Linaclotide in irritable bowel syndrome with constipation: A Phase 3 randomized trial in China and other regions

Abstract

Once-daily 290-μg linaclotide improved bowel habits, abdominal symptoms, and global measures in a predominantly Chinese IBS-C population.

High‐dose linaclotide is effective and safe in patients with chronic constipation: A phase III randomized, double‐blind, placebo‐controlled study with a long‐term open‐label extension study in Japan

“…It is of interest that North America approved a lower dose of linaclotide for constipated patients than has been approved in Japan. In these countries, 0.29 mg per day of linaclotide is indicated for IBS‐C . Even lower doses of linaclotide, 0.145 mg per day and 0.072 mg per day, have been shown to be effective and safe and have been approved in the United States for the treatment of CC patients .…”

“…16 The recommended doses of linaclotide from these studies are 0.29 mg for IBS-C and 0.145 mg for CC. [12][13][14][15][16] By contrast, results [8][9][10] obtained in Japan have been somewhat different. A phase II study of IBS-C patients showed 0.5 mg per day of linaclotide to be the optimal dose.…”

“…Earlier clinical studies of linaclotide in North America, Oceania and China have demonstrated efficacy and safety in patients with IBS‐C as well as CC . The recommended doses of linaclotide from these studies are 0.29 mg for IBS‐C and 0.145 mg for CC . By contrast, results obtained in Japan have been somewhat different.…”

“…11 Increased cGMP in the epithelial cells eventually stimulates cystic fibrosis transmembrane conductance regulator (CFTR), which acts as a chloride ion channel and causes secretion of chloride ions with water molecules. 12 Earlier clinical studies of linaclotide in North America, Oceania and China have demonstrated efficacy and safety in patients with IBS-C [12][13][14][15] as well as CC. 16 The recommended doses of linaclotide from these studies are 0.29 mg for IBS-C and 0.145 mg for CC.…”

Linaclotide increases cecal pH, accelerates colonic transit, and increases colonic motility in irritable bowel syndrome with constipation

“…Linaclotide is an orally active agonist of the guanylate cyclase C receptor (GC‐C), which is approved for the treatment of irritable bowel syndrome with constipation (IBS‐C) . Linaclotide binds with the GC‐C receptor on the luminal aspect of enterocytes and via a number of intracellular signaling cascades lead to increased intracellular cyclic guanosine monophosphate (cGMP).…”