Determining an optimal clinical dose of elobixibat, a novel inhibitor of the ileal bile acid transporter, in Japanese patients with chronic constipation: a phase II, multicenter, double-blind, placebo-controlled randomized clinical trial

摘要

Abstract Background Elobixibat is an oral treatment candidate for chronic constipation with a novel mechanism of action via inhibition of the ileal bile acid transporter. We performed this randomized, double-blind, placebo-controlled, dose-finding phase IIb study in Japanese patients with chronic constipation to determine the optimal clinical dose of elobixibat. Methods Japanese patients with chronic constipation were randomized to receive elobixibat (5, 10, or 15?mg) or placebo once daily for 2?weeks. The primary efficacy endpoint was the change from baseline in frequency of spontaneous bowel movements at Week?1 of treatment. Secondary endpoints and adverse events were also examined. Results Among 226 patients who provided informed consent, 163 patients were randomized and included in the full analysis set. In the 10- and 15-mg groups, frequency of spontaneous bowel movements (±standard deviation) were significantly higher than baseline (5.7?±?4.2 and 5.6?±?3.5?times per week, respectively, compared with 2.6?±?2.9?times per week in the placebo group [ P ?=?0.0005, P ?=?0.0001, respectively]). Subgroup analysis indicated that elobixibat was equally effective in patients with or without constipation-predominant irritable bowel syndrome. Common adverse events included mild abdominal pain and diarrhea in the elobixibat groups; no serious or severe adverse events occurred. Elobixibat was well tolerated at once-daily oral doses up to 15?mg for 2?weeks. Conclusions Our study results suggest that 10?mg of elobixibat is a clinically optimal dose for Japanese patients with chronic constipation. Clinical trial registration number JapicCTI-142608.