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

Kosuke Tanaka, Takaomi Kessoku, Atsushi Yamamoto, Kota Takahashi, Yuki Kasai, Anna Ozaki, Michihiro Iwaki, Takashi Kobayashi, Tsutomu Yoshihara, Noboru Misawa, Takayuki Kato, Jun Arimoto, Akiko Fuyuki, Eiji Sakai, Takuma Higurashi, Hideyuki Chiba, Kunihiro Hosono, Masato Yoneda, Tomoyuki Iwasaki, Takeo Kurihashi, Machiko Nakatogawa, Ayao Suzuki, Masataka Taguri, Shunsuke Oyamada, Keisuke Ariyoshi, Noritoshi Kobayashi, Yasushi Ichikawa, Atsushi Nakajima, Kosuke Tanaka, Takaomi Kessoku, Atsushi Yamamoto, Kota Takahashi, Yuki Kasai, Anna Ozaki, Michihiro Iwaki, Takashi Kobayashi, Tsutomu Yoshihara, Noboru Misawa, Takayuki Kato, Jun Arimoto, Akiko Fuyuki, Eiji Sakai, Takuma Higurashi, Hideyuki Chiba, Kunihiro Hosono, Masato Yoneda, Tomoyuki Iwasaki, Takeo Kurihashi, Machiko Nakatogawa, Ayao Suzuki, Masataka Taguri, Shunsuke Oyamada, Keisuke Ariyoshi, Noritoshi Kobayashi, Yasushi Ichikawa, Atsushi Nakajima

Abstract

Introduction: Chronic constipation (CC) is a functional disorder that negatively impacts the quality of life of patients. This is a protocol for a multicentre, 12-week, randomised, double-blind, placebo-controlled study to test the efficacy and safety of elobixibat (EXB) versus placebo in patients with CC.

Methods and analysis: This will be a multicentre, double-blind, placebo-control, randomised controlled trial. A total of 100 adult patients with CC, diagnosed based on Rome IV criteria, who fulfil the inclusion/exclusion criteria will be enrolled. The patients will be randomly assigned to receive EXB (10 mg) or placebo treatment (n=50 per group). Blood tests and stool sampling will be performed 12 weeks following initiation of treatment and questionnaires will be issued to participants. The primary outcome will be the change in complete spontaneous bowel movements after 12 weeks of administration. The secondary outcomes will include the change in Japanese Patient Assessment of Constipation Quality of Life and absolute serum and faecal bile acid.

Ethics and dissemination: Ethics approval has been obtained from Yokohama City University Certified Institutional Review Board before participant enrolment. The results of this study will be submitted for publication in international peer-reviewed journals and the key findings will be presented at international scientific conferences.

Protocol version: V.3.0, 15 June 2021.

Trial registration number: ClinicalTrials.gov (number NCT04784780).

Keywords: adult palliative care; functional bowel disorders; gastroenterology; palliative care.

Conflict of interest statement

Competing interests: The authors declare that they have competing interests. This study is funded by EA Pharma and Mochida Pharma., which is the distributor of elobixibat in Japan.

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Flowchart of the study design. EXB, elobixibat; PBO, placebo.

