Clinical Trial Results:
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

Trial information Top of page
Trial identification
Sponsor protocol code	RDEA594-302
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, MD, Ardea Biosciences, Inc., US 858-652-6671, 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	20 Jul 2014
Is this the analysis of the primary completion data?	Yes
Primary completion date	03 Jul 2014
Global end of trial reached?	Yes
Global end of trial date	03 Jul 2014
Was the trial ended prematurely?	No
General information about the trial
Main objective of the trial	To determine the efficacy of lesinurad by Month 6 when used in combination with allopurinol compared to allopurinol monotherapy
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	16 Dec 2011
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: 309
Country: Number of subjects enrolled	Canada: 25
Country: Number of subjects enrolled	Belgium: 4
Country: Number of subjects enrolled	Germany: 25
Country: Number of subjects enrolled	Spain: 8
Country: Number of subjects enrolled	Poland: 22
Country: Number of subjects enrolled	Switzerland: 1
Country: Number of subjects enrolled	Ukraine: 74
Country: Number of subjects enrolled	New Zealand: 26
Country: Number of subjects enrolled	Australia: 17
Country: Number of subjects enrolled	South Africa: 99
Worldwide total number of subjects	610
EEA total number of subjects	59
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)	544
From 65 to 84 years	66
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 Day 1.
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 200 mg + allopurinol
Arm description	lesinurad 200 mg qd plus allopurinol
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	200 mg
Arm title	lesinurad 400 mg + allopurinol
Arm description	-
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 + allopurinol
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 200 mg + allopurinol lesinurad 400 mg + allopurinol Placebo + allopurinol Started 204 200 206 Completed 163 150 158 Not completed 41 50 48      Adverse event, serious fatal - 1 -      Consent withdrawn by subject 16 13 11      Adverse event, non-fatal 4 12 9      Gout flare 3 - 2      Lost to follow-up 5 7 11      Sponsor terminated study 5 2 3      Protocol deviation 8 15 12

Subject disposition Top of page

Baseline characteristics Top of page
Baseline characteristics reporting groups
Reporting group title	lesinurad 200 mg + allopurinol
Reporting group description	lesinurad 200 mg qd plus allopurinol
Reporting group title	lesinurad 400 mg + allopurinol
Reporting group description	-
Reporting group title	Placebo + allopurinol
Reporting group description	-
Reporting group values lesinurad 200 mg + allopurinol lesinurad 400 mg + allopurinol Placebo + allopurinol Total Number of subjects 204 200 206 610 Age categorical Units: Subjects     <65 184 175 185 544     >=65 20 25 21 66 Age Continuous | Units: years     arithmetic mean (standard deviation) 51 ± 11.1 51.3 ± 11.1 51.4 ± 10.6 - Gender, Male/Female Units: Participants     Male 197 194 196 587     Female 7 6 10 23 Region of Enrollment Units: Subjects     Australia 4 9 4 17     Belgium 1 1 2 4     Canada 7 6 12 25     Germany 9 8 8 25     New Zealand 12 7 7 26     Poland 5 11 6 22     South Africa 30 36 33 99     Spain 2 4 2 8     Switzerland 1 0 0 1     Ukraine 25 24 25 74     United States 108 94 107 309

Baseline characteristics Top of page

End points Top of page
End points reporting groups
Reporting group title	lesinurad 200 mg + allopurinol
Reporting group description	lesinurad 200 mg qd plus allopurinol
Reporting group title	lesinurad 400 mg + allopurinol
Reporting group description	-
Reporting group title	Placebo + allopurinol
Reporting group description	-

End points Top of page

Primary: Number of Subjects with sUA < 6.0 mg/dL Top of page
End point title	Number of Subjects with sUA < 6.0 mg/dL
End point description
End point type	Primary
End point timeframe	6 months, analysis after all subjects complete 12 months
End point values lesinurad 200 mg + allopurinol lesinurad 400 mg + allopurinol Placebo + allopurinol Number of subjects analysed 204 200 206 Units: Number of Subjects 113 33 48
Statistical analysis title	Number of Subjects with sUA < 6.0 mg/dL
Statistical analysis description	The primary endpoint for this study was the proportion of subjects with sUA < 6.0 mg/dL by Month 6.
Comparison groups	Placebo + allopurinol v lesinurad 200 mg + allopurinol
Number of subjects included in analysis	410
Analysis specification	Pre-specified
Analysis type	other
P-value	< 0.0001
Method	Cochran-Mantel-Haenszel
Parameter type	Risk difference (RD)
Point estimate	0.32
Confidence interval
level	95%
sides	2-sided
lower limit	0.23
upper limit	0.41
Statistical analysis title	Number of Subjects with sUA < 6.0 mg/dL
Comparison groups	lesinurad 400 mg + allopurinol v Placebo + allopurinol
Number of subjects included in analysis	406
Analysis specification	Pre-specified
Analysis type	other
P-value	< 0.0001
Method	Cochran-Mantel-Haenszel
Parameter type	Risk difference (RD)
Point estimate	0.43
Confidence interval
level	95%
sides	2-sided
lower limit	0.34
upper limit	0.52

