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

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSION:

These pooled analyses of patients treated for ≤104 weeks confirm linaclotide's overall safety.

• Authors: Judy W Nee, Jeffrey M Johnston, Elizabeth P Shea, Courtney E Walls, Kenneth Tripp, Steven Shiff, Susan M Fox, Wieslaw Bochenek, Darren Weissman, Mark G Currie, Anthony J Lembo
• Journal: Expert review of gastroenterology & hepatology (Expert Rev Gastroenterol Hepatol) Vol. 13 Issue 4 Pg. 397-406 (Apr 2019) ISSN: 1747-4132 [Electronic] England
• PMID: 30791771 (Publication Type: Journal Article)

Chemical References

• Guanylyl Cyclase C Agonists
• Peptides
• linaclotide

Topics

• Chronic Disease
• Clinical Trials, Phase III as Topic
• Constipation (diagnosis, drug therapy, physiopathology)
• Defecation (drug effects)
• Diarrhea (chemically induced, physiopathology)
• Guanylyl Cyclase C Agonists (adverse effects, therapeutic use)
• Humans
• Irritable Bowel Syndrome (diagnosis, drug therapy, physiopathology)
• Peptides (adverse effects, therapeutic use)
• Randomized Controlled Trials as Topic
• Recovery of Function
• Risk Factors
• Treatment Outcome