Combination Treatment Study in Subjects With Tophaceous Gout With Lesinurad and Febuxostat

NCT01510769 | Completed Phase 3 Results DMC

• 2 other identifiers: RDEA594-3042011-003768-55
• Study Type: interventional
• Target: 330
• Locations: 6 countries
• Sites: 124

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.

Conditions

Tophaceous Gout

Outcome Measures

Primary Outcomes (1)

• Subjects With a Serum Urate (sUA) Level That is < 5.0 mg/dL by Month 6

  Proportion of subjects with an sUA level that is \< 5.0 mg/dL by Month 6

  6 months, analysis after all subjects complete 12 months

Secondary Outcomes (3)

• Complete Resolution of at Least One Target Tophus

  12 Months

• Complete or Partial Response of at Least One Tophus

  12 Months

• Quality of Life

  12 Months

Study Arms (3)

lesinurad 400 mg + febuxostat 80 mg

EXPERIMENTAL

Drug: Lesinurad; Drug: Febuxostat

lesinurad 200 mg + febuxostat 80 mg

EXPERIMENTAL

Drug: Lesinurad; Drug: Febuxostat

placebo + febuxostat 80 mg

PLACEBO COMPARATOR

Drug: Placebo; Drug: Febuxostat

Interventions

Lesinurad DRUG

Tablets, 400 mg once daily (QD)

lesinurad 400 mg + febuxostat 80 mg

Placebo DRUG

Tablets, Placebo QD

placebo + febuxostat 80 mg

Febuxostat DRUG

80 mg

lesinurad 200 mg + febuxostat 80 mg; lesinurad 400 mg + febuxostat 80 mg; placebo + febuxostat 80 mg

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ardea Biosciences, Inc.: lead

Study Sites (124)

