Randomized, placebo-controlled, phase IV pilot study of ramosetron to evaluate the co-primary end points in male patients with irritable bowel syndrome with diarrhea

BACKGROUND Global assessment allows patients to assess improvement in multiple irritable bowel syndrome (IBS) symptoms. However, it was deemed important to assess "clinically meaningful improvements, focusing on the patient's chief complaint and the severity of major IBS symptoms" in addition to global assessment to show how ramosetron is effective for individual IBS symptoms. This is a pilot study to explore clinical endpoints focusing on the chief complaint of patients with IBS with diarrhea (IBS-D). METHODS The same database was used in a previously reported post-marketing phase IV, randomized placebo-controlled pilot trial in male patients with IBS-D. The hypothesis is completely different from that of the other study. Patients with IBS-D diagnosed according to Rome III criteria were given either 5 μg of ramosetron (n = 47) or placebo (n = 51) once daily for 12 weeks after a one-week baseline period. To explore and examine endpoints that allow evaluation of "clinically meaningful improvements focusing on the patient's chief complaint," the chief complaint and its relief by this study drug were assessed in this exploratory study. RESULTS Rates of patients with abdominal pain/discomfort, stool form and stool frequency which patients had as a chief complaint before administration were 34.0, 19.1 and 25.5%, respectively, in the ramosetron 5 μg group and 42.0, 18.0, and 20.0% in the placebo group. Responder rates for improvement in symptoms of the chief complaint that patients had before administration were 53.2% in the ramosetron 5 μg group and 42.0% in the placebo group at the last point. The greatest symptomatic improvement in the chief complaint in the ramosetron 5 μg group compared to the placebo group was shown with respect to stool consistency. Bristol Stool Form Scale (BSFS) scores were significantly lower in the ramosetron group than in the placebo group (4.36 ± 1.195 vs 4.85 ± 0.890 at the last point, P = 0.027) throughout the treatment period, except at week 6. CONCLUSIONS Ramosetron acted most effectively on stool consistency. Improvement in stool consistency is considered to be a clinically meaningful endpoint in showing how ramosetron was effective for individual IBS symptoms. (Clinicaltrials.gov ID: NCT00918411. Registered 9 June 2009).