Background & Aims

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.

Methods

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.

Results

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).

Conclusions

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.

中文翻译：

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一项随机对照试验中 5-HT4 受体激动剂米奈沙必利治疗便秘型肠易激综合征的疗效和安全性

背景与目标

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。我们在日本 IBS-C 患者中评估了 Minesapride (DSP-6952)（一种对 5-HT4 受体具有高亲和力的部分激动剂）的疗效和安全性。

方法

我们对 2012 年 12 月至 2013 年 8 月在日本 33 个中心的 171 名罗马 III 定义的 IBS-C 患者进行了一项双盲 2 期研究。患者被随机分配到接受米沙必利治疗的组（1、4、12 或 40 mg) 或安慰剂，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、腹部症状和 IBS-C 症状（根据日本版 IBS 严重程度指数评分）的改善。为了评估安全性，记录了不良事件 (AE)。

结果

第 4 周时，所有米沙必利组的每周 CSBM 频率自基线的最小二乘平均变化大于安慰剂组（40 毫克 vs 安慰剂，P = .040）。米沙必利40mg组腹部症状评分有所改善。所有治疗组的整体 IBS 严重程度指数评分从基线到第 4 周都有所下降，尤其是在 12 毫克和 40 毫克组中（与安慰剂相比，分别为P = .048 和 <.001）。合并的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%。最常见的治疗中出现的 AE 是腹泻（分别在米沙必利和安慰剂组中分别为 42.9% 和 37.1% 的患者）。

结论

在日本对 IBS-C 患者进行的 2 期试验中，米沙必利增加了排便频率（通过 CSBM 测量），减少了腹部和整体 IBS-C 症状，并且耐受性良好。日本药品信息中心试验编号：JapicCTI-122041。