Eluxadoline for Irritable Bowel Syndrome with Diarrhea
Eluxadoline for Irritable Bowel Syndrome with Diarrhea
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DOI：
10.1056/nejmoa1505180
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发表时间：
2016-01-21
影响因子：
158.5
通讯作者：
Covington, Paul S.
中科院分区：
文献类型：
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作者：
Lembo, Anthony J.;Lacy, Brian E.;Covington, Paul S.
背景：患有腹泻的肠易激综合征（IBS）患者需要有效且安全的治疗。我们进行了两项 3 期试验，以评估 eluxadoline（一种具有混合阿片类作用的新型口服药物（mu-和 kappa-阿片受体激动剂和 δ-阿片受体拮抗剂））对腹泻 IBS 患者的疗效和安全性。方法我们将 2427 名患有腹泻 IBS 的成人随机分配至 eluxadoline（剂量为 75 mg）。 或 100 毫克）或安慰剂，每天两次，持续 26 周（IBS-3002 试验）或 52 周（IBS-3001 试验）。主要终点是在第 1 至 12 周和第 1 至 26 周的至少 50% 的天数中，当天出现腹痛减轻和大便稠度改善的复合反应的患者比例。 结果 在第 1 至 12 周，eluxadoline 组（75 mg 和 100 mg）中达到主要终点的患者数量多于安慰剂组（IBS-3001 试验，23.9%） 75毫克剂量 100 毫克剂量组为 25.1%，安慰剂组为 17.1%；分别为 P = 0.01 和 P = 0.004； IBS-3002 试验分别为 28.9% 和 29.6% vs. 16.2%；磷
BACKGROUNDEffective and safe treatments are needed for patients who have irritable bowel syndrome (IBS) with diarrhea. We conducted two phase 3 trials to assess the efficacy and safety of eluxadoline, a new oral agent with mixed opioid effects (mu- and kappa-opioid receptor agonist and delta-opioid receptor antagonist), in patients with IBS with diarrhea.METHODSWe randomly assigned 2427 adults who had IBS with diarrhea to eluxadoline (at a dose of 75 mg or 100 mg) or placebo twice daily for 26 weeks (IBS-3002 trial) or 52 weeks (IBS-3001 trial). The primary end point was the proportion of patients who had a composite response of decrease in abdominal pain and improvement in stool consistency on the same day for at least 50% of the days from weeks 1 through 12 and from weeks 1 through 26.RESULTSFor weeks 1 through 12, more patients in the eluxadoline groups (75 mg and 100 mg) than in the placebo group reached the primary end point (IBS-3001 trial, 23.9% with the 75-mg dose and 25.1% with the 100-mg dose vs. 17.1% with placebo; P = 0.01 and P = 0.004, respectively; IBS-3002 trial, 28.9% and 29.6%, respectively, vs. 16.2%; P