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Randomised clinical trial: minesapride vs placebo for irritable bowel syndrome with predominant constipation
Author(s) -
Hamatani Tatsuto,
Fukudo Shin,
Nakada Yosuke,
Inada Hiroshi,
Kazumori Kiyoyasu,
Miwa Hiroto
Publication year - 2020
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1111/apt.15907
Subject(s) - medicine , placebo , irritable bowel syndrome , constipation , clinical endpoint , abdominal pain , adverse effect , gastroenterology , tegaserod , population , defecation , clinical trial , alternative medicine , pathology , environmental health
Summary Background Agonists of 5‐hydroxytryptamine 4 receptor are potential agents for irritable bowel syndrome with predominant constipation (IBS‐C). However, only tegaserod has been approved for a very limited population in the US. Aim To evaluate the efficacy and safety of minesapride in patients with Rome IV defined IBS‐C. Methods A double‐blind, placebo‐controlled, dose‐finding study was performed. Overall, 411 patients were randomised to receive minesapride at 10, 20 or 40 mg/d, or placebo for 12 weeks. The primary endpoint was Food and Drug Administration (FDA) composite endpoint (responder: a patient who reported an increase in one or more complete spontaneous bowel movements from baseline and improvement of ≥30% from baseline in weekly average of worst abdominal pain score, both in the same week for ≥6/12 weeks). Results The FDA composite responder rate was 13.6% (14/103) in the placebo group, 13.6% (14/103) in the 10 mg group, 19.2% (20/104) in the 20 mg group and 14.9% (15/101) in the 40 mg group, and no dose‐response relationship was found. A greater percentage of minesapride 40 mg‐treated patients than placebo‐treated patients met both responder requirements for ≥9/12 weeks as the stricter composite evaluation ( P < 0.05). Furthermore, minesapride 40 mg significantly increased SBM frequency compared with placebo (adjusted P < 0.001 at Week 12). The most common adverse event was mild diarrhoea. Conclusions Minesapride was safe and well‐tolerated. Although the primary endpoint was negative, minesapride 40 mg is likely to improve the stricter composite endpoint and SBM frequency. Japan Pharmaceutical Information Center Number: Japic CTI‐163459.