Salix Pharmaceuticals has begun the Phase 3 study, TARGET 3, to investigate the efficacy and safety of repeat treatment with Rifaximin (Xifaxan) 550mg TID (three times daily dosage) for 14 days in patients suffering from irritable bowel syndrome with diarrhea (IBS-D).
Rifaximin is a gut-selective antibiotic with negligible systemic absorption and broad-spectrum activity in vitro against both gram-positive and gram-negative pathogens.
The randomised double-blind placebo-controlled TARGET 3 study will be conducted in approximately 250 sites across the US.
In the trial, approximately 800 patients with IBS-D will be screened and randomised into the double blind retreatment phase of the study with either another course of Rifaximin 550mg TID for 14 days or matching placebo.
The Phase 3 study's primary endpoint is the proportion of subjects who responded to repeat treatment in both IBS-related abdominal pain and stool consistency during the four week treatment-free follow-up period (Primary Evaluation Period or PEP) in the Double Blind Repeat (or DBR) treatment phase as compared to the placebo treated group.
The trial includes several treatment phases, such as screening/treatment 1 phase, treatment 2 phase, maintenance phase 1, treatment 3 phase/ double blind repeat (DBR) treatment phase, maintenance phase 2 and treatment 4 phase/second repeat treatment (SRT) phase.
In the screening/treatment 1 phase, subjects will receive single-blind placebo TID and respond to daily IBS symptom-related questions.
In treatment 2 phase and maintenance phase 1, eligible subjects will receive open-label rifaximin 550mg TID for two weeks with a four-week treatment-free follow-up, and will continue the treatment-free follow-up period for up to 24 weeks.
The trial in treatment 3 phase/DBR treatment phase will be randomised 1:1 to receive either rifaximin 550mg TID or placebo TID for two weeks with a four-week treatment-free follow-up.
All patients eligible for maintenance phase 2 will continue with an additional treatment-free follow-up period of up to six weeks.
The subjects in the treatment 4 phase/SRT phase will receive the same double-blind treatment as previously assigned in the treatment 3 phase for two weeks with a four-week treatment-free follow-up.
The company said the findings from the study will be submitted to the US Food and Drug Administration (FDA) as the basis of a response to the FDA's complete response letter (CRL).