CLEAR 2: Combining Lesinurad With Allopurinol in Inadequate Responders

• Sponsor: Ardea Biosciences, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01493531
• Collaborator: (none)
• Enrollment: 610
• Locations: 175
• Arms: 3
• Duration (Months): 31
• Patients Per Site: 3.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This study will compare the serum uric acid lowering effects, clinical benefits, and safety of lesinurad in combination with allopurinol to allopurinol alone in subjects with gout who have had an inadequate response to allopurinol.

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

Detailed Description

Allopurinol is the standard of care for the treatment of gout. Nevertheless, most patients treated with allopurinol do not achieve the recommended sUA target of < 6.0 mg/dL and need additional therapy to achieve the target. Probenecid and benzbromarone are URAT1 inhibitors, generally recommended as second-line agents for patients who are either resistant to or intolerant of allopurinol. However, benzbromarone is not available in the US and probenecid is rarely used. Consequently, there is a clear unmet medical need for a new safe and effective therapy for gout, such as lesinurad, a potent URAT1 inhibitor, that can be used in combination with allopurinol in patients not responding adequately to allopurinol monotherapy so that very high rates of response can be achieved by nearly all gout patients, rather than a minority.The subjects selected for this study will have moderate to severe gout with an inadequate response to allopurinol

Study Design

• Study Type: Interventional
• Actual Enrollment: 610 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 3 Randomized, Double-Blind, Multicenter, Placebo- Controlled, Combination Study to Evaluate the Efficacy and Safety of Lesinurad and Allopurinol Compared to Allopurinol Alone in Subjects With Gout Who Have Had an Inadequate Hypouricemic Response to Standard of Care Allopurinol
• Study Start Date: Dec 1, 2011
• Actual Primary Completion Date: May 1, 2014
• Actual Study Completion Date: Jul 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: lesinurad 200 mg + allopurinol	Drug: Lesinurad; Tablets, 200 mg QD; Drug: Allopurinol; Tablets
Experimental: lesinurad 400 mg + allopurinol	Drug: Lesinurad; Tablets, 400 mg QD; Drug: Allopurinol; Tablets
Placebo Comparator: Placebo + allopurinol	Drug: Placebo; Tablets, Placebo QD; Drug: Allopurinol; Tablets

Outcome Measures

Primary Outcome Measures

1. Subjects With a Serum Urate (sUA) < 6.0 mg/dL by Month 6. [6 months]

   Proportion of subjects with an sUA level that is < 6.0 mg/dL by Month 6.

Secondary Outcome Measures

1. Gout Flares [12 Months]

   Mean rate of gout flares requiring treatment for the 6-month period from the end of Month 6 to the end of Month 12.

2. Subjects With ≥ 1 Target Tophus at Baseline Who Experience Complete Resolution of at Least 1 Target Tophus by Month 12 [12 months]

   Proportion of subjects with ≥ 1 target tophus at Baseline who experience complete resolution of at least 1 target tophus by Month 12

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Subject is able to understand the study procedures, the risks involved and willing to provide written informed consent before the first study related activity.

• Subject meets the diagnosis of gout as per the American Rheumatism Association Criteria for the Classification of Acute Arthritis of Primary Gout.

• Subject has been taking allopurinol as the sole urate-lowering therapy indicated for the treatment of gout for at least 8 weeks prior to the Screening Visit at a stable, medically appropriate dose, as determined by the investigator, of at least 300 mg per day (at least 200 mg for subjects with moderate renal impairment).

• Subject must be able to take gout flare prophylaxis with colchicine or an NSAID (including Cox-2 selective NSAID) ±PPI.

• Subject has an sUA level ≥ 6.5 mg/dL at the Screening Visit and ≥ 6.0 mg/dL at Day -7 Visit.

• Subject has reported at least 2 gout flares in the prior 12 months.

• Body mass index (BMI) < 45 kg/m2

Exclusion Criteria:

• Subject with known hypersensitivity or allergy to allopurinol.

