Minesapride safe, well-tolerated in IBS-C
Minesapride, an agonist of 5-hydroxytryptamine 4 receptor, was safe and well-tolerated among patients with constipation-predominant irritable bowel syndrome, according to study results.
“Serotonin 4 (5-hydroxytryptamine 4 [5-HT4]) receptor agonists are believed to exert their therapeutic effect by acting on the 5-HT4 receptors in the gastrointestinal tract and lead to the release of acetylcholine, thereby promoting gastrointestinal motility,” Tatsuto Hamatani, of the drug development division at Sumitomi Dainippon Pharma Co, and colleagues wrote. “Minesapride has potent enterokinetic effects and shows minimal effects on human Ether-a-go-go related gene potassium channels in pre-clinical studies.”
Researchers conducted a placebo-controlled, dose-findings study in 411 patients with IBS-C defined by Rome IV criteria. They randomly assigned patients to received 10 mg, 20 mg or 40 mg of minesapride per day or placebo for 12 weeks.
The primary endpoint of the study was the FDA composite endpoint, in which a responder is defined as a patient who reports an increase in one or more complete spontaneous bowel movements from baseline and improvement of at least 30% from baseline in weekly average of worst abdominal pain score, both in the same week for at least 6 of 12 weeks.
Investigators found that the responder rate was 13.6% in the placebo group, 13.6% in the 10 mg group, 19.2% in the 30 mg group and 14.9% in the 40 mg group and found no dose-response relationship.
Hamatani and colleagues found that a greater percentage of patients in the 40 mg group met both responder requirements for at least 9 weeks, and the 40 mg dose increased spontaneous bowel movement frequency compared with placebo (adjusted P < .001 at week 12).
The most common treatment-related adverse event was mild diarrhea.
“Study results suggested that minesapride was safe and well-tolerated at doses up to 40 mg per day,” Hamatani and colleagues wrote. “Although the primary endpoint was negative, minesapride 40 mg is likely to improve a stricter composite responder evaluation and spontaneous bowel movement frequency in IBS-C patients.”