Nature communications · 2025
HSK21542 in patients with postoperative pain: two phase 3, multicentre, double-blind, randomized, controlled trials.
СтатьяРандомизированное исследованиеКлиническое исследование III фазыМногоцентровое исследованиеНазвание и аннотация: Перевод пока не подготовлен
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Zhong Yinbo, Xu Younian, Lei Qian, Yang Mengchang, Wang Saiying, Hu Xiaoling, Xie Haihui, Li Yalan, Qin Zhong, Gu Zhengfeng, Zhang Jiaqiang, Wang Yuexin, Wu Jinglei, Wang Haiying, Ming Yue, Xia Zhongyuan, Zhai Haoyu, Jiang Ke, Zhang Peng, Wang Zhiping, Wang Liangrong, Li Lin, Cheng Zhigang, Jiang Huayong, Wang Guonian, Chen Jingli, Zhao Zhibin, Chen Xiangdong, Yan Min
Аннотация
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.