Investigating the efficacy and safety of elobixibat, an ileal bile acid transporter inhibitor, in patients with Parkinson’s disease with chronic constipation: a multicentre, placebo-controlled, randomised, double-blind, parallel-group study (CONST-PD)

Abstract

IntroductionChronic constipation worsens the quality of life (QOL) of patients with Parkinson’s disease (PD). Elobixibat, an ileal bile acid transporter inhibitor, is a useful laxative, but its effect on chronic constipation in patients with PD remains unclear. Therefore, we designed a placebo-controlled, randomised, double-blind study to investigate the efficacy and safety of elobixibat in patients with PD with chronic constipation.Methods and analysisThe study will consist of 2-week observation and 4-week treatment periods. Patients with clinically established PD will record the status of spontaneous bowel movements and use of rescue medications/concomitant medications in a Bowel Movement Diary from the start of the observation period at visit 1 (week −2). At visit 2 (week 0), patients will be assessed for final registration based on the diary records and physical examinations, and allocated to either the elobixibat or placebo group. Daily intake of the investigational drug will be recorded in the diary. Patients will undergo laboratory tests and answer constipation-related, PD-related and QOL-related questionnaires at visits 2 and 4 (week 4). Subjective symptoms and objective findings will be collected at visits 2, 3 (week 2) and 4. Since patients’ motor function might be improved by treatment of constipation, the use of dopamine preparations will also be monitored. Bowel movement data and other parameters will be compared between groups.Safety information will be collected as adverse events, specifically focusing on those occurring in association with study conduct.Ethics and disseminationThis study will be conducted in accordance with the Helsinki Declaration, the Clinical Trials Act of the Japan Ministry of Health, Labour and Welfare, and related laws and regulations. The study was approved by the Juntendo University Certified Review Board. The results will be disseminated through an online study registry (Japan Registry of Clinical Trials), presented at scientific conferences, and published in medical journals.Trial registration numberJPRN-jRCTs031200172; Pre-results.

Probiotics for constipation in Parkinson’s: A systematic review and meta-analysis of randomized controlled trials

“…However, The International Parkinson and Movement Disorder Society (MDS) Evidence‐Based Medicine (EBM) Committee only recommended Macrogol, Lubiprostone, and Probiotics/Prebiotic fibers as three medicines/foods used to treat PD-related constipation ( Hatano et al., 2022 ). Chronic constipation is the earliest symptom of PD prodrome and one of the universal NMS in PD ( Kalia and Lang, 2015 ).…”

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

“…Drug allocation to either Elo or its indistinguishable, matched placebo (Pbo) was based on a stratified, permuted block method with sex as an allocation factor. Eligible patients were randomized and double‐blinded via an Interactive Web Response System (IWRS) 16 …”

“…Once‐daily, preprandial intake of the investigational drug was scheduled during the 4‐week treatment period. The patients visited their institutional sites twice more (Week 2/Visit 3 and Week 4/Visit 4) 16 . One‐tablet dose adjustment was allowed at the discretion of investigator or subinvestigator, hereinafter collectively termed (sub)investigator, or individual patient, in case of no spontaneous bowel movements (SBMs), or excessive movements or discomfort observed during the next 24 h. Patients were allowed to interrupt intake of the investigational drug due to an adverse event (AE).…”

“…Concomitant medications were given to the patients for parkinsonism throughout the study period, except for Duodopa pump therapy (Abbvie, North Chicago, IL, USA) with levodopa/carbidopa hydrate intestinal gel. Bisacodyl suppositories (10 mg, once daily; given at Week −2) were allowed for rescue purpose in case of no bowel movement for ≥72 consecutive hours, and no other agents for constipation were allowed in this study 16 . Prohibited drugs or measures were defined throughout the entire period to avoid potential effects on the study results and data interpretation 16 …”

Management of Gastrointestinal Symptoms in Parkinson’s Disease

“…In addition, an ileal bile acid transporter inhibitor, elobixibat, is being studied in a Japanese multicenter double-blind randomized controlled trial in patients with PD with constipation 110 . Elobixibat is currently approved in certain Asian countries for chronic constipation, and is not yet available in the United States.…”