LIGHT: Lesinurad Monotherapy in Gout Subjects Intolerant to Xanthine Oxidase Inhibitors

• Sponsor: Ardea Biosciences, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01508702
• Collaborator: (none)
• Enrollment: 214
• Locations: 106
• Arms: 2
• Duration (Months): 22
• Patients Per Site: 2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This study will assess the serum uric acid lowering effects and safety of lesinurad compared to placebo in patients who are intolerant or have a contraindication to allopurinol or febuxostat.

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

Detailed Description

Allopurinol is the standard of care for the treatment of gout. In practice, approximately 20% of patients report side effects with allopurinol and 5% discontinue allopurinol due to side effects. Allopurinol can cause gastrointestinal intolerance, such as nausea and diarrhea, which appears to be dosedependent. Rash develops in about 2% of patients treated with allopurinol, and in about 20% of patients treated with allopurinol and ampicillin or amoxicillin. Allopurinol hypersensitivity syndrome remains a major concern among physicians. Mortality has been estimated to be up to nearly one quarter of AHS cases, with multiorgan system disease including hepatocellular changes and renal failure being a serious concern. Allopurinol is also relatively contraindicated for use in combination with 6-mercaptopurine and azathioprine, for which 1/4 to 1/3 lower doses must be given in order to avoid hematologic toxicity. Febuxostat, in clinical trials, has shown a similar AE profile to allopurinol. Liver function abnormalities, nausea, arthralgia and rash were the most commonly reported AEs. In postmarketing experience, Stevens Johnson Syndrome and hypersensitivity rashes have been reported (febuxostat prescribing information). Withdrawals due to AEs were similar in frequency to allopurinol as well. Relative contraindications in combination with 6-mercaptopurine and azathioprine are similar to allopurinol as well. Lesinurad may be an important therapeutic option for patients who either cannot tolerate or who have a contraindication to the use of allopurinol or febuxostat.

Study Design

• Study Type: Interventional
• Actual Enrollment: 214 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 Study to Assess the Efficacy and Safety of Lesinurad Monotherapy Compared to Placebo in Subjects With Gout and an Intolerance or Contraindication to a Xanthine Oxidase Inhibitor
• Study Start Date: Jan 1, 2012
• Actual Primary Completion Date: Oct 1, 2013
• Actual Study Completion Date: Nov 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: lesinurad 400 mg	Drug: lesinurad; Tablets, 400 mg QD
Placebo Comparator: placebo	Drug: Placebo; Tablets, Placebo QD

Outcome Measures

Primary Outcome Measures

1. Number of Subjects With an sUA Level That is < 6.0 mg/dL [6 months]

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 an sUA level ≥ 6.5 mg/dL at the Screening and Day -7 Visits.

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

• Subject has a history (either by medical record or subject interview) of intolerance or a contraindication to either allopurinol or febuxostat.

• Body mass index (BMI) < 45 kg/m2

Exclusion Criteria:

• Subject who is taking any other approved urate-lowering medication that is indicated for the treatment of gout at the Screening Visit.

• Subject with a documented history or suspicion of kidney stones.

• 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 a 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 active liver disease, or hepatic dysfunction.

