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 1111 allocation based on weight (18 to <35 kg18 µg, 36 µg, or 72 µg; or ≥35 kg 36 µg, 72 µg, or 145 µg), and those aged 12-17 years in a 11111 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.