Efficacy and safety of epaminurad, a potent hURAT1 inhibitor, in patients with gout: a randomized, placebo-controlled, dose-finding study
Abstract Background 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) leve...
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BMC
2025-05-01
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| Series: | Arthritis Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13075-025-03577-w |
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| author | Jae-Bum Jun Hye-Soon Lee Sang-Hyon Kim Seung-Geun Lee Doo-Ho Lim Jinhyun Kim Yong-Beom Park Mie Jin Lim Seung-Jae Hong Hyo-Jin Choi Shin-Seok Lee Hyun Ah Kim Jiwon Hwang Chang-Hee Suh Seungwoo Han Jung-Yoon Choe Wan-Hee Yoo Jung Soo Song |
| author_facet | Jae-Bum Jun Hye-Soon Lee Sang-Hyon Kim Seung-Geun Lee Doo-Ho Lim Jinhyun Kim Yong-Beom Park Mie Jin Lim Seung-Jae Hong Hyo-Jin Choi Shin-Seok Lee Hyun Ah Kim Jiwon Hwang Chang-Hee Suh Seungwoo Han Jung-Yoon Choe Wan-Hee Yoo Jung Soo Song |
| author_sort | Jae-Bum Jun |
| collection | DOAJ |
| description | Abstract Background 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. Methods 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. Results 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. Conclusions 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. Trial registration ClinicalTrials.gov NCT04804111 (registered on 15 November 2020). |
| format | Article |
| id | doaj-art-0e5e48b329fb44989373473da1daced4 |
| institution | DOAJ |
| issn | 1478-6362 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
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| series | Arthritis Research & Therapy |
| spelling | doaj-art-0e5e48b329fb44989373473da1daced42025-08-20T03:16:34ZengBMCArthritis Research & Therapy1478-63622025-05-0127111310.1186/s13075-025-03577-wEfficacy and safety of epaminurad, a potent hURAT1 inhibitor, in patients with gout: a randomized, placebo-controlled, dose-finding studyJae-Bum Jun0Hye-Soon Lee1Sang-Hyon Kim2Seung-Geun Lee3Doo-Ho Lim4Jinhyun Kim5Yong-Beom Park6Mie Jin Lim7Seung-Jae Hong8Hyo-Jin Choi9Shin-Seok Lee10Hyun Ah Kim11Jiwon Hwang12Chang-Hee Suh13Seungwoo Han14Jung-Yoon Choe15Wan-Hee Yoo16Jung Soo Song17Department of Rheumatology, Hanyang University Hospital for Rheumatic DiseasesDivision of Rheumatology, Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of MedicineDivision of Rheumatology, Department of Internal Medicine, Keimyung University College of MedicineDivision of Rheumatology, Department of Internal Medicine, Pusan National University School of MedicineDivision of Rheumatology, Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of MedicineDivision of Rheumatology, Department of Internal Medicine, Chungnam National University College of MedicineDivision of Rheumatology, Department of Internal Medicine, Yonsei University College of MedicineDivision of Rheumatology, Department of Internal Medicine, Inha UniversityDepartment of Rheumatology, College of Medicine, Kyung Hee University Hospital, Kyung Hee UniversityDivision of Rheumatology, Department of Internal Medicine, Gachon University Gil Medical CenterDivision of Rheumatology, Department of Internal Medicine, Chonnam National University Medical School & HospitalDivision of Rheumatology, Department of Internal Medicine, Hallym University Sacred Heart HospitalDepartment of Rheumatology, College of Medicine, Kyung Hee University Hospital, Kyung Hee UniversityDepartment of Rheumatology, Ajou University School of MedicineDivision of Rheumatology, Departments of Internal Medicine, School of Medicine, Kyungpook National UniversityDivision of Rheumatology, Department of Internal Medicine, Daegu Catholic University School of MedicineDivision of Rheumatology, Department of Internal Medicine, Jeonbuk National University Medical SchoolDivision of Rheumatology, Department of Internal Medicine, Chung-Ang University School of MedicineAbstract Background 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. Methods 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. Results 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. Conclusions 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. Trial registration ClinicalTrials.gov NCT04804111 (registered on 15 November 2020).https://doi.org/10.1186/s13075-025-03577-wEpaminuradGoutHuman urate transport 1hURAT1 inhibitorHyperuricemiaURC102 |
| spellingShingle | Jae-Bum Jun Hye-Soon Lee Sang-Hyon Kim Seung-Geun Lee Doo-Ho Lim Jinhyun Kim Yong-Beom Park Mie Jin Lim Seung-Jae Hong Hyo-Jin Choi Shin-Seok Lee Hyun Ah Kim Jiwon Hwang Chang-Hee Suh Seungwoo Han Jung-Yoon Choe Wan-Hee Yoo Jung Soo Song Efficacy and safety of epaminurad, a potent hURAT1 inhibitor, in patients with gout: a randomized, placebo-controlled, dose-finding study Arthritis Research & Therapy Epaminurad Gout Human urate transport 1 hURAT1 inhibitor Hyperuricemia URC102 |
| title | Efficacy and safety of epaminurad, a potent hURAT1 inhibitor, in patients with gout: a randomized, placebo-controlled, dose-finding study |
| title_full | Efficacy and safety of epaminurad, a potent hURAT1 inhibitor, in patients with gout: a randomized, placebo-controlled, dose-finding study |
| title_fullStr | Efficacy and safety of epaminurad, a potent hURAT1 inhibitor, in patients with gout: a randomized, placebo-controlled, dose-finding study |
| title_full_unstemmed | Efficacy and safety of epaminurad, a potent hURAT1 inhibitor, in patients with gout: a randomized, placebo-controlled, dose-finding study |
| title_short | Efficacy and safety of epaminurad, a potent hURAT1 inhibitor, in patients with gout: a randomized, placebo-controlled, dose-finding study |
| title_sort | efficacy and safety of epaminurad a potent hurat1 inhibitor in patients with gout a randomized placebo controlled dose finding study |
| topic | Epaminurad Gout Human urate transport 1 hURAT1 inhibitor Hyperuricemia URC102 |
| url | https://doi.org/10.1186/s13075-025-03577-w |
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