Pharmaceutical companies Astellas Pharma and Ironwood Pharmaceuticals have reported positive Phase III trial top-line results of linaclotide to treat patients with chronic constipation (CC) in Japan.
Based on non-clinical data, linaclotide is a guanylate cyclase-C (GC-C) agonist thought to bind the GC-C receptor within the intestinal epithelium, resulting in enhanced intestinal fluid secretion and transit, as well as a reduction in the activity of pain-sensing nerves in the intestine.
The double-blind, placebo-controlled Phase III trial is designed to evaluate either 500mcg of linaclotide or placebo for four weeks in 186 randomised adults with CC in Japan.
The results showed that the primary endpoint change from baseline in mean spontaneous bowel movement frequency during the first week has improved comparitively in patients treated with the drug.
The patients in the Phase III study in Japan will be given open-label linaclotide for an additional 52 weeks, the data from which will be combined with the blinded efficacy data as a basis for regulatory review and potential approval for this indication in Japan.
The most common adverse event reported in the Phase III trial was mild or moderate diarrhea.
Linaclotide is currently approved in the country as the first prescription treatment for adults with irritable bowel syndrome and constipation (IBS-C).
The drug has also secured approval in the US for the treatment of adults with IBS-C or chronic idiopathic constipation (CIC) along with approval for adults with IBS-C or CIC in more than 30 other countries.
Ironwood has also collaborated with AstraZeneca for development and commercialisation of linaclotide in China, Hong Kong and Macau.