Effect of single and multiple doses of elobixibat, an ileal bile acid transporter inhibitor, on chronic constipation: A randomized controlled trial

Abstract

AimsElobixibat is a minimally absorbed ileal bile acid transporter inhibitor. This study aimed to investigate the safety, tolerability, efficacy, pharmacokinetics and pharmacodynamics of elobixibat in Japanese patients with chronic constipation.MethodsThis study consisted of single‐dose and multiple‐dose tests with a dose‐escalating design. Sixty patients including females and males were randomized into five dose levels of elobixibat (2.5, 5, 10, 15 or 20 mg, n = 10 per level) and corresponding placebo (n = 2 per group). A crossover design was used to examine food effect in single‐dose test. Patients received test tablets once daily for 14 days in multiple‐dose test. We assessed pharmacokinetic‐dose proportionality, levels of serum high‐ and low‐density lipoprotein cholesterol and plasma 7α‐hydroxy‐4‐cholesten‐3‐one (C4), food effect and sex‐specific effect. Adverse events and bowel functions such as bowel movements, stool consistency and straining were also evaluated.ResultsFood consumption reduced systemic exposure by around 80% [e.g. least squares mean (ratio of breakfast/no breakfast) maximum plasma concentration: 0.2085 (90% confidence interval, 0.1371–0.3172) at 15 mg] while increased plasma C4 level (P < 0.001). In the multiple‐dose test, elobixibat reduced low‐density lipoprotein cholesterol and increased C4 whilst unaltering high‐density lipoprotein cholesterol level. The increased spontaneous bowel movement frequency was correlated with higher dosage and higher C4 level (R2 = 0.5929 at Week 2). Adverse events were mainly gastrointestinal symptoms, most of which were mild.ConclusionsElobixibat should be taken before breakfast. Once‐daily administration of elobixibat was found to be safe and tolerated up to 20 mg in female and male patients with chronic constipation.

Elobixibat alleviates chronic constipation in hemodialysis patients: a questionnaire-based study

“…Elobixibat was reported to lower serum LDL cholesterol by approximately 10% [29]. However, in this study, the LDL and HDL levels did not change significantly after elobixibat administration for 4 weeks.…”

Bile pigment in small-bowel water content reflects bowel habits: a retrospective analysis of a capsule-endoscopy imaging series

“…Elobixibat is a minimally absorbed ileal bile-acid-transporter inhibitor and is used clinically to treat constipation by augmenting the level of BA that flows to the colon. Increased dosage causes an increased frequency of diarrhea and corresponding abdominal symptoms [38], as BA can affect stool consistency or cause liquefying of the stool.…”

Rationale and design of a randomised, double-blind, placebo-controlled, parallel-group, investigator-initiated phase 2a study to investigate the efficacy and safety of elobixibat in combination with cholestyramine for non-alcoholic fatty liver disease

“…The pharmacodynamic assessment of EXB in a Japanese phase I study showed decreased serum low-density lipoprotein cholesterol (LDL-C) levels in groups that received repeated doses of ≥5 mg EXB. 8 In addition, a study on NAFLD mouse model reported that treatment with another IBAT inhibitor (IBATi) promoted BA biosynthesis from cholesterol, which accumulated in the liver of mice that received a high-fat diet. 9 Furthermore, converting the BA pool in the liver into hydrophobic BAs decreases hepatic cholesterol accumulation via farnesoid X receptor (FXR) activation, thereby improves the NAFLD status.…”