Combining Lesinurad With Allopurinol in Inadequate Responders
Condition: Gout
MeSH terms: Gout
Intervention: Lesinurad; Lesinurad; Placebo; Allopurinol
Intervention description: Tablets, 200 mg QD; Tablets, 400 mg QD; Tablets, Placebo QD; Tablets
Intervention MeSH terms: Allopurinol; Lesinurad
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 610.0
Sex: All
Minimum age: 18 Years
Maximum age: 85 Years
Healthy volunteers: No
Keywords: Gout

Summary:

      This study will compare the serum uric acid lowering effects, clinical benefits, and safety
      of lesinurad in combination with allopurinol to allopurinol alone in subjects with gout who
      have had an inadequate response to allopurinol.
    

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 been taking allopurinol as the sole urate-lowering therapy indicated for
             the treatment of gout for at least 8 weeks prior to the Screening Visit at a stable,
             medically appropriate dose, as determined by the investigator, of at least 300 mg per
             day (at least 200 mg for subjects with moderate renal impairment).

          -  Subject must be able to take gout flare prophylaxis with colchicine or an NSAID
             (including Cox-2 selective NSAID) ±PPI.

          -  Subject has an sUA level ≥ 6.5 mg/dL at the Screening Visit and ≥ 6.0 mg/dL at Day -7
             Visit.

          -  Subject has reported at least 2 gout flares in the prior 12 months.

          -  Body mass index (BMI) < 45 kg/m2

        Exclusion Criteria:

          -  Subject with known hypersensitivity or allergy to allopurinol.

          -  Subject who is taking any other approved urate-lowering medication that is indicated
             for the treatment of gout other than allopurinol within 8 weeks of the Screening
             Visit.

          -  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 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 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 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.