Combining Lesinurad With Allopurinol in Inadequate Responders

NCT ID: NCT01510158

Last Updated: 2016-08-18

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

607 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-01-31

Study Completion Date

2014-08-31

Brief Summary

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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.

Detailed Description

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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

Conditions

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Gout

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Caregivers

Study Groups

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lesinurad 200 mg + allopurinol

Group Type EXPERIMENTAL

Lesinurad

Intervention Type DRUG

Tablets, 200 mg once daily (qd)

Allopurinol

Intervention Type DRUG

Tablets, ≥ 300 mg QD (≥ 200 mg qd for subjects with moderate renal impairment)

lesinurad 400 mg + allopurinol

Group Type EXPERIMENTAL

Lesinurad

Intervention Type DRUG

Tablets, 400 mg qd

Allopurinol

Intervention Type DRUG

Tablets, ≥ 300 mg QD (≥ 200 mg qd for subjects with moderate renal impairment)

Placebo + allopurinol

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Tablets, Placebo qd

Allopurinol

Intervention Type DRUG

Tablets, ≥ 300 mg QD (≥ 200 mg qd for subjects with moderate renal impairment)

Interventions

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Lesinurad

Tablets, 200 mg once daily (qd)

Intervention Type DRUG

Lesinurad

Tablets, 400 mg qd

Intervention Type DRUG

Placebo

Tablets, Placebo qd

Intervention Type DRUG

Allopurinol

Tablets, ≥ 300 mg QD (≥ 200 mg qd for subjects with moderate renal impairment)

Intervention Type DRUG

Allopurinol

Tablets, ≥ 300 mg QD (≥ 200 mg qd for subjects with moderate renal impairment)

Intervention Type DRUG

Allopurinol

Tablets, ≥ 300 mg QD (≥ 200 mg qd for subjects with moderate renal impairment)

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ardea Biosciences, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Chris Storgard, MD

Role: STUDY_DIRECTOR

Ardea Biosciences, Inc.

Locations

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Athens, Alabama, United States

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Birmingham, Alabama, United States

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Birmingham, Alabama, United States

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Birmingham, Alabama, United States

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Birmingham, Alabama, United States

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Gulf Shores, Alabama, United States

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Mobile, Alabama, United States

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Mobile, Alabama, United States

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Pinson, Alabama, United States

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Glendale, Arizona, United States

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Goodyear, Arizona, United States

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Little Rock, Arizona, United States

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Little Rock, Arizona, United States

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Peoria, Arizona, United States

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Phoenix, Arizona, United States

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Tucson, Arizona, United States

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Tuscon, Arizona, United States

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Little Rock, Arkansas, United States

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Covina, California, United States

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Glendale, California, United States

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Huntington Beach, California, United States

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Inglewood, California, United States

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Lancaster, California, United States

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Lincoln, California, United States

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Orange, California, United States

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Sacramento, California, United States

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San Leandro, California, United States

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Santa Maria, California, United States

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Colorado Springs, Colorado, United States

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Colorado Springs, Colorado, United States

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Denver, Colorado, United States

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Englewood, Colorado, United States

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Milford, Connecticut, United States

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New London, Connecticut, United States

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Brooksville, Florida, United States

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Clearwater, Florida, United States

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Daytona Beach, Florida, United States

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East Bradenton, Florida, United States

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Gainesville, Florida, United States

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Miami, Florida, United States

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Miami, Florida, United States

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Miami, Florida, United States

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Miami, Florida, United States

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Miami, Florida, United States

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Naples, Florida, United States

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Ocala, Florida, United States

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Ormond Beach, Florida, United States

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Pembroke Pines, Florida, United States

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Pembroke Pines, Florida, United States

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Port Orange, Florida, United States

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Tampa, Florida, United States

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Vero Beach, Florida, United States

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Atlanta, Georgia, United States

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Atlanta, Georgia, United States

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Augusta, Georgia, United States

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Conyers, Georgia, United States

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Johns Creek, Georgia, United States

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Marietta, Georgia, United States

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Newnan, Georgia, United States

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Honolulu, Hawaii, United States

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Idaho Falls, Idaho, United States

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Meridian, Idaho, United States

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Meridian, Idaho, United States

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Chicago, Illinois, United States

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Gurnee, Illinois, United States

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Evansville, Indiana, United States

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Franklin, Indiana, United States

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La Porte, Indiana, United States

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Cedar Rapids, Iowa, United States

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Shawnee, Kansas, United States

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Elizabethtown, Kentucky, United States

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Paducah, Kentucky, United States

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Eunice, Louisiana, United States

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Metairie, Louisiana, United States

