Bimodal Release Ondansetron Improves Stool Consistency and Symptomatology in Diarrhea-Predominant Irritable Bowel Syndrome: A Randomized, Double-Blind, Trial

Abstract

Previous, small studies have suggested that ondansetron has beneficial effects in diarrhea-predominant irritable bowel syndrome (IBS-D). This randomized, double-blind study evaluated the efficacy and safety of daily 12 mg RHB-102, an investigational bimodal release ondansetron tablet, in IBS-D. Men and women with IBS-D by the Rome III criteria, Bristol Stool Scale ≥6 on 2 or more days weekly, and average daily worst pain intensity ≥3/10 were randomized 60:40 to RHB-102 or placebo once daily for 8 weeks. The primary end point was overall stool consistency response for at least 4 of 8 weeks. Secondary end points included overall worst abdominal pain and overall composite response, defined as response on both abdominal pain and stool consistency end points. Overall stool consistency response rates were 56.0% and 35.3% (RHB-102 vs placebo, P = 0.036) and similar among male and female patients. Overall pain response (50.7% vs 39.2%) and composite response rates (40.0% vs 25.5%) favored RHB-102, although these differences were not statistically significant. Stool consistency response rates were enhanced in patients with baseline C-reactive protein above the median (2.09 mg/L), 59.5%, vs 23.1% (P = 0.009). Overall rates of adverse events were similar, with a higher rate of constipation in RHB-102 patients (13.3% vs 3.9%) that resolved rapidly on withholding treatment. RHB-102 was effective and safe in the treatment of men and women with IBS-D. Baseline C-reactive protein seemed to be predictive of response.