Combination Treatment Study in Subjects With Tophaceous Gout With Lesinurad and Febuxostat (CRYSTAL)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Ardea Biosciences, Inc.
ClinicalTrials.gov Identifier:
NCT01510769
First received: January 12, 2012
Last updated: August 5, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Tophaceous Gout
Drug: Lesinurad
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Ardea Biosciences, Inc.:

Primary Outcome Measures:
  • Efficacy [ Time Frame: 6 months, analysis after all subjects complete 12 months ] [ Designated as safety issue: No ]
    Proportion of subjects with an sUA level that is < 5.0 mg/dL by Month 6


Secondary Outcome Measures:
  • Complete Tophus Reduction [ Time Frame: 12 Months ] [ Designated as safety issue: No ]
    Proportion of subjects who experience complete resolution of at least 1 target tophus by Month 12

  • Best Tophus Response [ Time Frame: 12 Months ] [ Designated as safety issue: No ]
    Proportion of subjects with a best tophus response on at least 1 target tophus of complete or partial resolution by Month 12

  • Quality of Life [ Time Frame: 12 Months ] [ Designated as safety issue: No ]
    Proportion of subjects with an improvement from Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) of at least 0.25 at Month 12


Enrollment: 330
Study Start Date: January 2012
Study Completion Date: June 2014
Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: lesinurad 400 mg + febuxostat 80 mg Drug: Lesinurad
Tablets, 400 mg once daily (QD)
Experimental: lesinurad 200 mg + febuxostat 80 mg Drug: Lesinurad
Tablets, 200 mg QD
Placebo Comparator: placebo + febuxostat 80 mg Drug: Placebo
Tablets, Placebo QD

