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A randomized controlled and long-term linaclotide study of irritable bowel syndrome with constipation patients in Japan.
Neurogastroenterol Motil. 2018 12; 30(12):e13444.NM

Abstract

BACKGROUND

Clinical testing was required to verify the effect of linaclotide 0.5 mg/d in patients with irritable bowel syndrome with constipation (IBS-C) in Japan.

METHODS

This was a randomized, double-blind, placebo-controlled (Part 1) and long-term, open-label extension (Part 2) study of linaclotide at 60 hospitals and clinics in Japan. Patients with IBS-C diagnosed using Rome III criteria (n = 500) were randomly assigned to linaclotide 0.5 mg (n = 249) or placebo (n = 251) for a 12-week treatment period followed by open-label treatment with linaclotide (n = 324) for an additional 40 weeks. The primary endpoints were the responder rate of global improvement of IBS symptoms and complete spontaneous bowel movement (CSBM) during 12 weeks. The secondary endpoints included responder rates of SBM and abdominal pain/discomfort relief.

KEY RESULTS

Part 1: The responder rates for global improvement and for CSBM frequency were significantly higher for linaclotide compared to placebo (P < 0.001). Secondary endpoints including responder rates for SBM and abdominal pain/discomfort relief in the linaclotide group were also significantly greater than those in the placebo group. Part 2: Patients switched from placebo to linaclotide showed similar responder rates for global improvement and CSBM frequency to those in patients who continued to receive linaclotide, supporting sustained efficacy. Diarrhea was seen in 14.5% of patients; all cases were mild or moderate.

CONCLUSIONS AND INFERENCES

This study suggests that a linaclotide dose of 0.5 mg is effective and safe for IBS-C patients in Japan.

Authors+Show Affiliations

Department of Behavioral Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.Department of Gastroenterology and Hepatology, Yokohama City University, Yokohama, Japan.General Internal Medicine 2, General Medical Center, Kawasaki Medical School, Kurashiki, Japan.Japan-Asia Clinical Development 2, Development, Astellas Pharma Inc., Tokyo, Japan.Japan-Asia Clinical Development 2, Development, Astellas Pharma Inc., Tokyo, Japan.Japan-Asia Clinical Development 2, Development, Astellas Pharma Inc., Tokyo, Japan.Japan-Asia Data Science, Development, Astellas Pharma Inc., Tokyo, Japan.Ironwood Pharmaceuticals Inc., Cambridge, Massachusetts.Ironwood Pharmaceuticals Inc., Cambridge, Massachusetts.Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan.

Pub Type(s)

Clinical Trial, Phase III
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30136447

Citation

Fukudo, Shin, et al. "A Randomized Controlled and Long-term Linaclotide Study of Irritable Bowel Syndrome With Constipation Patients in Japan." Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society, vol. 30, no. 12, 2018, pp. e13444.
Fukudo S, Miwa H, Nakajima A, et al. A randomized controlled and long-term linaclotide study of irritable bowel syndrome with constipation patients in Japan. Neurogastroenterol Motil. 2018;30(12):e13444.
Fukudo, S., Miwa, H., Nakajima, A., Haruma, K., Kosako, M., Nakagawa, A., Akiho, H., Yamaguchi, Y., Johnston, J. M., Currie, M., & Kinoshita, Y. (2018). A randomized controlled and long-term linaclotide study of irritable bowel syndrome with constipation patients in Japan. Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society, 30(12), e13444. https://doi.org/10.1111/nmo.13444
Fukudo S, et al. A Randomized Controlled and Long-term Linaclotide Study of Irritable Bowel Syndrome With Constipation Patients in Japan. Neurogastroenterol Motil. 2018;30(12):e13444. PubMed PMID: 30136447.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A randomized controlled and long-term linaclotide study of irritable bowel syndrome with constipation patients in Japan. AU - Fukudo,Shin, AU - Miwa,Hiroto, AU - Nakajima,Atsushi, AU - Haruma,Ken, AU - Kosako,Masanori, AU - Nakagawa,Ayako, AU - Akiho,Hiraku, AU - Yamaguchi,Yusuke, AU - Johnston,Jeffrey M, AU - Currie,Mark, AU - Kinoshita,Yoshikazu, Y1 - 2018/08/22/ PY - 2018/03/27/received PY - 2018/07/16/accepted PY - 2018/8/24/pubmed PY - 2019/11/5/medline PY - 2018/8/24/entrez KW - FDA composite responder KW - guanylate cyclase C activator KW - multicultural aspects KW - phase 3 study KW - secretagogue SP - e13444 EP - e13444 JF - Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society JO - Neurogastroenterol Motil VL - 30 IS - 12 N2 - BACKGROUND: Clinical testing was required to verify the effect of linaclotide 0.5 mg/d in patients with irritable bowel syndrome with constipation (IBS-C) in Japan. METHODS: This was a randomized, double-blind, placebo-controlled (Part 1) and long-term, open-label extension (Part 2) study of linaclotide at 60 hospitals and clinics in Japan. Patients with IBS-C diagnosed using Rome III criteria (n = 500) were randomly assigned to linaclotide 0.5 mg (n = 249) or placebo (n = 251) for a 12-week treatment period followed by open-label treatment with linaclotide (n = 324) for an additional 40 weeks. The primary endpoints were the responder rate of global improvement of IBS symptoms and complete spontaneous bowel movement (CSBM) during 12 weeks. The secondary endpoints included responder rates of SBM and abdominal pain/discomfort relief. KEY RESULTS: Part 1: The responder rates for global improvement and for CSBM frequency were significantly higher for linaclotide compared to placebo (P < 0.001). Secondary endpoints including responder rates for SBM and abdominal pain/discomfort relief in the linaclotide group were also significantly greater than those in the placebo group. Part 2: Patients switched from placebo to linaclotide showed similar responder rates for global improvement and CSBM frequency to those in patients who continued to receive linaclotide, supporting sustained efficacy. Diarrhea was seen in 14.5% of patients; all cases were mild or moderate. CONCLUSIONS AND INFERENCES: This study suggests that a linaclotide dose of 0.5 mg is effective and safe for IBS-C patients in Japan. SN - 1365-2982 UR - https://www.unboundmedicine.com/medline/citation/30136447/A_randomized_controlled_and_long_term_linaclotide_study_of_irritable_bowel_syndrome_with_constipation_patients_in_Japan_ L2 - https://doi.org/10.1111/nmo.13444 DB - PRIME DP - Unbound Medicine ER -