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Combining Lesinurad With Allopurinol in Inadequate Responders (CLEAR 1)

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ClinicalTrials.gov Identifier: NCT01510158
Recruitment Status : Completed
First Posted : January 13, 2012
Results First Posted : August 18, 2016
Last Update Posted : August 18, 2016
Sponsor:
Information provided by (Responsible Party):
Ardea Biosciences, Inc.

Brief Summary:
This study that 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 serum urate (sUA) target of < 6.0 mg/dL and need additional therapy to achieve the target. Probenecid and benzbromarone are uric acid transporter 1 (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

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 607 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Care Provider)
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 : January 2012
Actual Primary Completion Date : July 2014
Actual Study Completion Date : August 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Gout
U.S. FDA Resources

Arm Intervention/treatment
Experimental: lesinurad 200 mg + allopurinol Drug: Lesinurad
Tablets, 200 mg once daily (qd)
Drug: Allopurinol
Tablets, ≥ 300 mg QD (≥ 200 mg qd for subjects with moderate renal impairment)
Experimental: lesinurad 400 mg + allopurinol Drug: Lesinurad
Tablets, 400 mg qd
Drug: Allopurinol
Tablets, ≥ 300 mg QD (≥ 200 mg qd for subjects with moderate renal impairment)
Placebo Comparator: Placebo + allopurinol Drug: Placebo
Tablets, Placebo qd
Drug: Allopurinol
Tablets, ≥ 300 mg QD (≥ 200 mg qd for subjects with moderate renal impairment)



Primary Outcome Measures :
  1. Proportion of Subjects With an sUA Level That is < 6.0 mg/dL [ Time Frame: 6 Months, analysis after all subjects complete 12 months ]

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. Tophus [ 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, Senior)
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 Nonsteroidal anti-inflammatory drug (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): NCT01510158


