Lesinurad and Febuxostat Combination Extension Study in Gout

• Sponsor: Ardea Biosciences, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01808144
• Collaborator: (none)
• Enrollment: 196
• Locations: 72
• Arms: 2
• Actual Duration (Months): 43.2
• Patients Per Site: 2.7
• 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 in combination with febuxostat over a long-term timeframe.

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

Detailed Description

This is a Phase 3 extension study to assess the long-term efficacy and safety of lesinurad in combination with febuxostat in subjects who completed the double-blind treatment period in Study RDEA594-304.

Study Design

• Study Type: Interventional
• Actual Enrollment: 196 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Long-Term Extension Study of Lesinurad in Combination With Febuxostat for Subjects With Gout Completing an Efficacy and Safety Study of Lesinurad and Febuxostat
• Actual Study Start Date: Mar 1, 2013
• Actual Primary Completion Date: Aug 9, 2016
• Actual Study Completion Date: Oct 6, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: lesinurad 400 mg + febuxostat 80 mg Patients on lesinurad 400 mg had their dose changed to lesinurad 200 mg after implementation of protocol amendment 3, dated 07 October 2015.	Drug: lesinurad; Tablets, 400 mg once daily (QD); Drug: febuxostat; Tabletsm 80 mg QD
Experimental: lesinurad 200 mg + febuxostat 80 mg	Drug: lesinurad; Tablets, 200 mg QD; Drug: febuxostat; Tabletsm 80 mg QD

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With an sUA Level That is < 5.0 mg/dL [Up to approximately 2.5 years (at Extension Month 12)]

   Percentage of participants in Study 307 With sUA < 5.0 mg/dL from the Core Studies 304 and Extension Study 307 - Observed Cases

Secondary Outcome Measures

1. Percentage of Participants (With at Least One Target Tophus at Baseline) Who Experience Complete Resolution of at Least One Target Tophus [Up to approximatley 2.5 years (at Extension Month 12)]

   Percentage of participants (With at Least One Target Tophus at Baseline) Who Experience Complete Resolution of at Least One Target Tophus During the Core and Extension Studies at Extension Month 12 (Observed Cases)

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 and the risks involved and is willing to provide written informed consent before the first study related activity.

• Subject completed the double-blind treatment period in Study RDEA594-304 and was actively receiving and tolerating study medication (lesinurad or placebo) and febuxostat 80 mg at the Month 12 visit.

• Subject is male or female; female subjects of childbearing potential must agree to use an effective non-hormonal method of birth control during the study and for at least 14 days after the last dose of study medication.

Exclusion Criteria:

