Clinical trial NCT01510158: Combining Lesinurad With Allopurinol in Inadequate Responders
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Gout
Lead sponsor: Ardea Biosciences, Inc.
Sponsor class: INDUSTRY
First posted: 2012-01-13
Enrollment: 607
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Eligibility 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.

Primary outcomes:
measure: Proportion of Subjects With an sUA Level That is < 6.0 mg/dL
timeFrame: 6 Months, analysis after all subjects complete 12 months
Secondary outcomes:
measure: Gout Flares
timeFrame: 12 Months
measure: Tophus
timeFrame: 12 Months
Other outcomes:
Locations:
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country: United States
state: Alabama
city: Birmingham
country: United States
state: Alabama
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city: Birmingham
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state: Alabama
city: Gulf Shores
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state: Alabama
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city: Pinson
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city: Little Rock
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state: Arkansas
city: Covina
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state: California
city: Glendale
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state: California
city: Huntington Beach
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state: California
city: Inglewood
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state: California
city: Lancaster
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state: California
city: Lincoln
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city: Orange
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city: Sacramento
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state: Oregon
city: Altoona
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city: Belle Vernon
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city: Pittsburgh
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city: Upper St. Clair
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city: Mount Pleasant
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city: Myrtle Beach
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city: Rock Hill
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city: Spartanburg
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city: Brentwood
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city: Jackson
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city: Knoxville
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city: Memphis
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city: Austin
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city: Corpus Christi
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city: Dallas
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city: El Paso
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city: Fort Worth
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city: Houston
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city: Houston
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city: Houston
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state: Texas
city: Houston
country: United States
state: Texas
city: Kingwood
country: United States
state: Texas
city: Nassau Bay
country: United States
state: Texas
city: Plabo
country: United States
state: Texas
city: Plano
country: United States
state: Texas
city: San Angelo
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Sealy
country: United States
state: Texas
city: Waco
country: United States
state: Texas
city: Bountiful
country: United States
state: Utah
city: Salt Lake City
country: United States
state: Utah
city: West Jordan
country: United States
state: Utah
city: Chesapeake
country: United States
state: Virginia
city: Manassas
country: United States
state: Virginia
city: Midlothian
country: United States
state: Virginia
city: Richmond
country: United States
state: Virginia
city: Richmond
country: United States
state: Virginia
city: Suffolk
country: United States
state: Virginia
city: Virginia Beach
country: United States
state: Virginia
city: Port Orchard
country: United States
state: Washington
city: Spokane
country: United States
state: Washington
city: Spokane
country: United States
state: Washington
city: Morgantown
country: United States
state: West Virginia
city: Milwaukee
country: United States
state: Wisconsin
city: Monroe
country: United States
state: Wisconsin
Study officials:
affiliation: Ardea Biosciences, Inc.
name: Chris Storgard, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.