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Abstract：
Treatment options for irritable bowel syndrome with constipation (IBS-C) are limited-new prokinetic drugs are needed. We evaluated the efficacy and safety of minesapride (DSP-6952), a partial agonist with high affinity for 5-HT4 receptors, in patients with IBS-C in Japan.
We performed a double-blind phase 2 study of 171 patients with Rome III-defined IBS-C at 33 centers in Japan, from December 2012 through August 2013. Patients were randomly assigned to groups given minesapride (1, 4, 12, or 40 mg) or placebo once daily for 4 weeks. The primary outcome was efficacy, defined as improvement in the weekly frequency of complete spontaneous bowel movements (CSBMs), abdominal symptoms, and IBS-C symptoms (according to the Japanese version of the IBS severity index score). For evaluation of safety, adverse events (AEs) were recorded.
The least squares mean change from baseline in the weekly frequency of CSBMs was greater in all minesapride groups than in the placebo group at week 4 (40 mg vs placebo, P = .040). The abdominal symptoms score improved in minesapride 40 mg group. The overall IBS severity index score decreased from baseline to week 4 in all treatment groups-especially in the 12 mg and 40 mg groups (P = .048 and <.001 vs placebo, respectively). The proportions of patients with treatment-emergent AEs in the pooled minesapride and placebo groups were 55.0% and 60.0%, respectively. The most common treatment-emergent AE was diarrhea (in 42.9% and 37.1% of patients in the pooled minesapride and placebo groups, respectively).
In a phase 2 trial of patients with IBS-C in Japan, minesapride increased stool frequency (measured by CSBMs), reduced abdominal and overall IBS-C symptoms, and was well tolerated. Japan Pharmaceutical Information Center trial no: JapicCTI-122041.
We performed a double-blind phase 2 study of 171 patients with Rome III-defined IBS-C at 33 centers in Japan, from December 2012 through August 2013. Patients were randomly assigned to groups given minesapride (1, 4, 12, or 40 mg) or placebo once daily for 4 weeks. The primary outcome was efficacy, defined as improvement in the weekly frequency of complete spontaneous bowel movements (CSBMs), abdominal symptoms, and IBS-C symptoms (according to the Japanese version of the IBS severity index score). For evaluation of safety, adverse events (AEs) were recorded.
The least squares mean change from baseline in the weekly frequency of CSBMs was greater in all minesapride groups than in the placebo group at week 4 (40 mg vs placebo, P = .040). The abdominal symptoms score improved in minesapride 40 mg group. The overall IBS severity index score decreased from baseline to week 4 in all treatment groups-especially in the 12 mg and 40 mg groups (P = .048 and <.001 vs placebo, respectively). The proportions of patients with treatment-emergent AEs in the pooled minesapride and placebo groups were 55.0% and 60.0%, respectively. The most common treatment-emergent AE was diarrhea (in 42.9% and 37.1% of patients in the pooled minesapride and placebo groups, respectively).
In a phase 2 trial of patients with IBS-C in Japan, minesapride increased stool frequency (measured by CSBMs), reduced abdominal and overall IBS-C symptoms, and was well tolerated. Japan Pharmaceutical Information Center trial no: JapicCTI-122041.
摘要：
便秘型肠易激综合征（IBS-C）的治疗选择有限，需要新的促动力药物。我们评估了雷沙必利（DSP-6952）的疗效和安全性，对5-HT4受体具有高亲和力的部分激动剂，在日本的IBS-C患者中。
我们在日本的33个中心对171名罗马III定义的IBS-C患者进行了一项双盲2期研究。从2012年12月到2013年8月。患者被随机分配到给予米沙必利（1、4、12或40mg）或安慰剂组，每天一次，持续4周。主要结果是疗效，定义为每周完全自发排便（CSBM）频率的改善，腹部症状,和IBS-C症状（根据日本版本的IBS严重程度指数评分）。为了评估安全性，记录不良事件(AE).
在第4周时，所有Minesapride组的每周CSBM频率自基线的最小二乘平均变化均大于安慰剂组（40mgvs安慰剂，P=.040）。Minesapride40mg组腹部症状评分改善。在所有治疗组中，从基线到第4周，总体IBS严重程度指数评分均下降，尤其是在12mg和40mg组中（与安慰剂组相比，P=0.048和<.001，分别)。合并米沙必利和安慰剂组中出现治疗紧急AE的患者比例分别为55.0%和60.0%，分别。最常见的治疗引起的AE是腹泻（在合并的Minesapride和安慰剂组中，分别为42.9％和37.1％的患者，分别)。
在日本IBS-C患者的2期试验中，Minesapride增加了粪便频率（通过CSBM测量），减少腹部和整体IBS-C症状，并被很好地容忍。日本医药信息中心试验编号：JapicCTI-122041。
我们在日本的33个中心对171名罗马III定义的IBS-C患者进行了一项双盲2期研究。从2012年12月到2013年8月。患者被随机分配到给予米沙必利（1、4、12或40mg）或安慰剂组，每天一次，持续4周。主要结果是疗效，定义为每周完全自发排便（CSBM）频率的改善，腹部症状,和IBS-C症状（根据日本版本的IBS严重程度指数评分）。为了评估安全性，记录不良事件(AE).
在第4周时，所有Minesapride组的每周CSBM频率自基线的最小二乘平均变化均大于安慰剂组（40mgvs安慰剂，P=.040）。Minesapride40mg组腹部症状评分改善。在所有治疗组中，从基线到第4周，总体IBS严重程度指数评分均下降，尤其是在12mg和40mg组中（与安慰剂组相比，P=0.048和<.001，分别)。合并米沙必利和安慰剂组中出现治疗紧急AE的患者比例分别为55.0%和60.0%，分别。最常见的治疗引起的AE是腹泻（在合并的Minesapride和安慰剂组中，分别为42.9％和37.1％的患者，分别)。
在日本IBS-C患者的2期试验中，Minesapride增加了粪便频率（通过CSBM测量），减少腹部和整体IBS-C症状，并被很好地容忍。日本医药信息中心试验编号：JapicCTI-122041。