• Subject who is taking any other approved urate-lowering medication that is indicated for the treatment of gout other than allopurinol within 8 weeks of the Screening Visit.

• Subject who is pregnant or breastfeeding.

• Subject who consumes more than 14 drinks of alcohol per week (eg, 1 drink = 5 oz [150 mL] of wine, 12 oz [360 mL] of beer, or 1.5 oz [45 mL] of hard liquor).

• Subject with a history or suspicion of drug abuse within the past 5 years.

• Subject that requires or may require systemic immunosuppressive or immunomodulatory treatment.

• Subject with known or suspected human immunodeficiency virus (HIV) infection.

• Subject with a positive test for active hepatitis B or hepatitis C infection.

• Subject with a history of malignancy within the previous 5 years with the exception of non-melanoma skin cancer that has been treated with no evidence of recurrence, treated cervical dysplasia or treated in situ Grade 1 cervical cancer.

• Subject within the last 12 months with: unstable angina, New York Heart Association class III or IV heart failure, myocardial infarction, stroke, or deep venous thrombosis; or subjects currently receiving anticoagulants.

• Subject with uncontrolled hypertension.

• Subject with an estimated creatinine clearance < 30 mL/min.

• Subject with active peptic ulcer disease requiring treatment.

• Subject with a history of xanthinuria, active liver disease, or hepatic dysfunction.

• Subject receiving chronic treatment with more than 325 mg of salicylates per day.

• Subject taking valpromide, progabide, or valproic acid.

• Subject who has received an investigational therapy within 8 weeks or 5 half-lives (whichever is longer) prior to the Screening Visit.

