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Combining Lesinurad With Allopurinol in Inadequate Responders (CLEAR 2)

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ClinicalTrials.gov Identifier: NCT01493531
Recruitment Status : Completed
First Posted : December 16, 2011
Results First Posted : May 26, 2016
Last Update Posted : May 26, 2016
Sponsor:
Information provided by (Responsible Party):
Ardea Biosciences, Inc.

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: 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

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Study Type : Interventional  (Clinical Trial)
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 : December 2011
Actual Primary Completion Date : May 2014
Actual Study Completion Date : July 2014

Resource links provided by the National Library of Medicine

Genetics Home Reference related topics: Gout
MedlinePlus related topics: Gout

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




Primary Outcome Measures :
  1. Subjects With a Serum Urate (sUA) < 6.0 mg/dL by Month 6. [ Time Frame: 6 months ]
    Proportion of subjects with an sUA level that is < 6.0 mg/dL by Month 6.


Secondary Outcome Measures :
  1. Gout Flares [ Time Frame: 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 [ Time Frame: 12 months ]
    Proportion of subjects with ≥ 1 target tophus at Baseline who experience complete resolution of at least 1 target tophus by Month 12



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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01493531


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Locations
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United States, Alabama
Mobile, Alabama, United States, 36608
United States, Arizona
Chandler, Arizona, United States, 85224
Mesa, Arizona, United States, 85203
Pheonix, Arizona, United States, 85028
United States, Arkansas
Jonesboro, Arkansas, United States, 72401
Jonesboro, Arkansas, United States, 72404
Little Rock, Arkansas, United States, 72223
United States, California
Anaheim, California, United States, 92805
Gold River, California, United States, 95670
Irvine, California, United States, 92618
La Jolla, California, United States, 92037
Roseville, California, United States, 95661
San Diego, California, United States, 92108
San Diego, California, United States, 92123
San Ramon, California, United States, 94582
United States, Colorado
Colorado Springs, Colorado, United States, 80922
Denver, Colorado, United States, 80220
Glenwood Springs, Colorado, United States, 81601
United States, Connecticut
Trumbull, Connecticut, United States, 06611
United States, District of Columbia
Washington DC, District of Columbia, United States, 20060
Washington, District of Columbia, United States, 20422
United States, Florida
Boynton Beach, Florida, United States, 33472
Brandon, Florida, United States, 33511
Fleming Island, Florida, United States, 32003
Jacksonville, Florida, United States, 32205
Jacksonville, Florida, United States, 32216
Jupiter, Florida, United States, 33458
Plant City, Florida, United States, 33563
Tampa, Florida, United States, 33606
Tampa, Florida, United States, 33607
Winter Haven, Florida, United States, 33880
United States, Georgia
Dunwoody, Georgia, United States, 30338
Roswell, Georgia, United States, 30075
Savannah, Georgia, United States, 31406
United States, Idaho
Boise, Idaho, United States, 83702
Meridian, Idaho, United States, 83642
United States, Illinois
Addison, Illinois, United States, 60101
Chicago, Illinois, United States, 60602
United States, Indiana
Evansville, Indiana, United States, 47713
United States, Kentucky
Lexington, Kentucky, United States, 40503
Lexington, Kentucky, United States, 40504
United States, Maryland
Cumberland, Maryland, United States, 21502
Wheaton, Maryland, United States, 20902
United States, Massachusetts
Fall River, Massachusetts, United States, 02720
Hyannis, Massachusetts, United States, 02601
United States, Michigan
Ann Arbor, Michigan, United States, 48109
Flint, Michigan, United States, 48504
United States, Mississippi
Olive Branch, Mississippi, United States, 38654
United States, Missouri
Louis, Missouri, United States, 63117
United States, Nebraska
Omaha, Nebraska, United States, 68114
United States, Nevada
Reno, Nevada, United States, 89502
United States, New Mexico
Albuquerque, New Mexico, United States, 87106
United States, New York
Brooklyn, New York, United States, 11201
Brooklyn, New York, United States, 11215
United States, North Carolina
Calabash, North Carolina, United States, 28467
Charlotte, North Carolina, United States, 28210
Durham, North Carolina, United States, 27710
Hickory, North Carolina, United States, 28602
Shelby, North Carolina, United States, 28152
Winston-Salem, North Carolina, United States, 27103
United States, North Dakota
Fargo, North Dakota, United States, 58103
United States, Ohio
Cincinnati, Ohio, United States, 45242
Cleveland, Ohio, United States, 44122
Columbus, Ohio, United States, 43203
Dayton, Ohio, United States, 45424
Franklin, Ohio, United States, 45005
Middleburgh Heights, Ohio, United States, 44130
United States, Oklahoma
Oklahoma City, Oklahoma, United States, 73103
