Summary of randomised controlled trials of febuxostat (all dosages shown are mg/day)
| Clinical trial | Febuxostat versus allopurinol controlled trial (FACT), 200516 | Allopurinol and placebo-controlled study in gout subjects (APEX), 200817 | Febuxostat open-label clinical trial of urate-lowering efficacy and safety (FOCUS), 200918 | Confirmation of febuxostat In reducing and maintaining serum urate (CONFIRMS), 201019 |
|---|---|---|---|---|
| Type of trial | Phase III; randomised, double-blind clinical trial | Phase III; randomised, double-blind clinical trial | Open label extension study of a 4-week Phase II trial comparing febuxostat versus allopurinol and placebo23 | Phase III; randomised, double-blind clinical trial |
| Total number of patients | 762 | 1072 | 116 | 2269 |
| Patient ethnicity and gender | >75% Caucasian; >95% male | >75% Caucasian; >92% male | 85% Caucasian; 91% male | >80% Caucasian; 94% male |
| Comparison groups | Febuxostat 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) |
| Inclusions | Adults with gout and serum uric acid>8.0 mg/dl | Age 18–85 years old with gout and serum uric acid ≥8.0 mg/dl | Subjects who met American College of Rheumatology preliminary criteria for gout and completed the prior Phase II study23 | Age 18–85 years old with gout and serum uric acid ≥8.0 mg/dl |
| Exclusions | * | † | * | ‡ |
| Duration | 52 weeks | 28 weeks | 5 years | 6 months |
| Per cent of patients meeting primary efficacy endpoint; (% of patients with serum uric acid <6.0 mg/dl | Febuxostat 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-point | Febuxostat 40 mg: 45%; febuxostat 80 mg: 67%; allopurinol 300/200 mg (combined groups): 42% |
| Adverse events: Skin rash | Febuxostat 80 mg: <1%; febuxostat 120 mg: 1%; allopurinol 300 mg: 2%; no serious rashes seen | Febuxostat 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 tests | Febuxostat 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.