• Subject with any other medical or psychological condition, which might create undue risk to the subject or interfere with the subject's ability to comply with the protocol requirements, or to complete the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Mobile	Alabama	United States	36608
2		Chandler	Arizona	United States	85224
3		Mesa	Arizona	United States	85203
4		Pheonix	Arizona	United States	85028
5		Jonesboro	Arkansas	United States	72401
6		Jonesboro	Arkansas	United States	72404
7		Little Rock	Arkansas	United States	72223
8		Anaheim	California	United States	92805
9		Gold River	California	United States	95670
10		Irvine	California	United States	92618
11		La Jolla	California	United States	92037
12		Roseville	California	United States	95661
13		San Diego	California	United States	92108
14		San Diego	California	United States	92123
15		San Ramon	California	United States	94582
16		Colorado Springs	Colorado	United States	80922
17		Denver	Colorado	United States	80220
18		Glenwood Springs	Colorado	United States	81601
19		Trumbull	Connecticut	United States	06611
20		Washington DC	District of Columbia	United States	20060
21		Washington	District of Columbia	United States	20422
22		Boynton Beach	Florida	United States	33472
23		Brandon	Florida	United States	33511
24		Fleming Island	Florida	United States	32003
25		Jacksonville	Florida	United States	32205
26		Jacksonville	Florida	United States	32216
27		Jupiter	Florida	United States	33458
28		Plant City	Florida	United States	33563
29		Tampa	Florida	United States	33606
30		Tampa	Florida	United States	33607
31		Winter Haven	Florida	United States	33880
32		Dunwoody	Georgia	United States	30338
33		Roswell	Georgia	United States	30075
34		Savannah	Georgia	United States	31406
35		Boise	Idaho	United States	83702
36		Meridian	Idaho	United States	83642
37		Addison	Illinois	United States	60101
38		Chicago	Illinois	United States	60602
39		Evansville	Indiana	United States	47713
40		Lexington	Kentucky	United States	40503
41		Lexington	Kentucky	United States	40504
42		Cumberland	Maryland	United States	21502
43		Wheaton	Maryland	United States	20902
44		Fall River	Massachusetts	United States	02720
45		Hyannis	Massachusetts	United States	02601
46		Ann Arbor	Michigan	United States	48109
47		Flint	Michigan	United States	48504
48		Olive Branch	Mississippi	United States	38654
49		Louis	Missouri	United States	63117
50		Omaha	Nebraska	United States	68114
51		Reno	Nevada	United States	89502
52		Albuquerque	New Mexico	United States	87106
53		Brooklyn	New York	United States	11201
54		Brooklyn	New York	United States	11215
55		Calabash	North Carolina	United States	28467
56		Charlotte	North Carolina	United States	28210
57		Durham	North Carolina	United States	27710
58		Hickory	North Carolina	United States	28602
59		Shelby	North Carolina	United States	28152
60		Winston-Salem	North Carolina	United States	27103
61		Fargo	North Dakota	United States	58103
62		Cincinnati	Ohio	United States	45242
63		Cleveland	Ohio	United States	44122
64		Columbus	Ohio	United States	43203
65		Dayton	Ohio	United States	45424
66		Franklin	Ohio	United States	45005
67		Middleburgh Heights	Ohio	United States	44130
68		Oklahoma City	Oklahoma	United States	73103
69		Portland	Oregon	United States	97220
70		Portland	Oregon	United States	97239
71		Indiana	Pennsylvania	United States	15701
72		Scottdale	Pennsylvania	United States	15683
73		Greenville	South Carolina	United States	29601
74		Greer	South Carolina	United States	29651
75		Spartanburg	South Carolina	United States	29303
76		Union	South Carolina	United States	29379
