Using delay-released linaclotide (MD-7246) to manage irritable bowel syndrome with diarrhea
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Reviewed by Dat Tien Nguyen, B.A, ScM.
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Posted on January 27th, 2023
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A previous phase 3 clinical trial had shown that linaclotide can alleviate abdominal discomfort in patients with irritable bowel syndrome (IBS) with constipation. The agent acts on the guanylate cyclase-C on intestinal epithelial cells to increase fluid secretion. The delayed-release formulation 2 of linaclotide (MD-7246) was designed to act in the distal region of the ileocaecal junction and cecum, and a recent study had investigated its effectiveness in treating IBS with diarrhea.
The phase 2 clinical trial was conducted with the objective of evaluating the agent’s effectiveness and safety in addition to finding the optimal dosage. The trial included 7246 patients who had been diagnosed with IBS-D using the Rome IV criteria. The patients were randomly assigned to receive either placebo, 300, 600, or 1200 μg of MD-7246. The treatment was administered orally once daily for 12 weeks. When compared to placebo, MD-7246, at all 3 dose levels, did not result in any significant improvement in baseline abdominal pain. This lack of efficacy can be explained due to the heterogeneity in the origin of abdominal pain and IBS subtypes. In terms of tolerability, the safety profile of MD-7246 was very similar to placebo. Diarrhea and nausea are the two most commonly reported side effects; the reported frequency was approximately 1% to 2%.
The phase 2 clinical trial was conducted with the objective of evaluating the agent’s effectiveness and safety in addition to finding the optimal dosage. The trial included 7246 patients who had been diagnosed with IBS-D using the Rome IV criteria. The patients were randomly assigned to receive either placebo, 300, 600, or 1200 μg of MD-7246. The treatment was administered orally once daily for 12 weeks. When compared to placebo, MD-7246, at all 3 dose levels, did not result in any significant improvement in baseline abdominal pain. This lack of efficacy can be explained due to the heterogeneity in the origin of abdominal pain and IBS subtypes. In terms of tolerability, the safety profile of MD-7246 was very similar to placebo. Diarrhea and nausea are the two most commonly reported side effects; the reported frequency was approximately 1% to 2%.