• Subject has any medical or psychological condition, which in the opinion of the Investigator and/or the 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		Tempe	Arizona	United States	85282
3		Glendale	California	United States	91204
4		Huntington Beach	California	United States	92646
5		Irvine	California	United States	92618
6		San Diego	California	United States	92108
7		Denver	Colorado	United States	80220
8		Englewood	Colorado	United States	80113
9		Boynton Beach	Florida	United States	33472
10		Naples	Florida	United States	34102
11		Pembroke Pines	Florida	United States	33027
12		Tampa	Florida	United States	33606
13		Tampa	Florida	United States	33614
14		Winter Haven	Florida	United States	33880
15		Johns Creek	Georgia	United States	30097
16		Honolulu	Hawaii	United States	96814
17		Meridian	Idaho	United States	83646
18		Gurnee	Illinois	United States	60031
19		Springfield	Illinois	United States	62704
20		Elizabethtown	Kentucky	United States	42701
21		Frederick	Maryland	United States	21702
22		Ann Arbor	Michigan	United States	48109
23		Southfield	Michigan	United States	48034
24		Jackson	Mississippi	United States	39202
25		Olive Branch	Mississippi	United States	38654
26		Jefferson City	Missouri	United States	65109
27		Saint Louis	Missouri	United States	63117
28		New York	New York	United States	10036
29		Wilmington	North Carolina	United States	28401
30		Fargo	North Dakota	United States	58103
31		Columbus	Ohio	United States	43203
32		Middleburg Heights	Ohio	United States	44130
33		Wadsworth	Ohio	United States	44281
34		Oklahoma City	Oklahoma	United States	73103
35		Belle Vernon	Pennsylvania	United States	15012
36		Lansdale	Pennsylvania	United States	19446
37		Pittsburgh	Pennsylvania	United States	15206
38		Sellersville	Pennsylvania	United States	18960
39		Columbia	South Carolina	United States	29204
40		Mount Pleasant	South Carolina	United States	29464
41		Spartanburg	South Carolina	United States	29303
42		Memphis	Tennessee	United States	38119
43		Austin	Texas	United States	78705
44		Austin	Texas	United States	78758
45		Dallas	Texas	United States	75218
46		Houston	Texas	United States	77074
47		San Antonio	Texas	United States	78229
48		Sugar Land	Texas	United States	77479
49		Victoria	Texas	United States	77901
50		Waco	Texas	United States	76710
51		Chesapeake	Virginia	United States	23320
52		Danville	Virginia	United States	24541
53		Richmond	Virginia	United States	23235
54		Seattle	Washington	United States	98104
55		Morgantown	West Virginia	United States	26505
56		Camperdown	New South Wales	Australia	2050
57		Woodville South	South Australia	Australia	5011
58		Hobart	Tasmania	Australia	7000
59		Mississauga	Ontario	Canada	L5M 2V8
60		Toronto	Ontario	Canada	M9W4L6
61		Grafton	Auckland	New Zealand	1023
62		Tauranga		New Zealand	3143
63		Kutno	Iodzkie	Poland	99-300
64		Krakow	Malopolskie	Poland	30-510
65		Krakow	Malopolskie	Poland	31-501
66		Bialystok	Podlaskie	Poland	15-430
67		Katowice	Slaskie	Poland	40-954
68		Konskie	Swietokrzyskie	Poland	26-200
69		Elblag	Warminsko-Mazurskie	Poland	82-300
70		Poznan	Wielkopolskie	Poland	60-773
71		Fribourg		Switzerland	1705
72		Fribourg		Switzerland	1708

Sponsors and Collaborators

• Ardea Biosciences, Inc.

Investigators

• Study Director: Nihar Bhakta, MD, Ardea Biosciences, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ardea Biosciences, Inc.
• ClinicalTrials.gov Identifier: NCT01808144
• Other Study ID Numbers: RDEA594-307; 2012-004390-54
• First Posted: Mar 11, 2013
• Last Update Posted: Jan 30, 2018
• Last Verified: Jan 1, 2018

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

Study Results

Participant Flow

Recruitment Details	Subjects entered this extension Study RDEA594-307 while the core Study RDEA594-304 was ongoing and the database was not yet locked. To maintain the blind of the core study for subjects entering the extension, the lesinurad dose for all subjects in this extension study was blinded to the Sponsor until database lock of Study RDEA594-304.
Pre-assignment Detail	Subjects randomized to lesinurad (RDEA594) 200 mg or 400 mg + febuxostat (FBX) 80 mg in Study RDEA594-304 continued to receive the same dose in this study. Subjects randomized to placebo + febuxostat 80 mg in Study RDEA594-304 were randomized in a double-blind, 1:1 fashion to either lesinurad 200 mg or 400 mg + febuxostat 80 mg.

Arm/Group Title	Lesinurad 200 mg + Febuxostat 80 mg	Lesinurad 400 mg + Febuxostat 80 mg
Arm/Group Description
Period Title: Overall Study
STARTED	97	99
COMPLETED	57	51
NOT COMPLETED	40	48

Baseline Characteristics

Arm/Group Title	Lesinurad 400 mg + Febuxostat 80 mg	Lesinurad 200 mg + Febuxostat 80 mg	Total
Arm/Group Description	Total of all reporting groups
Overall Participants	99	97	196
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	52.1 (10.58)	52.9 (10.24)	52.5 (10.41)
Age, Customized (Number) [Number]
< 65 years	88 88.9%	87 89.7%	175 89.3%
>=65 years	11 11.1%	10 10.3%	21 10.7%
Sex/Gender, Customized (Participant) [Number]
Male	7	1	8
Female	92	96	188
Region of Enrollment (Number) [Number]
United States	72 72.7%	72 74.2%	144 73.5%
Canada	2 2%	6 6.2%	8 4.1%
Poland	12 12.1%	13 13.4%	25 12.8%
Switzerland	1 1%	0 0%	1 0.5%
Australia	5 5.1%	3 3.1%	8 4.1%
New Zealand	7 7.1%	3 3.1%	10 5.1%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With an sUA Level That is < 5.0 mg/dL
Description	Percentage of participants in Study 307 With sUA < 5.0 mg/dL from the Core Studies 304 and Extension Study 307 - Observed Cases
Time Frame	Up to approximately 2.5 years (at Extension Month 12)

