Salix Pharmaceuticals, Ltd. announced that the company has initiated patient enrolment in TARGET 1 and TARGET 2, its phase 3, randomized, double-blind, placebo-controlled, multicenter studies to assess the efficacy and safety of rifaximin 550 mg, dosed three times daily, in the treatment of subjects with non-constipation irritable bowel syndrome (IBS). Two 600-subject trials will be conducted simultaneously in approximately 180 study centres throughout the United States and Canada. Subjects will receive rifaximin or placebo (1:1 randomization) for 14 days and then be followed for 10 weeks for a study duration of 12 weeks.
TARGET 1 and TARGET 2 (T-Targeted, non-systemic; A-Antibiotic; R-Rifaximin; G-Gut-selective; E-Evaluation of; T-Treatment for non-C IBS) are intended to assess the clinical efficacy and safety of a 550 mg TID dosing regimen of rifaximin (1650 mg/day) compared with placebo in subjects with IBS who are not currently experiencing symptoms of constipation, referred to as non-constipation IBS. The primary efficacy endpoint of TARGET 1 and TARGET 2 is the proportion of subjects who achieve adequate relief of IBS symptoms for at least 2 weeks during the first 4 weeks of the 10-week follow-up phase.
Salix previously announced the successful completion and outcome of its Phase 2b trial to assess the efficacy and safety of rifaximin in the treatment of patients with diarrhoea-associated irritable bowel syndrome. As reported in a May 20, 2008, top-line results of the 680-patient study demonstrated that a 14-day course of rifaximin at 550 mg twice-a-day provides a statistically significant improvement in both adequate relief of diarrhoea-associated IBS symptoms and adequate relief of bloating, compared to placebo. Based upon an analysis of the data from the Phase 2b study, TARGET 1 and TARGET 2 are designed to evaluate rifaximin in a broad population comprised of males and females 18 years of age and older who have been diagnosed with non-constipation IBS, e.g., diarrhoea-predominant IBS or alternating IBS.
"Irritable bowel syndrome is the most common functional gastrointestinal disorder experienced in patients and seen by physicians in clinical practice," stated Bill Forbes, Pharm.D., Vice President, Research and Development, Salix. "Primary symptoms of IBS are recurrent abdominal pain, bloating and altered bowel function such as diarrhoea. Unfortunately, the cause of IBS is not completely understood. Early investigations for the treatment of IBS focused on a relationship between psychological factors and IBS symptoms. In the 1980s, studies demonstrated that abnormal gut motility was commonly found in patients diagnosed with IBS. More recent research has investigated alterations of bacterial flora in the gut as a potential factor in IBS. To date, the use of antidepressants, serotonin mediators and systemically available antibiotics have not yielded a satisfactory treatment for IBS. Based on the most current understanding of IBS, it is thought that a broad spectrum, gut-selective antibiotic with negligible systemic absorption, minimal side effects and good efficacy for controlling bacterial overgrowth would relieve the symptoms by altering the bacteria responsible for creating the symptoms. Rifaximin, a gut-specific antibiotic, may be a strong candidate for the treatment of IBS by targeting small intestinal bacterial overgrowth. We are very pleased to now initiate these two multicenter trials - TARGET 1 and TARGET 2 - to further evaluate the efficacy of rifaximin as a treatment option in this disease which is associated with widespread prevalence, incapacitating symptoms and substantial medical costs."
Rifaximin is a gut-selective antibiotic with negligible systemic absorption (<0.4%) and broad-spectrum activity in vitro against both gram-positive and gram-negative pathogens. Rifaximin has a similar tolerability profile to that of placebo.