Jun Jae-Bum, Lee Hye-Soon, Kim Sang-Hyon, Lee Seung-Geun, Lim Doo-Ho, Kim Jinhyun, Park Yong-Beom, Lim Mie Jin, Hong Seung-Jae, Choi Hyo-Jin, Lee Shin-Seok, Kim Hyun Ah, Hwang Jiwon, Suh Chang-Hee, Han Seungwoo, Choe Jung-Yoon, Yoo Wan-Hee, Song Jung Soo
Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea.
Division of Rheumatology, Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea.
Arthritis Res Ther. 2025 May 26;27(1):113. doi: 10.1186/s13075-025-03577-w.
Gout is the most common inflammatory arthritis. Current urate-lowering therapies have limitations, such as adverse drug reactions or limited efficacy. Epaminurad is a novel selective human urate transporter 1 (hURAT1) inhibitor that has been shown to reduce serum urate (sUA) levels in healthy volunteers and patients with gout. The aims of the current study were to evaluate the urate-lowering efficacy and safety of epaminurad compared with placebo in patients with gout, and to determine the optimal dose.
This multicenter, randomized, double-blind, placebo-controlled, dose-finding phase 2b clinical trial, which incorporated a standard-treatment reference arm, enrolled patients aged 19-70 years with gout and sUA level ≥ 0.42 mmol/L. Participants received gout prophylaxis and followed therapeutic lifestyle changes, and were randomized to receive epaminurad 3 mg, 6 mg or 9 mg, or febuxostat 80 mg, or matching placebo, once daily for 12 weeks. The primary efficacy endpoint was the proportion of patients with sUA level < 0.36 mmol/L at week 4 after initiation of study treatment. Statistical comparisons were performed between the epaminurad and placebo groups.
Overall, 169 patients received study medication (99.40% male, mean ± SD age 48.26 ± 13.15 years, sUA level 0.53 ± 0.09 mmol/L). Mean adherence to treatment was > 90% in all groups. The proportion of patients with sUA < 0.36 mmol/L at week 4 was significantly higher in each epaminurad group (9 mg, 88.89%; 6 mg, 71.79%; 3 mg, 54.05%) compared with placebo (0.00%) (all p < 0.0001). The response rate in the febuxostat group was 84.21%. The proportion of patients who achieved sUA < 0.30 mmol/L, and mean percent and absolute change in sUA, were also significantly greater in all epaminurad groups versus placebo at week 4. Outcomes were consistent at weeks 8 and 12. The adverse event rate did not differ between epaminurad groups and placebo, and most events were mild. There were no significant differences in mean serum creatinine levels or liver function parameters between the epaminurad groups and placebo.
Epaminurad was effective at reducing sUA levels in patients with gout. The study also confirmed the safety and tolerability profile during 12 weeks of treatment.
ClinicalTrials.gov NCT04804111 (registered on 15 November 2020).
痛风是最常见的炎性关节炎。目前的降尿酸治疗存在局限性，如药物不良反应或疗效有限。依帕米拉德是一种新型选择性人尿酸转运蛋白1（hURAT1）抑制剂，已被证明可降低健康志愿者和痛风患者的血清尿酸（sUA）水平。本研究的目的是评估依帕米拉德与安慰剂相比在痛风患者中的降尿酸疗效和安全性，并确定最佳剂量。
这项多中心、随机、双盲、安慰剂对照、剂量探索性2b期临床试验纳入了一个标准治疗参考组，招募了年龄在19至70岁、痛风且sUA水平≥0.42 mmol/L的患者。参与者接受痛风预防并遵循治疗性生活方式改变，被随机分配接受每日一次的依帕米拉德3 mg、6 mg或9 mg，或非布司他80 mg，或匹配的安慰剂，共12周。主要疗效终点是研究治疗开始后第4周时sUA水平<0.36 mmol/L的患者比例。在依帕米拉德组和安慰剂组之间进行了统计比较。
总体而言，169名患者接受了研究药物治疗（男性占99.40%，平均±标准差年龄48.26±13.15岁，sUA水平0.53±0.09 mmol/L）。所有组的平均治疗依从性均＞９０％。与安慰剂组（0.00%）相比，各依帕米拉德组（9 mg组为88.89%；6 mg组为71.79%；3 mg组为54.05%）在第4周时sUA<0.36 mmol/L的患者比例显著更高（所有p<0.0001）。非布司他组的缓解率为84.21%。在第4周时，所有依帕米拉德组中达到sUA<0.30 mmol/L的患者比例、sUA的平均百分比变化和绝对变化也均显著高于安慰剂组。在第8周和第12周时结果一致。依帕米拉德组和安慰剂组之间的不良事件发生率没有差异，且大多数事件为轻度。依帕米拉德组和安慰剂组之间的平均血清肌酐水平或肝功能参数没有显著差异。
依帕米拉德在降低痛风患者sUA水平方面有效。该研究还证实了12周治疗期间的安全性和耐受性。
ClinicalTrials.gov NCT04804111（于2020年11月15日注册）
