Lesinurad Monotherapy in Gout Subjects Intolerant to Xanthine Oxidase Inhibitors

NCT ID: NCT01508702

Last Updated: 2016-02-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 214 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-01-31
• Study Completion Date: 2013-11-30

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.

Conditions

Gout

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

lesinurad 400 mg

Group Type: EXPERIMENTAL

lesinurad

Intervention Type: DRUG

Tablets, 400 mg QD

placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Tablets, Placebo QD

Interventions

lesinurad

Tablets, 400 mg QD

Intervention Type: DRUG

Placebo

Tablets, Placebo QD

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ardea Biosciences, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Chris Storgard, MD

Role: STUDY_DIRECTOR

Ardea Biosciences, Inc.

Locations

Birmingham, Alabama, United States

Birmingham, Alabama, United States

Glendale, Arizona, United States

Phoenix, Arizona, United States

Tucson, Arizona, United States

Jonesboro, Arkansas, United States

Little Rock, Arkansas, United States

Anaheim, California, United States

Carmichael, California, United States

Covina, California, United States

Huntington Park, California, United States

Irvine, California, United States

Colorado Springs, Colorado, United States

Denver, Colorado, United States

Denver, Colorado, United States

Englewood, Colorado, United States

Milford, Connecticut, United States

Trumbull, Connecticut, United States

Boynton Beach, Florida, United States

Jacksonville, Florida, United States

Miami, Florida, United States

Miami, Florida, United States

Plant City, Florida, United States

Port Orange, Florida, United States

Tampa, Florida, United States

Winter Haven, Florida, United States

Newnan, Georgia, United States

Honolulu, Hawaii, United States

Meridian, Idaho, United States

Chicago, Illinois, United States

Elizabethtown, Kentucky, United States

Lexington, Kentucky, United States

Louisville, Kentucky, United States

Metairie, Louisiana, United States

South Traverse, Michigan, United States

Jackson, Mississippi, United States

Olive Branch, Mississippi, United States

Southfield, Missouri, United States

Washington, Missouri, United States

Albuquerque, New Mexico, United States

Albuquerque, New Mexico, United States

Brooklyn, New York, United States

Hartsdale, New York, United States

New Windsor, New York, United States

New York, New York, United States

Hickory, North Carolina, United States

Raleigh, North Carolina, United States

Winston-Salem, North Carolina, United States

Fargo, North Dakota, United States

Cincinnati, Ohio, United States

Cincinnati, Ohio, United States

Middleburg Heights, Ohio, United States

Perrysburg, Ohio, United States

Willoughby Hills, Ohio, United States

Norman, Oklahoma, United States

Jenkintown, Pennsylvania, United States

Lancaster, Pennsylvania, United States

Lansdale, Pennsylvania, United States

Pittsburgh, Pennsylvania, United States

Reading, Pennsylvania, United States

Sellersville, Pennsylvania, United States

Myrtle Beach, South Carolina, United States

Rock Hill, South Carolina, United States

Spartanburg, South Carolina, United States

Brentwood, Tennessee, United States

Spring Hill, Tennessee, United States

Dallas, Texas, United States

Houston, Texas, United States

San Antonio, Texas, United States

Victoria, Texas, United States

South Bountiful, Utah, United States

West Jordon, Utah, United States

West Layton, Utah, United States

Chesapeake, Virginia, United States

Richmond, Virginia, United States

Suffolk, Virginia, United States

Seattle, Washington, United States

Spokane, Washington, United States

Morgantown, West Virginia, United States

Butterfield, Queensland, Australia

Hobart, Tasmania, Australia

Tasmania, , Australia

Anderlecht, Brussels Capital, Belgium

Genk, Limburg, Belgium

Gozée, , Belgium

Kortrijk, , Belgium

Yvoir, , Belgium

Coquitiam, British Columbia, Canada

Coquitlam, British Columbia, Canada

Victoria, British Columbia, Canada

London, Ontario, Canada

Mississauga, Ontario, Canada

Toronto, Ontario, Canada

Québec, Quebec, Canada

Rimouski, Quebec, Canada

Dresden, Saxony, Germany

Leipzig, Saxony, Germany

Dresden, , Germany

Tauranga, Bay of Plenty, New Zealand

Auckland, , New Zealand

Auckland, , New Zealand

Durban, , South Africa

Pretoria, , South Africa

Rondebosch, , South Africa

Stellenbosch, , South Africa

Thabazimbi, , South Africa

Countries

United States; Australia; Belgium; Canada; Germany; New Zealand; South Africa

References

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)

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.

Reference Type: DERIVED

PMID: 29029210 (View on PubMed)

Related Links

http://www.gouttrial.com

Related Info

Other Identifiers

2011-003756-39

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

RDEA594-303

Identifier Type: -

Identifier Source: org_study_id