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

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 (SPID<sub>0-24 h</sub>). 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 SPID<sub>0-24 h</sub>, 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.

Authors

Institutions

Publication Details

Journal
Nature Communications
Published
2025-05-24
DOI
https://doi.org/10.1038/s41467-025-60013-y
Citations
8
Primary Topic
Anesthesia and Pain Management
Type
article
Field-Weighted Citation Impact
16.05
Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

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

Zhong Qin, Ke Jiang, Min Yan, Zhigang Cheng et al.
8 citations
Nature Communications
Anesthesia and Pain Management
16.05
article

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

Zhong Qin, Ke Jiang, Min Yan, Zhigang Cheng, Xiaoling Hu, Zhibin Zhao, Zhengfeng Gu, Haihui Xie, Liangrong Wang, Younian Xu, Mengchang Yang, Jingli Chen, Haiying Wang, Zhiping Wang, Jiaqiang Zhang, Xiangdong Chen, Yalan Li, Jinglei Wu, Peng Zhang, Hui Zhai, Guonian Wang, Yue Ming, Yuexin Wang, Qian Lei, Li Li, Huayong Jiang, Zhongyuan Xia, Yinbo Zhong, Saiying Wang
article en
8 citations

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 (SPID<sub>0-24 h</sub>). 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 SPID<sub>0-24 h</sub>, 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.

Nature CommunicationsVol. 16(1)
Union Hospital (HK), Central South University (CN), Guiyang Medical University (CN), University of Electronic Science and Technology of China (CN), Harbin Medical University (CN), Xuzhou Medical College (CN), Wenzhou Medical University (CN), First Affiliated Hospital of Wenzhou Medical University (CN), Wuhan University (CN), Liuzhou General Hospital (CN), Third People's Hospital of Chengdu (CN), Affiliated Hospital of Guizhou Medical University (CN), People's Hospital of Cangzhou (CN), Fourth Affiliated Hospital of Harbin Medical University (CN), Dongguan People’s Hospital (CN), The First People’s Hospital of Lianyungang (CN), Wuhan Union Hospital (CN), General Hospital of Shenyang Military Region (CN), Henan Provincial People's Hospital (CN), Fourth Affiliated Hospital of Guangxi Medical University (CN), Renmin Hospital of Wuhan University (CN), First Affiliated Hospital of University of South China (CN), Central Hospital of Wuhan (CN), Second People’s Hospital of Yibin (CN), Third Xiangya Hospital (CN), Wuxi People's Hospital (CN), Second Affiliated Hospital of Zhejiang University (CN), Xiangya Hospital Central South University (CN), Shaoxing People's Hospital (CN), First Affiliated Hospital of Jinan University (CN), Union Hospital (CN), The First People's Hospital of Guangyuan, Huazhong University of Science and Technology (CN), University of South China (CN)
Good health and well-being
Openalex Percentile: Top 1%
Anesthesia and Pain Management
16.05
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.