Long-term Elobixibat for Chronic Constipation (TANK-27)

Long-term Efficacy and Safety of Elobixibat for Chronic Constipation: a Multicenter, Randomised, Double-blind, Placebo-controlled Trial.

In this double-blind comparative study, AJG533 (elobixibat) 10 mg or AJG533 placebo was orally administered once daily before meals for 12 weeks in patients with chronic constipation, and the primary endpoint was the change from Week 2 of the observation period in the number of complete spontaneous bowel movements (CSBM) at Week 12 of the treatment period. The primary endpoint was the change in the number of complete spontaneous bowel movements (CSBM) from Week 2 of the observation period.

Study Overview

• Status: Recruiting
• Conditions: Chronic Constipation
• Intervention / Treatment: Drug: Elobixibat 10mg; Drug: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Takaomi Kessoku, M.D., PhD.; Phone Number: 2640 +81-45-787-2800; Email: kessoku-tho@umin.ac.jp
• Study Contact Backup: Name: Atsushi Nakajima, M.D., PhD.; Phone Number: 2640 +81-45-787-2800; Email: nakajima-tky@umin.ac.jp

Study Locations

• Japan
  • Kanagawa
    • Yokohama, Kanagawa, Japan, 236-0004
      • Recruiting
      • Yokohama City University
      • Contact: Takaomi Kessoku, MD., PhD.; Phone Number: 2640 +81-45-787-2800; Email: kessoku-tho@umin.ac.jp

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients diagnosed with chronic constipation by the "Rome IV" criteria for chronic constipation
• Age: 20 years old or older and up to 85 years old (at the time of obtaining consent)
• Gender: any gender
• outpatients
• Patients who can obtain written consent
• Patients who can record their defecation, etc. in the patient's diary

At the time of allocation (dosing initiation criteria)

• Spontaneous bowel movements (SBM)* not more than 6 times during the 2-week observation period before the start of treatment
• Patients with no soft or watery stools (Bristol Stool Shape Scale 6 or 7) in spontaneous bowel movements during the 2-week observation period before the start of treatment.
• Patients who have not used concomitantly prohibited drugs or therapies during the observation period.

Exclusion Criteria:

