim analysis.
Method of Estimation	Estimation Parameter	Difference in Proportions
	Estimated Value	1.8
	Confidence Interval	(2-Sided) 95%; -5.1 to 8.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Febuxostat IR 80 mg, Febuxostat XR 80 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.869
	Comments	To adjust for multiple comparisons, a closed testing strategy was used. Febuxostat XR 40 and 80 mg were tested separately versus placebo and the corresponding febuxostat IR group at a Bonferroni-corrected significance level of 0.025.
	Method	Z-test
	Comments	Point estimates, confidence intervals, and p-values are presented using the CHW Z-test which accounts for the interim analysis.
Method of Estimation	Estimation Parameter	Difference in Proportions
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 95%; -8.0 to 6.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Percentage of Participants With Serum Urate <6.0 mg/dL at Month 3
Time Frame	Month 3

Outcome Measure Data

Analysis Population Description

FAS included all participants who were randomized and received at least 1 dose of double-blind study medication. Participants who discontinued double-blind study drug prior to the Month 3 visit were considered treatment failures, i.e. to have serum urate ≥ 5.0 mg/dL.

Arm/Group Title	Placebo	Febuxostat IR 40 mg	Febuxostat XR 40 mg	Febuxostat IR 80 mg	Febuxostat XR 80 mg
Arm/Group Description	Febuxostat placebo-matching capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.	Febuxostat Immediate Release (IR) 40 mg over-encapsulated tablet, orally, once daily, and colchicine 0.6 mg tablet, orally, every day (for participants with estimated glomerular filtration rate (eGFR) ≥ 60 mL/min) or every other day (if eGFR ≥ 15 - ≤ 59 mL/min), or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.	Febuxostat Extended Release (XR) 40 mg over-encapsulated capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.	Febuxostat IR 80 mg over-encapsulated tablet, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.	Febuxostat XR 80 mg over-encapsulated capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.
Measure Participants	357	357	355	357	357
Number [percentage of participants]	0.6 0.2%	40.3 11.3%	48.2 13.6%	57.7 16.2%	61.1 17.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Febuxostat XR 40 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	To adjust for multiple comparisons, a closed testing strategy was used. Febuxostat XR 40 and 80 mg were tested separately versus placebo and the corresponding febuxostat IR group at a Bonferroni-corrected significance level of 0.025.
	Method	Z-test
	Comments	Point estimates, confidence intervals, and p-values are presented using the CHW Z-test which accounts for the interim analysis.
Method of Estimation	Estimation Parameter	Difference in Proportions
	Estimated Value	47.6
	Confidence Interval	(2-Sided) 95%; 41.6 to 53.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Febuxostat XR 80 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	To adjust for multiple comparisons, a closed testing strategy was used. Febuxostat XR 40 and 80 mg were tested separately versus placebo and the corresponding febuxostat IR group at a Bonferroni-corrected significance level of 0.025.
	Method	Z-test
	Comments	Point estimates, confidence intervals, and p-values are presented using the CHW Z-test which accounts for the interim analysis.
Method of Estimation	Estimation Parameter	Difference in Proportions
	Estimated Value	60.5
	Confidence Interval	(2-Sided) 95%; 54.6 to 66.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Febuxostat IR 40 mg, Febuxostat XR 40 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.036
	Comments	To adjust for multiple comparisons, a closed testing strategy was used. Febuxostat XR 40 and 80 mg were tested separately versus placebo and the corresponding febuxostat IR group at a Bonferroni-corrected significance level of 0.025.
	Method	Z-test
	Comments	Point estimates, confidence intervals, and p-values are presented using the CHW Z-test which accounts for the interim analysis.
Method of Estimation	Estimation Parameter	Difference in Proportions
	Estimated Value	7.8
	Confidence Interval	(2-Sided) 95%; -0.5 to 16.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Febuxostat IR 80 mg, Febuxostat XR 80 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.364
	Comments	To adjust for multiple comparisons, a closed testing strategy was used. Febuxostat XR 40 and 80 mg were tested separately versus placebo and the corresponding febuxostat IR group at a Bonferroni-corrected significance level of 0.025.
	Method	Z-test
	Comments	Point estimates, confidence intervals, and p-values are presented using the CHW Z-test which accounts for the interim analysis.
Method of Estimation	Estimation Parameter	Difference in Proportions
	Estimated Value	3.3
	Confidence Interval	(2-Sided) 95%; -4.9 to 11.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months)
Adverse Event Reporting Description	At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.
