Tao Bai, Zhiyue Xu, Yanbo Zhen, Aijun Liao, Bangmao Wang, Rong Zhao, Yin Zhu, Ning Dai, Side Liu, Hong Zhao, Xi Chen, Kunming Huang, Min Xu, Weizhen Zhou, Baohong Xu, Bin Ye, Duowu Zou, Heng Zhang, Ruihua Shi, Juan Zhang, Yaowei Ai, Xiangming Fang, Lin Lin, Xiaolan Zhang, Ling Zhang, Junping Wang, Yueping Jiang, Jun Cui, Mingxin Zhang, Xiangwu Ding, Zhongyin Zhou, Peng Yan, Xiaoqing Li, Bo Jiang, Youli Liu, Yingcai Ma, Shaoqi Yang, Xiaoyan Wang, Yongdong Wu, Jianjun Wu, Huixin Chen, Xiaohua Hou
{"title":"Plecanatide对中国功能性便秘患者的疗效和安全性：一项多中心、随机、双盲、安慰剂对照试验。","authors":"Tao Bai, Zhiyue Xu, Yanbo Zhen, Aijun Liao, Bangmao Wang, Rong Zhao, Yin Zhu, Ning Dai, Side Liu, Hong Zhao, Xi Chen, Kunming Huang, Min Xu, Weizhen Zhou, Baohong Xu, Bin Ye, Duowu Zou, Heng Zhang, Ruihua Shi, Juan Zhang, Yaowei Ai, Xiangming Fang, Lin Lin, Xiaolan Zhang, Ling Zhang, Junping Wang, Yueping Jiang, Jun Cui, Mingxin Zhang, Xiangwu Ding, Zhongyin Zhou, Peng Yan, Xiaoqing Li, Bo Jiang, Youli Liu, Yingcai Ma, Shaoqi Yang, Xiaoyan Wang, Yongdong Wu, Jianjun Wu, Huixin Chen, Xiaohua Hou","doi":"10.1007/s40265-025-02205-w","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Plecanatide is a novel guanylate cyclase-C agonist for the treatment of functional constipation (FC). Its efficacy may vary across different racial populations.</p><p><strong>Objective: </strong>This study aimed to comprehensively evaluate the efficacy, safety, and pharmacokinetics of plecanatide in Chinese patients with FC.</p><p><strong>Methods: </strong>This phase III, randomized, double-blind, placebo-controlled trial was conducted across 40 hospitals in China. A total of 648 patients with FC were randomly assigned in a ratio of 1:1 to receive either plecanatide 3 mg or placebo for 12 weeks, followed by a 2-week follow-up. The primary efficacy endpoint was the durable overall complete spontaneous bowel movement (CSBM) response rate. Data on adverse events were collected. A post hoc logistic regression analysis was performed to identify predictors of durable overall CSBM response.</p><p><strong>Results: </strong>After 12 weeks of continuous treatment, the durable overall CSBM response rates were 23.5% in the plecanatide group and 10.2% in the placebo group (p < 0.001). Plecanatide significantly increased the mean weekly frequency of CSBM (1.89 vs 0.9) and SBM (2.33 vs 1.03) compared with placebo throughout the treatment period. In addition, all other secondary efficacy endpoints showed statistically significant improvements with plecanatide compared with placebo. The most common treatment-related emergent adverse event was diarrhea, which occurred in 4.3% of plecanatide-treated patients and 0.6% of placebo-treated patients (p = 0.002). Plasma concentrations of plecanatide and its metabolite SP-338 remained below the lower limit of quantification (0.500 ng/ml) at all assessed time points. Weekly CSBM response at week 2 (odds ratio 43.476; 95% confidence interval 18.274-103.432) and baseline stool consistency (odds ratio 0.550; 95% confidence interval 0.366-0.827) were identified as effective predictors of durable overall CSBM response. Even among plecanatide non-responders, a significant improvement in SBM frequency compared with placebo was observed over the 12-week treatment period.</p><p><strong>Conclusions: </strong>Plecanatide 3 mg was effective and well tolerated in the treatment of Chinese patients with FC. A weekly CSBM response at week 2 may serve as a predictor of 12-week durable overall efficacy. Patients who did not achieve the primary endpoint may still benefit from plecanatide treatment.</p><p><strong>Clinicaltrials: </strong>GOV: NCT0515132.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":""},"PeriodicalIF":13.0000,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Efficacy and Safety of Plecanatide in Chinese Patients with Functional Constipation: A Phase III Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial.\",\"authors\":\"Tao Bai, Zhiyue Xu, Yanbo Zhen, Aijun Liao, Bangmao Wang, Rong Zhao, Yin Zhu, Ning Dai, Side Liu, Hong Zhao, Xi Chen, Kunming Huang, Min Xu, Weizhen Zhou, Baohong Xu, Bin Ye, Duowu Zou, Heng Zhang, Ruihua Shi, Juan Zhang, Yaowei Ai, Xiangming Fang, Lin Lin, Xiaolan Zhang, Ling Zhang, Junping Wang, Yueping Jiang, Jun Cui, Mingxin Zhang, Xiangwu Ding, Zhongyin Zhou, Peng Yan, Xiaoqing Li, Bo Jiang, Youli Liu, Yingcai Ma, Shaoqi Yang, Xiaoyan Wang, Yongdong Wu, Jianjun Wu, Huixin Chen, Xiaohua Hou\",\"doi\":\"10.1007/s40265-025-02205-w\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Plecanatide is a novel guanylate cyclase-C agonist for the treatment of functional constipation (FC). Its efficacy may vary across different racial populations.</p><p><strong>Objective: </strong>This study aimed to comprehensively evaluate the efficacy, safety, and pharmacokinetics of plecanatide in Chinese patients with FC.</p><p><strong>Methods: </strong>This phase III, randomized, double-blind, placebo-controlled trial was conducted across 40 hospitals in China. A total of 648 patients with FC were randomly assigned in a ratio of 1:1 to receive either plecanatide 3 mg or placebo for 12 weeks, followed by a 2-week follow-up. The primary efficacy endpoint was the durable overall complete spontaneous bowel movement (CSBM) response rate. Data on adverse events were collected. A post hoc logistic regression analysis was performed to identify predictors of durable overall CSBM response.