Efficacy and safety of peripherally-restricted κ-opioid receptor agonist-HSK21542 for postoperative analgesia in patients undergoing laparoscopic abdominal surgery: a randomized, placebo-controlled phase 2 trial
BackgroundThis phase 2 trial comprised dose exploration (stage 1) and dose confirmation stages (stage 2) to determine the safety and efficacy of HSK21542 in patients undergoing laparoscopic abdominal surgery.MethodsIn stage 1, patients were randomly allocated at a ratio of 4:1 (12 to receive HSK2154...
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Frontiers Media S.A.
2025-07-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2025.1604790/full |
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| author | Yinbo Zhong Haiying Wang Min Yan Mengchang Yang Jiaqiang Zhang Ling Nan Zhiping Wang Jianjun Yang Jinglei Wu Qulian Guo Xiaoling Hu Hongmeng Xu Qiang Xu Dongxin Wang |
| author_facet | Yinbo Zhong Haiying Wang Min Yan Mengchang Yang Jiaqiang Zhang Ling Nan Zhiping Wang Jianjun Yang Jinglei Wu Qulian Guo Xiaoling Hu Hongmeng Xu Qiang Xu Dongxin Wang |
| author_sort | Yinbo Zhong |
| collection | DOAJ |
| description | BackgroundThis phase 2 trial comprised dose exploration (stage 1) and dose confirmation stages (stage 2) to determine the safety and efficacy of HSK21542 in patients undergoing laparoscopic abdominal surgery.MethodsIn stage 1, patients were randomly allocated at a ratio of 4:1 (12 to receive HSK21542, 3 to receive placebo) to 4 ascending dose groups in a sequential manner (group 1: preoperative HSK21542-0.4 μg/kg (or placebo) + HSK21542-0.2 μg/kg (or placebo) at postoperative 0 h, 8 h and 16 h; group 2: preoperative HSK21542-1.0 μg/kg (or placebo) + HSK21542-0.5 μg/kg (or placebo) at postoperative 0 h, 8 h and 16 h; groups 3 and 4: HSK21542-0.5 μg/kg or HSK21542-1.0 μg/kg (or placebo) at postoperative 0 h, 8 h and 16 h). In stage 2, patients received HSK21542-0.5 μg/kg, HSK21542-1.0 μg/kg or placebo postoperatively at 0 h, 8 h and 16 h in a 1:1:1 ratio. The primary endpoints in stage 1 were the safety outcomes including the incidence and severity of treatment-emergent adverse events (TEAEs) while the primary endpoint of stage 2 was the time-weighted summed pain intensity differences over 24 h (SPID0–24h).ResultsStage 1 enrolled 63 patients and 57 completed the trial, while 61 patients were enrolled in stage 2, and 60 completed the trial. The most common TEAEs were fever (22.9% vs. 41.7%), nausea (25.0% vs. 33.3%) and vomiting (22.9% vs. 25.0%) in the HSK21542 and placebo groups in stage 1. HSK21542 doses of 0.5 μg/kg and 1.0 μg/kg administered postoperatively were recommended for the subsequent stage 2. The pooled results revealed a slightly lower SPID0–24h in HSK21542-1.0 μg/kg group (−1,679.8 ± 2,284.3 scores × min) than those in HSK21542-0.5 μg/kg (−1,499.4 ± 2,487.2 scores × min) and placebo groups (−435.2 ± 2,852.9 scores × min; P = 0.114). A significantly higher least squares mean difference of pain intensity differences (PID) was found in HSK21542-1.0 μg/kg group compared to the placebo (P = 0.020).ConclusionHSK21542 at all dose regimens demonstrated well tolerability and safety comparable to that of the placebo among patients undergoing laparoscopic abdominal surgery in the phase 2 trial. The dosing regimen of HSK21542-1.0 μg/kg administered postoperatively at 0 h, 8 h and 16 h exhibited an acceptable efficacy, warranting its recommendation for further phase 3 trial.Clinical trial registrationhttps://clinicaltrials.gov/, identifier NCT04424251. |
| format | Article |
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| institution | Kabale University |
| issn | 2296-858X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Medicine |
| spelling | doaj-art-c2ea5169825b4044a0bbee84caad66752025-08-20T03:56:00ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2025-07-011210.3389/fmed.2025.16047901604790Efficacy and safety of peripherally-restricted κ-opioid receptor agonist-HSK21542 for postoperative analgesia in patients undergoing laparoscopic abdominal surgery: a randomized, placebo-controlled phase 2 trialYinbo Zhong0Haiying Wang1Min Yan2Mengchang Yang3Jiaqiang Zhang4Ling Nan5Zhiping Wang6Jianjun Yang7Jinglei Wu8Qulian Guo9Xiaoling Hu10Hongmeng Xu11Qiang Xu12Dongxin Wang13Department of Anesthesiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Anesthesiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Anesthesiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Anesthesiology, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, ChinaDepartment of Anesthesiology, Pain and Perioperative Medicine, Henan Provincial People’s Hospital, Zhengzhou, ChinaDepartment of Anesthesiology, The First Bethune Hospital of Jilin University, Changchun, ChinaDepartment of Anesthesiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, ChinaDepartment of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Anesthesiology, Liuzhou People’s Hospital Affiliated to Guangxi Medical University, Liuzhou, ChinaDepartment of Anesthesiology, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Anesthesiology, The