Linaclotide for Irritable Bowel Syndrome With Constipation: A 26-Week, Randomized, Double-blind, Placebo-Controlled Trial to Evaluate Efficacy and Safety
Linaclotide for Irritable Bowel Syndrome With Constipation: A 26-Week, Randomized, Double-blind, Placebo-Controlled Trial to Evaluate Efficacy and Safety
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DOI：
10.1038/ajg.2012.254
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发表时间：
2012-11-01
影响因子：
9.8
通讯作者：
Johnston, Jeffrey M.
中科院分区：
文献类型：
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作者：
Chey, William D.;Lembo, Anthony J.;Johnston, Jeffrey M.
目的：利那洛肽是一种吸收极少的肽鸟苷酸环化酶-C 激动剂。本试验的目的是确定利那洛肽治疗便秘型肠易激综合征 (IBS-C) 患者超过 26 周的有效性和安全性。 方法：这项 3 期、双盲、平行组、安慰剂对照试验将 IBS-C 患者随机分配至安慰剂组或每日一次口服利那洛肽，为期 26 周。在治疗的前 12 周内评估主要和次要疗效评估。主要终点包括美国食品和药物管理局 (FDA) 的 IBS-C 终点（应答者：患者报告 (i) 平均每日最严重腹痛评分较基线改善≥ 30%，以及 (ii) 完全自发排便 (CSBM) 较基线增加≥ 1 次，均在同一周内持续 >= 6/12 周）和其他三个主要终点，基于腹痛和 CSBM 的改善情况 9/12 周。监测不良事件 (AE)。 结果：总共对 804 名患者（平均年龄 = 44 岁，女性 = 90%，白人 = 78%）进行了评估；利那洛肽治疗的患者中有 33.7% 为 FDA 终点反应者，而安慰剂治疗的患者为 13.9%（P
OBJECTIVES: Linaclotide is a minimally absorbed peptide guanylate cyclase-C agonist. The objective of this trial was to determine the efficacy and safety of linaclotide treatment in patients with irritable bowel syndrome with constipation (IBS-C) over 26 weeks.METHODS: This phase 3, double-blind, parallel-group, placebo-controlled trial randomized IBS-C patients to placebo or 290 mu g of oral linaclotide once daily for a 26-week treatment period. The primary and the secondary efficacy assessments were evaluated over the first 12 weeks of treatment. Primary end points included the Food and Drug Administration's (FDA's) end point for IBS-C (responder: a patient who reported (i) improvement of >= 30% from baseline in average daily worst abdominal pain score and (ii) increase of >= 1 complete spontaneous bowel movement (CSBM) from baseline, both in the same week for >= 6/12 weeks) and three other primary end points, based on improvements in abdominal pain and CSBMs for 9/12 weeks. Adverse events (AEs) were monitored.RESULTS: In all, 804 patients (mean age=44 years, female=90%, white=78%) were evaluated; 33.7% of linaclotide-treated patients were FDA end point responders, vs. 13.9% of placebo-treated patients (P