Synergy Pharmaceuticals, Inc., a developer of new drugs to treat gastrointestinal (GI) disorders and diseases, has started dosing in a phase IIb clinical trial of plecanatide to treat patients with constipation-predominant irritable bowel syndrome (IBS-C).
This trial is being conducted at 70 sites in the United States and includes 350 patients with IBS-C who will be treated with one of four doses of plecanatide (0.3, 1.0, 3.0, or 9.0 mg) or placebo, taken once daily over a period of 12 weeks. PAREXEL International is the Contract Research Organization for the trial.
"We are pleased to be developing plecanatide for the treatment of IBS-C, a functional GI disorder of significant burden to patients," said Gary S Jacob, Ph.D., president and chief executive officer of Synergy. "Synergy is about to complete an independent study of plecanatide in patients with chronic idiopathic constipation, and will be releasing top-line data from this trial early in January, 2013. We believe that plecanatide, which is an analog of the natural GI hormone uroguanylin, has the potential to produce an ideal combination of efficacy and safety for patients with IBS-C."
Patients must meet the Rome III criteria for IBS as demonstrated by a history of recurrent abdominal pain or discomfort covering at least three days/month in the last three months associated with two or more of: improvement with defecation, onset associated with a change in frequency of stool, and onset associated with a change in form (appearance) of stool. Patients must also meet the criteria for the IBS-C subtype, which is further characterized by stool pattern such that = 25 per cent of defecations are hard or lumpy stools and = 25 per cent of defecations are loose or watery stools.
The trial will measure the mean change in complete spontaneous bowel movements (CSBM's) over the 12-week treatment period relative to patient's baseline weekly CSBM rate established during the screening phase of the study. The trial will also evaluate spontaneous bowel movements (SBM's) and daily abdominal pain, discomfort and bloating scores as well as the impact of plecanatide on disease-specific quality of life measures.
Plecanatide is a member of a new class of essentially non-systemic drugs, referred to as guanylate cyclase C (GC-C) agonists, that is currently in development to treat CIC and IBS-C. Plecanatide is a synthetic analogue of uroguanylin, a natriuretic hormone that regulates ion and fluid transport in the GI tract. Orally-administered plecanatide binds to and activates GC-C receptors expressed on epithelial cells lining the GI mucosa, resulting in activation of the cystic fibrosis transmembrane conductance regulator (CFTR), and leading to augmented flow of chloride and water into the lumen of the gut. Activation of the GC-C receptor pathway is believed to facilitate bowel movements as well as producing other beneficial physiological responses including improvement in abdominal pain and inflammation. In animal models, oral administration of plecanatide promotes intestinal secretion and also ameliorates GI inflammation.
IBS is one of the most common disorders diagnosed by doctors. It occurs more often in women than in men (2-3:1 ratio), and it begins before the age of 35 in about 50 per cent of people.
Irritable Bowel Syndrome (IBS) is characterized by recurrent episodes of abdominal pain and discomfort with associated alterations in bowel habits. Abdominal discomfort or pain is a universal feature required for the diagnosis of IBS and the predominant abnormal bowel pattern experienced by the patient leads to the subtyping of IBS as: diarrhoea-predominant (D-IBS), constipation-predominant (C-IBS), or mixed IBS (M-IBS). Only IBS-C patients, are targeted for treatment with plecanatide.