• Subject receiving chronic treatment with more than 325 mg 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 in the opinion of the Investigator and/or Medical Monitor, 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		Birmingham	Alabama	United States	35211
2		Birmingham	Alabama	United States	35294
3		Glendale	Arizona	United States	85308
4		Phoenix	Arizona	United States	85050
5		Tucson	Arizona	United States	85724
6		Jonesboro	Arkansas	United States	72401
7		Little Rock	Arkansas	United States	72205
8		Anaheim	California	United States	92805
9		Carmichael	California	United States	95608
10		Covina	California	United States	91723
11		Huntington Park	California	United States	90255
12		Irvine	California	United States	92618
13		Colorado Springs	Colorado	United States	80922
14		Denver	Colorado	United States	80220
15		Denver	Colorado	United States	80230
16		Englewood	Colorado	United States	80113
17		Milford	Connecticut	United States	06460
18		Trumbull	Connecticut	United States	06611
19		Boynton Beach	Florida	United States	33472
20		Jacksonville	Florida	United States	32216
21		Miami	Florida	United States	33135
22		Miami	Florida	United States	33143
23		Plant City	Florida	United States	33563
24		Port Orange	Florida	United States	32127
25		Tampa	Florida	United States	33607
26		Winter Haven	Florida	United States	33880
27		Newman	Georgia	United States	30265
28		Honolulu	Hawaii	United States	96814
29		Meridian	Idaho	United States	83646
30		Chicago	Illinois	United States	60624
31		Elizabethtown	Kentucky	United States	42701
32		Lexington	Kentucky	United States	40504
33		Louisville	Kentucky	United States	40213
34		Metairie	Louisiana	United States	70006
35		South Traverse	Michigan	United States	49684
36		Jackson	Mississippi	United States	39202
37		Olive Branch	Mississippi	United States	38654
38		Southfield	Missouri	United States	48034
39		Washington	Missouri	United States	63090
40		Albuquerque	New Mexico	United States	87102
41		Albuquerque	New Mexico	United States	87106
42		Brooklyn	New York	United States	11201
43		Hartsdale	New York	United States	10530
44		New Windsor	New York	United States	12553
45		New York	New York	United States	10016
46		Hickory	North Carolina	United States	28602
47		Raleigh	North Carolina	United States	27612
48		Winston-Salem	North Carolina	United States	27103
49		Fargo	North Dakota	United States	58103
50		Cincinnati	Ohio	United States	45224
51		Cincinnati	Ohio	United States	45242
52		Middleburgh Heights	Ohio	United States	44130
53		Perrysburgh	Ohio	United States	43551
54		Willoughby Hills	Ohio	United States	44904
55		Norman	Oklahoma	United States	73069
56		Jenkintown	Pennsylvania	United States	19046
57		Lancaster	Pennsylvania	United States	17601
58		Lansdale	Pennsylvania	United States	19446
59		Pittsburgh	Pennsylvania	United States	15237
60		Reading	Pennsylvania	United States	19606
61		Sellersville	Pennsylvania	United States	18960
62		Myrtle Beach	South Carolina	United States	29588
63		Rock Hill	South Carolina	United States	29732
64		Spartanburg	South Carolina	United States	29303
65		Brentwood	Tennessee	United States	37027
66		Spring Hill	Tennessee	United States	37174
67		Dallas	Texas	United States	75235
68		Houston	Texas	United States	77098
69		San Antonio	Texas	United States	78229
70		Victoria	Texas	United States	77901
71		South Bountiful	Utah	United States	84010
72		West Jordon	Utah	United States	84088
73		West Layton	Utah	United States	84041
74		Chesapeake	Virginia	United States	23320
75		Richmond	Virginia	United States	23235
76		Suffolk	Virginia	United States	23435
77		Seattle	Washington	United States	98104
78		Spokane	Washington	United States	99208
79		Morgantown	West Virginia	United States	26505
80		Butterfield	Queensland	Australia	4029
81		Hobart	Tasmania	Australia	7000
82		Tasmania		Australia	7000
83		Anderlecht	Brussels	Belgium	1070
84		Genk	Limburg	Belgium	3600
85		Gozee		Belgium	6534
86		Kortrijk		Belgium	8500
87		Yvoir		Belgium	5530
88		Coquitiam	British Columbia	Canada	V3K 3P4
89		Coquitlam	British Columbia	Canada	V3K 3P4
90		Victoria	British Columbia	Canada	V8V 3N7
91		London	Ontario	Canada	N6A 5R8
92		Mississauga	Ontario	Canada	L5M 2V8
93		Toronto	Ontario	Canada	M9W 4L6
94		Rimouski	Quebec	Canada	G5L 8W1
95		Quebec		Canada	G1V 3M7
96		Dresden	Saxony	Germany	01307
97		Leipzig	Saxony	Germany	04109
98		Dresden		Germany	01069
99		Tauranga	Bay of Plenty	New Zealand	3143
100		Auckland		New Zealand	1010
101		Auckland		New Zealand	1023
102		Durban		South Africa	4092
103		Pretoria		South Africa	0002
104		Rondebosch		South Africa	7700
105		Stellenbosch		South Africa	7600
106		Thabazimbi		South Africa	0380

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: NCT01508702
• Other Study ID Numbers: RDEA594-303; 2011-003756-39
• First Posted: Jan 12, 2012
• Last Update Posted: Feb 12, 2016
• Last Verified: Jul 1, 2015