</p><p><strong>Results: </strong>After 12 weeks of continuous treatment, the durable overall CSBM response rates were 23.5% in the plecanatide group and 10.2% in the placebo group (p < 0.001). Plecanatide significantly increased the mean weekly frequency of CSBM (1.89 vs 0.9) and SBM (2.33 vs 1.03) compared with placebo throughout the treatment period. In addition, all other secondary efficacy endpoints showed statistically significant improvements with plecanatide compared with placebo. The most common treatment-related emergent adverse event was diarrhea, which occurred in 4.3% of plecanatide-treated patients and 0.6% of placebo-treated patients (p = 0.002). Plasma concentrations of plecanatide and its metabolite SP-338 remained below the lower limit of quantification (0.500 ng/ml) at all assessed time points. Weekly CSBM response at week 2 (odds ratio 43.476; 95% confidence interval 18.274-103.432) and baseline stool consistency (odds ratio 0.550; 95% confidence interval 0.366-0.827) were identified as effective predictors of durable overall CSBM response. Even among plecanatide non-responders, a significant improvement in SBM frequency compared with placebo was observed over the 12-week treatment period.</p><p><strong>Conclusions: </strong>Plecanatide 3 mg was effective and well tolerated in the treatment of Chinese patients with FC. A weekly CSBM response at week 2 may serve as a predictor of 12-week durable overall efficacy. 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Efficacy and Safety of Plecanatide in Chinese Patients with Functional Constipation: A Phase III Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial.
Background: Plecanatide is a novel guanylate cyclase-C agonist for the treatment of functional constipation (FC). Its efficacy may vary across different racial populations.
Objective: This study aimed to comprehensively evaluate the efficacy, safety, and pharmacokinetics of plecanatide in Chinese patients with FC.
Methods: This phase III, randomized, double-blind, placebo-controlled trial was conducted across 40 hospitals in China. A total of 648 patients with FC were randomly assigned in a ratio of 1:1 to receive either plecanatide 3 mg or placebo for 12 weeks, followed by a 2-week follow-up. The primary efficacy endpoint was the durable overall complete spontaneous bowel movement (CSBM) response rate. Data on adverse events were collected. A post hoc logistic regression analysis was performed to identify predictors of durable overall CSBM response.
Results: After 12 weeks of continuous treatment, the durable overall CSBM response rates were 23.5% in the plecanatide group and 10.2% in the placebo group (p < 0.001). Plecanatide significantly increased the mean weekly frequency of CSBM (1.89 vs 0.9) and SBM (2.33 vs 1.03) compared with placebo throughout the treatment period. In addition, all other secondary efficacy endpoints showed statistically significant improvements with plecanatide compared with placebo. The most common treatment-related emergent adverse event was diarrhea, which occurred in 4.3% of plecanatide-treated patients and 0.6% of placebo-treated patients (p = 0.002). Plasma concentrations of plecanatide and its metabolite SP-338 remained below the lower limit of quantification (0.500 ng/ml) at all assessed time points. Weekly CSBM response at week 2 (odds ratio 43.476; 95% confidence interval 18.274-103.432) and baseline stool consistency (odds ratio 0.550; 95% confidence interval 0.366-0.827) were identified as effective predictors of durable overall CSBM response. Even among plecanatide non-responders, a significant improvement in SBM frequency compared with placebo was observed over the 12-week treatment period.
Conclusions: Plecanatide 3 mg was effective and well tolerated in the treatment of Chinese patients with FC. A weekly CSBM response at week 2 may serve as a predictor of 12-week durable overall efficacy. Patients who did not achieve the primary endpoint may still benefit from plecanatide treatment.
期刊介绍：
Drugs is a journal that aims to enhance pharmacotherapy by publishing review and original research articles on key aspects of clinical pharmacology and therapeutics. The journal includes:
Leading/current opinion articles providing an overview of contentious or emerging issues.
Definitive reviews of drugs and drug classes, and their place in disease management.
Therapy in Practice articles including recommendations for specific clinical situations.
High-quality, well designed, original clinical research.
Adis Drug Evaluations reviewing the properties and place in therapy of both newer and established drugs.
AdisInsight Reports summarising development at first global approval.
Moreover, the journal offers additional digital features such as animated abstracts, video abstracts, instructional videos, and podcasts to increase visibility and educational value. Plain language summaries accompany articles to assist readers with some knowledge of the field in understanding important medical advances.
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