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

<jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>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.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>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.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>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 [<jats:italic>P</jats:italic> = 0.0005, <jats:italic>P</jats:italic> = 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.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Our study results suggest that 10 mg of elobixibat is a clinically optimal dose for Japanese patients with chronic constipation.</jats:p> </jats:sec><jats:sec> <jats:title>Clinical trial registration number</jats:title> <jats:p>JapicCTI-142608.</jats:p> </jats:sec>