Randomised clinical trial: effects of MD-7246 on irritable bowel syndrome with diarrhoea.

BACKGROUND

MD-7246, a delayed-release formulation of linaclotide, is designed to target the ileocaecal junction and caecum with the aim of relieving abdominal pain independently of bowel function.

AIMS: To evaluate the efficacy, safety and dose-response of MD-7246 in patients with irritable bowel syndrome with diarrhoea (IBS-D).

METHODS

A randomised, double-blind, phase 2 clinical trial enrolled adult patients with IBS-D (Rome IV criteria). Patients were randomised to placebo or once-daily oral MD-7246 300, 600 or 1200 μg for 12 weeks. Abdominal and bowel symptoms were assessed daily. Key efficacy endpoints were change from baseline in abdominal pain and responder rates for a 30% reduction in abdominal pain in 6/12 weeks. Additional abdominal pain responder and exploratory bowel function endpoints were also assessed.

RESULTS

Among the 388 randomised patients, there was no significant difference in mean change from baseline in abdominal pain between the MD-7246 300 μg, 600 μg and 1200 μg groups and placebo (-1.93, -1.58, -1.95 and - 2.01, respectively; p > 0.05 for each group vs placebo). The abdominal pain responder rates in the MD-7246 groups were similar to or lower than those in the placebo group. All doses of MD-7246 had a minimal effect on bowel function and were generally well tolerated.

CONCLUSIONS

MD-7246 at the doses studied did not improve abdominal pain relative to placebo in an IBS-D patient population. Similarly, most additional efficacy endpoints showed no improvement with MD-7246 relative to placebo.