Outcome Measure Data

Analysis Population Description

Number of Participants Analyzed for this Outcome Measure reflects the number of participants who completed Extension Month 12.

Arm/Group Title	Lesinurad 400 mg + Febuxostat 80 mg	Lesinurad 200 mg + Febuxostat 80 mg
Arm/Group Description
Measure Participants	80	72
Number [Percentage of participants]	82.5 83.3%	77.8 80.2%

2. Secondary Outcome

Title	Percentage of Participants (With at Least One Target Tophus at Baseline) Who Experience Complete Resolution of at Least One Target Tophus
Description	Percentage of participants (With at Least One Target Tophus at Baseline) Who Experience Complete Resolution of at Least One Target Tophus During the Core and Extension Studies at Extension Month 12 (Observed Cases)
Time Frame	Up to approximatley 2.5 years (at Extension Month 12)

Outcome Measure Data

Analysis Population Description

ITT Population Number of Participants Analyzed for this Outcome Measure reflects the number of participants who completed through Month 12.

Arm/Group Title	Lesinurad 400 mg + Febuxostat 80 mg	Lesinurad 200 mg + Febuxostat 80 mg
Arm/Group Description
Measure Participants	77	70
Number [Percentage of participants]	61.0 61.6%	54.3 56%

Adverse Events

Time Frame	Up to approximately 2.5 years (at Extension Month 12)
Arm/Group Title	Lesinurad 200 mg + Febuxostat 80 mg		Lesinurad 400 mg + Febuxostat 80 mg
Arm/Group Description
All Cause Mortality
	Lesinurad 200 mg + Febuxostat 80 mg		Lesinurad 400 mg + Febuxostat 80 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/97 (1%)		0/99 (0%)
Serious Adverse Events
	Lesinurad 200 mg + Febuxostat 80 mg		Lesinurad 400 mg + Febuxostat 80 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/97 (16.5%)		19/99 (19.2%)
Blood and lymphatic system disorders
Anaemia	1/97 (1%)	1	0/99 (0%)	0
Cardiac disorders
Atrial fibrillation	2/97 (2.1%)	2	0/99 (0%)	0
Cardiac failure	1/97 (1%)	1	0/99 (0%)	0
Myocardial infarction	0/97 (0%)	0	1/99 (1%)	1
Gastrointestinal disorders
Abdominal pain upper	0/97 (0%)	0	1/99 (1%)	1
Gastrointestinal haemorrhage	1/97 (1%)	1	0/99 (0%)	0
Umbilical hernia	0/97 (0%)	0	1/99 (1%)	1
Hepatobiliary disorders
Cholecystitis	1/97 (1%)	1	0/99 (0%)	0
Infections and infestations
Pneumonia	2/97 (2.1%)	2	1/99 (1%)	1
Cellulitis	1/97 (1%)	1	0/99 (0%)	0
Device related infection	1/97 (1%)	1	0/99 (0%)	0
Diverticulitis	1/97 (1%)	1	0/99 (0%)	0
Localised infection	0/97 (0%)	0	1/99 (1%)	1
Urosepsis	0/97 (0%)	0	1/99 (1%)	1
Metabolism and nutrition disorders
Gout	1/97 (1%)	1	0/99 (0%)	0
Hyperglycaemia	0/97 (0%)	0	1/99 (1%)	1
Musculoskeletal and connective tissue disorders
Joint destruction	0/97 (0%)	0	1/99 (1%)	1
Lumbar spinal stenosis	0/97 (0%)	0	1/99 (1%)	1
Nervous system disorders
