FAQs

The efficacy of ULORIC has been demonstrated in three large phase 3, randomized, double blind, controlled, head-to-head clinical trials with allopurinol.

All 3 trials—APEX, FACT, and CONFIRMS—demonstrated the superiority of ULORIC 80 mg over allopurinol 300 mg in lowering serum uric acid to < 6 mg/dL at final visit. Patients with mild to moderate renal impairment* or high baseline serum uric acid level also benefited from ULORIC.

Important Safety Information

§ In APEX, allopurinol patients (n=10) with serum creatinine > 1.5 mg/dL and ≤ 2.0 mg/dL were dosed at 100 mg daily. In CONFIRMS, allopurinol patients (n=145) with estimated
Cl_Cr ≥ 30 mL/min and Cl_Cr ≤ 59 mL/min were dosed at 200 mg daily. All other patients received 300 mg daily.

The participants in the three ULORIC phase 3 clinical trials had a mean baseline serum uric acid level of 9.7 mg/dL and were reflective of the chronic gout population:

Clinical Study Details

APEX: Allopurinol and Placebo Controlled Efficacy Study of FebuXostat

• Design:
  A 6-month, multicenter, double-blind trial comparing the efficacy of ULORIC versus placebo and allopurinol in achieving a target serum uric acid level of < 6 mg/dL at final visit in patients with hyperuricemia and gout. All participants had a baseline serum uric acid level of ≥ 8 mg/dL.
• Study arms:
  There were 5 study arms: placebo (n=134), allopurinol 300 mg/100 mg* (n=268), ULORIC 80 mg (n=267), ULORIC 120 mg (n=269), and ULORIC 240 mg (n=134, for safety assessment only). Patients received anti-inflammatory prophylaxis for 8 or 10 weeks (naproxen 250 mg twice daily or colchicine 0.6 mg once daily), with length and start date dependent on previous use of urate-lowering therapy.
  
  *

  Allopurinol-treated patients (n=10) with serum creatinine > 1.5 mg/dL and ≤ 2 mg/dL received a dose of 100 mg daily. All other patients received 300 mg daily.
• Results:
  A significantly higher proportion of patients achieved a serum uric acid level of < 6 mg/dL on ULORIC 80 mg (72%, n=253)* than on allopurinol^† (39%, n=263) at the final visit.
  * p< 0.001 vs allopurinol.
  ^†

  Allopurinol patients (n=10) with serum creatinine > 1.5 mg/dL and ≤ 2 mg/dL were dosed at 100 mg daily.

FACT: Febuxostat and Allopurinol Controlled Trial

• Design:
  A 12-month, multicenter, double-blind trial comparing the efficacy of ULORIC versus allopurinol in achieving a target serum uric acid level of < 6 mg/dL at final visit in patients with hyperuricemia and gout. All participants had a baseline serum uric acid level of ≥ 8 mg/dL.
• Study arms:
  There were 3 study arms: allopurinol 300 mg (n=253), ULORIC 80 mg (n=256), and ULORIC 120 mg (n=251). Patients received anti-inflammatory prophylaxis for 8 or 10 weeks (naproxen 250 mg twice daily or colchicine 0.6 mg once daily), with length and start date dependent on previous use of urate-lowering therapy.
• Results:
  A significantly higher proportion of patients achieved a serum uric acid level of < 6 mg/dL on ULORIC 80 mg (74%, n=249)* than on allopurinol (36%, n=242) at the final visit.
  
  * p< 0.001 vs allopurinol.

CONFIRMS: CONfirmation of Febuxostat In Reducing and Maintaining Serum Urate

• Design:
  A 6-month, multicenter, double-blind trial comparing the efficacy of ULORIC versus allopurinol in achieving a target serum uric acid level of < 6 mg/dL at final visit in patients with hyperuricemia and gout. All participants had a baseline serum uric acid level ≥ 8 mg/dL.
• Study arms:
  There were 3 study arms: allopurinol 300 mg/200 mg* (n=756), ULORIC 40 mg (n=757), and ULORIC 80 mg (n=756). Patients received anti-inflammatory prophylaxis for 6 months (colchicine 0.6 mg once daily or naproxen 250 mg twice daily); subjects on previous urate-lowering therapy received prophylaxis for an additional month before the study began.
  
  *

  Allopurinol-treated patients (n=145) with estimated Cl_Cr ≥ 30 mL/min and Cl_Cr ≤ 59 mL/min received 200 mg daily. All other patients received 300 mg daily.
• Results:
  • All study participants
    ULORIC 40 mg (n=757) was as effective as allopurinol in lowering serum uric acid to < 6 mg/dL at the final visit
    ULORIC 80 mg (n=756) was superior to allopurinol (n=755) at lowering serum uric acid to < 6 mg/dL at the final visit (67% vs 42%)*
    

    * p< 0.001 vs allopurinol and p< 0.001 vs ULORIC 40 mg.

  • Patients with mild to moderate renal impairment*
    ULORIC was superior to allopurinol in patients with mild to moderate renal impairment.* A significantly higher proportion of patients achieved a serum uric acid level of < 6 mg/dL on ULORIC 80 mg (72%, n=503)^† and ULORIC 40 mg (50%, n=479)^‡ than on allopurinol^§ (42%, n=501) at the final visit.
    
