Combining Lesinurad With Allopurinol in Inadequate Responders

Allopurinol is the standard of care for the treatment of gout. Nevertheless, most patients
treated with allopurinol do not achieve the recommended sUA target of < 6.0 mg/dL and need
additional therapy to achieve the target. Probenecid and benzbromarone are URAT1 inhibitors,
generally recommended as second-line agents for patients who are either resistant to or
intolerant of allopurinol. However, benzbromarone is not available in the US and probenecid
is rarely used. Consequently, there is a clear unmet medical need for a new safe and
effective therapy for gout, such as lesinurad, a potent URAT1 inhibitor, that can be used in
combination with allopurinol in patients not responding adequately to allopurinol
monotherapy so that very high rates of response can be achieved by nearly all gout patients,
rather than a minority.The subjects selected for this study will have moderate to severe
gout with an inadequate response to allopurinol

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.