Cerebrovascular accident	1/97 (1%)	1	0/99 (0%)	0
Subarachnoid haemorrhage	1/97 (1%)	1	0/99 (0%)	0
Syncope	0/97 (0%)	0	1/99 (1%)	1
Psychiatric disorders
Depression	0/97 (0%)	0	1/99 (1%)	1
Renal and urinary disorders
Nephrolithiasis	0/97 (0%)	0	2/99 (2%)	2
Renal failure acute	0/97 (0%)	0	2/99 (2%)	2
Renal impairment	1/97 (1%)	1	0/99 (0%)	0
Stag horn calculus	0/97 (0%)	0	1/99 (1%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/97 (1%)	1	1/99 (1%)	1
Epistaxis	0/97 (0%)	0	1/99 (1%)	1
Vascular disorders
Hypertension	0/97 (0%)	0	1/99 (1%)	1
Other (Not Including Serious) Adverse Events
	Lesinurad 200 mg + Febuxostat 80 mg		Lesinurad 400 mg + Febuxostat 80 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	61/97 (62.9%)		70/99 (70.7%)
Gastrointestinal disorders
Toothache	4/97 (4.1%)	4	5/99 (5.1%)	5
Gastrooesophageal reflux disease	5/97 (5.2%)	5	1/99 (1%)	1
Nausea	2/97 (2.1%)	2	2/99 (2%)	2
General disorders
Influenza like illness	0/97 (0%)	0	4/99 (4%)	4
Pyrexia	0/97 (0%)	0	3/99 (3%)	5
Infections and infestations
Nasopharyngitis	6/97 (6.2%)	6	14/99 (14.1%)	20
Bronchitis	11/97 (11.3%)	12	4/99 (4%)	5
Upper respiratory tract infection	8/97 (8.2%)	10	6/99 (6.1%)	9
Sinusitis	8/97 (8.2%)	8	5/99 (5.1%)	5
Urinary tract infection	6/97 (6.2%)	11	5/99 (5.1%)	5
Influenza	0/97 (0%)	0	6/99 (6.1%)	7
Cellulitis	3/97 (3.1%)	3	2/99 (2%)	2
Tooth abscess	1/97 (1%)	1	2/99 (2%)	2
Pharyngitis	0/97 (0%)	0	2/99 (2%)	2
Injury, poisoning and procedural complications
Laceration	0/97 (0%)	0	6/99 (6.1%)	6
Muscle strain	6/97 (6.2%)	7	0/99 (0%)	0
Investigations
Blood creatinine increased	11/97 (11.3%)	14	13/99 (13.1%)	15
Creatinine renal clearance decreased	5/97 (5.2%)	6	3/99 (3%)	3
Gamma-glutamyltransferase increased	2/97 (2.1%)	2	4/99 (4%)	6
C-reactive protein increased	2/97 (2.1%)	3	2/99 (2%)	2
Liver function test abnormal	1/97 (1%)	1	2/99 (2%)	2
Metabolism and nutrition disorders
Diabetes mellitus	0/97 (0%)	0	5/99 (5.1%)	6
Hyperlipidaemia	0/97 (0%)	0	2/99 (2%)	2
Vitamin D deficiency	0/97 (0%)	0	2/99 (2%)	2
Musculoskeletal and connective tissue disorders
Back pain	6/97 (6.2%)	10	5/99 (5.1%)	5
Arthralgia	4/97 (4.1%)	5	6/99 (6.1%)	11
Osteoarthritis	5/97 (5.2%)	5	4/99 (4%)	4
Musculoskeletal pain	5/97 (5.2%)	5	2/99 (2%)	2
Bursitis	3/97 (3.1%)	3	2/99 (2%)	2
Myalgia	2/97 (2.1%)	2	3/99 (3%)	3
Joint swelling	0/97 (0%)	0	4/99 (4%)	4
Flank pain	0/97 (0%)	0	2/99 (2%)	3
Neck pain	2/97 (2.1%)	2	0/99 (0%)	0
Nervous system disorders
Headache	5/97 (5.2%)	6	7/99 (7.1%)	9
Psychiatric disorders
Insomnia	4/97 (4.1%)	4	0/99 (0%)	0
Reproductive system and breast disorders
Benign prostatic hyperplasia	1/97 (1%)	1	6/99 (6.1%)	7
Vascular disorders
Hypertension	6/97 (6.2%)	6	10/99 (10.1%)	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.