Combination Treatment Study in Subjects With Tophaceous Gout With Lesinurad and Febuxostat
Condition: Tophaceous Gout
MeSH terms: Gout
Intervention: Lesinurad; Lesinurad; Placebo; Febuxostat
Intervention description: Tablets, 400 mg once daily (QD); Tablets, 200 mg QD; Tablets, Placebo QD; 80 mg
Intervention MeSH terms: Febuxostat; Lesinurad
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 330.0
Sex: All
Minimum age: 18 Years
Maximum age: 85 Years
Healthy volunteers: No

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.
    

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 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.