Linaclotide is Effective and Safe for Treating Pediatric Functional Constipation

Linaclotide, a guanylate cyclase C agonist approved for chronic idiopathic constipation and irritable bowel syndrome with constipation in adults, was evaluated for its efficacy and safety in children aged 6-17 with functional constipation. 
This phase 3, randomized, double-blind, placebo-controlled trial was conducted across 64 sites in seven countries. A total of 330 participants meeting modified Rome III criteria were randomly assigned to receive linaclotide 72 μg or placebo once daily for 12 weeks. The primary outcome was the change in spontaneous bowel movement (SBM) frequency, and the secondary outcome was stool consistency over the treatment period.
Out of 330 enrolled patients, 328 were analyzed (164 per group). Baseline SBM rates were 1.28 per week for placebo and 1.16 for linaclotide, increasing to 2.29 and 3.41 SBMs per week, respectively. Linaclotide significantly improved SBM frequency compared to placebo (LSM change: 2.22 vs. 1.05 SBMs per week; difference: 1.17; 95% CI: 0.65-1.69; p < 0.0001) and stool consistency (LSM change: 1.11 vs. 0.69; difference: 0.42; 95% CI: 0.21-0.64; p = 0.0001). 
The most common adverse event was diarrhea, reported in 4% of the linaclotide group compared to 2% of placebo. One case of severe diarrhea led to hospitalization but resolved without complications. No deaths occurred. 
Linaclotide demonstrated efficacy and tolerability in treating pediatric functional constipation and is now approved by the FDA for this indication.