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
N1 - Funding Information:
This research was funded by Astellas Pharma Inc., Tokyo, Japan.
Funding Information:
Funding information This research was funded by Astellas Pharma Inc., Tokyo, Japan. The authors thank the investigators for participating in the study. Takashi Ando, Tetsu Aoki, Nobuo Aoyama, Takehiro Arai, Masaaki Arima, Masae Banno, Kazutada Egawa, Shin Fukui, Yukihiro Hamahata, Koichi Hirahata, Hitoshi Hongo, Hiroshi Iida, Atsushi Isono, Yoshifumi Jinnouchi, Shigeyasu Kamata, Hitoshi Kaneko, Daijo Kasahara, Hyeteok Kim, Naoya Kimoto, Hiroyuki Kimura, Kensuke Kitamura, Shunichi Kobayashi, Toshio Komazaki, Kenji Kondo, Yoshiya Kumagai, Hidenori Kurakata, Kenji Maenou, Yoshio Matsuda, Yasuhiro Matsumoto, Kenzo Matsumura, Mitsuki Miyata, Shinichi Miyazaki, Mari Mizuno, Koji Mori, Hiroshi Morikawa, Kouetsu Morita, Yasuo Nakajima, Toshihide Ohmori, Naomi Ono, Hitoshi Sakai, Hideo Sawada, Koji Sawada, Shigeru Shirota, Masato Shitara, Masashi Sotokawa, Tomohiro Tada, Masahiro Takada, Hiroyuki Takahashi, Tokuma Tanuma, Toshiaki Terada, Kazunari Tominaga, Kentaro Tsuji, Mitsuhiro Tsukui, Osamu Ueda, Nobutoshi Watanabe, Asako Yamada, Norimichi Yamada, and Hideki Yamakoshi. The authors thank the following personnel for assisting with the study: Masataka Morita, Kenta Hayashi, Michie Yagi, Ayano Higa, and Takuma Ito. Statistical analyses of the entire dataset were performed in accordance with the standard procedures of Astellas Pharma Inc. Writing Assistance: was provided by SunFlare Co., Ltd., Tokyo, Japan.
Publisher Copyright:
© 2018 The Authors. Neurogastroenterology & Motility Published by John Wiley & Sons Ltd.
PY - 2018/12
Y1 - 2018/12
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.
AB - 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.
KW - FDA composite responder
KW - guanylate cyclase C activator
KW - multicultural aspects
KW - phase 3 study
KW - secretagogue
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U2 - 10.1111/nmo.13444
DO - 10.1111/nmo.13444
M3 - Article
C2 - 30136447
AN - SCOPUS:85052460412
SN - 1350-1925
VL - 30
JO - Neurogastroenterology and Motility
JF - Neurogastroenterology and Motility
IS - 12
M1 - e13444
ER -
