Table 1

Summary of randomised controlled trials of febuxostat (all dosages shown are mg/day)

Clinical trialFebuxostat versus allopurinol controlled trial (FACT), 200516Allopurinol and placebo-controlled study in gout subjects (APEX), 200817Febuxostat open-label clinical trial of urate-lowering efficacy and safety (FOCUS), 200918Confirmation of febuxostat In reducing and maintaining serum urate (CONFIRMS), 201019
Type of trialPhase III; randomised, double-blind clinical trialPhase III; randomised, double-blind clinical trialOpen label extension study of a 4-week Phase II trial comparing febuxostat versus allopurinol and placebo23Phase III; randomised, double-blind clinical trial
Total number of patients76210721162269
Patient ethnicity and gender>75% Caucasian; >95% male>75% Caucasian; >92% male85% Caucasian; 91% male>80% Caucasian; 94% male
Comparison groupsFebuxostat 80 mg (n=256); febuxostat 120 mg (n=251); allopurinol 300 mg (n=253)Febuxostat 80 mg (n=267); febuxostat 120 mg (n=269); febuxostat 240 mg (n=134); allopurinol 300 mg (n=268); placebo (n=134)Febuxostat 40 mg (n=8); febuxostat 80 mg (n=79); febuxostat 120 mg (n=29)Febuxostat 40 mg (n=757); febuxostat 80 mg (n=756); allopurinol 300 mg (n=611 which included patients with normal renal function CrCl≥90 ml/min or mild renal impairment CrCl 60–89 ml/min); allopurinol 200 mg (n=145 which included patients with moderate renal impairment Cr Cl 30–59 ml/min)
InclusionsAdults with gout and serum uric acid>8.0 mg/dlAge 18–85 years old with gout and serum uric acid ≥8.0 mg/dlSubjects who met American College of Rheumatology preliminary criteria for gout and completed the prior Phase II study23Age 18–85 years old with gout and serum uric acid ≥8.0 mg/dl
Duration52 weeks28 weeks5 years6 months
Per cent of patients meeting primary efficacy endpoint; (% of patients with serum uric acid <6.0 mg/dlFebuxostat 80 mg: 53%; febuxostat 120 mg: 62%; allopurinol 300 mg: 21%Febuxostat 80 mg: 48%; febuxostat 120 mg: 65%; febuxostat 240 mg: 69%; allopurinol 300 mg: 22%; placebo: 0%End of study: 83% met primary end-pointFebuxostat 40 mg: 45%; febuxostat 80 mg: 67%; allopurinol 300/200 mg (combined groups): 42%
Adverse events: Skin rashFebuxostat 80 mg: <1%; febuxostat 120 mg: 1%; allopurinol 300 mg: 2%; no serious rashes seenFebuxostat 80 mg: 5%; febuxostat 120 mg: 6%; febuxostat 240 mg: 4%; allopurinol 300 mg: 5%; placebo: 5%Overall rate of rashes amongst all dosage groups (n=116): 12%Febuxostat 40 mg: 6%; febuxostat 80 mg: 6%; allopurinol 300/200 mg (combined groups): 7%
Adverse events: abnormal liver function testsFebuxostat 80 mg: 4%; febuxostat 120 mg: 5%; allopurinol 300 mg: 4%Febuxostat 80 mg: 6%; febuxostat 120 mg: 4%; febuxostat 240 mg: 4%; allopurinol: 6%; placebo: 2%Overall rate of liver function test abnormalities amongst all dosage groups (n=116):13%; study withdrawals due to abnormal liver function test: 2.6% (three patients)Febuxostat 40 mg: 1%; febuxostat 80 mg: 2%; allopurinol 300/200 mg (combined groups): 1%
  • * Exclusion criteria were as follows: serum creatinine level >1.5 mg/dl (or calculated creatinine clearance <50 ml/min); pregnancy or lactation; concurrent therapy with urate-lowering agents, azathioprine, 6-mercaptopurine, or medications containing aspirin (>325 mg) or other salicylates; a body mass index >50 kg/m2; a history of xanthinuria, active liver disease, or hepatic dysfunction; changes in thiazide or steroid therapy (within 1 month of study) or in hormone replacement/oral contraceptive therapy (within 3 months of study); or a history of alcohol abuse or intake of ≥14 alcohol-containing drinks per week.

  • Exclusion criteria included intolerance to allopurinol, naproxen, or colchicine: history of renal calculi; intake of >=14 drinks/week; hepatic dysfunction with alanine aminotranserase (ALT) and aspartate aminotransgerase (AST) both 1.5 times the upper limit of normal; and any other significant medical conditions.

  • At least 35% of subjects enrolled were to have minor moderate renal impairment, defined as baseline estimated creatinine clearance (eClcr) of 60 to 89 ml/min or 30 to 59 ml/min, respectively calculated by the Cockcroft-Gault formula corrected for ideal body weight.