77		Knoxville	Tennessee	United States	37919
78		Spring Hill	Tennessee	United States	37174
79		Austin	Texas	United States	78705
80		Austin	Texas	United States	78758
81		Houston	Texas	United States	77074
82		Irving	Texas	United States	75061
83		Sugarland	Texas	United States	77479
84		West Layton	Utah	United States	84041
85		Danville	Virginia	United States	24541
86		Richmond	Virginia	United States	23219
87		Seattle	Washington	United States	98104
88		Tacoma	Washington	United States	98405
89		Camperdown,	New South Wales	Australia	2050
90		Wollongong	New South Wales	Australia	2522
91		Bisbane	Queensland	Australia	4152
92		Herston	Queensland	Australia	4029
93		Woodville South	South Australia	Australia	5011
94		Clayton	Victoria	Australia	3168
95		Heidelberg West	Victoria	Australia	3081
96		Perth	Western Australia	Australia	6001
97		Shenton Park	Western Australia	Australia	6008
98		Genk	Limburg	Belgium	3600
99		Gozee		Belgium	6534
100		Kortrijk		Belgium	8500
101		Lommel		Belgium	3920
102		Mouscron		Belgium	7700
103		Yvoir		Belgium	5530
104		Coquitlam	British Columbia	Canada	V3K 3P4
105		Kamloops	British Columbia	Canada	V2C 1K7
106		Penticton	British Columbia	Canada	V2A 5C8
107		Paradise	Newfoundland and Labrador	Canada	A1L 1E5
108		Halifax	Nova Scotia	Canada	B3K 2M5
109		Corunna	Ontario	Canada	N0N 1G0
110		Kitchener	Ontario	Canada	N2G 1H6
111		Kitchener	Ontario	Canada	N2M 5N6
112		London	Ontario	Canada	N6A 5R8
113		Sudbury	Ontario	Canada	P3A 1Y8
114		Sudbury	Ontario	Canada	P3E 1H5
115		Thornhill	Ontario	Canada	L4J 1W3
116		Toronto	Ontario	Canada	M9W 4L6
117		Quebec		Canada	G1V3M7
118		Kamenz	Sachsen	Germany	01917
119		Berlin		Germany	14059
120		Dresden		Germany	01069
121		Dresden		Germany	01307
122		Eichstatt		Germany	85072
123		Goch		Germany	47574
124		Leipzig		Germany	04109
125		Mannheim		Germany	68161
126		Munich		Germany	80336
127		Osnabruck		Germany	49074
128		Tauranga	Bay of Plenty	New Zealand	3143
129		Becken ham	Christchurch	New Zealand	8024
130		Garden Place	Hamilton	New Zealand	3240
131		Bay of Plenty	Rotorua	New Zealand	3010
132		Auckland		New Zealand	1023
133		Auckland		New Zealand	2025
134		Takapuna		New Zealand	0626
135		Krakow	Malopolskie	Poland	30-510
136		Bialystok	Podlaskie	Poland	15-430
137		Elblag	Warminsko-Mazurskie	Poland	82 300
138		Katowice		Poland	40 954
139		Konskie		Poland	26-200
140		Krakow		Poland	31-501
141		Poznan		Poland	60-773
142		Radom		Poland	26 610
143		Warszawa		Poland	01-192
144		Warszawa		Poland	01-868
145		Wroclaw		Poland	53-114
146		Fichardt Park	Bloemfontein	South Africa	9301
147		Rondebosch	Cape Town	South Africa	7700
148		Newlands	Durban	South Africa	4037
149		Silverglen	Durban	South Africa	4092
150		Newtown	Johannesburg	South Africa	2113
151		Parktown	Johannesburg	South Africa	2193
152		Radiokop	Johannesburg	South Africa	7700
153		Stellenbosch	Western Cape	South Africa	7600
154		Cape Town		South Africa	7500
155		Durban		South Africa	4001
156		East London		South Africa	5201
157		Paarl		South Africa	7646
158		Pretoria		South Africa	0002
159		Pretoria		South Africa	0084
160		Soweto		South Africa	1804
161		Thabazimbi		South Africa	0380
162		Witbank		South Africa	1035
163		Worcester		South Africa	6850
164		La Coruna	Galicia	Spain	15006
165		Barakaldo	Vizcaya	Spain	48903
166		Merida		Spain	06800
167		Lausanne		Switzerland	1011
168		Dnipropetrovsk		Ukraine	49005
169		Kharkiv		Ukraine	61157
170		Kharkiv		Ukraine	61176
171		Kyiv		Ukraine	01680
172		Kyiv		Ukraine	03680
173		Lutsk		Ukraine	43024
174		Poltava		Ukraine	36011
175		Vinnytsia		Ukraine	21018

