HSK21542 in patients with postoperative pain: two phase 3, multicentre, double-blind, randomized, controlled trials

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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Main Authors: 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
Format: Article
Language:English
Published: Nature Portfolio 2025-05-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-60013-y
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Summary: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.
ISSN:2041-1723

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