Department of Pathophysiology and Therapy in Chronic Kidney Disease, Jikei University School of Medicine, Tokyo, Japan.
Medical Affairs Department, Reliability and Quality Assurance Division, Fuji Yakuhin Co., Ltd., 4-383, Sakuragi-cho, Omiya-ku, Saitama-shi, Saitama, 330-9508, Japan.
Clin Drug Investig. 2018 Dec;38(12):1135-1143. doi: 10.1007/s40261-018-0699-0.
Topiroxostat-a novel selective xanthine oxidoreductase inhibitor-has been reported to reduce serum urate levels. The purpose of this study was to assess the efficacy and safety of long-term topiroxostat administration in Japanese hyperuricemic patients with or without gout.
This multicenter, open-label study evaluated the efficacy and safety of long-term twice-daily oral topiroxostat administration in patients with or without gout. The initial topiroxostat dosage was 40-80 mg/day, and the maintenance dosage was 120 mg/day, which was increased to 240 mg/day at 40 mg increments if the serum urate level exceeded 6.0 mg/dL.
Serum urate level, which was the primary endpoint, decreased stably over time and showed significant reduction on the final visit (38.44% ± 13.34%) compared with that at the baseline. Both urinary albumin/creatinine ratio and mean blood pressure significantly improved. The overall incidence rate of adverse drug reactions to topiroxostat was 67.8%; on the final visit, the rate of adverse drug reactions was 66.7% with 120 mg/day, 72.2% with 160 mg/day, 53.8% with ≥ 200 mg/day, and 100% with the other dosages. On the final visit, the incidence of gouty arthritis, for which a causal relationship with topiroxostat could not be ruled out, was 4.1% overall, 4.8% with 120 mg/day, 0% with 160 mg/day, and 7.7% with ≥ 200 mg/day.
We verified the efficacy and safety of 58-week oral topiroxostat administration at stepwise increments to up to 240 mg/day.
JAPIC CTI-101068.
托匹司他是一种新型选择性黄嘌呤氧化还原酶抑制剂，已被报道可降低血清尿酸水平。本研究的目的是评估长期口服托匹司他治疗日本高尿酸血症患者（伴或不伴痛风）的疗效和安全性。
这是一项多中心、开放标签研究，评估了长期每日两次口服托匹司他治疗伴或不伴痛风的患者的疗效和安全性。初始托匹司他剂量为 40-80mg/天，维持剂量为 120mg/天，如果血清尿酸水平超过 6.0mg/dL，则以每次 40mg 的增量增加至 240mg/天。
血清尿酸水平是主要终点，随时间稳定下降，与基线相比，最后一次访视时显著降低（38.44%±13.34%）。尿白蛋白/肌酐比值和平均血压均显著改善。托匹司他的总体不良反应发生率为 67.8%；最后一次访视时，120mg/天组的不良反应发生率为 66.7%，160mg/天组为 72.2%，≥200mg/天组为 53.8%，其他剂量组为 100%。最后一次访视时，总体上不能排除与托匹司他有关的痛风性关节炎发生率为 4.1%，120mg/天组为 4.8%，160mg/天组为 0%，≥200mg/天组为 7.7%。
我们验证了 58 周递增至 240mg/天口服托匹司他的疗效和安全性。
JAPIC CTI-101068。
