Targeting of Rifamycin SV to the Colon for Treatment of Travelers' Diarrhea: A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study

摘要: Background Rifamycin SV is under development for treatment of travelers' diarrhea (TD) in a new oral formulation, MMX® (RIF‐MMX; Santarus Inc., San Diego, CA, USA), which targets its delivery to the colon, making it unique rifamycin drug. Methods This was randomized, double‐blind, phase 3 study adult travelers Mexico or Guatemala experiencing acute diarrhea. A total 264 patients received RIF‐MMX (2 × 200 mg twice daily 3 days, n  = 199) placebo (  = 65) 3 : 1 ratio. The primary endpoint length time between administration first dose drug and passage last unformed stool (TLUS; after clinical cure declared). Other endpoints included eradication pathogens from stools, pathogen minimum inhibitory concentration (MIC), adverse events (AEs). Results TLUS significantly shorter group (median: 46.0 hours) compared with 68.0 hours; p  = 0.0008) larger percentage treated (81.4%) achieved (56.9%). subgroups enteroaggregative, enterotoxigenic, diffusely adherent Escherichia coli infections  = 0.0035) nonsignificant activity against invasive bacteria  = 0.3804). Overall rates were numerically higher (67.0%) (54.8%) but difference did not reach significance  = 0.0836). In vitro resistance observed some remaining associated lower efficacy them. AEs appeared be more frequent (38.5%) than (29.6%). Conclusions shortened duration TD broad range well tolerated. pharmacokinetic properties offer evidence that work at level colon.