Background and 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 mug 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.
• All doses of linaclotide improved the weekly rate of spontaneous bowel movements (primary end point) compared with placebo;
• The increases in overall weekly number of spontaneous bowel movements from baseline were 2.6, 3.3, 3.6, and 4.3 for linaclotide doses of 75, 150, 300, and 600 mug, respectively, compared with 1.5 for placebo (P = .05 for each pair-wise comparison of a linaclotide dose to placebo).
• Likewise, linaclotide significantly improved the weekly rate of complete spontaneous bowel movements, 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.
Source: Gastroenterology, Jan 4, 2010. PMID: 20045700 by Lembo AJ, Kurtz CB, Macdougall JE, Lavins BJ, Currie MG, Fitch DA, Jeglinski BI, Johnston JM. Department of Medicine, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts (BIDMC). [Email: firstname.lastname@example.org]