Microbia has announced the presentation of data from phase II study in which linaclotide accelerated colonic transit and improved bowel function in patients with constipation-predominant irritable bowel syndrome (IBS-C).
These data also showed linaclotide was well tolerated with a low incidence of adverse events. Linaclotide is a first-in-class compound currently being developed for the treatment of IBS-C, chronic constipation (CC), and other gastrointestinal disorders. Linaclotide is an agonist of the guanylate cyclase type-C receptor and acts by a different mechanism than agents targeting the serotonergic system.
Thirty-six women suffering from IBS-C were evaluated in a double-blind, placebo-controlled study, which consisted of a five-day baseline and a five-day treatment period. The endpoints were measurements of gastrointestinal transit and bowel function. Gastrointestinal transit is the process of moving food or other substances through the intestinal tract. Gastrointestinal transit time is generally delayed in patients with IBS-C and is associated with the symptoms of constipation, such as hard stools. Patients who received linaclotide had a significant acceleration of ascending colon emptying and colonic transit at 48 hours post dose as measured by scintigraphy.
"We are pleased that these results complement our previous study with linaclotide in patients suffering from chronic constipation," said Mark Currie, Ph.D., Microbia's senior vice president of research and development. "These data greatly expand our understanding of the potential beneficial actions of linaclotide in patients with lower bowel dysfunction and provide an impetus to advance this agent in later stage clinical development."
Linaclotide is a first-in-class compound currently being tested for the treatment of IBS-C, CC and other gastrointestinal disorders. Linaclotide is an agonist of guanylate cyclase type-C, a receptor found on the lining of the intestine. In preclinical testing linaclotide was shown to increase fluid secretion into the intestine, accelerate intestinal transit, and decrease visceral pain. Linaclotide was designed to exert its effect on the intestine with minimal systemic exposure. In phase I testing linaclotide was well tolerated and was not detected in the systemic circulation of healthy subjects. Linaclotide is currently being studied in a pair of phase II dose-ranging trials for IBS-C and CC.