Clinical trial NCT01508702: Lesinurad Monotherapy in Gout Subjects Intolerant to Xanthine Oxidase Inhibitors
Official title: A Phase 3 Randomized, Double-Blind, Multicenter, Placebo- Controlled Study to Assess the Efficacy and Safety of Lesinurad Monotherapy Compared to Placebo in Subjects With Gout and an Intolerance or Contraindication to a Xanthine Oxidase Inhibitor
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Gout
Keywords: Gout
Lead sponsor: Ardea Biosciences, Inc.
Sponsor class: INDUSTRY
First posted: 2012-01-12
Enrollment: 214
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 assess the serum uric acid lowering effects and safety of lesinurad compared to placebo in patients who are intolerant or have a contraindication to allopurinol or febuxostat.

Detailed description: Allopurinol is the standard of care for the treatment of gout. In practice, approximately 20% of patients report side effects with allopurinol and 5% discontinue allopurinol due to side effects. Allopurinol can cause gastrointestinal intolerance, such as nausea and diarrhea, which appears to be dosedependent. Rash develops in about 2% of patients treated with allopurinol, and in about 20% of patients treated with allopurinol and ampicillin or amoxicillin. Allopurinol hypersensitivity syndrome remains a major concern among physicians. Mortality has been estimated to be up to nearly one quarter of AHS cases, with multiorgan system disease including hepatocellular changes and renal failure being a serious concern. Allopurinol is also relatively contraindicated for use in combination with 6-mercaptopurine and azathioprine, for which 1/4 to 1/3 lower doses must be given in order to avoid hematologic toxicity. Febuxostat, in clinical trials, has shown a similar AE profile to allopurinol. Liver function abnormalities, nausea, arthralgia and rash were the most commonly reported AEs. In postmarketing experience, Stevens Johnson Syndrome and hypersensitivity rashes have been reported (febuxostat prescribing information). Withdrawals due to AEs were similar in frequency to allopurinol as well. Relative contraindications in combination with 6-mercaptopurine and azathioprine are similar to allopurinol as well. Lesinurad may be an important therapeutic option for patients who either cannot tolerate or who have a contraindication to the use of allopurinol or febuxostat.

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 an sUA level ≥ 6.5 mg/dL at the Screening and Day -7 Visits.
* Subject must be able to take gout flare prophylaxis with colchicine or NSAID (including Cox-2 selective NSAID) ± PPI.
* Subject has a history (either by medical record or subject interview) of intolerance or a contraindication to either allopurinol or febuxostat.
* Body mass index (BMI) \< 45 kg/m2

Exclusion Criteria:

