Safety and efficacy of elobixibat for chronic constipation: results from a randomised, double-blind, placebo-controlled, phase 3 trial and an open-label, single-arm, phase 3 trial

Nakajima, Atsushi; Seki, Mitsunori; Taniguchi, Shinya; Ohta, Akira; Gillberg, Per Göran; Mattsson, Jan P.; Camilleri, Michael

doi:10.1016/s2468-1253(18)30123-7

Cited by 125 publications

(167 citation statements)

References 27 publications

Supporting

Mentioning

153

Contrasting

Unclassified

Order By: Relevance

“…Table shows the SBMs or CSBMs baseline characteristics of the included populations or subgroups that satisfied the criteria for severe constipation in the second week of the 2‐week run‐in period before the 2‐week and 52‐week trials. The data of the included participants were derived from those previously reported . As shown, both SBMs and CSBMs between placebo and elobixibat in each subgroup were well balanced except for CSBMs in patients with not severe constipation.…”

Section: Resultsmentioning

confidence: 99%

“…All efficacy analyses, including post hoc analyses, were based on a modified intention‐to‐treat population (ie, defined as patients who received at least one dose of the study drug) . Subgroup analysis of efficacy was performed among subgroups by IBS‐C diagnosis (with and without), sex, age (<65 and ≥65 years), or more severe constipation.…”

Section: Methodsmentioning

confidence: 99%

“…The prespecified secondary endpoints were change in frequency of complete SBMs (CSBMs; ie, SBMs associated with a sense of complete evacuation), proportions of weekly SBM and CSBM responders (defined as three or more SBMs or CSBMs per week and an increase of at least one SBM or CSBM per week from baseline), time to the first SBM, and so on. As a post hoc secondary endpoint, we included time to first CSBM . The subgroup post hoc analyses of efficacy were not prespecified except for prespecified subgroup analysis of the primary endpoint among subgroups by IBS‐C diagnosis, sex, and age.…”

Section: Methodsmentioning

confidence: 99%

“…Complementing the existing research, our research groups have recently published the results of phase 1, 2, and 3 trials in Japan . Among these, there have been two phase 3 trials sharing similar methodologies.…”

Section: Introductionmentioning

confidence: 99%

“…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. The first was a randomized, double-blind, placebocontrolled, 2-week trial in Japanese patients with chronic constipation, which showed that 10 mg of elobixibat once daily was safe and effective.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

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

View full text Add to dashboard Cite

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.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

View full text Add to dashboard Cite

show abstract

Diagnosis and Treatment of Irritable Bowel Syndrome

Camilleri

2021

JAMA

Self Cite

184

135

View full text Add to dashboard Cite

ImportanceThe prevalence of irritable bowel syndrome (IBS) in the United States is between 7% and 16%, most common in women and young people, with annual direct costs estimated at more than $1 billion dollars in the United States. Traditionally, the diagnosis of IBS has been based on the positive identification of symptoms that correlate with several different syndromes associated with disorders such as IBS diarrhea, IBS constipation, functional diarrhea, functional constipation, chronic functional abdominal pain, or bloating. Several peripheral and central mechanisms initiate gastrointestinal motor and sensory dysfunctions leading to IBS symptoms. Those dysfunctions may require evaluation in patients whose symptoms do not respond to first-line treatments.ObservationsValidation studies of consensus symptom-based criteria have identified deficiencies that favor a simpler identification of the predominant symptoms of abdominal pain, bowel dysfunction, and bloating and exclusion of alarm symptoms such as unintentional weight loss, rectal bleeding, or recent change in bowel function. Symptom-based diagnosis of IBS is enhanced with additional history for symptoms of somatoform and psychological disorders and alarm symptoms, physical examination including digital rectal examination, and screening tests to exclude organic disease (by measuring hemoglobin and C-reactive protein concentrations). The initial treatment plan should include patient education, reassurance, and first-line treatments such as fiber and osmotic laxatives for constipation, opioids for diarrhea, antispasmodics for pain and for management of associated psychological disorders. For patients who do not respond to those IBS treatments, testing for specific functional disorders may be required in a minority of patients with IBS. These disorders include rectal evacuation disorder, abnormal colonic transit, and bile acid diarrhea. Their identification is followed by individualized treatment, such as pelvic floor retraining for rectal evacuation disorders, sequestrants for bile acid diarrhea, and secretory agents for constipation, although there is only limited evidence that this individualized management approach is effective.Conclusions and RelevanceAdvances in the identification of specific dysfunctions as causes of individual symptoms in the “IBS spectrum” leads to the potential to enhance the diagnosis and management of symptoms for the majority of patients for whom first-line therapies of IBS and management of comorbid psychological disorders are insufficient.

show abstract

Intestinal Absorption of Bile Acids in Health and Disease

Ticho

Malhotra

Dudeja

et al. 2019

Comprehensive Physiology

148

108

View full text Add to dashboard Cite

The intestinal reclamation of bile acids is crucial for the maintenance of their enterohepatic circulation. The majority of bile acids are actively absorbed via specific transport proteins that are highly expressed in the distal ileum. The uptake of bile acids by intestinal epithelial cells modulates the activation of cytosolic and membrane receptors such as the farnesoid X receptor (FXR) and G protein-coupled bile acid receptor 1 (GPBAR1), which has a profound effect on hepatic synthesis of bile acids as well as glucose and lipid metabolism. Extensive research has focused on delineating the processes of bile acid absorption and determining the contribution of dysregulated ileal signaling in the development of intestinal and hepatic disorders. For example, a decrease in the levels of the bile acid-induced ileal hormone FGF15/19 is implicated in bile acidinduced diarrhea (BAD). Conversely, the increase in bile acid absorption with subsequent overload of bile acids could be involved in the pathophysiology of liver and metabolic disorders such as fatty liver diseases and type 2 diabetes mellitus. This review article will attempt to provide a comprehensive overview of the mechanisms involved in the intestinal handling of bile acids, the pathological implications of disrupted intestinal bile acid homeostasis, and the potential therapeutic targets for the treatment of bile acid-related disorders.

show abstract

Safety and efficacy of elobixibat for chronic constipation: results from a randomised, double-blind, placebo-controlled, phase 3 trial and an open-label, single-arm, phase 3 trial

Cited by 125 publications

References 27 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

Diagnosis and Treatment of Irritable Bowel Syndrome

Intestinal Absorption of Bile Acids in Health and Disease

Contact Info

Product

Resources

About