Clinical trial NCT01493531: 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
Keywords: Gout
Lead sponsor: Ardea Biosciences, Inc.
Sponsor class: INDUSTRY
First posted: 2011-12-16
Enrollment: 610
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 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 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

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 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: Subjects With a Serum Urate (sUA) < 6.0 mg/dL by Month 6.
timeFrame: 6 months
Secondary outcomes:
measure: Gout Flares
timeFrame: 12 Months
measure: Subjects With ≥ 1 Target Tophus at Baseline Who Experience Complete Resolution of at Least 1 Target Tophus by Month 12
timeFrame: 12 months
Other outcomes:
Locations:
city: Mobile
country: United States
state: Alabama
city: Chandler
country: United States
state: Arizona
city: Mesa
country: United States
state: Arizona
city: Pheonix
country: United States
state: Arizona
city: Jonesboro
country: United States
state: Arkansas
city: Jonesboro
country: United States
state: Arkansas
city: Little Rock
country: United States
state: Arkansas
city: Anaheim
country: United States
state: California
city: Gold River
country: United States
state: California
city: Irvine
country: United States
state: California
city: La Jolla
country: United States
state: California
city: Roseville
country: United States
state: California
city: San Diego
country: United States
state: California
city: San Diego
country: United States
state: California
city: San Ramon
country: United States
state: California
city: Colorado Springs
country: United States
state: Colorado
city: Denver
country: United States
state: Colorado
city: Glenwood Springs
country: United States
state: Colorado
city: Trumbull
country: United States
state: Connecticut
city: Washington DC
country: United States
state: District of Columbia
city: Washington
country: United States
state: District of Columbia
city: Boynton Beach
country: United States
state: Florida
city: Brandon
country: United States
state: Florida
city: Fleming Island
country: United States
state: Florida
city: Jacksonville
country: United States
state: Florida
city: Jacksonville
country: United States
state: Florida
city: Jupiter
country: United States
state: Florida
city: Plant City
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Winter Haven
country: United States
state: Florida
city: Dunwoody
country: United States
state: Georgia
city: Roswell
country: United States
state: Georgia
city: Savannah
country: United States
state: Georgia
city: Boise
country: United States
state: Idaho
city: Meridian
country: United States
state: Idaho
city: Addison
country: United States
state: Illinois
city: Chicago
country: United States
state: Illinois
city: Evansville
country: United States
state: Indiana
city: Lexington
country: United States
state: Kentucky
city: Lexington
country: United States
state: Kentucky
city: Cumberland
country: United States
state: Maryland
city: Wheaton
country: United States
state: Maryland
city: Fall River
country: United States
state: Massachusetts
city: Hyannis
country: United States
state: Massachusetts
city: Ann Arbor
country: United States
state: Michigan
city: Flint
country: United States
state: Michigan
city: Olive Branch
country: United States
state: Mississippi
city: Louis
country: United States
state: Missouri
city: Omaha
country: United States
state: Nebraska
city: Reno
country: United States
state: Nevada
city: Albuquerque
country: United States
state: New Mexico
city: Brooklyn
country: United States
state: New York
city: Brooklyn
country: United States
state: New York
city: Calabash
country: United States
state: North Carolina
city: Charlotte
country: United States
state: North Carolina
city: Durham
country: United States
state: North Carolina
city: Hickory
country: United States
state: North Carolina
city: Shelby
country: United States
state: North Carolina
city: Winston-Salem
country: United States
state: North Carolina
city: Fargo
country: United States
state: North Dakota
city: Cincinnati
country: United States
state: Ohio
city: Cleveland
country: United States
state: Ohio
city: Columbus
country: United States
state: Ohio
city: Dayton
country: United States
state: Ohio
city: Franklin
country: United States
state: Ohio
city: Middleburgh Heights
country: United States
state: Ohio
city: Oklahoma City
country: United States
state: Oklahoma
city: Portland
country: United States
state: Oregon
city: Portland
country: United States
state: Oregon
city: Indiana
country: United States
state: Pennsylvania
city: Scottdale
country: United States
state: Pennsylvania
city: Greenville
country: United States
state: South Carolina
city: Greer
country: United States
state: South Carolina
