Clinical trial NCT01510769: Combination Treatment Study in Subjects With Tophaceous Gout With Lesinurad and Febuxostat
Official title: A Phase 3 Randomized, Double-Blind, Multicenter, Placebo- Controlled, Combination Study to Evaluate the Efficacy and Safety of Lesinurad and Febuxostat Compared to Febuxostat Alone at Lowering Serum Uric Acid and Resolving Tophi in Subjects With Tophaceous Gout
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Tophaceous Gout
Lead sponsor: Ardea Biosciences, Inc.
Sponsor class: INDUSTRY
First posted: 2012-01-16
Enrollment: 330
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 will compare the serum uric acid lowering effects, clinical benefits, and safety of lesinurad in combination with febuxostat to febuxostat alone in patients with tophaceaous gout.

Detailed description: Febuxostat is an XO (Xanthine Oxidase) Inhibitor approved Urate Lowering Therapy (ULT) for patients with gout. Although febuxostat has been demonstrated to be superior to allopurinol in lowering serum urate (sUA) to \< 6mg/dL in 3 randomized, controlled clinical trials, proportions of subjects experiencing a reduction in tophus area and gout flares were not significantly different compared to allopurinol. Although this study will allow subjects who are naïve to ULT to enroll, it is anticipated that the majority of subjects will currently be taking or have previously experienced XO Inhibitor therapy. This trial will enroll a population of subjects with high uric acid body burden, as all must demonstrate the presence of tophi.

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 is willing to adhere to the visit/protocol schedules.
* Subject meets the diagnosis of gout as per the American Rheumatism Association
* Criteria for the Classification of Acute Arthritis of Primary Gout.
* Subject meets one of the following criteria:
* Subjects who are not currently taking an approved ULT must have an sUA value of ≥ 8 mg/dL (476 µmol/L).
* Subjects entering the study on a medically appropriate dose of febuxostat or allopurinol must have an sUA value of ≥ 6.0 mg/dL (357 µmol/L).
* Subject must be able to take gout flare prophylaxis with colchicine or non-steroidal anti-inflammatory drug (NSAID) (including Cox-2 selective NSAID) ± PPI.
* Subject with at least 1 measurable tophus on the hands/wrists and/or feet/ankles ≥ 5 mm and ≤ 20 mm in the longest diameter.
* Body mass index (BMI) \< 45 kg/m2

Exclusion Criteria:

* Subject with known hypersensitivity or allergy to febuxostat.
* Subject who is taking any approved urate-lowering medication other than allopurinol or febuxostat that is indicated for the treatment of gout within 8 weeks of the Screening Visit.
* Subject who previously received pegloticase.
* 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 with a history of myositis/myopathy or rhabdomyolysis.
* 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 thrombosis; or subjects currently receiving anticoagulants.
* Subject with uncontrolled hypertension.
* Subject with an estimated creatinine clearance \< 30 mL/min.
* Subjects with a creatine kinase \> 2.5 x ULN at any time during the Screening Period.
* 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 in the opinion of the Investigator and/or 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.