Sponsors and Collaborators

• Ardea Biosciences, Inc.

Investigators

• Study Director: Chris Storgard, MD, Ardea Biosciences, Inc.

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: Ardea Biosciences, Inc.
• ClinicalTrials.gov Identifier: NCT01493531
• Other Study ID Numbers: RDEA594-302; 2011-003767-29
• First Posted: Dec 16, 2011
• Last Update Posted: May 26, 2016
• Last Verified: Apr 1, 2016

• Keywords provided by Ardea Biosciences, Inc.: Gout
• Additional relevant MeSH terms: Gout; Allopurinol; Lesinurad

Study Results

Participant Flow

Arm/Group Title	Lesinurad 200 mg + Allopurinol	Lesinurad 400 mg + Allopurinol	Placebo + Allopurinol
Arm/Group Description	lesinurad 200 mg qd plus allopurinol	lesinurad 400 mg qd plus allopurinol
Period Title: Overall Study
STARTED	204	200	206
COMPLETED	163	150	158
NOT COMPLETED	41	50	48

Baseline Characteristics

Arm/Group Title	Lesinurad 200 mg + Allopurinol	Lesinurad 400 mg + Allopurinol	Placebo + Allopurinol	Total
Arm/Group Description	lesinurad 200 mg qd plus allopurinol	lesinurad 400 mg qd plus allopurinol	Total of all reporting groups
Overall Participants	204	200	206	610
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	51.0 (11.1)	51.3 (11.1)	51.4 (10.6)	51.2 (10.9)
Age, Customized (Number) [Number]
<65	184 90.2%	175 87.5%	185 89.8%	544 89.2%
>=65	20 9.8%	25 12.5%	21 10.2%	66 10.8%
Sex: Female, Male (Count of Participants)
Female	7 3.4%	6 3%	10 4.9%	23 3.8%
Male	197 96.6%	194 97%	196 95.1%	587 96.2%
Region of Enrollment (Number) [Number]
Australia	4 2%	9 4.5%	4 1.9%	17 2.8%
Belgium	1 0.5%	1 0.5%	2 1%	4 0.7%
Canada	7 3.4%	6 3%	12 5.8%	25 4.1%
Germany	9 4.4%	8 4%	8 3.9%	25 4.1%
New Zealand	12 5.9%	7 3.5%	7 3.4%	26 4.3%
Poland	5 2.5%	11 5.5%	6 2.9%	22 3.6%
South Africa	30 14.7%	36 18%	33 16%	99 16.2%
Spain	2 1%	4 2%	2 1%	8 1.3%
Switzerland	1 0.5%	0 0%	0 0%	1 0.2%
Ukraine	25 12.3%	24 12%	25 12.1%	74 12.1%
United States	108 52.9%	94 47%	107 51.9%	309 50.7%

Outcome Measures

1. Primary Outcome

Title	Subjects With a Serum Urate (sUA) < 6.0 mg/dL by Month 6.
Description	Proportion of subjects with an sUA level that is < 6.0 mg/dL by Month 6.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Population

Arm/Group Title	Lesinurad 200 mg + Allopurinol	Lesinurad 400 mg + Allopurinol	Placebo + Allopurinol
Arm/Group Description	lesinurad 200 mg qd plus allopurinol	lesinurad 400 mg qd plus allopurinol	placebo qd plus allopurinol
Measure Participants	204	200	206
Number [Proportion of Subjects]	0.554	0.665	0.233

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lesinurad 200 mg + Allopurinol, Placebo + Allopurinol
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0.32
	Confidence Interval	(2-Sided) 95%; 0.23 to 0.41
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.05
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Lesinurad 400 mg + Allopurinol, Placebo + Allopurinol
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0.43
	Confidence Interval	(2-Sided) 95%; 0.34 to 0.52
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.05
	Estimation Comments

2. Secondary Outcome

Title	Gout Flares
Description	Mean rate of gout flares requiring treatment for the 6-month period from the end of Month 6 to the end of Month 12.
Time Frame	12 Months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lesinurad 200 mg + Allopurinol	Lesinurad 400 mg + Allopurinol	Placebo + Allopurinol
Arm/Group Description	lesinurad 200 mg qd plus allopurinol	lesinurad 400 mg qd plus allopurinol	placebo qd plus allopurinol
Measure Participants	204	200	206
Mean (Standard Deviation) [Gout Flares]	0.7 (1.4)	0.8 (1.7)	0.9 (1.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lesinurad 200 mg + Allopurinol, Placebo + Allopurinol
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5716
	Comments
	Method	Negative Binomial Regression
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.88
	Confidence Interval	(2-Sided) 95%; 0.57 to 1.37
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Lesinurad 400 mg + Allopurinol, Placebo + Allopurinol
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7454
	Comments
	Method	Negative Binomial Regression
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.93
	Confidence Interval	(2-Sided) 95%; 0.60 to 1.45
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Subjects With ≥ 1 Target Tophus at Baseline Who Experience Complete Resolution of at Least 1 Target Tophus by Month 12
Description	Proportion of subjects with ≥ 1 target tophus at Baseline who experience complete resolution of at least 1 target tophus by Month 12
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lesinurad 200 mg + Allopurinol	Lesinurad 400 mg + Allopurinol	Placebo + Allopurinol
Arm/Group Description	lesinurad 200 mg qd plus allopurinol	lesinurad 400 mg qd plus allopurinol	placebo qd plus allopurinol
Measure Participants	35	29	33
Number [Proportion of Subjects]	0.314	0.276	0.333

