High‐dose linaclotide is effective and safe in patients with chronic constipation: A phase III randomized, double‐blind, placebo‐controlled study with a long‐term open‐label extension study in Japan

Background A previous phase II dose‐ranging study of linaclotide in a Japanese chronic constipation (CC) population showed that 0.5 mg was the most effective dose. This study aimed to verify the hypothesis that 0.5 mg of linaclotide is effective and safe in Japanese CC patients. Methods This was a J...

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Published in:Neurogastroenterology and motility 2019-01, Vol.31 (1), p.e13487-n/a
Main Authors: Fukudo, Shin, Miwa, Hiroto, Nakajima, Atsushi, Kinoshita, Yoshikazu, Kosako, Masanori, Hayashi, Kenta, Akiho, Hiraku, Kuroishi, Kentaro, Johnston, Jeffrey M, Currie, Mark, Ohkusa, Toshifumi
Format: Article
Language:English
Subjects:
Adult
Aged
chronic constipation
Chronic Disease
Constipation
Constipation - drug therapy
Diarrhea
Double-Blind Method
Double-blind studies
Female
Gastrointestinal Agents - therapeutic use
guanylate cyclase C activator
Guanylyl Cyclase C Agonists - therapeutic use
Humans
Intestine
Japan
linaclotide
Male
Middle Aged
Original
Patients
Peptides - therapeutic use
stool consistency
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Summary:Background A previous phase II dose‐ranging study of linaclotide in a Japanese chronic constipation (CC) population showed that 0.5 mg was the most effective dose. This study aimed to verify the hypothesis that 0.5 mg of linaclotide is effective and safe in Japanese CC patients. Methods This was a Japanese phase III randomized, double‐blind, placebo‐controlled (part 1), and long‐term, open‐label extension (part 2) study of linaclotide. CC patients (n = 186) diagnosed using the Rome III criteria were randomly assigned to linaclotide 0.5 mg (n = 95) or placebo (n = 91) for a 4‐week double‐blind treatment period in part 1, followed by an additional 52 weeks of open‐label treatment with linaclotide in part 2. The primary efficacy endpoint was the change from baseline in weekly spontaneous bowel movement (SBM) frequency at the first week. Secondary endpoints included responder rate for complete SBM (CSBM), changes in stool consistency, and severity of straining. Key Results Part 1: Change in weekly mean SBM frequency in the first week of treatment with linaclotide (4.02) was significantly greater than that with placebo (1.48, P 
ISSN:1350-1925
1365-2982
DOI:10.1111/nmo.13487