Safety and tolerability of linaclotide for the treatment of chronic idiopathic constipation and irritable bowel syndrome with constipation: pooled Phase 3 analysis

Expert Review of Gastroenterology & Hepatology
Judy W NeeAnthony J Lembo

Abstract

Linaclotide is approved for treating irritable bowel syndrome with constipation (IBS-C; 290 µg QD) and chronic idiopathic constipation (CIC; 145 µg or 72 µg QD). These analyses aimed to assess linaclotide safety in a large, pooled Phase 3 population. In six randomized controlled trials (RCTs), patients received linaclotide (72 µg, 145 µg, 290 µg) or placebo daily for 12-26 weeks; in two long-term safety (LTS) studies, patients received open-label linaclotide for ≤78 additional weeks. Laboratory values, vital signs, and treatment-emergent adverse events (TEAEs) were assessed. Overall, 3853 patients received ≥1 dose of linaclotide. The most common TEAE was diarrhea (majority [90.5% in RCTs] mild/moderate). Linaclotide patients experienced 1.1 diarrhea TEAE per patient-year in the RCTs (0.2 in placebo), and 0.3 in the LTS studies. In RCTs, 6.9% linaclotide and 3.0% placebo patients discontinued due to any adverse event (AE); 4.0% linaclotide and 0.3% placebo patients discontinued due to diarrhea. In LTS studies, 9.4% patients discontinued due to any AE, and 3.8% due to diarrhea. Serious AEs (SAEs) were rare and similar across treatment groups; there were no SAEs of diarrhea. These pooled analyses of patients treated for ≤104 weeks...Continue Reading

References

Feb 22, 2007·Alimentary Pharmacology & Therapeutics·D-C SuhM Shetzline
Dec 23, 2008·The American Journal of Gastroenterology·Jeffrey M JohnstonMark G Currie
Aug 27, 2009·Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society·H EutameneL Bueno
Sep 22, 2009·Clinical Gastroenterology and Hepatology : the Official Clinical Practice Journal of the American Gastroenterological Association·George F Longstreth, Janis F Yao
Jan 5, 2010·Gastroenterology·Anthony J LemboJeffrey M Johnston
Aug 13, 2011·The New England Journal of Medicine·Anthony J LemboJeffrey M Johnston
Jul 11, 2012·Therapeutic Advances in Gastroenterology·Susan Lucak
Aug 6, 2014·The American Journal of Gastroenterology·Alexander C FordEamonn M M Quigley

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Citations

May 27, 2020·Drugs·Jasper PannemansJan Tack
Oct 17, 2020·The American Journal of Gastroenterology·William D CheyNiels Borgstein
Jan 23, 2021·Current Opinion in Endocrinology, Diabetes, and Obesity·Abishek Arokiadoss, H Christian Weber

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