Safety and efficacy of linaclotide in children aged 7–17 years with irritable bowel syndrome with constipation

Abstract Objectives Linaclotide, a guanylate cyclase‐C agonist, was recently approved in the United States for the treatment of children 6–17 years old with functional constipation. This study evaluated the safety and efficacy of various linaclotide doses in children 7–17 years old with irritable bowel syndrome with constipation (IBS‐C). Methods In this 4‐week, randomized, double‐blind, placebo‐controlled, parallel‐group, Phase 2 study, children with IBS‐C were randomized to once‐daily placebo or linaclotide (Dose A: 18 or 36 µg, B: 36 or 72 µg, and C: 72 µg or 145 µg, or 290 µg); those aged 7–11 years in a 1:1:1:1 allocation based on weight (18 to <35 kg:18 µg, 36 µg, or 72 µg; or ≥35 kg: 36 µg, 72 µg, or 145 µg), and those aged 12–17 years in a 1:1:1:1:1 allocation (the higher option of Doses A–C or 290 µg). The primary efficacy endpoint was a change from baseline in 4‐week overall spontaneous bowel movement (SBM) frequency rate over the treatment period. Adverse events and clinical laboratory measures were also assessed. Results Efficacy, safety, and tolerability were assessed in 101 patients. In the intent‐to‐treat population, numerical improvement was observed in overall SBM frequency rate with increasing linaclotide doses (A: 1.62, B: 1.52, and C: 2.30, 290 µg: 3.26) compared with placebo. The most reported treatment‐emergent adverse events were diarrhea and pain, with most cases being mild and none being severe. Conclusions Linaclotide was tolerated well in this pediatric population, showing numerical improvement in SBM frequency compared with placebo.