NDLI: Two randomized trials of linaclotide for chronic constipation.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Schneier, Harvey A. Shao, James Z. Lembo, Anthony J. Eng, Paul Shiff, Steven J. Macdougall, James E. Jia, Xinwei D. Currie, Mark G. Jeglinski, Brenda I. Kurtz, Caroline B. Lavins, Bernard J. Fitch, Donald A. Fox, Susan M. Johnston, Jeffrey M.
Description	Author Affiliation: Lembo AJ ( Department of Medicine, Division of Gastroenterology, Beth Israel Deaconess Medical Center, and Harvard Medical School, Boston, MA, USA.)
Abstract	BACKGROUND: Linaclotide is a minimally absorbed peptide agonist of the guanylate cyclase C receptor. In two trials, we aimed to determine the efficacy and safety of linaclotide in patients with chronic constipation. METHODS: We conducted two randomized, 12-week, multicenter, double-blind, parallel-group, placebo-controlled, dual-dose trials (Trials 303 and 01) involving 1276 patients with chronic constipation. Patients received either placebo or linaclotide, 145 µg or 290 µg, once daily for 12 weeks. The primary efficacy end point was three or more complete spontaneous bowel movements (CSBMs) per week and an increase of one or more CSBMs from baseline during at least 9 of the 12 weeks. Adverse events were also monitored. RESULTS: For Trials 303 and 01, respectively, the primary end point was reached by 21.2% and 16.0% of the patients who received 145 µg of linaclotide and by 19.4% and 21.3% of the patients who received 290 µg of linaclotide, as compared with 3.3% and 6.0% of those who received placebo (P<0.01 for all comparisons of linaclotide with placebo). Improvements in all secondary end points were significantly greater in both linaclotide groups than in the placebo groups. The incidence of adverse events was similar among all study groups, with the exception of diarrhea, which led to discontinuation of treatment in 4.2% of patients in both linaclotide groups. CONCLUSIONS: In these two 12-week trials, linaclotide significantly reduced bowel and abdominal symptoms in patients with chronic constipation. Additional studies are needed to evaluate the potential long-term risks and benefits of linaclotide in chronic constipation. (Funded by Ironwood Pharmaceuticals and Forest Research Institute; ClinicalTrials.gov numbers, NCT00765882 and NCT00730015.).
ISSN	00284793
Issue Number	6
Volume Number	365
e-ISSN	15334406
Journal	New England Journal of Medicine
Language	English
Publisher	Massachusetts Medical Society (United States)
Publisher Date	2011-08-11
Publisher Place	United States
Access Restriction	Subscribed
Subject Keyword	Constipation Drug Therapy Laxatives Therapeutic Use Peptides Adolescent Adult Aged Aged, 80 And Over Chronic Disease Defecation Drug Effects Diarrhea Chemically Induced Double-Blind Method Female Guanylate Cyclase Humans Adverse Effects Male Middle Aged Quality Of Life Receptors, Guanylate Cyclase-Coupled Agonists Withholding Treatment Young Adult Clinical Trial, Phase III Journal Article Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't Medicine
Content Type	Text
Resource Type	Article
Subject	Medicine

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in