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Neurogastroenterol Motil. 2018 Dec;30(12):e13444. doi: 10.1111/nmo.13444. Epub 2018 Aug 22.

A randomized controlled and long-term linaclotide study of irritable bowel syndrome with constipation patients in Japan.

Author information

1
Department of Behavioral Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
2
Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
3
Department of Gastroenterology and Hepatology, Yokohama City University, Yokohama, Japan.
4
General Internal Medicine 2, General Medical Center, Kawasaki Medical School, Kurashiki, Japan.
5
Japan-Asia Clinical Development 2, Development, Astellas Pharma Inc., Tokyo, Japan.
6
Japan-Asia Data Science, Development, Astellas Pharma Inc., Tokyo, Japan.
7
Ironwood Pharmaceuticals Inc., Cambridge, Massachusetts.
8
Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan.

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.

KEYWORDS:

FDA composite responder; guanylate cyclase C activator; multicultural aspects; phase 3 study; secretagogue

PMID:
30136447
DOI:
10.1111/nmo.13444

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