* Subject who is taking any other approved urate-lowering medication that is indicated for the treatment of gout at the Screening Visit.
* Subject with a documented history or suspicion of kidney stones.
* 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 a 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 active liver disease, or hepatic dysfunction.
* Subject receiving chronic treatment with more than 325 mg 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: Number of Subjects With an sUA Level That is < 6.0 mg/dL
timeFrame: 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Birmingham
country: United States
state: Alabama
city: Glendale
country: United States
state: Arizona
city: Phoenix
country: United States
state: Arizona
city: Tucson
country: United States
state: Arizona
city: Jonesboro
country: United States
state: Arkansas
city: Little Rock
country: United States
state: Arkansas
city: Anaheim
country: United States
state: California
city: Carmichael
country: United States
state: California
city: Covina
country: United States
state: California
city: Huntington Park
country: United States
state: California
city: Irvine
country: United States
state: California
city: Colorado Springs
country: United States
state: Colorado
city: Denver
country: United States
state: Colorado
city: Denver
country: United States
state: Colorado
city: Englewood
country: United States
state: Colorado
city: Milford
country: United States
state: Connecticut
city: Trumbull
country: United States
state: Connecticut
city: Boynton Beach
country: United States
state: Florida
city: Jacksonville
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Plant City
country: United States
state: Florida
city: Port Orange
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Winter Haven
country: United States
state: Florida
city: Newman
country: United States
state: Georgia
city: Honolulu
country: United States
state: Hawaii
city: Meridian
country: United States
state: Idaho
city: Chicago
country: United States
state: Illinois
city: Elizabethtown
country: United States
state: Kentucky
city: Lexington
country: United States
state: Kentucky
city: Louisville
country: United States
state: Kentucky
city: Metairie
country: United States
state: Louisiana
city: South Traverse
country: United States
state: Michigan
city: Jackson
country: United States
state: Mississippi
city: Olive Branch
country: United States
state: Mississippi
city: Southfield
country: United States
state: Missouri
city: Washington
country: United States
state: Missouri
city: Albuquerque
country: United States
state: New Mexico
city: Albuquerque
country: United States
state: New Mexico
city: Brooklyn
country: United States
state: New York
city: Hartsdale
country: United States
state: New York
city: New Windsor
country: United States
state: New York
city: New York
country: United States
state: New York
city: Hickory
country: United States
state: North Carolina
city: Raleigh
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: Cincinnati
country: United States
state: Ohio
city: Middleburgh Heights
country: United States
state: Ohio
city: Perrysburgh
country: United States
state: Ohio
city: Willoughby Hills
country: United States
state: Ohio
city: Norman
country: United States
state: Oklahoma
city: Jenkintown
country: United States
state: Pennsylvania
city: Lancaster
country: United States
state: Pennsylvania
city: Lansdale
country: United States
state: Pennsylvania
city: Pittsburgh
country: United States
state: Pennsylvania
city: Reading
country: United States
state: Pennsylvania
city: Sellersville
country: United States
state: Pennsylvania
city: Myrtle Beach
country: United States
state: South Carolina
city: Rock Hill
country: United States
state: South Carolina
city: Spartanburg
country: United States
state: South Carolina
city: Brentwood
country: United States
state: Tennessee
city: Spring Hill
country: United States
state: Tennessee
city: Dallas
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Victoria
country: United States
state: Texas
city: South Bountiful
country: United States
state: Utah
city: West Jordon
country: United States
state: Utah
city: West Layton
country: United States
state: Utah
city: Chesapeake
country: United States
state: Virginia
city: Richmond
country: United States
state: Virginia
city: Suffolk
country: United States
state: Virginia
city: Seattle
country: United States
state: Washington
city: Spokane
country: United States
state: Washington
city: Morgantown
country: United States
state: West Virginia
city: Butterfield
country: Australia
state: Queensland
city: Hobart
country: Australia
state: Tasmania
city: Tasmania
country: Australia
city: Anderlecht
country: Belgium
state: Brussels
city: Genk
country: Belgium
state: Limburg
city: Gozee
country: Belgium
city: Kortrijk
country: Belgium
city: Yvoir
country: Belgium
city: Coquitiam
country: Canada
state: British Columbia
city: Coquitlam
country: Canada
state: British Columbia
city: Victoria
country: Canada
state: British Columbia
city: London
country: Canada
state: Ontario
city: Mississauga
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Rimouski
country: Canada
state: Quebec
city: Quebec
country: Canada
city: Dresden
country: Germany
state: Saxony
city: Leipzig
country: Germany
state: Saxony
city: Dresden
country: Germany
city: Tauranga
country: New Zealand
state: Bay of Plenty
city: Auckland
country: New Zealand
city: Auckland
country: New Zealand
city: Durban
country: South Africa
city: Pretoria
country: South Africa
city: Rondebosch
country: South Africa
city: Stellenbosch
country: South Africa
city: Thabazimbi
country: South Africa
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: Tausche AK, Alten R, Dalbeth N, Kopicko J, Fung M, Adler S, Bhakta N, Storgard C, Baumgartner S, Saag K. Lesinurad monotherapy in gout patients intolerant to a xanthine oxidase inhibitor: a 6 month phase 3 clinical trial and extension study. Rheumatology (Oxford). 2017 Dec 1;56(12):2170-2178. doi: 10.1093/rheumatology/kex350.