TY - JOUR
T1 - Efficacy and Safety of 5-HT4 Receptor Agonist Minesapride for Irritable Bowel Syndrome with Constipation in a Randomized Controlled Trial
AU - Fukudo, Shin
AU - Nakamura, Masatoshi
AU - Hamatani, Tatsuto
AU - Kazumori, Kiyoyasu
AU - Miwa, Hiroto
N1 - Funding Information:
List of participating institutions: Ohmori Toshihide Gastro-intestinal Clinic, Ishikubo Clinic, Inage Hospital, Tsurumachi Clinic, Kasai Shoikai Hospital, Minoyama Clinic, Tama Medical Clinic, Kameido Minamiguchi Clinic, Stella Matutina Clinic of Internal Medicine, Soare Medical Clinic, Tokyo-Eki Center-building Clinic, Kugayama Clinic, Nakano Sunbright Clinic, Yamada Clinic, Yokohama Minoru Clinic, Medical Corporation Inoue Clinic, Matsuda Hospital, Obata Medical Clinic, Morikawa Clinic, Clinic Komatsu, Nakajima Clinic, Aoyama Internal Medicine Clinic, Osamura Medical Clinic, Medical Shimada Hospital, Hatakeyama Clinic, Oishi Clinic, Tanaka Hiroaki Clinic, Yamada Gastroenterology Internal Medicine Clinic, Sadamoto Clinic, Yutaka Fukuda Clinic, Mori Clinic, Matsuo Internal Medicine Hospital, Kawamoto Gastrointestinal & Medical Clinic. Shin Fukudo, MD, PhD (Conceptualization: Lead; Data curation: Supporting; Formal analysis: Equal; Funding acquisition: Supporting; Investigation: Lead; Methodology: Lead; Project administration: Lead; Resources: Supporting; Software: Supporting; Supervision: Lead; Validation: Supporting; Visualization: Equal; Writing – original draft: Lead; Writing – review & editing: Lead; Data presentation and discussion: Lead), Masatoshi Nakamura, PhD (Conceptualization: Equal; Data curation: Equal; Formal analysis: Equal; Funding acquisition: Equal; Investigation: Supporting; Methodology: Equal; Project administration: Equal; Resources: Equal; Software: Supporting; Supervision: Supporting; Validation: Supporting; Visualization: Supporting; Writing – original draft: Supporting; Writing – review & editing: Supporting), Tatsuto Hamatani, BS (Data curation: Equal; Formal analysis: Equal; Funding acquisition: Supporting; Investigation: Supporting; Methodology: Supporting; Project administration: Supporting; Resources: Supporting; Software: Supporting; Supervision: Supporting; Validation: Supporting; Visualization: Supporting; Writing – original draft: Equal; Writing – review & editing: Supporting), Kiyoyasu Kazumori, BS (Conceptualization: Supporting; Data curation: Supporting; Formal analysis: Supporting; Funding acquisition: Supporting; Investigation: Supporting; Methodology: Supporting; Project administration: Supporting; Resources: Supporting; Software: Supporting; Validation: Supporting; Visualization: Supporting; Writing – original draft: Supporting; Writing – review & editing: Supporting), Hiroto Miwa, MD, PhD (Conceptualization: Supporting; Data curation: Supporting; Formal analysis: Supporting; Investigation: Supporting; Methodology: Supporting; Project administration: Supporting; Software: Supporting; Supervision: Equal; Validation: Supporting; Visualization: Supporting; Writing – original draft: Supporting; Writing – review & editing: Equal). Funding Supported by Sumitomo Dainippon Pharma Co, Ltd.
Funding Information:
Funding Supported by Sumitomo Dainippon Pharma Co, Ltd.
Publisher Copyright:
© 2021 The Authors
PY - 2021/3
Y1 - 2021/3
N2 - 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.
AB - 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.
KW - Drug
KW - Serotonin Receptors
KW - Side Effect
KW - Therapy
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U2 - 10.1016/j.cgh.2020.03.019
DO - 10.1016/j.cgh.2020.03.019
M3 - Article
C2 - 32184185
AN - SCOPUS:85095985564
VL - 19
SP - 538-546.e8
JO - Clinical Gastroenterology and Hepatology
JF - Clinical Gastroenterology and Hepatology
SN - 1542-3565
IS - 3
ER -