title: Optimal dose of ramosetron in female patients with irritable bowel syndrome with diarrhea: A randomized, placebo-controlled phase II study.
abstract: BACKGROUND
  Previous studies showed that 5 μg of ramosetron, a serotonin (5-hydroxytryptamine: 5-HT)-3 receptor antagonist, is only effective in male patients with irritable bowel syndrome (IBS) with diarrhea (IBS-D). We hypothesized that either dose 1.25, 2.5, or 5 μg of ramosetron would be effective in female patients with IBS-D.
  
  
  METHODS
  This randomized, double-blind, placebo-controlled, phase II dose-finding exploratory trial included 409 female outpatients with IBS-D treated in Japan. They were administered oral placebo (n=102), or 1.25 μg (n=104), 2.5 μg (n=104), or 5 μg (n=99) of ramosetron once daily for 12 weeks after a 1-week baseline period. The primary endpoint was monthly responder rates of global improvement of IBS symptoms in the first month. Secondary endpoints included global improvement in the other months, abdominal pain/discomfort, weekly mean changes in the Bristol Stool Form Scale (BSFS), and IBS-QOL.
  
  
  RESULTS
  Middle dose (2.5 μg) of ramosetron significantly improved abdominal pain/discomfort at second month (62.5%, P=.002), third month (60.6%, P=.005), and the last evaluation point (63.5%, P=.002) and weekly BSFS (P<.05) except at Week 8, 11, and 12 than placebo. IBS-QOL did not change. Ramosetron induced more constipation than placebo.
  
  
  CONCLUSIONS
  The trial suggested that 2.5 μg of ramosetron is the most effective and least harmful option for treating female patients with IBS-D (Clinicaltrials.gov ID: NCT01274000).
authors.affiliation: Department of Behavioral Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Fukudo
authors.affiliation: Sakura Life Clinic, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Matsueda
authors.affiliation: Department of Gastroenterology, Kawasaki Medical University, Kurashiki, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Haruma
authors.affiliation: Japan-Asia Planning & Administration, Medical & Development, Astellas Pharma Inc., Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Ida
authors.affiliation: Japan-Asia Clinical Development 2, Development, Astellas Pharma Inc., Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Hayase
authors.affiliation: Japan-Asia Clinical Development 2, Development, Astellas Pharma Inc., Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Akiho
authors.affiliation: Japan-Asia Data Science, Development, Astellas Pharma Inc., Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Nakashima
authors.affiliation: Kurokawa Hospital, Miyagi, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Hongo
mesh_terms: D015746:Abdominal Pain / Q000188:drug therapy; D000328:Adult; D001562:Benzimidazoles / Q000008:administration & dosage*; D003967:Diarrhea / Q000150:complications / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000150:complications / Q000188:drug therapy*; D008875:Middle Aged; D012702:Serotonin Antagonists / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D001562:Benzimidazoles; D012702:Serotonin Antagonists; C071315:ramosetron
keywords: 5-hydroxytryptamine; abdominal discomfort; abdominal pain; global improvement; stool consistency