Furiex Pharmaceuticals, Morrisville, North Carolina 27560, USA.
Gastroenterology. 2013 Aug;145(2):329-38.e1. doi: 10.1053/j.gastro.2013.04.006. Epub 2013 Apr 9.
BACKGROUND & AIMS: Simultaneous agonism of the μ-opioid receptor and antagonism of the δ-opioid receptor can reduce abdominal pain and diarrhea in patients with irritable bowel syndrome with diarrhea (IBS-D) without constipating side effects. We evaluated the efficacy and safety of a minimally absorbed, μ-opioid receptor agonist and δ-opioid receptor antagonist (eluxadoline) in a phase 2 study in patients with IBS-D.
We randomly assigned 807 patients to groups that received oral placebo twice daily or 5, 25, 100, or 200 mg oral eluxadoline for 12 weeks. The primary end point was clinical response at week 4, defined by a mean reduction in daily pain score from baseline of ≥ 30%, and of at least 2 points on 0-10 scale, as well as a stool consistency score of 3 or 4 on the Bristol Stool Scale (1-7) for at least 66% of daily diary entries during that week.
Significantly more patients receiving 25 mg (12.0%) or 200 mg (13.8%) eluxadoline met the primary end point of clinical response than patients given placebo (5.7%; P < .05). Patients receiving eluxadoline at 100 mg and 200 mg also had greater improvements in bowel movement frequency and urgency, global symptoms, quality of life, and adequate relief assessments (P < .05). Additionally, patients receiving 100 mg (28.0%) or 200 mg (28.5%) eluxadoline were significantly more likely than those receiving placebo (13.8%; P < .005) to meet the US Food and Drug Administration response end point during the full 12 weeks of the study. Eluxadoline was well tolerated with a low incidence of constipation.
In a phase 2 study of the mixed μ-opioid receptor agonist/δ-opioid receptor antagonist eluxadoline vs placebo in patients with IBS-D, patients given eluxadoline were significantly more likely to be clinical responders, based on a composite of improvement in abdominal pain and stool consistency. Further study of eluxadoline is warranted to assess its potential as a treatment for IBS-D.
同时激动μ阿片受体和拮抗 δ 阿片受体可以减少腹泻型肠易激综合征（IBS-D）患者的腹痛和腹泻，而没有便秘的副作用。我们评估了一种低吸收的 μ 阿片受体激动剂和 δ 阿片受体拮抗剂（eluxadoline）在 IBS-D 患者中的疗效和安全性。
我们将 807 名患者随机分为两组，分别接受每日两次口服安慰剂或 5、25、100 或 200mg 口服 eluxadoline 治疗 12 周。主要终点是第 4 周的临床反应，定义为每日疼痛评分较基线下降≥30%，0-10 评分至少下降 2 分，同时在该周的至少 66%的日常日记记录中，布里斯托尔粪便性状评分达到 3 或 4 分。
接受 25mg（12.0%）或 200mg（13.8%）eluxadoline 的患者显著多于接受安慰剂的患者（5.7%；P<.05）达到临床反应的主要终点。接受 100mg 和 200mg eluxadoline 的患者在改善排便频率和急迫感、整体症状、生活质量和充分缓解评估方面也有更大的改善（P<.05）。此外，接受 100mg（28.0%）或 200mg（28.5%）eluxadoline 的患者比接受安慰剂的患者（13.8%；P<.005）更有可能在整个 12 周的研究中达到美国食品和药物管理局的反应终点。eluxadoline的耐受性良好，便秘发生率低。
在一项 IBS-D 患者混合 μ 阿片受体激动剂/δ 阿片受体拮抗剂 eluxadoline 与安慰剂的 2 期研究中，根据腹痛和粪便稠度改善的综合情况，接受 eluxadoline 的患者更有可能成为临床应答者。进一步研究 eluxadoline 以评估其治疗 IBS-D 的潜力是有必要的。