Primary: Number of Subjects with sUA < 6.0 mg/dL Top of page

Secondary: Gout flares Top of page
End point title	Gout flares
End point 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.
End point type	Secondary
End point timeframe	12 Months
End point values lesinurad 200 mg + allopurinol lesinurad 400 mg + allopurinol Placebo + allopurinol Number of subjects analysed 204 200 206 Units: number of gout flares     arithmetic mean (standard deviation) 0.7 ± 1.4 0.8 ± 1.7 0.9 ± 1.8
Statistical analysis title	Gout flares
Statistical analysis 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.
Comparison groups	lesinurad 200 mg + allopurinol v Placebo + allopurinol
Number of subjects included in analysis	410
Analysis specification	Pre-specified
Analysis type	other
P-value	< 0.5716
Method	Negative Binomial Regression
Parameter type	Risk ratio (RR)
Point estimate	0.88
Confidence interval
level	95%
sides	2-sided
lower limit	0.57
upper limit	1.37
Statistical analysis title	Gout flares
Comparison groups	lesinurad 400 mg + allopurinol v Placebo + allopurinol
Number of subjects included in analysis	406
Analysis specification	Pre-specified
Analysis type	other
P-value	< 0.7454
Method	Negative Binomial Regression
Parameter type	Risk ratio (RR)
Point estimate	0.93
Confidence interval
level	95%
sides	2-sided
lower limit	0.6
upper limit	1.45

Secondary: Gout flares Top of page

Secondary: Tophus Top of page
End point title	Tophus
End point description	Proportion of subjects with ≥ 1 target tophus at Baseline who experience complete resolution of at least 1 target tophus by Month 12
End point type	Secondary
End point timeframe	12 months
End point values lesinurad 200 mg + allopurinol lesinurad 400 mg + allopurinol Placebo + allopurinol Number of subjects analysed 35 29 38 Units: Number of subjects 11 8 11
Statistical analysis title	Tophus
Comparison groups	lesinurad 400 mg + allopurinol v Placebo + allopurinol
Number of subjects included in analysis	67
Analysis specification	Pre-specified
Analysis type	other
P-value	< 0.6301
Method	Cochran-Mantel-Haenszel
Parameter type	Risk difference (RD)
Point estimate	-0.06
Confidence interval
level	95%
sides	2-sided
lower limit	-0.29
upper limit	0.17
Statistical analysis title	Tophus
Statistical analysis description	Proportion of subjects with greater than or equal 1 target tophus at Baseline who experience complete resolution of at least 1 target tophus by Month 12.
Comparison groups	lesinurad 200 mg + allopurinol v Placebo + allopurinol
Number of subjects included in analysis	73
Analysis specification	Pre-specified
Analysis type	other
P-value	< 0.8466
Method	Cochran-Mantel-Haenszel
Parameter type	Risk difference (RD)
Point estimate	-0.02
Confidence interval
level	95%
sides	2-sided
lower limit	-0.24
upper limit	0.2

