Safety and effectiveness of HSK21542 for hemodialysis patients: a multiple ascending dose study
Background: HSK21542, a novel selective peripherally-restricted κ-opioid receptor agonist has been proven to be a safe and effective analgesic and antipruritic drug in both in vitro and in vivo studies. We aimed to evaluate its safety, pharmacokinetics and efficacy in hemodialysis patients over a 1-...
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| Language: | English |
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Frontiers Media S.A.
2023-10-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2023.1203642/full |
| _version_ | 1797663540290519040 |
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| author | Mingming Pan Guihua Wang Li Zhou Yan Xu Li Yao Chaoqing Wu Changlin Mei Zhanzheng Zhao Dong Sun Tianjun Guan Qinkai Chen Ming Shi Hui Xu Weifang Zeng Fangqiong Li Rui Yan Bi-Cheng Liu |
| author_facet | Mingming Pan Guihua Wang Li Zhou Yan Xu Li Yao Chaoqing Wu Changlin Mei Zhanzheng Zhao Dong Sun Tianjun Guan Qinkai Chen Ming Shi Hui Xu Weifang Zeng Fangqiong Li Rui Yan Bi-Cheng Liu |
| author_sort | Mingming Pan |
| collection | DOAJ |
| description | Background: HSK21542, a novel selective peripherally-restricted κ-opioid receptor agonist has been proven to be a safe and effective analgesic and antipruritic drug in both in vitro and in vivo studies. We aimed to evaluate its safety, pharmacokinetics and efficacy in hemodialysis patients over a 1-week treatment period, and to establish the optimal dosage for a further 12-week stage 2 trial.Methods: In this multiple ascending dose study, hemodialysis patients were randomly assigned to receive HSK21542 (0.05–0.80 μg/kg), or a placebo three times within 2.5 h at the end of each dialysis session for 1 week. Safety evaluations included reports of treatment-emergent adverse events (TEAEs); pharmacokinetics and efficacy outcomes were also assessed.Results: Among the 44 screened patients, 41 were enrolled and completed the trial. The overall incidence of TEAEs was higher in the HSK21542 group compared to the placebo group, with an incidence of 75.0%, 50.0%, 75.0%, and 88.9% in the range of 0.05–0.80 μg/kg. All TEAEs were grade 1 or 2 in severity. HSK21542 exhibited linear pharmacokinetics characteristics within the dose range 0.05–0.80 μg/kg, without drug accumulation after multiple-doses. Compared to the placebo, a significant decrease of the weekly mean Worst Itching Intensity Numerical Rating Scale was found in the HSK21542-0.30 μg/kg group (p = 0.046), but without significant improvement in the Skindex-16 score.Conclusion: HSK21542 was well tolerated in the dose range 0.05–0.80 μg/kg in hemodialysis patients. HSK21542-0.3 μg/kg exhibited promising efficacy in patients with moderate to severe pruritus and warrants a further Stage 2 trial.Clinical Trial Registration:https://clinicaltrials.gov/, identifier NCT04470154. |
| first_indexed | 2024-03-11T19:16:09Z |
| format | Article |
| id | doaj.art-6ffce28274cf400f8494918263c44e91 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-03-11T19:16:09Z |
| publishDate | 2023-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-6ffce28274cf400f8494918263c44e912023-10-09T08:21:25ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122023-10-011410.3389/fphar.2023.12036421203642Safety and effectiveness of HSK21542 for hemodialysis patients: a multiple ascending dose studyMingming Pan0Guihua Wang1Li Zhou2Yan Xu3Li Yao4Chaoqing Wu5Changlin Mei6Zhanzheng Zhao7Dong Sun8Tianjun Guan9Qinkai Chen10Ming Shi11Hui Xu12Weifang Zeng13Fangqiong Li14Rui Yan15Bi-Cheng Liu16Department of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, Nanjing, ChinaDepartment of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, Nanjing, ChinaDivision of Nephrology, Kidney Research Institute, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, ChinaDepartment of Nephrology, The First Hospital of China Medical University, Shenyang, ChinaDepartment of Nephrology, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaDivision