Salix reports encouraging results from Phase III hepatic encephalopathy trial

The new data, from a large, randomized, placebo-controlled study of 299 patients, showed that patients who received rifaximin (1,100mg/day, dosed at 550mg twice daily) for six months had highly statistically significant protection against clinical hepatic encephalopathy (HE) breakthrough episodes (58% risk reduction, p<0.0001) in the intent to treat (ITT) population, the company said. The analyses also showed that reduction of the risk of HE breakthrough was maintained across all subgroups in the study, indicating a high degree of consistency of the ITT outcome. Additionally, the data also indicated that rifaximin taken 550mg twice daily (bid) had a safety profile comparable to placebo in patients treated up to six months. The Phase III study, a multinational, randomized, double-blind, placebo-controlled trial, was designed to assess the long-term (six months) efficacy, safety and tolerability of rifaximin in maintaining remission compared to placebo among patients with a history of HE. The patients were randomized to either rifaximin (n=140) 550mg/bid, or placebo (n=159). Patients with cirrhosis who had greater than or equal to two episodes of HE (defined as Conn score greater than or equal to two) within six months prior to screening and were currently in remission (defined as a Conn score equal to zero or one) were enrolled in the study. The primary endpoint was time to first breakthrough HE episode (increase of Conn score to greater than or equal to two; or a Conn score and asterixis grade increase of one each, if baseline Conn score is equal to zero). Nathan Bass, professor of medicine at the University of California San Francisco, said: "In this Phase III, placebo-controlled study, rifaximin produced a highly significant effect in protecting patients with a history of HE from clinical breakthrough, increasing the duration of remission over six months, which is a substantial clinical finding. Based on this study, and if approved, rifaximin could potentially be the first new clinical treatment option in the US for patients with HE in almost 30 years."