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lesinurad 200 mg + Allopurinol, Placebo + Allopurinol
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8466
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-0.02
	Confidence Interval	(2-Sided) 95%; -0.24 to 0.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Lesinurad 400 mg + Allopurinol, Placebo + Allopurinol
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6301
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-0.06
	Confidence Interval	(2-Sided) 95%; -0.29 to 0.17
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Arm/Group Title	Lesinurad 200 mg + Allopurinol		Lesinurad 400 mg + Allopurinol		Placebo + Allopurinol
Arm/Group Description	lesinurad 200 mg qd plus allopurinol		lesinurad 400 mg qd plus allopurinol
All Cause Mortality
	Lesinurad 200 mg + Allopurinol		Lesinurad 400 mg + Allopurinol		Placebo + Allopurinol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Lesinurad 200 mg + Allopurinol		Lesinurad 400 mg + Allopurinol		Placebo + Allopurinol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/204 (4.4%)		19/200 (9.5%)		8/206 (3.9%)
Cardiac disorders
Coronary artery disease	0/204 (0%)	0	1/200 (0.5%)	1	0/206 (0%)	0
Myocardial infarction	0/204 (0%)	0	3/200 (1.5%)	3	0/206 (0%)	0
Atrial fibrillation	1/204 (0.5%)	1	0/200 (0%)	0	0/206 (0%)	0
Intracardiac thrombus	0/204 (0%)	0	1/200 (0.5%)	1	0/206 (0%)	0
Gastrointestinal disorders
Duodenal ulcer haemorrhage	0/204 (0%)	0	1/200 (0.5%)	1	1/206 (0.5%)	1
Gastrointestinal haemorrhage	1/204 (0.5%)	1	0/200 (0%)	0	0/206 (0%)	0
General disorders
Adverse drug reaction	1/204 (0.5%)	1	0/200 (0%)	0	0/206 (0%)	0
Non-cardiac chest pain	1/204 (0.5%)	1	0/200 (0%)	0	0/206 (0%)	0
Infections and infestations
Pneumonia	2/204 (1%)	2	0/200 (0%)	0	0/206 (0%)	0
Bronchopneumonia	0/204 (0%)	0	1/200 (0.5%)	1	0/206 (0%)	0
Cellulitis	0/204 (0%)	0	1/200 (0.5%)	1	0/206 (0%)	0
Empyema	1/204 (0.5%)	1	0/200 (0%)	0	0/206 (0%)	0
Pyelonephritis chronic	0/204 (0%)	0	1/200 (0.5%)	1	0/206 (0%)	0
Sinobronchitis	1/204 (0.5%)	1	0/200 (0%)	0	0/206 (0%)	0
Abscess limb	0/204 (0%)	0	0/200 (0%)	0	1/206 (0.5%)	1
Appendicitis	0/204 (0%)	0	0/200 (0%)	0	1/206 (0.5%)	1
Diverticulitis	0/204 (0%)	0	0/200 (0%)	0	1/206 (0.5%)	1
Injury, poisoning and procedural complications
Multiple drug overdose	1/204 (0.5%)	1	0/200 (0%)	0	0/206 (0%)	0
Multiple injuries	1/204 (0.5%)	1	0/200 (0%)	0	0/206 (0%)	0
Femur fracture	0/204 (0%)	0	0/200 (0%)	0	1/206 (0.5%)	1
Metabolism and nutrition disorders
Gout	0/204 (0%)	0	2/200 (1%)	4	0/206 (0%)	0
Musculoskeletal and connective tissue disorders
Osteoarthritis	0/204 (0%)	0	2/200 (1%)	2	0/206 (0%)	0
Arthralgia	1/204 (0.5%)	1	0/200 (0%)	0	0/206 (0%)	0
Back pain	1/204 (0.5%)	1	0/200 (0%)	0	0/206 (0%)	0
