HSK21542 in patients with postoperative pain: two phase 3, multicentre, double-blind, randomized, controlled trials
Abstract HSK21542, a peripherally restricted kappa opioid receptor agonist, was evaluated for efficacy and safety in patients with postoperative pain following abdominal surgery. This was assessed in two phase 3, multicentre, randomized, double-blind, controlled trials (HSK21542-301 [ClinicalTrials....
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Nature Portfolio
2025-05-01
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| Online Access: | https://doi.org/10.1038/s41467-025-60013-y |
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| author | Yinbo Zhong Younian Xu Qian Lei Mengchang Yang Saiying Wang Xiaoling Hu Haihui Xie Yalan Li Zhong Qin Zhengfeng Gu Jiaqiang Zhang Yuexin Wang Jinglei Wu Haiying Wang Yue Ming Zhongyuan Xia Haoyu Zhai Ke Jiang Peng Zhang Zhiping Wang Liangrong Wang Lin Li Zhigang Cheng Huayong Jiang Guonian Wang Jingli Chen Zhibin Zhao Xiangdong Chen Min Yan |
| author_facet | Yinbo Zhong Younian Xu Qian Lei Mengchang Yang Saiying Wang Xiaoling Hu Haihui Xie Yalan Li Zhong Qin Zhengfeng Gu Jiaqiang Zhang Yuexin Wang Jinglei Wu Haiying Wang Yue Ming Zhongyuan Xia Haoyu Zhai Ke Jiang Peng Zhang Zhiping Wang Liangrong Wang Lin Li Zhigang Cheng Huayong Jiang Guonian Wang Jingli Chen Zhibin Zhao Xiangdong Chen Min Yan |
| author_sort | Yinbo Zhong |
| collection | DOAJ |
| description | Abstract HSK21542, a peripherally restricted kappa opioid receptor agonist, was evaluated for efficacy and safety in patients with postoperative pain following abdominal surgery. This was assessed in two phase 3, multicentre, randomized, double-blind, controlled trials (HSK21542-301 [ClinicalTrials.gov identifier, NCT04738357] and HSK21542-303 [ClinicalTrials.gov identifier, NCT05390905]) in China. HSK21542-301 was a dual-arm study comparing HSK21542 1.0 μg/kg with placebo, while HSK21542-303 involved three arms comparing HSK21542 1.0 μg/kg with tramadol 50 mg/dose and placebo. All treatments were administered intravenously. The primary endpoint was the time-weighted summed pain intensity differences over 24 h (SPID0-24 h). Both HSK21542-301 (least squares [LS] mean [± standard error], −39.1 [1.88] vs −27.4 [1.89]; P < 0.001) and HSK21542-303 (−64.0 [2.25] vs −45.9 [2.25]; P < 0.001) demonstrated superiority of HSK21542 over placebo in terms of SPID0-24 h, while HSK21542-303 showed non-inferiority to tramadol (LS mean difference, −1.1; 95% confidence interval, −7.4 to 5.1; P < 0.001). Furthermore, HSK21542 had a comparable safety profile to placebo, inducing fewer gastrointestinal adverse events compared with tramadol. Grade ≥3 treatment-emergent adverse events occurred in eight (5.9%) and three (2.3%) patients in the HSK21542 arm of HSK21542-301 and HSK21542-303, respectively. In conclusion, HSK21542 showed potent analgesic effect and was well tolerated in patients who underwent abdominal surgery and experienced postoperative pain. |
| format | Article |
| id | doaj-art-59d12aa3c42c46dab6f862676aed69ce |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
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| spelling | doaj-art-59d12aa3c42c46dab6f862676aed69ce2025-08-20T03:48:18ZengNature PortfolioNature Communications2041-17232025-05-0116111310.1038/s41467-025-60013-yHSK21542 in patients with postoperative pain: two phase 3, multicentre, double-blind, randomized, controlled trialsYinbo Zhong0Younian Xu1Qian Lei2Mengchang Yang3Saiying Wang4Xiaoling Hu5Haihui Xie6Yalan Li7Zhong Qin8Zhengfeng Gu9Jiaqiang Zhang10Yuexin Wang11Jinglei Wu12Haiying Wang13Yue Ming14Zhongyuan Xia15Haoyu Zhai16Ke Jiang17Peng Zhang18Zhiping Wang19Liangrong Wang20Lin Li21Zhigang Cheng22Huayong Jiang23Guonian Wang24Jingli Chen25Zhibin Zhao26Xiangdong Chen27Min Yan28Department of Anesthesiology, Second Affiliated Hospital of Zhejiang University School of MedicineDepartment of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Key Laboratory of Anesthesiology and Resuscitation (Huazhong University of Science and Technology), Ministry of Education, China; Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Anesthesiology, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of ChinaDepartment of Anesthesiology, The Third People’s Hospital of ChengduThe Third Xiangya Hospital of Central South UniversityThe First Affiliated Hospital of University of South ChinaDongguan People’s Hospital (The Tenth Affiliated Hospital of Southern