Efficacy, long-term safety, and impact on quality of life of elobixibat in more severe constipation: Post hoc analyses of two phase 3 trials in Japan

Background In two phase 3 trials, elobixibat, a locally acting ileal bile acid transporter inhibitor, resolved constipation and was well tolerated in Japanese patients with chronic constipation. We analyzed the efficacy, safety, and impact on quality of life (QOL) of elobixibat in patients with symptomatically more severe constipation in the two phase 3 trials. Methods This post hoc analysis of elobixibat treatment outcomes included data from a 2-week, randomized, placebo-controlled, phase 3 trial (10 mg/d), and a 52-week, open-label trial (5-15 mg/d) in subgroups with severe constipation defined as <= 2 spontaneous bowel movements (SBMs) and <= 3 Bristol Stool Form Scale score during the second week of the 2-week run-in period. We also analyzed the rates of abdominal pain, diarrhea, and QOL in subgroups according to sex, presence of constipation-predominant irritable bowel syndrome (IBS-C) and side effects. Key Results In patients with severe constipation, there was significant improvement in the 10 mg elobixibat group compared to the placebo group in change in SBMs from baseline at week 1 (primary endpoint) of the 2-week trial. The differences between groups were reduced in patients with more severe constipation. Increasing the dose to 15 mg was effective for more severe constipation in improving the number of SBMs per week in the 52-week trial. Overall, elobixibat was well tolerated and improved QOL scores, irrespective of gender, presence of IBS-C or side effects. Conclusions & Inferences Elobixibat is effective for symptomatically severe constipation, is well tolerated and improves QOL, irrespective of potentially confounding patient characteristics.