Unknown Facility

Birmingham, Alabama, 35211, United States

Location

Unknown Facility

Goodyear, Arizona, 85395, United States

Location

Unknown Facility

Peoria, Arizona, 85381, United States

Location

Unknown Facility

Pheonix, Arizona, 85023, United States

Location

Unknown Facility

Tucson, Arizona, 85724, United States

Location

Unknown Facility

Little Rock, Arkansas, 72204, United States

Location

Unknown Facility

Little Rock, Arkansas, 72223, United States

Location

Unknown Facility

Glendale, California, 91204, United States

Location

Unknown Facility

Huntington Beach, California, 92646, United States

Location

Unknown Facility

Irvine, California, 92618, United States

Location

Unknown Facility

La Jolla, California, 92037, United States

Location

Unknown Facility

Los Angeles, California, 90048, United States

Location

Unknown Facility

Rancho Cucamonga, California, 91730, United States

Location

Unknown Facility

San Diego, California, 92108, United States

Location

Unknown Facility

Denver, Colorado, 80220, United States

Location

Unknown Facility

Denver, Colorado, 80230, United States

Location

Unknown Facility

Englewood, Colorado, 80113, United States

Location

Unknown Facility

Trumball, Connecticut, 06611, United States

Location

Unknown Facility

Washington D.C., District of Columbia, 20422, United States

Location

Unknown Facility

Boynton Beach, Florida, 33472, United States

Location

Unknown Facility

Brooksville, Florida, 34601, United States

Location

Unknown Facility

East Brandenton, Florida, 34208, United States

Location

Unknown Facility

Fleming Island, Florida, 32003, United States

Location

Unknown Facility

Miami, Florida, 33135, United States

Location

Unknown Facility

Napels, Florida, 34102, United States

Location

Unknown Facility

Pembroke Pines, Florida, 33027, United States

Location

Unknown Facility

Pembroke Pines, Florida, 33029, United States

Location

Unknown Facility

Port Orange, Florida, 32127, United States

Location

Unknown Facility

Tampa, Florida, 33606, United States

Location

Unknown Facility

Tampa, Florida, 33607, United States

Location

Unknown Facility

Tampa, Florida, 33614, United States

Location

Unknown Facility

Vero Beach, Florida, 32960, United States

Location

Unknown Facility

Winter Haven, Florida, 33880, United States

Location

Unknown Facility

Conyers, Georgia, 30013, United States

Location

Unknown Facility

Johns Creek, Georgia, 30097, United States

Location

Unknown Facility

Newnan, Georgia, 30265, United States

Location

Unknown Facility

Savannah, Georgia, 31406, United States

Location

Unknown Facility

Honolulu, Hawaii, 96814, United States

Location

Unknown Facility

Meridian, Idaho, 83642, United States

Location

Unknown Facility

Meridian, Idaho, 83646, United States

Location

Unknown Facility

Chicago, Illinois, 60624, United States

Location

Unknown Facility

Chicago, Illinois, 60637, United States

Location

Unknown Facility

Gurnee, Illinois, 60031, United States

Location

Unknown Facility

Springfield, Illinois, 62704, United States

Location

Unknown Facility

Springfield, Illinois, 62711, United States

Location

Unknown Facility

Elizabethtown, Kentucky, 42701, United States

Location

Unknown Facility

Lexington, Kentucky, 40504, United States

Location

Unknown Facility

Frederick, Maryland, 21702, United States

Location

Unknown Facility

Kalamazoo, Michigan, 49009, United States

Location

Unknown Facility

Southfield, Michigan, 48034, United States

Location

Unknown Facility

Jackson, Mississippi, 39202, United States

Location

Unknown Facility

Olive Branch, Mississippi, 38654, United States

Location

Unknown Facility

Jefferson City, Missouri, 65109, United States

Location

Unknown Facility

St Louis, Missouri, 63117, United States

Location

Unknown Facility

Missoula, Montana, 59808, United States

Location

Unknown Facility

Mineola, New York, 11501, United States

Location

Unknown Facility

New York, New York, 10016, United States

Location

Unknown Facility

Calabash, North Carolina, 28467, United States

Location

Unknown Facility

Durham, North Carolina, 27710, United States

Location

Unknown Facility

Greenville, North Carolina, 27834, United States

Location

Unknown Facility

Wilmington, North Carolina, 28401, United States

Location

Unknown Facility

Winston-Salem, North Carolina, 27103, United States

Location

Unknown Facility

Fargo, North Dakota, 58103, United States

Location

Unknown Facility

Columbus, Ohio, 43203, United States

Location

Unknown Facility

Middleburg, Ohio, 44130, United States

Location

Unknown Facility

Wadsworth, Ohio, 44281, United States

Location

Unknown Facility

Oklahoma City, Oklahoma, 73103, United States

Location