First Affiliated Hospital of University of South China, Hengyang, China0Department of Anesthesiology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China1Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China2Department of Anesthesiology, Peking University First Hospital, Beijing, ChinaBackgroundThis phase 2 trial comprised dose exploration (stage 1) and dose confirmation stages (stage 2) to determine the safety and efficacy of HSK21542 in patients undergoing laparoscopic abdominal surgery.MethodsIn stage 1, patients were randomly allocated at a ratio of 4:1 (12 to receive HSK21542, 3 to receive placebo) to 4 ascending dose groups in a sequential manner (group 1: preoperative HSK21542-0.4 μg/kg (or placebo) + HSK21542-0.2 μg/kg (or placebo) at postoperative 0 h, 8 h and 16 h; group 2: preoperative HSK21542-1.0 μg/kg (or placebo) + HSK21542-0.5 μg/kg (or placebo) at postoperative 0 h, 8 h and 16 h; groups 3 and 4: HSK21542-0.5 μg/kg or HSK21542-1.0 μg/kg (or placebo) at postoperative 0 h, 8 h and 16 h). In stage 2, patients received HSK21542-0.5 μg/kg, HSK21542-1.0 μg/kg or placebo postoperatively at 0 h, 8 h and 16 h in a 1:1:1 ratio. The primary endpoints in stage 1 were the safety outcomes including the incidence and severity of treatment-emergent adverse events (TEAEs) while the primary endpoint of stage 2 was the time-weighted summed pain intensity differences over 24 h (SPID0–24h).ResultsStage 1 enrolled 63 patients and 57 completed the trial, while 61 patients were enrolled in stage 2, and 60 completed the trial. The most common TEAEs were fever (22.9% vs. 41.7%), nausea (25.0% vs. 33.3%) and vomiting (22.9% vs. 25.0%) in the HSK21542 and placebo groups in stage 1. HSK21542 doses of 0.5 μg/kg and 1.0 μg/kg administered postoperatively were recommended for the subsequent stage 2. The pooled results revealed a slightly lower SPID0–24h in HSK21542-1.0 μg/kg group (−1,679.8 ± 2,284.3 scores × min) than those in HSK21542-0.5 μg/kg (−1,499.4 ± 2,487.2 scores × min) and placebo groups (−435.2 ± 2,852.9 scores × min; P = 0.114). A significantly higher least squares mean difference of pain intensity differences (PID) was found in HSK21542-1.0 μg/kg group compared to the placebo (P = 0.020).ConclusionHSK21542 at all dose regimens demonstrated well tolerability and safety comparable to that of the placebo among patients undergoing laparoscopic abdominal surgery in the phase 2 trial. The dosing regimen of HSK21542-1.0 μg/kg administered postoperatively at 0 h, 8 h and 16 h exhibited an acceptable efficacy, warranting its recommendation for further phase 3 trial.Clinical trial registrationhttps://clinicaltrials.gov/, identifier NCT04424251.https://www.frontiersin.org/articles/10.3389/fmed.2025.1604790/fullκ-opioid receptor agonistspostoperative analgesialaparoscopic abdominal surgeryHSK21542time-weighted summed pain intensity difference |
| spellingShingle | Yinbo Zhong Haiying Wang Min Yan Mengchang Yang Jiaqiang Zhang Ling Nan Zhiping Wang Jianjun Yang Jinglei Wu Qulian Guo Xiaoling Hu Hongmeng Xu Qiang Xu Dongxin Wang Efficacy and safety of peripherally-restricted κ-opioid receptor agonist-HSK21542 for postoperative analgesia in patients undergoing laparoscopic abdominal surgery: a randomized, placebo-controlled phase 2 trial Frontiers in Medicine κ-opioid receptor agonists postoperative analgesia laparoscopic abdominal surgery HSK21542 time-weighted summed pain intensity difference |
| title | Efficacy and safety of peripherally-restricted κ-opioid receptor agonist-HSK21542 for postoperative analgesia in patients undergoing laparoscopic abdominal surgery: a randomized, placebo-controlled phase 2 trial |
| title_full | Efficacy and safety of peripherally-restricted κ-opioid receptor agonist-HSK21542 for postoperative analgesia in patients undergoing laparoscopic abdominal surgery: a randomized, placebo-controlled phase 2 trial |
| title_fullStr | Efficacy and safety of peripherally-restricted κ-opioid receptor agonist-HSK21542 for postoperative analgesia in patients undergoing laparoscopic abdominal surgery: a randomized, placebo-controlled phase 2 trial |
| title_full_unstemmed | Efficacy and safety of peripherally-restricted κ-opioid receptor agonist-HSK21542 for postoperative analgesia in patients undergoing laparoscopic abdominal surgery: a randomized, placebo-controlled phase 2 trial |
| title_short | Efficacy and safety of peripherally-restricted κ-opioid receptor agonist-HSK21542 for postoperative analgesia in patients undergoing laparoscopic abdominal surgery: a randomized, placebo-controlled phase 2 trial |
| title_sort | efficacy and safety of peripherally restricted κ opioid receptor agonist hsk21542 for postoperative analgesia in patients undergoing laparoscopic abdominal surgery a randomized placebo controlled phase 2 trial |
| topic | κ-opioid receptor agonists postoperative analgesia laparoscopic abdominal surgery HSK21542 time-weighted summed pain intensity difference |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2025.1604790/full |
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