Secondary: Tophus 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 200 mg + allopurinol
Reporting group description	-
Reporting group title	Placebo + allopurinol
Reporting group description	-
Reporting group title	lesinurad 400 mg + allopurinol
Reporting group description	-
Serious adverse events lesinurad 200 mg + allopurinol Placebo + allopurinol lesinurad 400 mg + allopurinol Total subjects affected by serious adverse events      subjects affected / exposed 9 / 204 (4.41%) 8 / 206 (3.88%) 19 / 200 (9.50%)      number of deaths (all causes) 0 0 2      number of deaths resulting from adverse events 0 0 0 Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma      subjects affected / exposed 0 / 204 (0.00%) 0 / 206 (0.00%) 1 / 200 (0.50%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 Gastric cancer      subjects affected / exposed 0 / 204 (0.00%) 0 / 206 (0.00%) 1 / 200 (0.50%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 1 Ovarian adenoma      subjects affected / exposed 1 / 204 (0.49%) 0 / 206 (0.00%) 0 / 200 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 Pancreatic neuroendocrine tumour      subjects affected / exposed 0 / 204 (0.00%) 1 / 206 (0.49%) 0 / 200 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 Parathyroid tumour benign      subjects affected / exposed 1 / 204 (0.49%) 0 / 206 (0.00%) 0 / 200 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 Prostate cancer      subjects affected / exposed 0 / 204 (0.00%) 0 / 206 (0.00%) 1 / 200 (0.50%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 Vascular disorders Hypertensive crisis      subjects affected / exposed 0 / 204 (0.00%) 0 / 206 (0.00%) 1 / 200 (0.50%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 General disorders and administration site conditions Adverse drug reaction      subjects affected / exposed 1 / 204 (0.49%) 0 / 206 (0.00%) 0 / 200 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 Non-cardiac chest pain      subjects affected / exposed 1 / 204 (0.49%) 0 / 206 (0.00%) 0 / 200 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 Respiratory, thoracic and mediastinal disorders Pulmonary oedema      subjects affected / exposed 0 / 204 (0.00%) 0 / 206 (0.00%) 1 / 200 (0.50%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 1 Psychiatric disorders Depression      subjects affected / exposed 1 / 204 (0.49%) 0 / 206 (0.00%) 0 / 200 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 Dissociative disorder      subjects affected / exposed 0 / 204 (0.00%) 0 / 206 (0.00%) 1 / 200 (0.50%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 Injury, poisoning and procedural complications Femur fracture      subjects affected / exposed 0 / 204 (0.00%) 1 / 206 (0.49%) 0 / 200 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 Multiple drug overdose      subjects affected / exposed 1 / 204 (0.49%) 0 / 206 (0.00%) 0 / 200 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 Multiple injuries      subjects affected / exposed 1 / 204 (0.49%) 0 / 206 (0.00%) 0 / 200 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 Cardiac disorders Atrial fibrillation      subjects affected / exposed 1 / 204 (0.49%) 0 / 206 (0.00%) 0 / 200 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 Coronary artery disease      subjects affected / exposed 0 / 204 (0.00%) 0 / 206 (0.00%) 1 / 200 (0.50%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 Intracardiac thrombus      subjects affected / exposed 0 / 204 (0.00%) 0 / 206 (0.00%) 1 / 200 (0.50%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 Myocardial infarction      subjects affected / exposed 0 / 204 (0.00%) 0 / 206 (0.00%) 3 / 200 (1.50%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 3      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 Nervous system disorders Subarachnoid haemorrhage      subjects affected / exposed 0 / 204 (0.00%) 1 / 206 (0.49%) 0 / 200 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 Gastrointestinal disorders Duodenal ulcer haemorrhage      subjects affected / exposed 0 / 204 (0.00%) 1 / 206 (0.49%) 1 / 200 (0.50%)      occurrences causally related to treatment / all 0 / 0 0 / 1 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 Gastrointestinal haemorrhage      subjects affected / exposed 1 / 204 (0.49%) 0 / 206 (0.00%) 0 / 200 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 Renal and urinary disorders Nephrolithiasis      subjects affected / exposed 0 / 204 (0.00%) 0 / 206 (0.00%) 2 / 200 (1.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 2 / 2      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 Renal failure acute      subjects affected / exposed 0 / 204 (0.00%) 1 / 206 (0.49%) 1 / 200 (0.50%)      occurrences causally related to treatment / all 0 / 0 0 / 1 1 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 Renal impairment      subjects affected / exposed 0 / 204 (0.00%) 0 / 206 (0.00%) 1 / 200 (0.50%)      occurrences causally related to treatment / all 0 / 0 0 / 0 1 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 Musculoskeletal and connective tissue disorders Arthralgia      subjects affected / exposed 1 / 204 (0.49%) 0 / 206 (0.00%) 0 / 200 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 Back pain      subjects affected / exposed 1 / 204 (0.49%) 0 / 206 (0.00%) 0 / 200 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 Flank pain      subjects affected / exposed 1 / 204 (0.49%) 0 / 206 (0.00%) 0 / 200 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 Intervertebral disc degeneration      subjects affected / exposed 0 / 204 (0.00%) 0 / 206 (0.00%) 1 / 200 (0.50%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 Osteoarthritis      subjects affected / exposed 0 / 204 (0.00%) 0 / 206 (0.00%) 2 / 200 (1.