Medical University)The First Affiliated Hospital of Jinan University (Guangzhou Overseas Chinese Hospital, The First Clinical Medical College of Jinan University)Wuxi People’s HospitalWuxi People’s HospitalHenan Provincial People’s HospitalDepartment of Anesthesiology, Cangzhou People’s HospitalDepartment of Anesthesiology, Liuzhou People’s Hospital Affiliated to Guangxi Medical UniversityDepartment of Anesthesiology, Second Affiliated Hospital of Zhejiang University School of MedicineDepartment of Anesthesiology, Second Affiliated Hospital of Zhejiang University School of MedicineRenmin Hospital of Wuhan UniversityThe First People’s Hospital of GuangyuanThe Affiliated Hospital of Guizhou Medical UniversityYibin Second People’s HospitalAffiliated Hospital of Xuzhou Medical UniversityThe First Affiliated Hospital of Wenzhou Medical UniversityGeneral Hospital of the Northern Theater Command of Chinese PLAXiangya Hospital Central South UniversityShaoxing People’s HospitalThe Fourth Hospital of Harbin Medical UniversityDepartment of Anesthesiology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and TechnologyThe First People’s Hospital of LianyungangDepartment of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Key Laboratory of Anesthesiology and Resuscitation (Huazhong University of Science and Technology), Ministry of Education, China; Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Anesthesiology, Second Affiliated Hospital of Zhejiang University School of MedicineAbstract HSK21542, a peripherally restricted kappa opioid receptor agonist, was evaluated for efficacy and safety in patients with postoperative pain following abdominal surgery. This was assessed in two phase 3, multicentre, randomized, double-blind, controlled trials (HSK21542-301 [ClinicalTrials.gov identifier, NCT04738357] and HSK21542-303 [ClinicalTrials.gov identifier, NCT05390905]) in China. HSK21542-301 was a dual-arm study comparing HSK21542 1.0 μg/kg with placebo, while HSK21542-303 involved three arms comparing HSK21542 1.0 μg/kg with tramadol 50 mg/dose and placebo. All treatments were administered intravenously. The primary endpoint was the time-weighted summed pain intensity differences over 24 h (SPID0-24 h). Both HSK21542-301 (least squares [LS] mean [± standard error], −39.1 [1.88] vs −27.4 [1.89]; P < 0.001) and HSK21542-303 (−64.0 [2.25] vs −45.9 [2.25]; P < 0.001) demonstrated superiority of HSK21542 over placebo in terms of SPID0-24 h, while HSK21542-303 showed non-inferiority to tramadol (LS mean difference, −1.1; 95% confidence interval, −7.4 to 5.1; P < 0.001). Furthermore, HSK21542 had a comparable safety profile to placebo, inducing fewer gastrointestinal adverse events compared with tramadol. Grade ≥3 treatment-emergent adverse events occurred in eight (5.9%) and three (2.3%) patients in the HSK21542 arm of HSK21542-301 and HSK21542-303, respectively. In conclusion, HSK21542 showed potent analgesic effect and was well tolerated in patients who underwent abdominal surgery and experienced postoperative pain.https://doi.org/10.1038/s41467-025-60013-y |
| spellingShingle | Yinbo Zhong Younian Xu Qian Lei Mengchang Yang Saiying Wang Xiaoling Hu Haihui Xie Yalan Li Zhong Qin Zhengfeng Gu Jiaqiang Zhang Yuexin Wang Jinglei Wu Haiying Wang Yue Ming Zhongyuan Xia Haoyu Zhai Ke Jiang Peng Zhang Zhiping Wang Liangrong Wang Lin Li Zhigang Cheng Huayong Jiang Guonian Wang Jingli Chen Zhibin Zhao Xiangdong Chen Min Yan HSK21542 in patients with postoperative pain: two phase 3, multicentre, double-blind, randomized, controlled trials Nature Communications |
| title | HSK21542 in patients with postoperative pain: two phase 3, multicentre, double-blind, randomized, controlled trials |
| title_full | HSK21542 in patients with postoperative pain: two phase 3, multicentre, double-blind, randomized, controlled trials |
| title_fullStr | HSK21542 in patients with postoperative pain: two phase 3, multicentre, double-blind, randomized, controlled trials |
| title_full_unstemmed | HSK21542 in patients with postoperative pain: two phase 3, multicentre, double-blind, randomized, controlled trials |
| title_short | HSK21542 in patients with postoperative pain: two phase 3, multicentre, double-blind, randomized, controlled trials |
| title_sort | hsk21542 in patients with postoperative pain two phase 3 multicentre double blind randomized controlled trials |
| url | https://doi.org/10.1038/s41467-025-60013-y |
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