Clinical Trial Results:
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.

Trial information Top of page
Trial identification
Sponsor protocol code	RDEA594-303
Additional study identifiers
ISRCTN number	-
US NCT number	-
WHO universal trial number (UTN)	-
Sponsors
Sponsor organisation name	Ardea Biosciences, Inc.
Sponsor organisation address	9390 Towne Centre Dr, San Diego, United States, 92121
Public contact	Nihar Bhakta, Ardea Biosciences, Inc., US 858-652-6522, nbhakta@ardeabio.com
Scientific contact	Nihar Bhakta, MD, Ardea Biosciences, Inc., US 858-652-6671, nbhakta@ardeabio.com
Paediatric regulatory details
Is trial part of an agreed paediatric investigation plan (PIP)	No
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?	No
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?	No
Results analysis stage
Analysis stage	Final
Date of interim/final analysis	31 Oct 2013
Is this the analysis of the primary completion data?	Yes
Primary completion date	23 Oct 2013
Global end of trial reached?	Yes
Global end of trial date	23 Oct 2013
Was the trial ended prematurely?	No
General information about the trial
Main objective of the trial	To determine the efficacy of lesinurad monotherapy at Month 6 compared to placebo.
Protection of trial subjects	This study was conducted in accordance with the protocol, International Conference on Harmonisation (ICH) E6 Good Clinical Practice (GCP), the Declaration of Helsinki (2008), and all other applicable regulatory requirements.
Background therapy	-
Evidence for comparator	-
Actual start date of recruitment	03 Feb 2012
Long term follow-up planned	No
Independent data monitoring committee (IDMC) involvement?	Yes
Population of trial subjects
Number of subjects enrolled per country
Country: Number of subjects enrolled	United States: 157
Country: Number of subjects enrolled	Belgium: 9
Country: Number of subjects enrolled	Canada: 11
Country: Number of subjects enrolled	Germany: 7
Country: Number of subjects enrolled	New Zealand: 5
Country: Number of subjects enrolled	Australia: 2
Country: Number of subjects enrolled	South Africa: 23
Worldwide total number of subjects	214
EEA total number of subjects	16
Number of subjects enrolled per age group
In utero	0
Preterm newborn - gestational age < 37 wk	0
Newborns (0-27 days)	0
Infants and toddlers (28 days-23 months)	0
Children (2-11 years)	0
Adolescents (12-17 years)	0
Adults (18-64 years)	167
From 65 to 84 years	47
85 years and over	0

Trial information Top of page

Subject disposition Top of page
Recruitment
Recruitment details	-
Pre-assignment
Screening details	Screening procedures to determine subject eligibility were performed within approximately 28 days prior to the first dose of randomized study medication (lesinurad or placebo) on Day 1. Subjects had to have an sUA level ≥ 6.5 mg/dL (387 μmol/L) at the Screening and Day -7 Visits for study eligibility.
Period 1
Period 1 title	Overall Study (overall period)
Is this the baseline period?	Yes
Allocation method	Randomised - controlled
Blinding used	Double blind
Roles blinded	Subject, Investigator
Arms
Are arms mutually exclusive	Yes
Arm title	lesinurad 400 mg
Arm description	lesinurad 400 mg
Arm type	Experimental
Investigational medicinal product name	lesinurad
Investigational medicinal product code
Other name
Pharmaceutical forms	Tablet
Routes of administration	Oral use
Dosage and administration details	400 mg
Arm title	Placebo
Arm description	-
Arm type	Placebo Comparator
Investigational medicinal product name	No investigational medicinal product assigned in this arm
Number of subjects in period 1 lesinurad 400 mg Placebo Started 107 107 Completed 84 94 Not completed 23 13      Consent withdrawn by subject 11 7      Adverse event, non-fatal 7 3      Gout flare 2 -      Lost to follow-up 1 2      Protocol deviation 2 1

Subject disposition Top of page

Baseline characteristics Top of page
Baseline characteristics reporting groups
Reporting group title	lesinurad 400 mg
Reporting group description	lesinurad 400 mg
Reporting group title	Placebo
Reporting group description	-
Reporting group values lesinurad 400 mg Placebo Total Number of subjects 107 107 214 Age categorical Units: Subjects     <65 years 87 80 167     >=65 years 20 27 47 Age Continuous | Units: Years     arithmetic mean (standard deviation) 53.6 ± 12.5 55.3 ± 12 - Gender, Male/Female Units: Participants     Male 98 97 195     Female 9 10 19 Region of Enrollment Units: Subjects     Australia 1 1 2     Belgium 5 4 9     Canada 5 6 11     Germany 5 2 7     New Zealand 3 2 5     South Africa 12 11 23     United States 76 81 157

Baseline characteristics Top of page

End points Top of page
End points reporting groups
Reporting group title	lesinurad 400 mg
Reporting group description	lesinurad 400 mg
Reporting group title	Placebo
Reporting group description	-

End points Top of page

Primary: Number of subjects with an sUA level that is < 6.0 mg/dL Top of page
End point title	Number of subjects with an sUA level that is < 6.0 mg/dL
End point description
End point type	Primary
End point timeframe	6 months
End point values lesinurad 400 mg Placebo Number of subjects analysed 107 107 Units: Number of Subjects 32 2
Statistical analysis title	sUA level that is < 6.0 mg/dL
Comparison groups	lesinurad 400 mg v Placebo
Number of subjects included in analysis	214
Analysis specification	Pre-specified
Analysis type
P-value	< 0.0001
Method	Cochran-Mantel-Haenszel
Parameter type	Risk difference (RD)
Point estimate	0.28
Confidence interval
level	95%
sides	2-sided
lower limit	0.19
upper limit	0.37

