普卡那肽在中国功能性便秘患者中的疗效与安全性：一项III期多中心、随机、双盲、安慰剂对照试验

Efficacy and Safety of Plecanatide in Chinese Patients with Functional Constipation: A Phase III Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial.

作者信息

Bai Tao, Xu Zhiyue, Zhen Yanbo, Liao Aijun, Wang Bangmao, Zhao Rong, Zhu Yin, Dai Ning, Liu Side, Zhao Hong, Chen Xi, Huang Kunming, Xu Min, Zhou Weizhen, Xu Baohong, Ye Bin, Zou Duowu, Zhang Heng, Shi Ruihua, Zhang Juan, Ai Yaowei, Fang Xiangming, Lin Lin, Zhang Xiaolan, Zhang Ling, Wang Junping, Jiang Yueping, Cui Jun, Zhang Mingxin, Ding Xiangwu, Zhou Zhongyin, Yan Peng, Li Xiaoqing, Jiang Bo, Liu Youli, Ma Yingcai, Yang Shaoqi, Wang Xiaoyan, Wu Yongdong, Wu Jianjun, Chen Huixin, Hou Xiaohua

机构信息

Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Division of Gastroenterology, Jinan Central Hospital, Jinan, China.

出版信息

Drugs. 2025 Jun 26. doi: 10.1007/s40265-025-02205-w.

DOI:10.1007/s40265-025-02205-w

PMID:40571893

Abstract

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.

CLINICALTRIALS

GOV: NCT0515132.

摘要

背景

普卡那肽是一种新型鸟苷酸环化酶-C激动剂，用于治疗功能性便秘（FC）。其疗效在不同种族人群中可能有所不同。

目的

本研究旨在全面评估普卡那肽在中国FC患者中的疗效、安全性和药代动力学。

方法

这项III期随机双盲安慰剂对照试验在中国40家医院进行。总共648例FC患者按1:1的比例随机分配，接受3mg普卡那肽或安慰剂治疗12周，随后进行2周随访。主要疗效终点是持久的总体完全自发排便（CSBM）反应率。收集不良事件数据。进行事后逻辑回归分析以确定持久总体CSBM反应的预测因素。

结果

连续治疗12周后，普卡那肽组的持久总体CSBM反应率为23.5%，安慰剂组为10.2%（p<0.001）。在整个治疗期间，与安慰剂相比，普卡那肽显著提高了CSBM的平均每周频率（1.89对0.9）和SBM（2.33对1.03）。此外，与安慰剂相比，普卡那肽在所有其他次要疗效终点上均显示出统计学上的显著改善。最常见的与治疗相关的紧急不良事件是腹泻，在接受普卡那肽治疗的患者中发生率为4.3%，在接受安慰剂治疗的患者中为0.6%（p=0.002）。在所有评估时间点，普卡那肽及其代谢物SP-338的血浆浓度均低于定量下限（0.500ng/ml）。第2周的每周CSBM反应（优势比43.476；95%置信区间18.274-103.432）和基线粪便稠度（优势比0.550；95%置信区间0.366-0.827）被确定为持久总体CSBM反应的有效预测因素。即使在普卡那肽无反应者中，在12周治疗期间与安慰剂相比，SBM频率也有显著改善。