Allopurinol Combination Study

Inclusion criteria

• Male or a post-menopausal or surgically sterile female.
• 18 - 80 years of age.
• Has been taking allopurinol as the sole urate lowering therapy for hyperuricemia for at least 6 weeks at a dose between 200 mg and 600 mg per day without an adequate response.
• Has a sUA level ≥ 6 mg/dL at screening.
• Meets criteria for the diagnosis of gout as per the American Rheumatism Association (ARA) Criteria for the Classification of Acute Arthritis of Primary Gout.
• Willing and able to give informed consent and adhere to visit/protocol schedules (informed consent must be given before the first study procedure is performed).
• Subjects entering the optional Extension Period must have completed 28 days of dosing in the Double-Blind Treatment Period and the Day 42 Visit in the Follow-up Period within 4 months and must not have experienced any serious adverse events considered possibly related to study drug.
• Subjects entering the optional Open-Label Extension Period must continue to be compliant with the protocol through Week 44 of the Double-Blind Extension Period and must not have experienced any serious adverse events considered possibly related to study drug.

Exclusion criteria

• Consumes more than 14 drinks of alcohol per week (e.g., 1 drink = 5 oz [150 ml] of wine, 12 oz [360 ml] of beer, or 1.5 oz [45 ml] of hard liquor).
• History or suspicion of drug abuse.
• History of documented or suspected kidney stones.
• Has rheumatoid arthritis or other autoimmune disease requiring treatment.
• Documented or suspicion of HIV infection.
• Positive serology to HCV antibodies (Abs), and/or hepatitis B surface antigen (HBsAg).
• History of malignancy within 5 years prior to the first dose of study medication, other than non-melanomatous skin cancer or cervical dysplasia.
• History of cardiac abnormalities, including abnormal and clinically relevant ECG changes
• Any condition predisposing to QT prolongation including pathological Q-wave (defined as Q-wave >40 msec or depth > 0.4-0.5 mV).
• Any use of concomitant medications that prolong the QT/QTc interval within the 14 days prior to Baseline (Day 1).
• QT interval corrected for heart rate according to Fridericia (QTcF) > 450 msec at Screening or pre-dose at Baseline (Day 1).
• Uncontrolled hypertension (above 150/95).
• Inadequate renal function [serum creatinine >1.5 mg/dL or creatinine clearance < 60 mL/min (by Cockroft-Gault formula)].
• Hemoglobin < 10 g/dL (males) or < 9 g/dL (females).
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5 x upper limit of normal (ULN).
• Gamma glutamyl transferase (GGT) > 3 x ULN.
• Active peptic ulcer disease requiring treatment.
• History of xanthinuria, active liver disease, or hepatic dysfunction.
• Requires therapy with any other urate-lowering medication, other than the study medications.
• Requires long-term use of salicylates; diuretics; losartan; azathioprine; mercaptopurine; theophylline; intravenous colchicine; cyclosporine; cyclophosphamide; pyrazinamide; sulfamethoxazole; or trimethoprim.
• Taking medications known as enzyme inducers (see section 3.7 for listing).
• Reports receiving a strong or moderate inhibitor of CYP3A4 or a P-gp inhibitor within 1 month prior to study drug dosing, due to potential interactions with colchicine.
• Acute gout flare (exclusive of chronic synovitis/ arthritis) during the Screening-Period that has not resolved one week prior to the Baseline Visit (Day 0).
• Pregnant or breast feeding.
• Has received an investigational medication within 4 weeks prior to the screening visit for this study.
• Previously participated in a clinical study involving RDEA806 or RDEA594.
• Known hypersensitivity or allergy to RDEA594, allopurinol or colchicine or any components in their formulations.
• Body mass index (BMI) >48 kg/m2.
• Taking greater than 1000 mg/day of Vitamin C.
• 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.
• Inadequate renal function after completing the Double-Blind Treatment period prior to entering Double-Blind Extension Period.
• Requiring treatment with prohibited medications noted in exclusion criteria numbers 20-23 after completing the Double-Blind Treatment Period prior to entering the Extension Period.
• Clinically relevant medical event as determined by the investigator in consultation with medical monitor prior to entering the Extension Period.