Randomised clinical trial: minesapride vs placebo for irritable bowel syndrome with predominant constipation

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.