• Patients with organic constipation or patients with suspected organic constipation.
• Patients with or suspected of having functional ileus.
• Patients with or suspected of having an inguinal hernia.
• Patients with a history of open surgery within 12 weeks before obtaining consent (excluding appendicitis resection).
• Patients with a history of surgical or endoscopic procedures related to cholecystectomy and papillotomy.
• Patients with complications of malignancy.
• Pregnant women, lactating women, women who may be currently pregnant, or patients who cannot consent to use contraception while participating in the study.
• Patients with serious renal, liver, or cardiac disease.
• Patients who are allergic to this study drug.
• Patients who have previously taken Goufis tablets (elobixibat).
• Patients with contraindications to rescue drugs (bisacodyl suppositories and prusenide tablets).
• Patients who are participating in another clinical study or who were participating in another clinical study within 4 weeks before consent was obtained, excluding observational studies.
• Patients who are judged by the principal investigator or sub-physician to be inappropriate for conducting this research.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Elobixibat; AJG533 (elobixibat) 10 mg orally once a day before meals for 12 weeks	Drug: Elobixibat 10mg; Patients with chronic constipation are administered Elobixibat 10mg for 12 weeks; Other Names: AJG533 10 mg
Placebo Comparator: Placebo; AJG533 placebo orally once a day before meals for 12 weeks	Drug: Placebo; Patients with chronic constipation are administered placebo for 12 weeks; Other Names: AJG533 placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the number of complete spontaneous bowel movements at week 12	Change in the number of complete spontaneous bowel movements at week 12 of the treatment period from week 2 of the observation period. *Spontaneous defecation without residual sensation.	Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the number of complete spontaneous bowel movements in each week of the treatment period.	Change in the number of complete spontaneous bowel movements in each week of the treatment period.	Each Week 1-11
Change in the number of spontaneous bowel movements in each week of the treatment.	Change in the number of spontaneous bowel movements in each week of the treatment.	Each Week 1-11
Proportion of responders** in the number of SBMs during each week.	Proportion of responders** in the number of spontaneous bowel movements (SBMs) during each week of the treatment period. **In this study, we will investigate the effect of the treatment on the number of SBMs of a subject who has at least one more SBM per week than in the second week of the observation period, and at least three times per week.	Each Week 1-11
Proportion of responders** in the number of CSBMs during each week.	Proportion of responders** in the number of complete spontaneous a bowel movements (CSBMs) during each week of the treatment period. **In this study, we will investigate the effect of the treatment on the number of CSBMs of a subject who has at least one more CSBMs per week than in the second week of the observation period, and at least three times per week.	Each Week 1-11
The rate of a responder in the number of CSBM during the treatment period.	Definition of Responder: Patients with 3 or more CSBM per week and 1 or more CSBM per week from baseline for 9 weeks out of the entire treatment period (12 weeks), including at least 3 weeks in the treatment period weeks 9 to 12.	Week 12
Percent change in fecal hardness based on the Bristol Stool Quality Scale at each week.	Percent change in fecal hardness from week 2 of the observation period based on the Bristol Stool Quality Scale at each week of the treatment period. the minimum is 1 and maximum values, is 7.Higher scores mean a better outcome.	Each Week 1-11
The percentage of change in the presence or absence of residual sensation at each week.	The percentage of change from week 2 of the observation period in the presence or absence of residual sensation at each week of the treatment period.	Each Week 1-11
Percent change in the degree of twitching at each week.	Percent change from week 2 of the observation period in the degree of twitching at each week of the treatment period.	Each Week 1-11
The percentage of change in the presence or absence of bowel movements at each week.	The percentage of change in the presence or absence of bowel movements at each week of the treatment period from week 2 of the observation period.	Each Week 1-11
Change in Japanese Patient assessment of constipation quality of life score	Change in Japanese Patient assessment of constipation quality of life score at 4 and 12 weeks of the treatment period from the baseline (V2) of the study drug.the minimum is 0 and maximum values is 4.Lower scores mean a better outcome.	Week 4, 12
The changes in occupancy rate of intestinal microbiota.	At 4 weeks and 12 weeks of the treatment period, the changes in occupancy rate of intestinal microbiota in feces from before the start of the study drug (V2) are examined.	Week 4, 12
The change in absolute values rates in blood and fecal bile acids.	At 4 weeks and 12 weeks of the treatment period, the change in absolute values in blood and fecal bile acids from before the start of the study drug (V2) are examined.	Week 4, 12
The change in absolute values for organic acids.	At 4 weeks and 12 weeks of the treatment period, the change in absolute values for organic acids in feces from before the start of the study drug (V2) are examined.	Week 4, 12
The change in absolute values of amino acids in blood and feces.	At 4 weeks and 12 weeks of the treatment period, the change in absolute values of amino acids in blood and feces. from before the start of the study drug (V2) are examined.	Week 4, 12
The change in amount blood C4.	At 4 weeks and 12 weeks of the treatment period, the change in amount blood C4 from before the start of the study drug (V2) are examined.	Week 4, 12

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events.	Incidence of adverse events.	Each Week 1-11

Collaborators and Investigators

• Sponsor: Yokohama City University
• Investigators: Principal Investigator: Takaomi Kessoku, M.D., PhD., Yokohama City University

Publications and helpful links

General Publications

• Nakajima A, Seki M, Taniguchi S, Ohta A, Gillberg PG, Mattsson JP, Camilleri M. 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. Lancet Gastroenterol Hepatol. 2018 Aug;3(8):537-547. doi: 10.1016/S2468-1253(18)30123-7. Epub 2018 May 25.
• Tanaka K, Kessoku T, Yamamoto A, Takahashi K, Kasai Y, Ozaki A, Iwaki M, Kobayashi T, Yoshihara T, Misawa N, Kato T, Arimoto J, Fuyuki A, Sakai E, Higurashi T, Chiba H, Hosono K, Yoneda M, Iwasaki T, Kurihashi T, Nakatogawa M, Suzuki A, Taguri M, Oyamada S, Ariyoshi K, Kobayashi N, Ichikawa Y, Nakajima A. Rationale and design of a multicentre, 12-week, randomised, double-blind, placebo-controlled, parallel-group, investigator-initiated trial to investigate the efficacy and safety of elobixibat for chronic constipation. BMJ Open. 2022 May 30;12(5):e060704. doi: 10.1136/bmjopen-2021-060704.

Study record dates

Study Major Dates

• Study Start (Actual): August 6, 2021
• Primary Completion (Anticipated): June 30, 2023
• Study Completion (Anticipated): November 30, 2023

Study Registration Dates

• First Submitted: February 28, 2021
• First Submitted That Met QC Criteria: March 4, 2021
• First Posted (Actual): March 5, 2021

Study Record Updates

• Last Update Posted (Actual): January 5, 2023
• Last Update Submitted That Met QC Criteria: January 3, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: Chronic constipation; Elobixibat; 12 week; Complete spontaneous bowel movement
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Constipation
• Other Study ID Numbers: jRCTs031200363

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No