Flank pain	1/204 (0.5%)	1	0/200 (0%)	0	0/206 (0%)	0
Intervertebral disc degeneration	0/204 (0%)	0	1/200 (0.5%)	1	0/206 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	0/204 (0%)	0	1/200 (0.5%)	1	0/206 (0%)	0
Gastric cancer	0/204 (0%)	0	1/200 (0.5%)	1	0/206 (0%)	0
Ovarian adenoma	1/204 (0.5%)	1	0/200 (0%)	0	0/206 (0%)	0
Parathyroid tumour benign	1/204 (0.5%)	1	0/200 (0%)	0	0/206 (0%)	0
Prostate cancer	0/204 (0%)	0	1/200 (0.5%)	1	0/206 (0%)	0
Pancreatic neuroendocrine tumour	0/204 (0%)	0	0/200 (0%)	0	1/206 (0.5%)	1
Nervous system disorders
Subarachnoid haemorrhage	0/204 (0%)	0	0/200 (0%)	0	1/206 (0.5%)	1
Psychiatric disorders
Depression	1/204 (0.5%)	1	0/200 (0%)	0	0/206 (0%)	0
Dissociative disorder	0/204 (0%)	0	1/200 (0.5%)	1	0/206 (0%)	0
Renal and urinary disorders
Nephrolithiasis	0/204 (0%)	0	2/200 (1%)	2	0/206 (0%)	0
Renal failure acute	0/204 (0%)	0	1/200 (0.5%)	1	1/206 (0.5%)	1
Renal impairment	0/204 (0%)	0	1/200 (0.5%)	1	0/206 (0%)	0
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema	0/204 (0%)	0	1/200 (0.5%)	1	0/206 (0%)	0
Vascular disorders
Hypertensive crisis	0/204 (0%)	0	1/200 (0.5%)	1	0/206 (0%)	0
Other (Not Including Serious) Adverse Events
	Lesinurad 200 mg + Allopurinol		Lesinurad 400 mg + Allopurinol		Placebo + Allopurinol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	85/204 (41.7%)		82/200 (41%)		60/206 (29.1%)
Gastrointestinal disorders
Diarrhoea	10/204 (4.9%)	13	14/200 (7%)	21	7/206 (3.4%)	8
Gastrooesophageal reflux disease	10/204 (4.9%)	10	4/200 (2%)	4	1/206 (0.5%)	1
Infections and infestations
Upper respiratory tract infection	14/204 (6.9%)	16	30/200 (15%)	39	21/206 (10.2%)	23
Influenza	14/204 (6.9%)	17	8/200 (4%)	9	4/206 (1.9%)	4
Bronchitis	9/204 (4.4%)	9	4/200 (2%)	4	4/206 (1.9%)	5
Injury, poisoning and procedural complications
Joint sprain	9/204 (4.4%)	9	2/200 (1%)	2	4/206 (1.9%)	4
Investigations
Blood creatinine increased	8/204 (3.9%)	9	19/200 (9.5%)	24	7/206 (3.4%)	7
Musculoskeletal and connective tissue disorders
Arthralgia	24/204 (11.8%)	24	6/200 (3%)	7	9/206 (4.4%)	14
Nervous system disorders
Headache	10/204 (4.9%)	11	12/200 (6%)	13	8/206 (3.9%)	8
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	5/204 (2.5%)	5	1/200 (0.5%)	1	0/206 (0%)	0
Vascular disorders
Hypertension	17/204 (8.3%)	17	16/200 (8%)	16	10/206 (4.9%)	10

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

PI shall submit a copy of the Publication to Sponsor for review at least 45 days prior to its proposed submission. Sponsor reserves the right to delay any such publication for an additional period of 60 days. Upon Sponsor's request, PI agrees to delete from the proposed publication any Confidential Information. PI agrees not to release any publication without the prior written permission of Sponsor.