References

    1. Belsey JD, Geraint M, Dixon TA. Systematic review and meta analysis: polyethylene glycol in adults with non-organic constipation. Int J Clin Pract 2010;64:944–55. 10.1111/j.1742-1241.2010.02397.x
    1. Wald A, Scarpignato C, Kamm MA, et al. . The burden of constipation on quality of life: results of a multinational survey. Aliment Pharmacol Ther 2007;26:227–36. 10.1111/j.1365-2036.2007.03376.x
    1. Koloski NA, Jones M, Wai R, et al. . Impact of persistent constipation on health-related quality of life and mortality in older community-dwelling women. Am J Gastroenterol 2013;108:1152–8. 10.1038/ajg.2013.137
    1. Salmoirago-Blotcher E, Crawford S, Jackson E, et al. . Constipation and risk of cardiovascular disease among postmenopausal women. Am J Med 2011;124:714–23. 10.1016/j.amjmed.2011.03.026
    1. Sumida K, Molnar MZ, Potukuchi PK, et al. . Constipation and risk of death and cardiovascular events. Atherosclerosis 2019;281:114–20. 10.1016/j.atherosclerosis.2018.12.021
    1. Sundbøll J, Szépligeti SK, Adelborg K, et al. . Constipation and risk of cardiovascular diseases: a Danish population-based matched cohort study. BMJ Open 2020;10:e037080. 10.1136/bmjopen-2020-037080
    1. Chang JY, Locke GR, McNally MA, et al. . Impact of functional gastrointestinal disorders on survival in the community. Am J Gastroenterol 2010;105:822–32. 10.1038/ajg.2010.40
    1. Acosta A, Camilleri M. Elobixibat and its potential role in chronic idiopathic constipation. Therap Adv Gastroenterol 2014;7:167–75. 10.1177/1756283X14528269
    1. Nakajima A, Seki M, Taniguchi S, et al. . 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;3:537–47. 10.1016/S2468-1253(18)30123-7
    1. Fukudo S, Hongo M, Kaneko H, et al. . Lubiprostone increases spontaneous bowel movement frequency and quality of life in patients with chronic idiopathic constipation. J Clin Gastroenterol 2015;13:294–301. 10.1016/j.cgh.2014.08.026
    1. Schulz KF, Altman DG, Moher D, et al. . Consort 2010 statement: updated guidelines for reporting parallel group randomised trials. BMJ 2010;340:c332. 10.1136/bmj.c332
    1. European Medicines Agency . Guideline on the evaluation of medicinal products for the treatment of chronic constipation (including opioid-induced constipation) and for bowel cleansing, 2015.
    1. Lembo AJ, Schneier HA, Shiff SJ, et al. . Two randomized trials of linaclotide for chronic constipation. N Engl J Med 2011;365:527–36. 10.1056/NEJMoa1010863
    1. Issue Information-Declaration of Helsinki. J Bone Miner Res 2018;33:BM i–BM ii. 10.1002/jbmr.3244
    1. Guidelines for safe pharmacotherapy of the elderly. Jpn. J. Geriatr 2015:108–20.
    1. Kienzle-Horn S, Vix J-M, Schuijt C, et al. . Efficacy and safety of bisacodyl in the acute treatment of constipation: a double-blind, randomized, placebo-controlled study. Aliment Pharmacol Ther 2006;23:1479–88. 10.1111/j.1365-2036.2006.02903.x
    1. Kamm MA, Mueller-Lissner S, Wald A, et al. . Oral bisacodyl is effective and well-tolerated in patients with chronic constipation. J Clin Gastroenterol 2011;9:577–83. 10.1016/j.cgh.2011.03.026
    1. Mueller-Lissner S, Kamm MA, Wald A, et al. . Multicenter, 4-week, double-blind, randomized, placebo-controlled trial of sodium picosulfate in patients with chronic constipation. Am J Gastroenterol 2010;105:897–903. 10.1038/ajg.2010.41
    1. Gwee K-A, Ghoshal UC, Gonlachanvit S, et al. . Primary care management of chronic constipation in Asia: the ANMA chronic constipation tool. J Neurogastroenterol Motil 2013;19:149–60. 10.5056/jnm.2013.19.2.149
    1. Mori S, Tomita T, Fujimura K, et al. . A randomized double-blind placebo-controlled trial on the effect of magnesium oxide in patients with chronic constipation. J Neurogastroenterol Motil 2019;25:563–75. 10.5056/jnm18194
    1. Morishita D, Tomita T, Mori S, et al. . Senna versus magnesium oxide for the treatment of chronic constipation: a randomized, placebo-controlled trial. Am J Gastroenterol 2021;116:152–61. 10.14309/ajg.0000000000000942
    1. Ohkubo H, Takatsu T, Yoshihara T, et al. . Difference in defecation desire between patients with and without chronic constipation: a large-scale Internet survey. Clin Transl Gastroenterol 2020;11:e00230. 10.14309/ctg.0000000000000230
    1. Bampton PA, Dinning PG, Kennedy ML, et al. . The proximal colonic motor response to rectal mechanical and chemical stimulation. Am J Physiol Gastrointest Liver Physiol 2002;282:G443–9. 10.1152/ajpgi.00194.2001
    1. Edwards CA, Brown S, Baxter AJ, et al. . Effect of bile acid on anorectal function in man. Gut 1989;30:383–6. 10.1136/gut.30.3.383
    1. Ohkubo H, Yoshihara T, Misawa N, et al. . Relationship between stool form and quality of life in patients with chronic constipation: an Internet questionnaire survey. Digestion 2021;102:147–54. 10.1159/000502815
    1. Tomita T, Kazumori K, Baba K, et al. . Impact of chronic constipation on health-related quality of life and work productivity in Japan. J Gastroenterol Hepatol 2021;36:1529–37. 10.1111/jgh.15295

Source: PubMed

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