    *

    Mild to moderate renal impairment is defined as serum creatinine levels of > 1.5 mg/dL and ≤ 2 mg/dL or estimated creatinine clearance ≥ 30 mL/min and ≤ 89 mL/min.
    ^† p< 0.05 vs allopurinol and ULORIC 40 mg.
    ^‡ p< 0.05 vs allopurinol.
    ^§

    Allopurinol patients (n=145) with estimated ClCr ≥ 30 mL/min and ClCr ≤ 59 mL/min were dosed at 200 mg daily. All other patients received 300 mg daily.

CONFIRMS included a group of patients with renal impairment as part of its trial design. Among patients with mild to moderate renal impairment,* a significantly higher proportion of patients achieved a serum uric acid level of < 6 mg/dL at the final visit with ULORIC 40 mg (50%, n=479)^† and ULORIC 80 mg (72%, n=503)^‡ than with allopurinol (42%, n=501).

More about ULORIC Efficacy

ULORIC has a non-purine-based structure and is not expected to inhibit other enzymes involved in purine and pyrimidine synthesis and metabolism at therapeutic concentrations.

ULORIC vs Allopurinol Comparison

ULORIC is eliminated by both hepatic and renal pathways. Therefore, no dose adjustment is required for patients with mild or moderate renal or hepatic impairment.*

ULORIC vs Allopurinol Comparison

ULORIC Mechanism of Action

For treatment of hyperuricemia in patients with gout, ULORIC is recommended at a 40 mg or 80 mg once-daily dose. The recommended starting dose of ULORIC is 40 mg once daily. For patients who do not achieve serum uric acid levels of < 6 mg/dL after 2 weeks with 40 mg, ULORIC 80 mg is recommended. ULORIC can be taken without regard to food.

More about ULORIC: Dosing

After initiation of any urate-lowering therapy, including ULORIC, an increase in gout flares may be observed as the reduction in serum uric acid can cause mobilization of urate from tissue deposits. Patients received anti-inflammatory prophylaxis for 6 months (colchicine 0.6 mg once daily or naproxen 250 mg twice daily) in ULORIC Clinical Trials. Subjects on previous urate-lowering therapy received prophylaxis for an additional month before the study began.

If a gout flare occurs during treatment, ULORIC need not be discontinued. The gout flare should be managed concurrently, as appropriate for the individual patient.

More about Dosing and Administration

No dose adjustment is necessary when administering ULORIC in patients with mild to moderate renal or hepatic impairment.*

No dose adjustments are needed for patients receiving certain common concomitant medications, including:

• Colchicine
• Naproxen
• Indomethacin
• Hydrochlorothiazide
• Warfarin
• Desipramine*

ULORIC is contraindicated in patients being treated with azathioprine, mercaptopurine, or theophylline.

More about ULORIC: Dosing and Administration

The following adverse reactions occurred in ≥1% of ULORIC-treated patients with a rate of at least 0.5% greater than seen in patients receiving placebo in phase 3 controlled studies.*

More about ULORIC: Safety Information

A higher rate of cardiovascular thromboembolic events was observed in patients treated with ULORIC than allopurinol in clinical trials. Monitor for signs and symptoms of MI and stroke.

Gout patients frequently have associated comorbidities, such as renal impairment, hypertension, hyperlipidemia and obesity, putting them at a higher risk of CV events. The patients included in ULORIC clinical trials were reflective of the chronic gout population with many of these comorbidities.

Cardiovascular thromboembolic events were adjudicated in the three phase 3 randomized controlled studies and the long-term extension studies. These events were adjudicated to one of the pre-defined endpoints from the Anti-Platelet Trialists' Collaborations (APTC) (cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke). The incidences of adjudicated Anti-Platelet Trialists' Collaboration (APTC) events per 100 patient-years of exposure were:

Overall, a higher rate of APTC events was observed in patients treated with ULORIC [0.74 per 100 patient-years (95% CI 0.36-1.37)] than allopurinol [0.60 per 100 patient-years (95% CI 0.16-1.53)].

• APTC end points were defined as non-fatal myocardial infarctions, non-fatal strokes, or cardiovascular deaths
• The rate of these events was calculated according to patient-years of exposure (number of patients multiplied by number of years patients were observed on the study drugs)
• The overall event rates indicate that less than 1 cardiovascular thromboembolic event (0.74 for ULORIC and 0.60 for allopurinol) occurred for every 100 patient-years of exposure
• A causal relationship with ULORIC has not been established. Monitor for signs and symptoms of myocardial infarction and stroke

More about ULORIC: Safety Information

Liver function abnormalities data were collected in two different ways:

• As elevations reported by the investigator as adverse events, regardless of the degree of elevation of the liver function test results

• As actual lab values of transaminase elevations greater than 3 times upper limit of normal (ULN) during phase 3 trials

Liver function abnormalities in most patients were transient, and the majority of patients remained on treatment. When laboratory evaluations of 3 times ULN were seen, there was not concomitant ALT and AST and bilirubin > 2 mg/dL in any of the patients treated with ULORIC 40 mg or 80 mg.

In the ULORIC phase 3 clinical trials, liver function analyses resulted in premature discontinuation in 1.8%, 1.2%, and 0.9% of patients in the ULORIC 40 mg, ULORIC 80 mg, and allopurinol groups, respectively. Premature discontinuation was determined by the investigator and not by the actual lab value cut-off point.

Monitor liver function tests periodically.

More about ULORIC: Safety Information