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Determining an optimal dose of linaclotide for use in Japanese patients with irritable bowel syndrome with constipation: A phase II randomized, double-blind, placebo-controlled study.
Neurogastroenterol Motil 2018; 30(5):e13275NM

Abstract

BACKGROUND

Clinical testing to determine a suitable dose of linaclotide for Japanese patients with irritable bowel syndrome with constipation (IBS-C) was needed.

METHODS

This was a randomized, double-blind, placebo-controlled, dose-finding trial. Japanese patients with IBS-C diagnosed using Rome III criteria (n = 559, men/women: 49/510) were randomly assigned to 1 of 4 linaclotide doses (0.0625, 0.125, 0.25, or 0.5 mg) or placebo for the 12-week treatment period. The primary endpoint was responder rate of global assessment of relief of IBS symptoms during 12 weeks. The secondary endpoints included responder rates of complete spontaneous bowel movement (CSBM), SBM and abdominal pain/discomfort relief and others.

KEY RESULTS

The primary endpoint was 23.2%, 36.2%, 38.7%, 34.8%, and 38.3% in placebo (n = 112), 0.0625 (n = 116), 0.125 (n = 111), 0.25 (n = 112), and 0.5 (n = 107) mg of linaclotide groups with the difference from the placebo group in each linaclotide group (13.0%, 15.5%, 11.6%, 15.1%, P > .05). Monthly responder rate of global assessment of relief of IBS symptoms at month 3 (48.6%), responder rate of CSBM during 12 weeks (45.8%), and responder rate of abdominal pain/discomfort relief during 12 weeks (32.7%) in the 0.5 mg were significantly higher than those in placebo group (29.5%, P < .01; 25.9%, P < .01; and 18.8%, P < .05 respectively). The most frequent adverse event in the linaclotide groups was diarrhea.

CONCLUSIONS & INFERENCES

This study suggests that a linaclotide dose of 0.5 mg may be appropriate in Japanese patients with IBS-C.

Authors+Show Affiliations

Department of Behavioral Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.Department of Gastroenterology, Yokohama City University, Yokohama, Japan.Shiga University of Medical Science, Ohtsu, 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, MA, USA.Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.

Pub Type(s)

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

Language

eng

PubMed ID

29278278

Citation

Fukudo, S, et al. "Determining an Optimal Dose of Linaclotide for Use in Japanese Patients With Irritable Bowel Syndrome With Constipation: a Phase II Randomized, Double-blind, Placebo-controlled Study." Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society, vol. 30, no. 5, 2018, pp. e13275.
Fukudo S, Nakajima A, Fujiyama Y, et al. Determining an optimal dose of linaclotide for use in Japanese patients with irritable bowel syndrome with constipation: A phase II randomized, double-blind, placebo-controlled study. Neurogastroenterol Motil. 2018;30(5):e13275.
Fukudo, S., Nakajima, A., Fujiyama, Y., Kosako, M., Nakagawa, A., Akiho, H., ... Miwa, H. (2018). Determining an optimal dose of linaclotide for use in Japanese patients with irritable bowel syndrome with constipation: A phase II randomized, double-blind, placebo-controlled study. Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society, 30(5), pp. e13275. doi:10.1111/nmo.13275.
Fukudo S, et al. Determining an Optimal Dose of Linaclotide for Use in Japanese Patients With Irritable Bowel Syndrome With Constipation: a Phase II Randomized, Double-blind, Placebo-controlled Study. Neurogastroenterol Motil. 2018;30(5):e13275. PubMed PMID: 29278278.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Determining an optimal dose of linaclotide for use in Japanese patients with irritable bowel syndrome with constipation: A phase II randomized, double-blind, placebo-controlled study. AU - Fukudo,S, AU - Nakajima,A, AU - Fujiyama,Y, AU - Kosako,M, AU - Nakagawa,A, AU - Akiho,H, AU - Nakashima,Y, AU - Johnston,J M, AU - Miwa,H, Y1 - 2017/12/26/ PY - 2017/05/06/received PY - 2017/12/04/accepted PY - 2017/12/27/pubmed PY - 2019/10/17/medline PY - 2017/12/27/entrez KW - abdominal pain KW - constipation KW - guanylate cyclase C activator KW - linaclotide KW - stool consistency SP - e13275 EP - e13275 JF - Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society JO - Neurogastroenterol. Motil. VL - 30 IS - 5 N2 - BACKGROUND: Clinical testing to determine a suitable dose of linaclotide for Japanese patients with irritable bowel syndrome with constipation (IBS-C) was needed. METHODS: This was a randomized, double-blind, placebo-controlled, dose-finding trial. Japanese patients with IBS-C diagnosed using Rome III criteria (n = 559, men/women: 49/510) were randomly assigned to 1 of 4 linaclotide doses (0.0625, 0.125, 0.25, or 0.5 mg) or placebo for the 12-week treatment period. The primary endpoint was responder rate of global assessment of relief of IBS symptoms during 12 weeks. The secondary endpoints included responder rates of complete spontaneous bowel movement (CSBM), SBM and abdominal pain/discomfort relief and others. KEY RESULTS: The primary endpoint was 23.2%, 36.2%, 38.7%, 34.8%, and 38.3% in placebo (n = 112), 0.0625 (n = 116), 0.125 (n = 111), 0.25 (n = 112), and 0.5 (n = 107) mg of linaclotide groups with the difference from the placebo group in each linaclotide group (13.0%, 15.5%, 11.6%, 15.1%, P > .05). Monthly responder rate of global assessment of relief of IBS symptoms at month 3 (48.6%), responder rate of CSBM during 12 weeks (45.8%), and responder rate of abdominal pain/discomfort relief during 12 weeks (32.7%) in the 0.5 mg were significantly higher than those in placebo group (29.5%, P < .01; 25.9%, P < .01; and 18.8%, P < .05 respectively). The most frequent adverse event in the linaclotide groups was diarrhea. CONCLUSIONS & INFERENCES: This study suggests that a linaclotide dose of 0.5 mg may be appropriate in Japanese patients with IBS-C. SN - 1365-2982 UR - https://www.unboundmedicine.com/medline/citation/29278278/Determining_an_optimal_dose_of_linaclotide_for_use_in_Japanese_patients_with_irritable_bowel_syndrome_with_constipation:_A_phase_II_randomized_double_blind_placebo_controlled_study_ L2 - https://doi.org/10.1111/nmo.13275 DB - PRIME DP - Unbound Medicine ER -