Ironwood Pharmaceuticals (IRWD) and AstraZeneca Pharmaceuticals have started a Phase III clinical study of linaclotide for the treatment of adults with irritable bowel syndrome with constipation (IBS-C) in China.
Around 800 adults with IBS-C in China, Australia and New Zealand will be enrolled in the double-blind, randomised, placebo-controlled Phase III clinical trial.
The design of the trial is similar to the 12-week Phase III IBS-C trial that supported linaclotide regulatory approval in the US and the EU.
As part of the trial, patients will be randomised 1:1 to receive either 290mcg of linaclotide or placebo during the treatment period.
Abdominal Pain/Discomfort Responder at 12 weeks, which is defined in the study protocol as a patient who has at least a 30% improvement in his/her abdominal pain/discomfort level for at least half of the treatment period, is one of the co-primary endpoints.
The other primary endpoint is IBS Degree of Relief Responder at 12 weeks, which is defined in the study protocol as a patient who is considerably or completely relieved of symptoms for at least half of the treatment period.
AstraZeneca China president David Snow said IBS-C is expected to affect an estimated 13 million adults in China, causing hallmark symptoms such as abdominal pain and constipation.
"If approved in China, linaclotide could be the first prescription treatment specifically for IBS-C and could then help address an unmet need for millions of suffering patients," Snow said.
Top-line data of the trial is scheduled to be released in the first half of 2015 and, if approved by the China Food and Drug Administration (CFDA), linaclotide is expected to be commercialised in China in 2017.
Currently, linaclotide is approved in the US for adults with IBS-C or chronic idiopathic constipation (CIC) and in the European Union (EU) for adults with moderate to severe IBS-C.
Ironwood senior vice-president, chief scientific officer and president of research and development Mark Currie said: "Linaclotide is approved in the US and in the European Union, and the initiation of this Phase III trial is a critical step along the regulatory pathway to support approval in China."
Pursuant to the terms of the deal signed in October 2012, while AstraZeneca is primarily responsible for local operational execution, Ironwood and AstraZeneca are collectively responsible for the development and commercialisation of linaclotide in China.
Linaclotide is a guanylate cyclase-C (GC-C) agonist that binds to guanylate cyclase-C locally in the intestine, increasing both intracellular and extracellular concentrations of cyclic guanosine monophosphate (cGMP).
While elevation in intracellular cGMP is believed to stimulate secretion of intestinal fluid and accelerate gastrointestinal transit, elevation in extracellular cGMP is thought to decrease the activity of pain-sensing nerves, responsible for lowering intestinal pain.