The study postulates that topiroxostat 120 mg/day provides non-inferior serum urate reduction as compared to allopurinol 200 mg/day. In terms of tolerance, topiroxostat has been found to be well tolerated than allopurinol in hyperuricemic patients who had or did not have gout.

Gout is one of the known disease that significantly impacts the quality of life of adult males. The increased level of uric acid (>416.4 µmol/L) is the major cause of gout. Thus, to prevent gout and related disorders, it is important to regulate uric acid levels in the body. The incidence of hyperuricemia in males was found to be approximately 20% in USA and 15–20% in Japan. In Japan, asymptomatic hyperuricemia (serum urate level ≥475.8 µmol/L) with lifestyle-related disease such as CKD, urinary lithiasis, hypertension, hyperlipidemia or diabetes can be treated with urate-lowering drugs according to the individual patient’s clinical condition. Topiroxostat also known as FYX-051, is a selective xanthine oxidoreductase (XOR) inhibitor recently approved in Japan for the treatment of hyperuricemia with or without gout. In contrast to allopurinol, the pharmacokinetics of topiroxostat was not affected by renal function. Compared with febuxostat, whereas a part of the metabolites of febuxostat consists of active oxidative metabolites, the major metabolites of topiroxostat (N-glucuronide and N-oxide form) were generally inactive to XOR (IC50 ≥10 µmol/L), and urinary excretion rate of topiroxostat is <0.1% in patients with moderate renal impairment. In view of the fact that hyperuricemic patients have CKD with relatively high frequency, these pharmacokinetic profiles are useful. Previous reports have suggested that topiroxostat significantly reduced serum urate levels and urinary albumin creatinine ratios in Japanese hyperuricemic stage 3 CKD patients without dose adjustment in a 22-week clinical trial. However, no clinical trial has reported that compared the serum urate-lowering efficacy of topiroxostat with other XOR inhibitors.

Rationale behind research:

There are no clinical reports that have compared topiroxostat, a selective xanthine oxidase inhibitor, with allopurinol in serum urate-lowering efficacy. Thus, this study was conducted to compare the efficacy and safety of topiroxostat and allopurinol in patients with or without gout.

Objective:

To test the serum urate-lowering efficacy and safety of topiroxostat compared with allopurinol in hyperuricemic patients with or without gout.

Study outcomes

Primary Outcomes: Percentage change in the serum urate level from baseline to the final visit.

Secondary Outcomes: Proportion of patients with serum urate levels ≤356.9 µmol/L at the final visit and percent change and change in serum urate levels from baseline to each visit.

Time Points: Baseline and up to 16 weeks

Outcomes

• Primary Outcomes: The percent change in serum urate level from baseline to the final visit was -34.3±11.1% in allopurinol group and -36.3±12.7% in topiroxostat group with between-group difference -2.0%. The percent changes in serum urate levels in the allopurinol group after 6 weeks of treatment were generally same with the percentage change of serum urate in the other clinical study of allopurinol. Also, the effect was constant until week 16 in the allopurinol group.
• Secondary Outcomes: The proportion of patients with a serum urate level ≤356.9 µmol/L was not significant with topiroxostat (72.4%) compared with allopurinol (73.3%). For each prespecified subgroup analysis, the percentage was similar between groups.

Figure 1: Proportion of patients with a serum urate level ≤356.9µmol/L. Error bars indicate 95% confidence interval

In the current study, the percent change in serum urate level from baseline to the final visit was -34.3±11.1% in allopurinol group and -36.3±12.7% in topiroxostat group. Non-inferiority of the serum urate lowering efficacy of topiroxostat to allopurinol was proved by the predefined non-inferiority margin. The overall incidences of adverse events and adverse drug reactions were similar between both groups.

In conclusion, topiroxostat 120mg/day provided non-inferior serum urate reduction compared with allopurinol 200mg/day and was well tolerated in Japanese hyperuricemic patients with or without gout.