Primary: Number of subjects with an sUA level that is < 6.0 mg/dL Top of page

Adverse events Top of page
Adverse events information
Timeframe for reporting adverse events	Adverse events were assessed from the time the subject provided informed consent through the duration of the study.
Assessment type	Systematic
Dictionary used for adverse event reporting
Dictionary name	MedDRA
Dictionary version	14.0
Reporting groups
Reporting group title	lesinurad 400 mg
Reporting group description	lesinurad 400 mg
Reporting group title	Placebo
Reporting group description	-
Serious adverse events lesinurad 400 mg Placebo Total subjects affected by serious adverse events      subjects affected / exposed 9 / 107 (8.41%) 4 / 107 (3.74%)      number of deaths (all causes) 1 0      number of deaths resulting from adverse events 0 0 Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian epithelial cancer      subjects affected / exposed 1 / 107 (0.93%) 0 / 107 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 Cardiac disorders Coronary artery disease      subjects affected / exposed 0 / 107 (0.00%) 1 / 107 (0.93%)      occurrences causally related to treatment / all 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 Pericardial effusion      subjects affected / exposed 0 / 107 (0.00%) 1 / 107 (0.93%)      occurrences causally related to treatment / all 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 Nervous system disorders Carpal tunnel syndrome      subjects affected / exposed 1 / 107 (0.93%) 0 / 107 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 General disorders and administration site conditions Death      subjects affected / exposed 1 / 107 (0.93%) 0 / 107 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 1 0 / 0 Renal and urinary disorders Calculus ureteric      subjects affected / exposed 1 / 107 (0.93%) 0 / 107 (0.00%)      occurrences causally related to treatment / all 1 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 Renal failure      subjects affected / exposed 2 / 107 (1.87%) 0 / 107 (0.00%)      occurrences causally related to treatment / all 1 / 2 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 Renal failure acute      subjects affected / exposed 2 / 107 (1.87%) 0 / 107 (0.00%)      occurrences causally related to treatment / all 2 / 2 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 Renal impairment      subjects affected / exposed 1 / 107 (0.93%) 0 / 107 (0.00%)      occurrences causally related to treatment / all 1 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 Infections and infestations Diverticulitis      subjects affected / exposed 0 / 107 (0.00%) 1 / 107 (0.93%)      occurrences causally related to treatment / all 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 Gastroenteritis      subjects affected / exposed 0 / 107 (0.00%) 1 / 107 (0.93%)      occurrences causally related to treatment / all 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 Metabolism and nutrition disorders Gout      subjects affected / exposed 1 / 107 (0.93%) 1 / 107 (0.93%)      occurrences causally related to treatment / all 0 / 1 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0
Frequency threshold for reporting non-serious adverse events: 0.02%
Non-serious adverse events lesinurad 400 mg Placebo Total subjects affected by non serious adverse events      subjects affected / exposed 39 / 107 (36.45%) 8 / 107 (7.48%) Investigations Blood creatinine increased      subjects affected / exposed 9 / 107 (8.41%) 0 / 107 (0.00%)      occurrences all number 10 0 General disorders and administration site conditions Oedema peripheral      subjects affected / exposed 3 / 107 (2.80%) 0 / 107 (0.00%)      occurrences all number 4 0 Pyrexia      subjects affected / exposed 3 / 107 (2.80%) 0 / 107 (0.00%)      occurrences all number 3 0 Gastrointestinal disorders Constipation      subjects affected / exposed 6 / 107 (5.61%) 0 / 107 (0.00%)      occurrences all number 6 0 Diarrhoea      subjects affected / exposed 10 / 107 (9.35%) 6 / 107 (5.61%)      occurrences all number 10 6 Respiratory, thoracic and mediastinal disorders Cough      subjects affected / exposed 4 / 107 (3.74%) 1 / 107 (0.93%)      occurrences all number 4 1 Renal and urinary disorders Renal impairment      subjects affected / exposed 4 / 107 (3.74%) 0 / 107 (0.00%)      occurrences all number 5 0 Musculoskeletal and connective tissue disorders Musculoskeletal stiffness      subjects affected / exposed 3 / 107 (2.80%) 0 / 107 (0.00%)      occurrences all number 3 0 Infections and infestations Bronchitis      subjects affected / exposed 5 / 107 (4.67%) 2 / 107 (1.87%)      occurrences all number 5 2 Metabolism and nutrition disorders Hyperkalaemia      subjects affected / exposed 3 / 107 (2.80%) 0 / 107 (0.00%)      occurrences all number 5 0

Adverse events Top of page

More information Top of page
Substantial protocol amendments (globally)
Were there any global substantial amendments to the protocol? Yes
Date	Amendment
06 Jul 2012	This amendment addressed comments from the FDA and clarified procedures and process for study conduct.
17 Jun 2013	This amendment expanded guidance on subject hydration and expanded the management algorithm if a subject experiences an elevated serum creatinine or kidney stones.
Interruptions (globally)
Were there any global interruptions to the trial? No
Limitations and caveats
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
None reported

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