city: Spartanburg
country: United States
state: South Carolina
city: Union
country: United States
state: South Carolina
city: Knoxville
country: United States
state: Tennessee
city: Spring Hill
country: United States
state: Tennessee
city: Austin
country: United States
state: Texas
city: Austin
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Irving
country: United States
state: Texas
city: Sugarland
country: United States
state: Texas
city: West Layton
country: United States
state: Utah
city: Danville
country: United States
state: Virginia
city: Richmond
country: United States
state: Virginia
city: Seattle
country: United States
state: Washington
city: Tacoma
country: United States
state: Washington
city: Camperdown,
country: Australia
state: New South Wales
city: Wollongong
country: Australia
state: New South Wales
city: Bisbane
country: Australia
state: Queensland
city: Herston
country: Australia
state: Queensland
city: Woodville South
country: Australia
state: South Australia
city: Clayton
country: Australia
state: Victoria
city: Heidelberg West
country: Australia
state: Victoria
city: Perth
country: Australia
state: Western Australia
city: Shenton Park
country: Australia
state: Western Australia
city: Genk
country: Belgium
state: Limburg
city: Gozee
country: Belgium
city: Kortrijk
country: Belgium
city: Lommel
country: Belgium
city: Mouscron
country: Belgium
city: Yvoir
country: Belgium
city: Coquitlam
country: Canada
state: British Columbia
city: Kamloops
country: Canada
state: British Columbia
city: Penticton
country: Canada
state: British Columbia
city: Paradise
country: Canada
state: Newfoundland and Labrador
city: Halifax
country: Canada
state: Nova Scotia
city: Corunna
country: Canada
state: Ontario
city: Kitchener
country: Canada
state: Ontario
city: Kitchener
country: Canada
state: Ontario
city: London
country: Canada
state: Ontario
city: Sudbury
country: Canada
state: Ontario
city: Sudbury
country: Canada
state: Ontario
city: Thornhill
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Quebec
country: Canada
city: Kamenz
country: Germany
state: Sachsen
city: Berlin
country: Germany
city: Dresden
country: Germany
city: Dresden
country: Germany
city: Eichstatt
country: Germany
city: Goch
country: Germany
city: Leipzig
country: Germany
city: Mannheim
country: Germany
city: Munich
country: Germany
city: Osnabruck
country: Germany
city: Tauranga
country: New Zealand
state: Bay of Plenty
city: Becken ham
country: New Zealand
state: Christchurch
city: Garden Place
country: New Zealand
state: Hamilton
city: Bay of Plenty
country: New Zealand
state: Rotorua
city: Auckland
country: New Zealand
city: Auckland
country: New Zealand
city: Takapuna
country: New Zealand
city: Krakow
country: Poland
state: Malopolskie
city: Bialystok
country: Poland
state: Podlaskie
city: Elblag
country: Poland
state: Warminsko-Mazurskie
city: Katowice
country: Poland
city: Konskie
country: Poland
city: Krakow
country: Poland
city: Poznan
country: Poland
city: Radom
country: Poland
city: Warszawa
country: Poland
city: Warszawa
country: Poland
city: Wroclaw
country: Poland
city: Fichardt Park
country: South Africa
state: Bloemfontein
city: Rondebosch
country: South Africa
state: Cape Town
city: Newlands
country: South Africa
state: Durban
city: Silverglen
country: South Africa
state: Durban
city: Newtown
country: South Africa
state: Johannesburg
city: Parktown
country: South Africa
state: Johannesburg
city: Radiokop
country: South Africa
state: Johannesburg
city: Stellenbosch
country: South Africa
state: Western Cape
city: Cape Town
country: South Africa
city: Durban
country: South Africa
city: East London
country: South Africa
city: Paarl
country: South Africa
city: Pretoria
country: South Africa
city: Pretoria
country: South Africa
city: Soweto
country: South Africa
city: Thabazimbi
country: South Africa
city: Witbank
country: South Africa
city: Worcester
country: South Africa
city: La Coruna
country: Spain
state: Galicia
city: Barakaldo
country: Spain
state: Vizcaya
city: Merida
country: Spain
city: Lausanne
country: Switzerland
city: Dnipropetrovsk
country: Ukraine
city: Kharkiv
country: Ukraine
city: Kharkiv
country: Ukraine
city: Kyiv
country: Ukraine
city: Kyiv
country: Ukraine
city: Lutsk
country: Ukraine
city: Poltava
country: Ukraine
city: Vinnytsia
country: Ukraine
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: Bardin T, Keenan RT, Khanna PP, Kopicko J, Fung M, Bhakta N, Adler S, Storgard C, Baumgartner S, So A. Lesinurad in combination with allopurinol: a randomised, double-blind, placebo-controlled study in patients with gout with inadequate response to standard of care (the multinational CLEAR 2 study). Ann Rheum Dis. 2017 May;76(5):811-820. doi: 10.1136/annrheumdis-2016-209213. Epub 2016 Nov 7.