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Two Randomized Trials of Linaclotide for Chronic Constipation
Open accessAbstract
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.).
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“The use of linaclotide leads to increases in the number of CSBMs per week (MD 1.37, 95% CI 1.07-1.95) and SBMs per week (MD 1.97, 95% CI 1.59-2.36), improves stool consistency (MD 1.25, 95% CI 1.1-1.39 higher), and increases the rates of global relief (RR 1.96, 95% CI 1.63-2.35).”
From American Gastroenterological Association-American College of Gastroenterology Clinical Practice Guideline: Pharmacological Management of Chronic Idiopathic Constipation (2023) · cites this paper as [64]
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“The use of linaclotide might improve the PAC-QOL scores compared with placebo; 64 however, data could not be pooled.”
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Lacy, B. E., Mearin, F., Chang, L., Chey, W. D., Lembo, A. J., Simren, M., & Spiller, R. (2016) · Gastroenterology · doi:10.1053/j.gastro.2016.02.031 · Cited by 2,866
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Metadata
- Authors
- Lembo, A. J., Schneier, H. A., Shiff, S. J., Kurtz, C. B., MacDougall, J. E., Jia, X. D., Shao, J. Z., Lavins, B. J., Currie, M. G., Fitch, D. A., Jeglinski, B. I., Eng, P., Fox, S. M., & Johnston, J. M.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Forest Laboratories (United States) (US)
- Ironwood Pharmaceuticals (United States) (US)
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2011-08-11
- Volume
- 365
- Issue
- 6
- Pages
- 527-536
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2129385409
- Cited by
- 373
- References
- 18
- Citations by year
- 2026: 16 · 2025: 12 · 2024: 28 · 2023: 22 · 2022: 19 · 2021: 23 · 2020: 23 · 2019: 20 · 2018: 31 · 2017: 24 · 2016: 32 · 2015: 26 · 2014: 26 · 2013: 40 · 2012: 25
- FWCI
- 31.44
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ironwood Pharmaceuticals, Incorporated
- Topics
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Health Sciences › Medicine › Urology › Pelvic floor disorders treatments
- Health Sciences › Medicine › Surgery › Congenital gastrointestinal and neural anomalies
- Keywords
- linaclotide, chronic constipation, spontaneous bowel movements, diarrhea, drug safety, treatment efficacy
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Chronic Disease, Constipation, Defecation, Diarrhea, Double-Blind Method, Female, Guanylate Cyclase, Humans, Male, Middle Aged, Peptides, Quality of Life, Withholding Treatment, Receptors, Guanylate Cyclase-Coupled, Laxatives, Young Adult
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