Arm/Group Title	Placebo		Febuxostat IR 40 mg		Febuxostat XR 40 mg		Febuxostat IR 80 mg		Febuxostat XR 80 mg
Arm/Group Description	Febuxostat placebo-matching capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.		Febuxostat Immediate Release (IR) 40 mg over-encapsulated tablet, orally, once daily, and colchicine 0.6 mg tablet, orally, every day (for participants with estimated glomerular filtration rate (eGFR) ≥ 60 mL/min) or every other day (if eGFR ≥ 15 - ≤ 59 mL/min), or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.		Febuxostat Extended Release (XR) 40 mg over-encapsulated capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.		Febuxostat IR 80 mg over-encapsulated tablet, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.		Febuxostat XR 80 mg over-encapsulated capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.
All Cause Mortality
	Placebo		Febuxostat IR 40 mg		Febuxostat XR 40 mg		Febuxostat IR 80 mg		Febuxostat XR 80 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Febuxostat IR 40 mg		Febuxostat XR 40 mg		Febuxostat IR 80 mg		Febuxostat XR 80 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/356 (2.2%)		12/358 (3.4%)		6/355 (1.7%)		8/357 (2.2%)		8/357 (2.2%)
Cardiac disorders
Hypertensive heart disease	0/356 (0%)		0/358 (0%)		1/355 (0.3%)		0/357 (0%)		0/357 (0%)
Cardiac failure congestive	0/356 (0%)		1/358 (0.3%)		1/355 (0.3%)		0/357 (0%)		1/357 (0.3%)
Acute myocardial infarction	0/356 (0%)		0/358 (0%)		1/355 (0.3%)		0/357 (0%)		0/357 (0%)
Atrial fibrillation	0/356 (0%)		1/358 (0.3%)		0/355 (0%)		0/357 (0%)		0/357 (0%)
Sinus node dysfunction	0/356 (0%)		0/358 (0%)		0/355 (0%)		1/357 (0.3%)		0/357 (0%)
Cardiac arrest	1/356 (0.3%)		0/358 (0%)		0/355 (0%)		0/357 (0%)		0/357 (0%)
Cardio-respiratory arrest	0/356 (0%)		0/358 (0%)		0/355 (0%)		1/357 (0.3%)		0/357 (0%)
Gastrointestinal disorders
Pancreatitis	0/356 (0%)		1/358 (0.3%)		0/355 (0%)		0/357 (0%)		0/357 (0%)
Pancreatitis acute	0/356 (0%)		1/358 (0.3%)		0/355 (0%)		0/357 (0%)		0/357 (0%)
Gastric ulcer haemorrhage	1/356 (0.3%)		0/358 (0%)		0/355 (0%)		0/357 (0%)		0/357 (0%)
Abdominal pain	2/356 (0.6%)		1/358 (0.3%)		0/355 (0%)		0/357 (0%)		0/357 (0%)
Nausea	1/356 (0.3%)		0/358 (0%)		0/355 (0%)		0/357 (0%)		1/357 (0.3%)
Vomiting	1/356 (0.3%)		0/358 (0%)		0/355 (0%)		0/357 (0%)		1/357 (0.3%)
General disorders
Malaise	0/356 (0%)		0/358 (0%)		0/355 (0%)		1/357 (0.3%)		0/357 (0%)
Oedema peripheral	0/356 (0%)		0/358 (0%)		0/355 (0%)		0/357 (0%)		1/357 (0.3%)
Non-cardiac chest pain	0/356 (0%)		1/358 (0.3%)		0/355 (0%)		0/357 (0%)		0/357 (0%)
Infections and infestations
Abdominal abscess	0/356 (0%)		1/358 (0.3%)		0/355 (0%)		0/357 (0%)		0/357 (0%)
Amoebiasis	0/356 (0%)		0/358 (0%)		0/355 (0%)		0/357 (0%)		1/357 (0.3%)
Influenza	0/356 (0%)		0/358 (0%)		0/355 (0%)		0/357 (0%)		1/357 (0.3%)
Pneumonia	1/356 (0.3%)		1/358 (0.3%)		1/355 (0.3%)		0/357 (0%)		0/357 (0%)
Viral infection	0/356 (0%)		0/358 (0%)		1/355 (0.3%)		1/357 (0.3%)		0/357 (0%)
Injury, poisoning and procedural complications
Lower limb fracture	0/356 (0%)		0/358 (0%)		0/355 (0%)		0/357 (0%)		1/357 (0.3%)
Road traffic accident	1/356 (0.3%)		0/358 (0%)		1/355 (0.3%)		0/357 (0%)		0/357 (0%)
Metabolism and nutrition disorders