Unknown Facility

Oklahoma City, Oklahoma, 73112, United States

Location

Unknown Facility

Belle Vernon, Pennsylvania, 15012, United States

Location

Unknown Facility

Clairton, Pennsylvania, 15025, United States

Location

Unknown Facility

Duncansville, Pennsylvania, 16635, United States

Location

Unknown Facility

Jenkintown, Pennsylvania, 19046, United States

Location

Unknown Facility

Lansdale, Pennsylvania, 19446, United States

Location

Unknown Facility

Pittsburgh, Pennsylvania, 15206, United States

Location

Unknown Facility

Scottdale, Pennsylvania, 15683, United States

Location

Unknown Facility

Sellersville, Pennsylvania, 18960, United States

Location

Unknown Facility

Columbia, South Carolina, 29204, United States

Location

Unknown Facility

Greenville, South Carolina, 29615, United States

Location

Unknown Facility

Mt. Pleasant, South Carolina, 29464, United States

Location

Unknown Facility

Spartanburg, South Carolina, 29303, United States

Location

Unknown Facility

Jackson, Tennessee, 38305, United States

Location

Unknown Facility

Memphis, Tennessee, 38119, United States

Location

Unknown Facility

Austin, Texas, 78705, United States

Location

Unknown Facility

Austin, Texas, 78758, United States

Location

Unknown Facility

Corpus Christi, Texas, 78413, United States

Location

Unknown Facility

Dallas, Texas, 75218, United States

Location

Unknown Facility

Houston, Texas, 77004, United States

Location

Unknown Facility

Houston, Texas, 77074, United States

Location

Unknown Facility

San Antonio, Texas, 78229, United States

Location

Unknown Facility

Sugar Land, Texas, 77479, United States

Location

Unknown Facility

Victoria, Texas, 77901, United States

Location

Unknown Facility

Waco, Texas, 76708, United States

Location

Unknown Facility

Chesapeake, Virginia, 23320, United States

Location

Unknown Facility

Danville, Virginia, 24541, United States

Location

Unknown Facility

Richmond, Virginia, 23235, United States

Location

Unknown Facility

Suffolk, Virginia, 23435, United States

Location

Unknown Facility

Virginia Beach, Virginia, 23462, United States

Location

Unknown Facility

Seattle, Washington, 98104, United States

Location

Unknown Facility

Morgantown, West Virginia, 26505, United States

Location

Unknown Facility

Camperdown, New South Wales, 2050, Australia

Location

Unknown Facility

Woodville South, South Australia, 5011, Australia

Location

Unknown Facility

Hobart, Tasmania, 7000, Australia

Location

Unknown Facility

Shenton Park, Western Australia, 6008, Australia

Location

Unknown Facility

Kelowna, British Columbia, V1Y 3G8, Canada

Location

Unknown Facility

Victoria, British Columbia, V8V 3N7, Canada

Location

Unknown Facility

Halifax, Nova Scotia, B3K 2M5, Canada

Location

Unknown Facility

London, Ontario, N6A 5R8, Canada

Location

Unknown Facility

Mississauga, Ontario, L5M 2V8, Canada

Location

Unknown Facility

Toronto, Ontario, M9W 4L6, Canada

Location

Unknown Facility

Québec, Quebec, G1V 3M7, Canada

Location

Unknown Facility

Grafton, Auckland, 1010, New Zealand

Location

Unknown Facility

Tauranga, Bay of Plenty, 3143, New Zealand

Location

Unknown Facility

Hamilton, 3240, New Zealand

Location

Unknown Facility

Kutno, Lodz Province, 99-300, Poland

Location

Unknown Facility

Biatystok, 15-430, Poland

Location

Unknown Facility

Elblag, 82-300, Poland

Location

Unknown Facility

Gmina Końskie, 26-200, Poland

Location

Unknown Facility

Katowice, 40-954, Poland

Location

Unknown Facility

Krakow, 30-510, Poland

Location

Unknown Facility

Krakow, 31-501, Poland

Location

Unknown Facility

Poznan, 60-539, Poland

Location

Unknown Facility

Poznan, 60-773, Poland

Location

Unknown Facility

Lausanne, Vlaud, 1011, Switzerland

Location

Unknown Facility

Fribourg, 1708, Switzerland

Location

Related Publications (3)

• 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.

  PMID: 35835008 DERIVED

• 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.

  PMID: 30616614 DERIVED

• 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.

  PMID: 28597604 DERIVED

Related Links

• Related Info

MeSH Terms

Interventions

lesinurad; Febuxostat

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Maple Fung, MD
• Organization: Ardea Biosciences, Inc.

mfung@ardeabio.com

1-858-652-6671

Study Officials

• Chris Storgard, MD

  Ardea Biosciences, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 12, 2012
• First Posted: January 16, 2012
• Study Start: January 1, 2012
• Primary Completion: June 1, 2014
• Study Completion: June 1, 2014
• Last Updated: May 26, 2016
• Results First Posted: May 26, 2016

Record last verified: 2016-04

Locations

CH (2); PL (9); AU (4); CA (7); NZ (3); US (99)