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 2      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 Infections and infestations Abscess limb      subjects affected / exposed 0 / 204 (0.00%) 1 / 206 (0.49%) 0 / 200 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 Appendicitis      subjects affected / exposed 0 / 204 (0.00%) 1 / 206 (0.49%) 0 / 200 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 Bronchopneumonia      subjects affected / exposed 0 / 204 (0.00%) 0 / 206 (0.00%) 1 / 200 (0.50%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 Cellulitis      subjects affected / exposed 0 / 204 (0.00%) 0 / 206 (0.00%) 1 / 200 (0.50%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 Diverticulitis      subjects affected / exposed 0 / 204 (0.00%) 1 / 206 (0.49%) 0 / 200 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 Empyema      subjects affected / exposed 1 / 204 (0.49%) 0 / 206 (0.00%) 0 / 200 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 Pneumonia      subjects affected / exposed 2 / 204 (0.98%) 0 / 206 (0.00%) 0 / 200 (0.00%)      occurrences causally related to treatment / all 0 / 2 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 Pyelonephritis chronic      subjects affected / exposed 0 / 204 (0.00%) 0 / 206 (0.00%) 1 / 200 (0.50%)      occurrences causally related to treatment / all 0 / 0 0 / 0 1 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 Sinobronchitis      subjects affected / exposed 1 / 204 (0.49%) 0 / 206 (0.00%) 0 / 200 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 Metabolism and nutrition disorders Gout      subjects affected / exposed 0 / 204 (0.00%) 0 / 206 (0.00%) 2 / 200 (1.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 3 / 4      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0
Frequency threshold for reporting non-serious adverse events: 0.02%
Non-serious adverse events lesinurad 200 mg + allopurinol Placebo + allopurinol lesinurad 400 mg + allopurinol Total subjects affected by non serious adverse events      subjects affected / exposed 85 / 204 (41.67%) 60 / 206 (29.13%) 82 / 200 (41.00%) Investigations Blood creatinine increased      subjects affected / exposed 8 / 204 (3.92%) 7 / 206 (3.40%) 19 / 200 (9.50%)      occurrences all number 9 7 24 Injury, poisoning and procedural complications Joint sprain      subjects affected / exposed 9 / 204 (4.41%) 4 / 206 (1.94%) 2 / 200 (1.00%)      occurrences all number 9 4 2 Vascular disorders Hypertension      subjects affected / exposed 17 / 204 (8.33%) 10 / 206 (4.85%) 16 / 200 (8.00%)      occurrences all number 17 10 16 Nervous system disorders Headache      subjects affected / exposed 10 / 204 (4.90%) 8 / 206 (3.88%) 12 / 200 (6.00%)      occurrences all number 11 8 13 Gastrointestinal disorders Diarrhoea      subjects affected / exposed 10 / 204 (4.90%) 7 / 206 (3.40%) 14 / 200 (7.00%)      occurrences all number 13 8 21 Gastrooesophageal reflux disease      subjects affected / exposed 10 / 204 (4.90%) 1 / 206 (0.49%) 4 / 200 (2.00%)      occurrences all number 10 1 4 Respiratory, thoracic and mediastinal disorders Oropharyngeal pain      subjects affected / exposed 5 / 204 (2.45%) 0 / 206 (0.00%) 1 / 200 (0.50%)      occurrences all number 5 0 1 Musculoskeletal and connective tissue disorders Arthralgia      subjects affected / exposed 24 / 204 (11.76%) 9 / 206 (4.37%) 6 / 200 (3.00%)      occurrences all number 24 14 7 Infections and infestations Bronchitis      subjects affected / exposed 9 / 204 (4.41%) 4 / 206 (1.94%) 4 / 200 (2.00%)      occurrences all number 9 5 4 Influenza      subjects affected / exposed 14 / 204 (6.86%) 4 / 206 (1.94%) 8 / 200 (4.00%)      occurrences all number 17 4 9 Upper respiratory tract infection      subjects affected / exposed 14 / 204 (6.86%) 21 / 206 (10.19%) 30 / 200 (15.00%)      occurrences all number 16 23 39

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
28 Aug 2012	This amendment addressed comments from the US FDA and incorporated newly acquired information regarding the inherent inter-day variability of serum urate to teh screening serum urate eligbility criteria.
20 Jun 2013	This amendment expanded the guidance on subject hydration and expanded the management algorithm if a subject experiences an elevated serum creatinine or kidney stone.
24 Dec 2013	This amendment clarified the risks associated with lesinurad in the monotherapy setting and emphasized the requirement for subjects to concomitantly take lesinurad with a xanthine oxidase inhibitor.
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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