Gout	1/356 (0.3%)		0/358 (0%)		0/355 (0%)		0/357 (0%)		0/357 (0%)
Hyperkalaemia	1/356 (0.3%)		0/358 (0%)		0/355 (0%)		0/357 (0%)		0/357 (0%)
Dehydration	0/356 (0%)		0/358 (0%)		0/355 (0%)		1/357 (0.3%)		0/357 (0%)
Musculoskeletal and connective tissue disorders
Gouty arthritis	1/356 (0.3%)		0/358 (0%)		0/355 (0%)		0/357 (0%)		0/357 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tongue neoplasm malignant stage unspecified	0/356 (0%)		1/358 (0.3%)		0/355 (0%)		0/357 (0%)		0/357 (0%)
Prostate cancer	1/356 (0.3%)		0/358 (0%)		0/355 (0%)		0/357 (0%)		0/357 (0%)
Nervous system disorders
Basal ganglia stroke	0/356 (0%)		0/358 (0%)		0/355 (0%)		1/357 (0.3%)		0/357 (0%)
Ischaemic stroke	0/356 (0%)		0/358 (0%)		0/355 (0%)		0/357 (0%)		1/357 (0.3%)
Hypoglycaemic unconsciousness	0/356 (0%)		1/358 (0.3%)		0/355 (0%)		0/357 (0%)		0/357 (0%)
Hemiparesis	0/356 (0%)		0/358 (0%)		0/355 (0%)		1/357 (0.3%)		0/357 (0%)
Psychiatric disorders
Bipolar I disorder	0/356 (0%)		0/358 (0%)		0/355 (0%)		1/357 (0.3%)		0/357 (0%)
Renal and urinary disorders
Acute kidney injury	1/356 (0.3%)		1/358 (0.3%)		0/355 (0%)		2/357 (0.6%)		0/357 (0%)
Renal failure	0/356 (0%)		1/358 (0.3%)		0/355 (0%)		0/357 (0%)		0/357 (0%)
Renal impairment	0/356 (0%)		1/358 (0.3%)		0/355 (0%)		0/357 (0%)		0/357 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/356 (0%)		0/358 (0%)		0/355 (0%)		0/357 (0%)		1/357 (0.3%)
Asthma	0/356 (0%)		1/358 (0.3%)		0/355 (0%)		0/357 (0%)		0/357 (0%)
Pleural effusion	0/356 (0%)		1/358 (0.3%)		0/355 (0%)		0/357 (0%)		0/357 (0%)
Pulmonary hypertension	0/356 (0%)		0/358 (0%)		0/355 (0%)		1/357 (0.3%)		0/357 (0%)
Acute respiratory failure	0/356 (0%)		1/358 (0.3%)		1/355 (0.3%)		0/357 (0%)		1/357 (0.3%)
Skin and subcutaneous tissue disorders
Angioedema	0/356 (0%)		0/358 (0%)		1/355 (0.3%)		0/357 (0%)		0/357 (0%)
Dermatitis contact	0/356 (0%)		0/358 (0%)		0/355 (0%)		1/357 (0.3%)		0/357 (0%)
Vascular disorders
Hypertension	1/356 (0.3%)		0/358 (0%)		0/355 (0%)		0/357 (0%)		0/357 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Febuxostat IR 40 mg		Febuxostat XR 40 mg		Febuxostat IR 80 mg		Febuxostat XR 80 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	53/356 (14.9%)		53/358 (14.8%)		45/355 (12.7%)		55/357 (15.4%)		38/357 (10.6%)
Gastrointestinal disorders
Diarrhoea	13/356 (3.7%)		9/358 (2.5%)		9/355 (2.5%)		21/357 (5.9%)		9/357 (2.5%)
Infections and infestations
Nasopharyngitis	11/356 (3.1%)		7/358 (2%)		7/355 (2%)		9/357 (2.5%)		4/357 (1.1%)
Upper respiratory tract infection	4/356 (1.1%)		6/358 (1.7%)		6/355 (1.7%)		5/357 (1.4%)		8/357 (2.2%)
Investigations
Alanine aminotransferase increased	6/356 (1.7%)		7/358 (2%)		8/355 (2.3%)		2/357 (0.6%)		4/357 (1.1%)
Musculoskeletal and connective tissue disorders
Arthralgia	7/356 (2%)		8/358 (2.2%)		5/355 (1.4%)		6/357 (1.7%)		4/357 (1.1%)
Nervous system disorders
Headache	6/356 (1.7%)		6/358 (1.7%)		8/355 (2.3%)		4/357 (1.1%)		4/357 (1.1%)
Respiratory, thoracic and mediastinal disorders
Cough	5/356 (1.4%)		9/358 (2.5%)		2/355 (0.6%)		3/357 (0.8%)		1/357 (0.3%)
Vascular disorders
Hypertension	9/356 (2.5%)		13/358 (3.6%)		6/355 (1.7%)		8/357 (2.2%)		5/357 (1.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.