Primary outcomes:
measure: Subjects With a Serum Urate (sUA) Level That is < 5.0 mg/dL by Month 6
timeFrame: 6 months, analysis after all subjects complete 12 months
Secondary outcomes:
measure: Complete Resolution of at Least One Target Tophus
timeFrame: 12 Months
measure: Complete or Partial Response of at Least One Tophus
timeFrame: 12 Months
measure: Quality of Life
timeFrame: 12 Months
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Goodyear
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state: Arizona
city: Peoria
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state: Arizona
city: Pheonix
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state: Arizona
city: Tucson
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state: Arizona
city: Little Rock
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state: Arkansas
city: Little Rock
country: United States
state: Arkansas
city: Glendale
country: United States
state: California
city: Huntington Beach
country: United States
state: California
city: Irvine
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state: California
city: La Jolla
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state: California
city: Los Angeles
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state: California
city: Rancho Cucamonga
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state: California
city: San Diego
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state: California
city: Denver
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state: Colorado
city: Denver
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state: Colorado
city: Englewood
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state: Colorado
city: Trumball
country: United States
state: Connecticut
city: Washington
country: United States
state: District of Columbia
city: Boynton Beach
country: United States
state: Florida
city: Brooksville
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state: Florida
city: East Brandenton
country: United States
state: Florida
city: Fleming Island
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state: Florida
city: Miami
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state: Florida
city: Napels
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state: Florida
city: Pembroke Pines
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state: Florida
city: Pembroke Pines
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state: Florida
city: Port Orange
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state: Florida
city: Tampa
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state: Florida
city: Tampa
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state: Florida
city: Tampa
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state: Florida
city: Vero Beach
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state: Florida
city: Winter Haven
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state: Florida
city: Conyers
country: United States
state: Georgia
city: Johns Creek
country: United States
state: Georgia
city: Newman
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state: Georgia
city: Savannah
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state: Georgia
city: Honolulu
country: United States
state: Hawaii
city: Meridian
country: United States
state: Idaho
city: Meridian
country: United States
state: Idaho
city: Chicago
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state: Illinois
city: Chicago
country: United States
state: Illinois
city: Gurnee
country: United States
state: Illinois
city: Springfield
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state: Illinois
city: Springfield
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state: Illinois
city: Elizabethtown
country: United States
state: Kentucky
city: Lexington
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state: Kentucky
city: Frederick
country: United States
state: Maryland
city: Kalamazoo
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state: Michigan
city: Southfield
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state: Michigan
city: Jackson
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state: Mississippi
city: Olive Branch
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state: Mississippi
city: Jefferson City
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state: Missouri
city: Saint Louis
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state: Missouri
city: Missoula
country: United States
state: Montana
city: Mineola
country: United States
state: New York
city: New York
country: United States
state: New York
city: Calabash
country: United States
state: North Carolina
city: Durham
country: United States
state: North Carolina
city: Greenville
country: United States
state: North Carolina
city: Wilmington
country: United States
state: North Carolina
city: Winston-Salem
country: United States
state: North Carolina
city: Fargo
country: United States
state: North Dakota
city: Columbus
country: United States
state: Ohio
city: Middleburg
country: United States
state: Ohio
city: Wadsworth
country: United States
state: Ohio
city: Oklahoma City
country: United States
state: Oklahoma
city: Oklahoma City
country: United States
state: Oklahoma
city: Belle Vernon
country: United States
state: Pennsylvania
city: Clairton
country: United States
state: Pennsylvania
city: Duncansville
country: United States
state: Pennsylvania
city: Jenkintown
country: United States
state: Pennsylvania
city: Lansdale
country: United States
state: Pennsylvania
city: Pittsburgh
country: United States
state: Pennsylvania
city: Scottdale
country: United States
state: Pennsylvania
city: Sellersville
country: United States
state: Pennsylvania
city: Columbia
country: United States
state: South Carolina
city: Greenville
country: United States
state: South Carolina
city: Mount Pleasant
country: United States
state: South Carolina
city: Spartanburg
country: United States
state: South Carolina
city: Jackson
country: United States
state: Tennessee
city: Memphis
country: United States
state: Tennessee
city: Austin
country: United States
state: Texas
city: Austin
country: United States
state: Texas
city: Corpus Christi
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Sugar Land
country: United States
state: Texas
city: Victoria
country: United States
state: Texas
city: Waco
country: United States
state: Texas
city: Chesapeake
country: United States
state: Virginia
city: Danville
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: Seattle
country: United States
state: Washington
city: Morgantown
country: United States
state: West Virginia
city: Camperdown
country: Australia
state: New South Wales
city: Woodville South
country: Australia
state: South Australia
city: Hobart
country: Australia
state: Tasmania
city: Shenton Park
country: Australia
state: Western Australia
city: Kelowna
country: Canada
state: British Columbia
city: Victoria
country: Canada
state: British Columbia
city: Halifax
country: Canada
state: Nova Scotia
city: London
country: Canada
state: Ontario
city: Mississauga
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Quebec
country: Canada
city: Grafton
country: New Zealand
state: Auckland
city: Tauranga
country: New Zealand
state: Bay of Plenty
city: Hamilton
country: New Zealand
city: Kutno
country: Poland
state: Lodz Province
city: Biatystok
country: Poland
city: Elblag
country: Poland
city: Katowice
country: Poland
city: Konskie
country: Poland
city: Krakow
country: Poland
city: Krakow
country: Poland
city: Poznan
country: Poland
city: Poznan
country: Poland
city: Lausanne
country: Switzerland
state: Vlaud
city: Fribourg
country: Switzerland
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: Dalbeth N, Jones G, Terkeltaub R, Khanna D, Fung M, Baumgartner S, Perez-Ruiz F. Efficacy and safety during extended treatment of lesinurad in combination with febuxostat in patients with tophaceous gout: CRYSTAL extension study. Arthritis Res Ther. 2019 Jan 7;21(1):8. doi: 10.1186/s13075-018-1788-4.
citation: Dalbeth N, Jones G, Terkeltaub R, Khanna D, Kopicko J, Bhakta N, Adler S, Fung M, Storgard C, Baumgartner S, Perez-Ruiz F. Lesinurad, a Selective Uric Acid Reabsorption Inhibitor, in Combination With Febuxostat in Patients With Tophaceous Gout: Findings of a Phase III Clinical Trial. Arthritis Rheumatol. 2017 Sep;69(9):1903-1913. doi: 10.1002/art.40159. Epub 2017 Aug 4.