Efficacy of linaclotide for patients with chronic constipation

Gastroenterology. 2010 Mar;138(3):886-95.e1. doi: 10.1053/j.gastro.2009.12.050. Epub 2010 Jan 4.


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.

Trial registration: ClinicalTrials.gov NCT00402337.

Publication types

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

MeSH terms

  • Abdominal Pain / etiology
  • Abdominal Pain / prevention & control
  • Administration, Oral
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Chronic Disease
  • Constipation / complications
  • Constipation / drug therapy*
  • Constipation / physiopathology
  • Defecation / drug effects*
  • Diarrhea / chemically induced
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Gastrointestinal Agents / administration & dosage*
  • Gastrointestinal Agents / adverse effects
  • Humans
  • Male
  • Middle Aged
  • Pain Measurement
  • Patient Satisfaction
  • Peptides / administration & dosage*
  • Peptides / adverse effects
  • Quality of Life
  • Severity of Illness Index
  • Surveys and Questionnaires
  • Time Factors
  • Treatment Outcome
  • United States
  • Young Adult


  • Gastrointestinal Agents
  • Peptides
  • linaclotide

Associated data

  • ClinicalTrials.gov/NCT00402337