Efficacy and Safety of Elobixibat in Parkinson's Disease with Chronic Constipation: CONST‐PD Study

Abstract

AbstractBackgroundChronic constipation is a common digestive complication of Parkinson's disease (PD).ObjectivesTo verify the usefulness of elobixibat, an ileal bile acid transporter inhibitor, for chronic constipation in PD.MethodsThis double‐blind, placebo‐controlled study consisted of a 2‐week observation/washout period and a 4‐week treatment period. All patients received a Bowel Movement Diary at Week ‐2 and were allocated to elobixibat (10 mg) or placebo at Week 0. Patients visited at Weeks 2 and 4 to report daily spontaneous bowel movements (SBM), stool form, drug use, quality of life (QOL), and safety. Changes in these parameters were assessed.ResultsThe study included 38 patients in the elobixibat group and 39 in the placebo group, and 37 each completed the study. SBM frequency/week (mean ± standard deviation) increased significantly from 4.2 ± 2.6 at baseline to 5.9 ± 3.2 at Week 4 in the elobixibat group (P = 0.0079), but not in the placebo group (4.5 ± 2.7 to 5.3 ± 3.5; P = 0.0889). On analysis of covariance, the between‐group difference in frequency changes at Week 4 (primary endpoint) was not significant after adjustment by baseline and sex (point estimate = 0.8; 95% confidence interval = −0.57 to 2.09, P = 0.2601), although a significant difference (P = 0.0011) was evidenced at Week 1 by a similar analysis. Stool form and scores of satisfaction and stigma were improved by elobixibat. Adverse events were as previously reported.ConclusionsElobixibat improved the SBM frequency, though the defined primary endpoint was not evidenced. QOL parameters (stool consistency and treatment satisfaction) were also improved. Elobixibat may have therapeutic benefits in PD patients suffering from chronic constipation.Trial Registration InformationTrial Registration Number: JPRN‐jRCTs031200172 (submitted: October 26, 2020; first patient enrolment: December 23, 2020; https://jrct.niph.go.jp/en-latest-detail/jRCTs031200172).