Randomized controlled trial of linaclotide in children aged 6−17 years with functional constipation

Abstract Objectives Linaclotide, a guanylate cyclase‐C agonist, was recently approved in the United States for treatment of children 6−17 years old with functional constipation (FC). This study evaluated the safety and efficacy of several linaclotide doses in children 6−17 years old with FC. Methods In this multicenter, randomized, double‐blind, placebo‐controlled phase 2 study, 173 children with FC (based on Rome III criteria) were randomized to once‐daily linaclotide (A: 9 or 18 μg, B: 18 or 36 μg, or C: 36 or 72 μg) or placebo in a 1:1:1:1 ratio for 6‐ to 11‐year‐olds (dosage determined by weight: 18 to <35 or ≥35 kg) and linaclotide (18, 36, 72, or 145 μg) or placebo in a 1:1:1:1:1 ratio for 12‐ to 17‐year‐olds. The primary efficacy endpoint was change from baseline in weekly spontaneous bowel movement (SBM) frequency throughout the 4‐week treatment period. Adverse events (AE), clinical laboratory values, and electrocardiograms were monitored. Results Efficacy and safety were assessed in 173 patients (52.0% aged 6−11 years; 48.0% aged 12−17 years); 162 (93.6%) completed the treatment period. A numerical improvement in mean SBM frequency was observed with increasing linaclotide doses (1.90 in 6‐ to 11‐year‐olds [36 or 72 μg] and 2.86 in 12‐ to 17‐year‐olds [72 μg]). The most reported treatment‐emergent AE was diarrhea, with most cases being mild; none were severe. Conclusions Linaclotide was well tolerated in this pediatric population, with a trend toward efficacy in the higher doses, warranting further evaluation.