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Efficacy of linaclotide for patients with chronic constipation.
Gastroenterology 2010; 138(3):886-95.e1G

Abstract

BACKGROUND & AIMS

Linaclotide is a minimally absorbed peptide agonist of the guanylate cyclase-C receptor that stimulates intestinal fluid secretion and transit and reduces pain in animal models. We assessed the safety and efficacy of a range of linaclotide doses in patients with chronic constipation.

METHODS

We performed a multicenter, double-blind, placebo-controlled, parallel-group study of 310 patients with chronic constipation. Patients were randomly assigned to groups given 75, 150, 300, or 600 microg oral linaclotide or placebo once daily for 4 weeks. Symptom assessments included spontaneous bowel movements (SBMs), complete SBMs, stool consistency, straining, abdominal discomfort, and bloating. Severity of constipation, adequate relief of constipation, global relief of constipation, treatment satisfaction, quality of life, adverse events, clinical laboratory data, and electrocardiogram results were assessed.

RESULTS

All doses of linaclotide improved the weekly rate of SBM (primary end point) compared with placebo; the increases in overall weekly number of SBMs from baseline were 2.6, 3.3, 3.6, and 4.3 for linaclotide doses of 75, 150, 300, and 600 microg, respectively, compared with 1.5 for placebo (P < or = .05 for each pair-wise comparison of a linaclotide dose to placebo). Likewise, linaclotide significantly improved the weekly rate of complete SBM, stool consistency, straining, abdominal discomfort, bloating, global assessments, and quality of life. The most common and only dose-related adverse event was diarrhea (only 6 patients discontinued treatment because of diarrhea).

CONCLUSIONS

Linaclotide therapy was associated with few adverse events and produced rapid and sustained improvement of bowel habits, abdominal symptoms, global relief, and quality of life in patients with chronic constipation.

Authors+Show Affiliations

Department of Medicine, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

20045700

Citation

Lembo, Anthony J., et al. "Efficacy of Linaclotide for Patients With Chronic Constipation." Gastroenterology, vol. 138, no. 3, 2010, pp. 886-95.e1.
Lembo AJ, Kurtz CB, Macdougall JE, et al. Efficacy of linaclotide for patients with chronic constipation. Gastroenterology. 2010;138(3):886-95.e1.
Lembo, A. J., Kurtz, C. B., Macdougall, J. E., Lavins, B. J., Currie, M. G., Fitch, D. A., ... Johnston, J. M. (2010). Efficacy of linaclotide for patients with chronic constipation. Gastroenterology, 138(3), pp. 886-95.e1. doi:10.1053/j.gastro.2009.12.050.
Lembo AJ, et al. Efficacy of Linaclotide for Patients With Chronic Constipation. Gastroenterology. 2010;138(3):886-95.e1. PubMed PMID: 20045700.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Efficacy of linaclotide for patients with chronic constipation. AU - Lembo,Anthony J, AU - Kurtz,Caroline B, AU - Macdougall,James E, AU - Lavins,B J, AU - Currie,Mark G, AU - Fitch,Donald A, AU - Jeglinski,Brenda I, AU - Johnston,Jeffrey M, Y1 - 2010/01/04/ PY - 2009/08/19/received PY - 2009/11/23/revised PY - 2009/12/08/accepted PY - 2010/1/5/entrez PY - 2010/1/5/pubmed PY - 2010/3/26/medline SP - 886 EP - 95.e1 JF - Gastroenterology JO - Gastroenterology VL - 138 IS - 3 N2 - BACKGROUND & AIMS: Linaclotide is a minimally absorbed peptide agonist of the guanylate cyclase-C receptor that stimulates intestinal fluid secretion and transit and reduces pain in animal models. We assessed the safety and efficacy of a range of linaclotide doses in patients with chronic constipation. METHODS: We performed a multicenter, double-blind, placebo-controlled, parallel-group study of 310 patients with chronic constipation. Patients were randomly assigned to groups given 75, 150, 300, or 600 microg oral linaclotide or placebo once daily for 4 weeks. Symptom assessments included spontaneous bowel movements (SBMs), complete SBMs, stool consistency, straining, abdominal discomfort, and bloating. Severity of constipation, adequate relief of constipation, global relief of constipation, treatment satisfaction, quality of life, adverse events, clinical laboratory data, and electrocardiogram results were assessed. RESULTS: All doses of linaclotide improved the weekly rate of SBM (primary end point) compared with placebo; the increases in overall weekly number of SBMs from baseline were 2.6, 3.3, 3.6, and 4.3 for linaclotide doses of 75, 150, 300, and 600 microg, respectively, compared with 1.5 for placebo (P < or = .05 for each pair-wise comparison of a linaclotide dose to placebo). Likewise, linaclotide significantly improved the weekly rate of complete SBM, stool consistency, straining, abdominal discomfort, bloating, global assessments, and quality of life. The most common and only dose-related adverse event was diarrhea (only 6 patients discontinued treatment because of diarrhea). CONCLUSIONS: Linaclotide therapy was associated with few adverse events and produced rapid and sustained improvement of bowel habits, abdominal symptoms, global relief, and quality of life in patients with chronic constipation. SN - 1528-0012 UR - https://www.unboundmedicine.com/medline/citation/20045700/Efficacy_of_linaclotide_for_patients_with_chronic_constipation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0016-5085(09)02247-1 DB - PRIME DP - Unbound Medicine ER -