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

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01510769

  Hide Study Locations
Locations
United States, Alabama
Birmingham, Alabama, United States, 35211
United States, Arizona
Goodyear, Arizona, United States, 85395
Peoria, Arizona, United States, 85381
Pheonix, Arizona, United States, 85023
Tucson, Arizona, United States, 85724
United States, Arkansas
Little Rock, Arkansas, United States, 72204
Little Rock, Arkansas, United States, 72223
United States, California
Glendale, California, United States, 91204
Huntington Beach, California, United States, 92646
Irvine, California, United States, 92618
La Jolla, California, United States, 92037
Los Angeles, California, United States, 90048
Rancho Cucamonga, California, United States, 91730
San Diego, California, United States, 92108
United States, Colorado
Denver, Colorado, United States, 80230
Denver, Colorado, United States, 80220
Englewood, Colorado, United States, 80113
United States, Connecticut
Trumball, Connecticut, United States, 06611
United States, District of Columbia
Washington, District of Columbia, United States, 20422
United States, Florida
Boynton Beach, Florida, United States, 33472
Brooksville, Florida, United States, 34601
East Brandenton, Florida, United States, 34208
Fleming Island, Florida, United States, 32003
Miami, Florida, United States, 33135
Napels, Florida, United States, 34102
Pembroke Pines, Florida, United States, 33027
Pembroke Pines, Florida, United States, 33029
Port Orange, Florida, United States, 32127
Tampa, Florida, United States, 33614
Tampa, Florida, United States, 33606
Tampa, Florida, United States, 33607
Vero Beach, Florida, United States, 32960
Winter Haven, Florida, United States, 33880
United States, Georgia
Conyers, Georgia, United States, 30013
Johns Creek, Georgia, United States, 30097
Newman, Georgia, United States, 30265
Savannah, Georgia, United States, 31406
United States, Hawaii
Honolulu, Hawaii, United States, 96814
United States, Idaho
Meridian, Idaho, United States, 83646
Meridian, Idaho, United States, 83642
United States, Illinois
Chicago, Illinois, United States, 60624
Chicago, Illinois, United States, 60637
Gurnee, Illinois, United States, 60031
Springfield, Illinois, United States, 62704
Springfield, Illinois, United States, 62711
United States, Kentucky
Elizabethtown, Kentucky, United States, 42701
Lexington, Kentucky, United States, 40504
United States, Maryland
Frederick, Maryland, United States, 21702
United States, Michigan
Kalamazoo, Michigan, United States, 49009
Southfield, Michigan, United States, 48034
United States, Mississippi
Jackson, Mississippi, United States, 39202
Olive Branch, Mississippi, United States, 38654
United States, Missouri
Jefferson City, Missouri, United States, 65109
Saint Louis, Missouri, United States, 63117
United States, Montana
Missoula, Montana, United States, 59808
United States, New York
Mineola, New York, United States, 11501
New York, New York, United States, 10016
United States, North Carolina
Calabash, North Carolina, United States, 28467
Durham, North Carolina, United States, 27710
Greenville, North Carolina, United States, 27834
Wilmington, North Carolina, United States, 28401
Winston-Salem, North Carolina, United States, 27103
United States, North Dakota
Fargo, North Dakota, United States, 58103
United States, Ohio
Columbus, Ohio, United States, 43203
Middleburg, Ohio, United States, 44130
Wadsworth, Ohio, United States, 44281
United States, Oklahoma
Oklahoma City, Oklahoma, United States, 73112
Oklahoma City, Oklahoma, United States, 73103
United States, Pennsylvania
Belle Vernon, Pennsylvania, United States, 15012
Clairton, Pennsylvania, United States, 15025
Duncansville, Pennsylvania, United States, 16635
Jenkintown, Pennsylvania, United States, 19046
Lansdale, Pennsylvania, United States, 19446
Pittsburgh, Pennsylvania, United States, 15206
Scottdale, Pennsylvania, United States, 15683
Sellersville, Pennsylvania, United States, 18960
United States, South Carolina
Columbia, South Carolina, United States, 29204
Greenville, South Carolina, United States, 29615
Mount Pleasant, South Carolina, United States, 29464
Spartanburg, South Carolina, United States, 29303
United States, Tennessee
Jackson, Tennessee, United States, 38305
Memphis, Tennessee, United States, 38119
United States, Texas
Austin, Texas, United States, 78705
Austin, Texas, United States, 78758
Corpus Christi, Texas, United States, 78413
Dallas, Texas, United States, 75218
Houston, Texas, United States, 77074
Houston, Texas, United States, 77004
San Antonio, Texas, United States, 78229
Sugar Land, Texas, United States, 77479
Victoria, Texas, United States, 77901
Waco, Texas, United States, 76708
United States, Virginia
Chesapeake, Virginia, United States, 23320
Danville, Virginia, United States, 24541
Richmond, Virginia, United States, 23235
Suffolk, Virginia, United States, 23435
Virginia Beach, Virginia, United States, 23462
United States, Washington
Seattle, Washington, United States, 98104
United States, West Virginia
Morgantown, West Virginia, United States, 26505
Australia, New South Wales
Camperdown, New South Wales, Australia, 2050
Australia, South Australia
Woodville South, South Australia, Australia, 5011
Australia, Tasmania
Hobart, Tasmania, Australia, 7000
Australia, Western Australia
Shenton Park, Western Australia, Australia, 6008
Canada, British Columbia
Kelowna, British Columbia, Canada, V1Y 3G8
Victoria, British Columbia, Canada, V8V 3N7
Canada, Nova Scotia
Halifax, Nova Scotia, Canada, B3K 2M5
Canada, Ontario
London, Ontario, Canada, N6A 5R8
Mississauga, Ontario, Canada, L5M 2V8
Toronto, Ontario, Canada, M9W 4L6
Canada
Quebec, Canada, G1V 3M7
New Zealand
Grafton, Auckland, New Zealand, 1010
Tauranga, Bay of Plenty, New Zealand, 3143
Hamilton, New Zealand, 3240
Poland
Kutno, Lodz Province, Poland, 99-300
Biatystok, Poland, 15-430
Elblag, Poland, 82-300
Katowice, Poland, 40-954
Konskie, Poland, 26-200
Krakow, Poland, 30-510
Krakow, Poland, 31-501
Poznan, Poland, 60-773
Poznan, Poland, 60-539
Switzerland
Lausanne, Vlaud, Switzerland, 1011
Fribourg, Switzerland, 1708
Sponsors and Collaborators
Ardea Biosciences, Inc.
Investigators
Study Director: Chris Storgard, MD Ardea Biosciences, Inc.
  More Information

Additional Information:
No publications provided

Responsible Party: Ardea Biosciences, Inc.
ClinicalTrials.gov Identifier: NCT01510769     History of Changes
Other Study ID Numbers: RDEA594-304, 2011-003768-55
Study First Received: January 12, 2012
Last Updated: August 5, 2014
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
Canada: Health Canada
New Zealand: Medsafe
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
United States: Food and Drug Administration
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Switzerland: Swissmedic

Additional relevant MeSH terms:
Gout
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Purine-Pyrimidine Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases
Febuxostat
Gout Suppressants
Antirheumatic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 11, 2014