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Locations
United States, Alabama
Athens, Alabama, United States, 35611
Birmingham, Alabama, United States, 35209
Birmingham, Alabama, United States, 35213
Birmingham, Alabama, United States, 35242
Birmingham, Alabama, United States, 35294
Gulf Shores, Alabama, United States, 36542
Mobile, Alabama, United States, 36604
Mobile, Alabama, United States, 36608
Pinson, Alabama, United States, 35126
United States, Arizona
Glendale, Arizona, United States, 85308
Goodyear, Arizona, United States, 85395
Little Rock, Arizona, United States, 72204
Little Rock, Arizona, United States, 72211
Peoria, Arizona, United States, 85381
Phoenix, Arizona, United States, 85050
Tucson, Arizona, United States, 85704
Tuscon, Arizona, United States, 85723
United States, Arkansas
Little Rock, Arkansas, United States, 72206
United States, California
Covina, California, United States, 91723
Glendale, California, United States, 91204
Huntington Beach, California, United States, 92646
Inglewood, California, United States, 90301
Lancaster, California, United States, 93534
Lincoln, California, United States, 95648
Orange, California, United States, 92868
Sacramento, California, United States, 95825
San Leandro, California, United States, 94578
Santa Maria, California, United States, 93454
United States, Colorado
Colorado Springs, Colorado, United States, 80907
Colorado Springs, Colorado, United States, 80918
Denver, Colorado, United States, 80230
Englewood, Colorado, United States, 80113
United States, Connecticut
Milford, Connecticut, United States, 06460
New London, Connecticut, United States, 06320
United States, Florida
Brooksville, Florida, United States, 34601
Clearwater, Florida, United States, 33765
Daytona Beach, Florida, United States, 32114
East Bradenton, Florida, United States, 34208
Gainesville, Florida, United States, 32607
Miami, Florida, United States, 33125
Miami, Florida, United States, 33135
Miami, Florida, United States, 33143
Miami, Florida, United States, 33165
Miami, Florida, United States, 33186
Naples, Florida, United States, 34102
Ocala, Florida, United States, 34474
Ormond Beach, Florida, United States, 32174
Pembroke Pines, Florida, United States, 33027
Pembroke Pines, Florida, United States, 33029
Port Orange, Florida, United States, 32127
Tampa, Florida, United States, 33614
Vero Beach, Florida, United States, 32960
United States, Georgia
Atlanta, Georgia, United States, 30308
Atlanta, Georgia, United States, 30328
Augusta, Georgia, United States, 30909
Conyers, Georgia, United States, 30013
Johns Creek, Georgia, United States, 30097
Marietta, Georgia, United States, 30060
Newman, Georgia, United States, 30265
Newnan, Georgia, United States, 30265
United States, Hawaii
Honolulu, Hawaii, United States, 96814
United States, Idaho
Idaho Falls, Idaho, United States, 83404
Meridian, Idaho, United States, 83642
Meridian, Idaho, United States, 83646
United States, Illinois
Chicago, Illinois, United States, 60612
Gurnee, Illinois, United States, 60031
United States, Indiana
Evansville, Indiana, United States, 47714
Franklin, Indiana, United States, 46131
LaPorte, Indiana, United States, 46350
United States, Iowa
Cedar Rapids, Iowa, United States, 52403
United States, Kansas
Shawnee, Kansas, United States, 66218
United States, Kentucky
Elizabethtown, Kentucky, United States, 41701
Paducah, Kentucky, United States, 42003
United States, Louisiana
Eunice, Louisiana, United States, 70535
Metairie, Louisiana, United States, 70006
Monroe, Louisiana, United States, 71203
Natchitoches, Louisiana, United States, 71457
United States, Massachusetts
Worcester, Massachusetts, United States, 01605
United States, Michigan
Ann Arbor, Michigan, United States, 48106
Kalamazoo, Michigan, United States, 49009
Southfield, Michigan, United States, 48034
Traverse City, Michigan, United States, 49684
United States, Mississippi
Jackson, Mississippi, United States, 39202
United States, Missouri
Florissant, Missouri, United States, 63031
Hazelwood, Missouri, United States, 63042
Jefferson City, Missouri, United States, 65109
Kansas City, Missouri, United States, 64114
Saint Louis, Missouri, United States, 63117
St. Louis, Missouri, United States, 63128
Washington, Missouri, United States, 63090
United States, Montana
Missoula, Montana, United States, 59808
United States, Nevada
Las Vegas, Nevada, United States, 89119
Las Vegas, Nevada, United States, 89183
United States, New Mexico
Albuquerque, New Mexico, United States, 87102
United States, New York
Endwell, New York, United States, 13760
New York, New York, United States, 10016
Syracuse, New York, United States, 13210
Williamsville, New York, United States, 14221
United States, North Carolina
Greensboro, North Carolina, United States, 27405
Raleigh, North Carolina, United States, 27609
Raleigh, North Carolina, United States, 27612
Shelby, North Carolina, United States, 28150
Tabor City, North Carolina, United States, 28463
Wilmington, North Carolina, United States, 28401
Winston-Salem, North Carolina, United States, 27103
United States, Ohio
Columbus, Ohio, United States, 43235
Dayton, Ohio, United States, 45417
Perrysburgh, Ohio, United States, 43551
Willoughby Hills, Ohio, United States, 44904
United States, Oklahoma
Oklahoma City, Oklahoma, United States, 73103
Tulsa, Oklahoma, United States, 74104
United States, Oregon
Ashland, Oregon, United States, 97520
United States, Pennsylvania
Altoona, Pennsylvania, United States, 16602
Belle Vernon, Pennsylvania, United States, 15012
Clairton, Pennsylvania, United States, 15025
Duncansville, Pennsylvania, United States, 16635
Jenkintown, Pennsylvania, United States, 19046
Lansdale, Pennsylvania, United States, 19446
Pittsburgh, Pennsylvania, United States, 15206
Sellersville, Pennsylvania, United States, 18960
Upper St. Clair, Pennsylvania, United States, 15241
Wexford, Pennsylvania, United States, 15090
United States, South Carolina
Columbia, South Carolina, United States, 29204
Mount Pleasant, South Carolina, United States, 29464
Myrtle Beach, South Carolina, United States, 29588
Rock Hill, South Carolina, United States, 29732
Spartanburg, South Carolina, United States, 29303
United States, Tennessee
Brentwood, Tennessee, United States, 37027
Jackson, Tennessee, United States, 38305
Knoxville, Tennessee, United States, 37923
Memphis, Tennessee, United States, 38119
United States, Texas
Austin, Texas, United States, 78756
Corpus Christi, Texas, United States, 78414
Dallas, Texas, United States, 75218
El Paso, Texas, United States, 79902
Fort Worth, Texas, United States, 76135
Houston, Texas, United States, 77004
Houston, Texas, United States, 77043
Houston, Texas, United States, 77062
Houston, Texas, United States, 77098
Kingwood, Texas, United States, 77339
Nassau Bay, Texas, United States, 77058
Plabo, Texas, United States, 75024
Plano, Texas, United States, 75075
San Angelo, Texas, United States, 76904
San Antonio, Texas, United States, 78209
San Antonio, Texas, United States, 78215
San Antonio, Texas, United States, 78229
Sealy, Texas, United States, 77474
Waco, Texas, United States, 76708
United States, Utah
Bountiful, Utah, United States, 84010
Salt Lake City, Utah, United States, 84102
West Jordan, Utah, United States, 84088
United States, Virginia
Chesapeake, Virginia, United States, 23320
Manassas, Virginia, United States, 20110
Midlothian, Virginia, United States, 23114
Richmond, Virginia, United States, 23233
Richmond, Virginia, United States, 23235
Suffolk, Virginia, United States, 23435
Virginia Beach, Virginia, United States, 23462
United States, Washington
Port Orchard, Washington, United States, 98366
Spokane, Washington, United States, 99204
Spokane, Washington, United States, 99208
United States, West Virginia
Morgantown, West Virginia, United States, 26505
United States, Wisconsin
Milwaukee, Wisconsin, United States, 53226
Monroe, Wisconsin, United States, 53566
Sponsors and Collaborators
Ardea Biosciences, Inc.
Investigators
Study Director: Chris Storgard, MD Ardea Biosciences, Inc.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Ardea Biosciences, Inc.
ClinicalTrials.gov Identifier: NCT01510158     History of Changes
Other Study ID Numbers: RDEA594-301
First Posted: January 13, 2012    Key Record Dates
Results First Posted: August 18, 2016
Last Update Posted: August 18, 2016
Last Verified: July 2016

Additional relevant MeSH terms:
Lesinurad
Allopurinol
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Gout Suppressants
Antirheumatic Agents
Free Radical Scavengers
Antioxidants
Protective Agents
Physiological Effects of Drugs
Uricosuric Agents
Renal Agents