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

Study Results

Participant Flow

Arm/Group Title	Lesinurad 400 mg	Placebo
Arm/Group Description	lesinurad 400 mg
Period Title: Overall Study
STARTED	107	107
COMPLETED	84	94
NOT COMPLETED	23	13

Baseline Characteristics

Arm/Group Title	Lesinurad 400 mg	Placebo	Total
Arm/Group Description	lesinurad 400 mg	Total of all reporting groups
Overall Participants	107	107	214
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	53.6 (12.5)	55.3 (12.0)	54.4 (12.2)
Age, Customized (Number) [Number]
<65	87 81.3%	80 74.8%	167 78%
>=65	20 18.7%	27 25.2%	47 22%
Sex: Female, Male (Count of Participants)
Female	9 8.4%	10 9.3%	19 8.9%
Male	98 91.6%	97 90.7%	195 91.1%
Region of Enrollment (Number) [Number]
Australia	1 0.9%	1 0.9%	2 0.9%
Belgium	5 4.7%	4 3.7%	9 4.2%
Canada	5 4.7%	6 5.6%	11 5.1%
Germany	5 4.7%	2 1.9%	7 3.3%
New Zealand	3 2.8%	2 1.9%	5 2.3%
South Africa	12 11.2%	11 10.3%	23 10.7%
United States	76 71%	81 75.7%	157 73.4%

Outcome Measures

1. Primary Outcome

Title	Number of Subjects With an sUA Level That is < 6.0 mg/dL
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Lesinurad 400 mg	Placebo
Arm/Group Description	lesinurad 400 mg	Placebo qd
Measure Participants	107	107
Measure Subjects	107	107
Number [Number of Subjects]	32	2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lesinurad 400 mg, Placebo
	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 Ratio (RR)
	Estimated Value	0.28
	Confidence Interval	(2-Sided) 95%; 0.19 to 0.37
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Arm/Group Title	Lesinurad 400 mg		Placebo
Arm/Group Description	lesinurad 400 mg
All Cause Mortality
	Lesinurad 400 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Lesinurad 400 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/107 (8.4%)		4/107 (3.7%)
Cardiac disorders
Coronary artery disease	0/107 (0%)	0	1/107 (0.9%)	1
Pericardial effusion	0/107 (0%)	0	1/107 (0.9%)	1
General disorders
Death	1/107 (0.9%)	1	0/107 (0%)	0
Infections and infestations
Diverticulitis	0/107 (0%)	0	1/107 (0.9%)	1
Gastroenteritis	0/107 (0%)	0	1/107 (0.9%)	1
Metabolism and nutrition disorders
Gout	1/107 (0.9%)	1	1/107 (0.9%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Ovarian epithelial cancer	1/107 (0.9%)	1	0/107 (0%)	0
Renal and urinary disorders
Renal failure	2/107 (1.9%)	2	0/107 (0%)	0
Renal failure acute	2/107 (1.9%)	2	0/107 (0%)	0
Renal impairment	1/107 (0.9%)	1	0/107 (0%)	0
Calculus ureteric	1/107 (0.9%)	1	0/107 (0%)	0
Other (Not Including Serious) Adverse Events
	Lesinurad 400 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	39/107 (36.4%)		8/107 (7.5%)
Gastrointestinal disorders
Constipation	6/107 (5.6%)	6	0/107 (0%)	0
Diarrhoea	10/107 (9.3%)	10	6/107 (5.6%)	6
General disorders
Oedema peripheral	3/107 (2.8%)	4	0/107 (0%)	0
Pyrexia	3/107 (2.8%)	3	0/107 (0%)	0
Infections and infestations
Bronchitis	5/107 (4.7%)	5	2/107 (1.9%)	2
Investigations
Blood creatinine increased	9/107 (8.4%)	10	0/107 (0%)	0
Metabolism and nutrition disorders
Hyperkalaemia	3/107 (2.8%)	5	0/107 (0%)	0
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness	3/107 (2.8%)	3	0/107 (0%)	0
Renal and urinary disorders
Renal impairment	4/107 (3.7%)	5	0/107 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	4/107 (3.7%)	4	1/107 (0.9%)	1

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.