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Monroe, Louisiana, United States

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Natchitoches, Louisiana, United States

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Worcester, Massachusetts, United States

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Ann Arbor, Michigan, United States

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Kalamazoo, Michigan, United States

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Southfield, Michigan, United States

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Traverse City, Michigan, United States

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Jackson, Mississippi, United States

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Florissant, Missouri, United States

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Hazelwood, Missouri, United States

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Jefferson City, Missouri, United States

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Kansas City, Missouri, United States

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St Louis, Missouri, United States

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St Louis, Missouri, United States

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Washington, Missouri, United States

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Missoula, Montana, United States

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Las Vegas, Nevada, United States

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Las Vegas, Nevada, United States

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Albuquerque, New Mexico, United States

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Endwell, New York, United States

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New York, New York, United States

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Syracuse, New York, United States

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Williamsville, New York, United States

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Greensboro, North Carolina, United States

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Raleigh, North Carolina, United States

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Raleigh, North Carolina, United States

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Shelby, North Carolina, United States

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Tabor City, North Carolina, United States

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Wilmington, North Carolina, United States

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Winston-Salem, North Carolina, United States

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Columbus, Ohio, United States

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Dayton, Ohio, United States

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Perrysburg, Ohio, United States

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Willoughby Hills, Ohio, United States

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Oklahoma City, Oklahoma, United States

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Tulsa, Oklahoma, United States

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Ashland, Oregon, United States

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Altoona, Pennsylvania, United States

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Belle Vernon, Pennsylvania, United States

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Clairton, Pennsylvania, United States

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Duncansville, Pennsylvania, United States

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Jenkintown, Pennsylvania, United States

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Lansdale, Pennsylvania, United States

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Pittsburgh, Pennsylvania, United States

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Sellersville, Pennsylvania, United States

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Upper Saint Clair, Pennsylvania, United States

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Wexford, Pennsylvania, United States

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Columbia, South Carolina, United States

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Mt. Pleasant, South Carolina, United States

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Myrtle Beach, South Carolina, United States

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Rock Hill, South Carolina, United States

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Spartanburg, South Carolina, United States

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Brentwood, Tennessee, United States

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Jackson, Tennessee, United States

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Knoxville, Tennessee, United States

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Memphis, Tennessee, United States

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Austin, Texas, United States

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Corpus Christi, Texas, United States

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Dallas, Texas, United States

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El Paso, Texas, United States

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Fort Worth, Texas, United States

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Houston, Texas, United States

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Houston, Texas, United States

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Houston, Texas, United States

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Houston, Texas, United States

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Kingwood, Texas, United States

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Nassau Bay, Texas, United States

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Plabo, Texas, United States

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Plano, Texas, United States

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San Angelo, Texas, United States

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San Antonio, Texas, United States

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San Antonio, Texas, United States

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San Antonio, Texas, United States

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Sealy, Texas, United States

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Waco, Texas, United States

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Bountiful, Utah, United States

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Salt Lake City, Utah, United States

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West Jordan, Utah, United States

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Chesapeake, Virginia, United States

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Manassas, Virginia, United States

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Midlothian, Virginia, United States

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Richmond, Virginia, United States

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Richmond, Virginia, United States

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Suffolk, Virginia, United States

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Virginia Beach, Virginia, United States

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Port Orchard, Washington, United States

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Spokane, Washington, United States

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Spokane, Washington, United States

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Morgantown, West Virginia, United States

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Milwaukee, Wisconsin, United States

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Monroe, Wisconsin, United States

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Countries

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United States

References

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Topless R, Noorbaloochi S, Merriman TR, Singh JA. Change in serum urate level with urate-lowering therapy initiation associates in the immediate term with patient-reported outcomes in people with gout. Semin Arthritis Rheum. 2022 Oct;56:152057. doi: 10.1016/j.semarthrit.2022.152057. Epub 2022 Jun 29.

Reference Type DERIVED
PMID: 35835008 (View on PubMed)

Saag KG, Fitz-Patrick D, Kopicko J, Fung M, Bhakta N, Adler S, Storgard C, Baumgartner S, Becker MA. Lesinurad Combined With Allopurinol: A Randomized, Double-Blind, Placebo-Controlled Study in Gout Patients With an Inadequate Response to Standard-of-Care Allopurinol (a US-Based Study). Arthritis Rheumatol. 2017 Jan;69(1):203-212. doi: 10.1002/art.39840.

Reference Type DERIVED
PMID: 27564409 (View on PubMed)

Related Links

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Other Identifiers

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RDEA594-301

Identifier Type: -

Identifier Source: org_study_id

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