Nee JW¹, Johnston JM², Shea EP², Walls CE², Tripp K², Shiff S³, Fox SM³, Bochenek W³, Weissman D³, Currie MG², Lembo AJ¹. Expert Rev Gastroenterol Hepatol. 2019 Feb 6:1-10. doi: 10.1080/17474124.2019.1575203. [Epub ahead of print]

Author information

1 a Division of Gastroenterology, Department of Medicine , Beth Israel Deaconess Medical Center, Harvard Medical School , Boston , MA , USA.

2 b Ironwood Pharmaceuticals, Inc ., Cambridge , MA , USA.

3 c Allergan plc , Madison , NJ , USA.

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.