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

Aliment Pharmacol Ther. 2023 Jan;57(2):192-204. doi: 10.1111/apt.17274.Epub 2022 Nov 2.


Anthony Lembo 1Braden Kuo 2Ramesh Boinpally 3Ella Li 4Madhuja Mallick 3Wieslaw Bochenek 3Wilmin Bartolini 4


Author information

1Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.

2Massachusetts General Hospital, Boston, Massachusetts, USA.

3AbbVie Inc., Madison, New Jersey, USA.

4Ironwood Pharmaceuticals, Inc., Boston, Massachusetts, USA.


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.


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