United States, Oregon
Portland, Oregon, United States, 97220
Portland, Oregon, United States, 97239
United States, Pennsylvania
Indiana, Pennsylvania, United States, 15701
Scottdale, Pennsylvania, United States, 15683
United States, South Carolina
Greenville, South Carolina, United States, 29601
Greer, South Carolina, United States, 29651
Spartanburg, South Carolina, United States, 29303
Union, South Carolina, United States, 29379
United States, Tennessee
Knoxville, Tennessee, United States, 37919
Spring Hill, Tennessee, United States, 37174
United States, Texas
Austin, Texas, United States, 78705
Austin, Texas, United States, 78758
Houston, Texas, United States, 77074
Irving, Texas, United States, 75061
Sugarland, Texas, United States, 77479
United States, Utah
West Layton, Utah, United States, 84041
United States, Virginia
Danville, Virginia, United States, 24541
Richmond, Virginia, United States, 23219
United States, Washington
Seattle, Washington, United States, 98104
Tacoma, Washington, United States, 98405
Australia, New South Wales
Camperdown,, New South Wales, Australia, 2050
Wollongong, New South Wales, Australia, 2522
Australia, Queensland
Bisbane, Queensland, Australia, 4152
Herston, Queensland, Australia, 4029
Australia, South Australia
Woodville South, South Australia, Australia, 5011
Australia, Victoria
Clayton, Victoria, Australia, 3168
Heidelberg West, Victoria, Australia, 3081
Australia, Western Australia
Perth, Western Australia, Australia, 6001
Shenton Park, Western Australia, Australia, 6008
Belgium
Genk, Limburg, Belgium, 3600
Gozee, Belgium, 6534
Kortrijk, Belgium, 8500
Lommel, Belgium, 3920
Mouscron, Belgium, 7700
Yvoir, Belgium, 5530
Canada, British Columbia
Coquitlam, British Columbia, Canada, V3K 3P4
Kamloops, British Columbia, Canada, V2C 1K7
Penticton, British Columbia, Canada, V2A 5C8
Canada, Newfoundland and Labrador
Paradise, Newfoundland and Labrador, Canada, A1L 1E5
Canada, Nova Scotia
Halifax, Nova Scotia, Canada, B3K 2M5
Canada, Ontario
Corunna, Ontario, Canada, N0N 1G0
Kitchener, Ontario, Canada, N2G 1H6
Kitchener, Ontario, Canada, N2M 5N6
London, Ontario, Canada, N6A 5R8
Sudbury, Ontario, Canada, P3A 1Y8
Sudbury, Ontario, Canada, P3E 1H5
Thornhill, Ontario, Canada, L4J 1W3
Toronto, Ontario, Canada, M9W 4L6
Canada
Quebec, Canada, G1V3M7
Germany
Kamenz, Sachsen, Germany, 01917
Berlin, Germany, 14059
Dresden, Germany, 01069
Dresden, Germany, 01307
Eichstatt, Germany, 85072
Goch, Germany, 47574
Leipzig, Germany, 04109
Mannheim, Germany, 68161
Munich, Germany, 80336
Osnabruck, Germany, 49074
New Zealand
Tauranga, Bay of Plenty, New Zealand, 3143
Becken ham, Christchurch, New Zealand, 8024
Garden Place, Hamilton, New Zealand, 3240
Bay of Plenty, Rotorua, New Zealand, 3010
Auckland, New Zealand, 1023
Auckland, New Zealand, 2025
Takapuna, New Zealand, 0626
Poland
Krakow, Malopolskie, Poland, 30-510
Bialystok, Podlaskie, Poland, 15-430
Elblag, Warminsko-Mazurskie, Poland, 82 300
Katowice, Poland, 40 954
Konskie, Poland, 26-200
Krakow, Poland, 31-501
Poznan, Poland, 60-773
Radom, Poland, 26 610
Warszawa, Poland, 01-192
Warszawa, Poland, 01-868
Wroclaw, Poland, 53-114
South Africa
Fichardt Park, Bloemfontein, South Africa, 9301
Rondebosch, Cape Town, South Africa, 7700
Newlands, Durban, South Africa, 4037
Silverglen, Durban, South Africa, 4092
Newtown, Johannesburg, South Africa, 2113
Parktown, Johannesburg, South Africa, 2193
Radiokop, Johannesburg, South Africa, 7700
Stellenbosch, Western Cape, South Africa, 7600
Cape Town, South Africa, 7500
Durban, South Africa, 4001
East London, South Africa, 5201
Paarl, South Africa, 7646
Pretoria, South Africa, 0002
Pretoria, South Africa, 0084
Soweto, South Africa, 1804
Thabazimbi, South Africa, 0380
Witbank, South Africa, 1035
Worcester, South Africa, 6850
Spain
La Coruna, Galicia, Spain, 15006
Barakaldo, Vizcaya, Spain, 48903
Merida, Spain, 06800
Switzerland
Lausanne, Switzerland, 1011
Ukraine
Dnipropetrovsk, Ukraine, 49005
Kharkiv, Ukraine, 61157
Kharkiv, Ukraine, 61176
Kyiv, Ukraine, 01680
Kyiv, Ukraine, 03680
Lutsk, Ukraine, 43024
Poltava, Ukraine, 36011
Vinnytsia, Ukraine, 21018
Sponsors and Collaborators
Ardea Biosciences, Inc.
Investigators
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Study Director: Chris Storgard, MD Ardea Biosciences, Inc.

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Ardea Biosciences, Inc.
ClinicalTrials.gov Identifier: NCT01493531     History of Changes
Other Study ID Numbers: RDEA594-302
2011-003767-29 ( EudraCT Number )
First Posted: December 16, 2011    Key Record Dates
Results First Posted: May 26, 2016
Last Update Posted: May 26, 2016
Last Verified: April 2016
Keywords provided by Ardea Biosciences, Inc.:
Gout
Additional relevant MeSH terms:
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Gout
Gout Suppressants
Arthritis
Joint Diseases
Musculoskeletal Diseases
Crystal Arthropathies
Rheumatic Diseases
Purine-Pyrimidine Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases
Allopurinol
Lesinurad
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Antirheumatic Agents
Free Radical Scavengers
Antioxidants
Protective Agents
Physiological Effects of Drugs
Uricosuric Agents
Renal Agents