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

  Show 124 Study Locations
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
Genetic Diseases, Inborn
Joint Diseases
Metabolic Diseases
Metabolism, Inborn Errors
Musculoskeletal Diseases
Purine-Pyrimidine Metabolism, Inborn Errors
Rheumatic Diseases
Febuxostat
Antirheumatic Agents
Gout Suppressants
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014