of Nephrology, The Second Affiliated Hospital Navy Medical University, Shanghai, ChinaDepartment of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Nephrology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, ChinaDivision of Nephrology, Zhongshan Hospital, Xiamen University, Xiamen, China0Department of Nephrology, The First Affiliated Hospital of Nanchang University, Nanchang, China1Department of Nephrology, Renmin Hospital of Wuhan University, Wuhan, China2Division of Nephrology, Xiangya Hospital of the Central South University, Changsha, China3Sichuan Haisco Pharmaceutical Co., Ltd., Chengdu, China3Sichuan Haisco Pharmaceutical Co., Ltd., Chengdu, China4Department of Nephrology, Affiliated Hospital of Guizhou Medical University, Guiyang, ChinaDepartment of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, Nanjing, ChinaBackground: HSK21542, a novel selective peripherally-restricted κ-opioid receptor agonist has been proven to be a safe and effective analgesic and antipruritic drug in both in vitro and in vivo studies. We aimed to evaluate its safety, pharmacokinetics and efficacy in hemodialysis patients over a 1-week treatment period, and to establish the optimal dosage for a further 12-week stage 2 trial.Methods: In this multiple ascending dose study, hemodialysis patients were randomly assigned to receive HSK21542 (0.05–0.80 μg/kg), or a placebo three times within 2.5 h at the end of each dialysis session for 1 week. Safety evaluations included reports of treatment-emergent adverse events (TEAEs); pharmacokinetics and efficacy outcomes were also assessed.Results: Among the 44 screened patients, 41 were enrolled and completed the trial. The overall incidence of TEAEs was higher in the HSK21542 group compared to the placebo group, with an incidence of 75.0%, 50.0%, 75.0%, and 88.9% in the range of 0.05–0.80 μg/kg. All TEAEs were grade 1 or 2 in severity. HSK21542 exhibited linear pharmacokinetics characteristics within the dose range 0.05–0.80 μg/kg, without drug accumulation after multiple-doses. Compared to the placebo, a significant decrease of the weekly mean Worst Itching Intensity Numerical Rating Scale was found in the HSK21542-0.30 μg/kg group (p = 0.046), but without significant improvement in the Skindex-16 score.Conclusion: HSK21542 was well tolerated in the dose range 0.05–0.80 μg/kg in hemodialysis patients. HSK21542-0.3 μg/kg exhibited promising efficacy in patients with moderate to severe pruritus and warrants a further Stage 2 trial.Clinical Trial Registration:https://clinicaltrials.gov/, identifier NCT04470154.https://www.frontiersin.org/articles/10.3389/fphar.2023.1203642/fullCKD-aPHSK21542hemodialysisκ-opioid receptor agonisturemic pruritus |
| spellingShingle | Mingming Pan Guihua Wang Li Zhou Yan Xu Li Yao Chaoqing Wu Changlin Mei Zhanzheng Zhao Dong Sun Tianjun Guan Qinkai Chen Ming Shi Hui Xu Weifang Zeng Fangqiong Li Rui Yan Bi-Cheng Liu Safety and effectiveness of HSK21542 for hemodialysis patients: a multiple ascending dose study Frontiers in Pharmacology CKD-aP HSK21542 hemodialysis κ-opioid receptor agonist uremic pruritus |
| title | Safety and effectiveness of HSK21542 for hemodialysis patients: a multiple ascending dose study |
| title_full | Safety and effectiveness of HSK21542 for hemodialysis patients: a multiple ascending dose study |
| title_fullStr | Safety and effectiveness of HSK21542 for hemodialysis patients: a multiple ascending dose study |
| title_full_unstemmed | Safety and effectiveness of HSK21542 for hemodialysis patients: a multiple ascending dose study |
| title_short | Safety and effectiveness of HSK21542 for hemodialysis patients: a multiple ascending dose study |
| title_sort | safety and effectiveness of hsk21542 for hemodialysis patients a multiple ascending dose study |
| topic | CKD-aP HSK21542 hemodialysis κ-opioid receptor agonist uremic pruritus |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2023.1203642/full |
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