Elobixibat, an ileal bile acid transporter inhibitor, induces giant migrating contractions during natural defecation in conscious dogs

Taniguchi, Shinya; Yano, Tetsuo; Imaizumi, Masakazu; Manabe, Noriaki

doi:10.1111/nmo.13448

Cited by 19 publications

(19 citation statements)

References 26 publications

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“…Moreover, elobixibat was well tolerated in terms of abdominal pain and diarrhea, which were observed with similar incidence in those with IBS‐C diagnosis compared to the rest of the cohort; similarly, there were no significant differences between the two groups in the JPAC‐QOL scores in the 52‐week trial. It has been speculated that the abdominal pain experienced by some while taking elobixibat might be different from that of IBS because elobixibat induces HAPCs, which might be associated with mass movements and short‐lived pain due to the temporary increase in colonic pressure. Other potential mechanisms for the abdominal pain may result from the increased colonic BAs, since BAs reduced rectal sensory thresholds in humans and increased mucosal permeability in rabbits .…”

Section: Discussionmentioning

confidence: 99%

“…Increased concentrations of BAs in the colon then enhance colonic transit by stimulating fluid and electrolyte secretion and by inducing high‐amplitude propagated contractions (HAPCs), as demonstrated experimentally by the effects of intraluminal chenodeoxycholate . In phase 2 clinical trials in North America, elobixibat significantly accelerated colonic transit and improved bowel function; in dogs, it successfully induced HAPCs …”

Section: Introductionmentioning

confidence: 99%

“…11 In phase 2 clinical trials in North America, elobixibat significantly accelerated colonic transit and improved bowel function 12,13 ; in dogs, it successfully induced HAPCs. 14 Complementing the existing research, our research groups have recently published the results of phase 1, 2, and 3 trials in Japan. [15][16][17] Among these, there have been two phase 3 trials sharing similar methodologies.…”

Section: Introductionmentioning

confidence: 99%

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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

Nakajima

Taniguchi

Kurosu

et al. 2019

Neurogastroenterology Motil

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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

Nakajima

Taniguchi

Kurosu

et al. 2019

Neurogastroenterology Motil

Self Cite

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“…Elobixibat is a new laxative that inhibits the ileal bile acid transporter expressed in the epithelial cells of the terminal ileum; it inhibits bile acid reabsorption and increases the amount of bile acids flowing into the colon lumen [10]. Owing to the increased amount of bile acids in the colon, elobixibat increases water secretion into the large intestinal lumen and induces high amplitudepropagating pressure wave [11]. In other words, elobixibat has dual actions, which are water secretion into the large intestine and promotion of bowel movement.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of elobixibat in hemodialysis patients with chronic constipation: a retrospective study

Shono

Hyakutake

2020

Ren Replace Ther

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Background: Hemodialysis patients are likely to develop constipation as a complication due to food and fluid restrictions. Elobixibat is a new laxative that inhibits the ileal bile acid transporter expressed in the terminal ileum, suppresses bile acid reabsorption, increases the amount of bile acid flowing into the colon lumen, and promotes water secretion in the colon and colon motility. In this study, we examined the efficacy and safety of elobixibat in maintenance hemodialysis patients with chronic constipation. Methods: In a study conducted on maintenance hemodialysis patients with chronic constipation, comparisons were conducted retrospectively based on constipation symptoms such as the frequency of spontaneous bowel movements before elobixibat treatment and 12 weeks after the administration of elobixibat, as well as based on blood electrolyte levels. Results: The study was conducted on 23 patients, 19 of whom were subjected to treatment efficacy analysis. The frequency of spontaneous bowel movements was 2.0 ± 0.7 times/week before administration of elobixibat and reached 4.9 ± 2.3 times/week after 12 weeks of administration. The increase started after 1 week of treatment. Elobixibat treatment improved the constipation score (baseline, 10.4 ± 3.2; after 12 weeks, 5.7 ± 3.2), the Bristol Stool Form Scale (baseline, 2.2 ± 1.0; after 12 weeks, 4.2 ± 0.7), and patient satisfaction regarding defecation (baseline, 2.9 ± 0.9; after 12 weeks, 1.7 ± 1.1). The interdialytic weight gain (IDWG) was 5.68 ± 0.82% before initiation of treatment and decreased to 4.54 ± 1.34% after 12 weeks. The serum inorganic phosphorus (IP) levels were 5.68 ± 1.25 mg/dL and decreased to 4.93 ± 1.10 mg/dL after 12 weeks. Conclusions: Elobixibat was effective in improving constipation symptoms in maintenance hemodialysis patients with chronic constipation. Elobixibat also improved dialysis-related laboratory test results, such as a decrease in serum IP levels and IDWG.

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“…Thus, elobixibat induces colonic peristalsis, leading to a strong and fast defecation-promoting effect mediated by the above dual functions. 9 , 10 , 11 In the Japanese Phase III study of patients with chronic constipation, pre-breakfast administration of elobixibat improved spontaneous defecation frequency and Bristol Stool Form Scale (BSFS) scores compared with placebo. Furthermore, long-term sustainability of the effect has been confirmed for 52 weeks in long-term administration studies.…”

Section: Introductionmentioning

confidence: 99%

Uncontrolled, Open-Label Pre-Dinner Administration of Elobixibat in Japanese Adults with Chronic Constipation: A Retrospective Chart Review

Odaka¹,

Tominaga

2020

Current Therapeutic Research

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Elobixibat, an ileal bile acid transporter inhibitor, induces giant migrating contractions during natural defecation in conscious dogs

Abstract: Elobixibat induces bowel movements faster than sennoside through a different mechanism. Elobixibat locally inhibits IBAT in the ileal lumen, leading to elevated fecal BAs in the colon and induced mild GMCs during defecation.

Cited by 19 publications

References 26 publications

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

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

Efficacy and safety of elobixibat in hemodialysis patients with chronic constipation: a retrospective study

Uncontrolled, Open-Label Pre-Dinner Administration of Elobixibat in Japanese Adults with Chronic Constipation: A Retrospective Chart Review

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