1151 Linaclotide Safety and Efficacy in Children Aged 6 to 17 Years With Functional Constipation

Abstract

INTRODUCTION: Functional constipation (FC), also known as chronic idiopathic constipation, is a common problem in children that may severely impact quality of life and persist into adulthood. Currently there are no approved therapies for children and more effective treatments are needed to provide symptomatic relief. This study evaluated the safety and efficacy of a range of linaclotide (LIN) doses for treatment of FC in children aged 6–17 years. METHODS: This multicenter, randomized, double-blind, placebo (PBO)-controlled, parallel-group safety and efficacy study of a range of LIN doses compared to PBO randomized participants aged 6–11 years to once-daily PBO or LIN doses A, B, or C based on weight and those aged 12–17 years to once-daily PBO or LIN doses A, B, C, or 145 μg (Table 1) for 4 weeks. Primary efficacy endpoint was change from baseline (CFB) in 4-week overall spontaneous bowel movement (SBM) frequency rate. Secondary efficacy endpoints included CFB in 4-week daytime abdominal pain and bloating, stool consistency, straining severity, overall complete SBMs frequency rate, and daytime fecal incontinence. Safety assessments included adverse events (AEs), specifically AEs of special interest, treatment-emergent AEs (TEAEs), causality, severity, and serious AEs (SAEs). RESULTS: 173 participants were randomized; 90 (52%) aged 6–11 years and 83 (48%) aged 12–17 years. For the primary endpoint, or the secondary efficacy endpoints, none of the LIN doses (A, B, C) led to a clear improvement over PBO (P ≥ 0.1502) in the ITT population. A trend toward improved efficacy at the high LIN dose vs. PBO was observed for the primary endpoint, stool consistency, and straining severity (Table 2). Similar results were observed in each age group. TEAEs were reported in 16.7% (LIN A), 29.3% (LIN B), 38.5% (LIN C), 22.0% (PBO), and 25% in the LIN 145 μg group (Table 3). The most commonly reported TEAE was diarrhea; the majority of cases were mild, and none were severe. No SAEs or AEs leading to discontinuation were reported in participants aged 6–11 years. Two SAEs were reported in participants aged 12–17 years (suicidal ideation and vomiting; 1 each); neither were considered related to study treatment. CONCLUSION: In children with FC, no clear improvement over PBO was observed for LIN; however, a trend for improved efficacy was observed at higher doses. LIN was well tolerated with a safety profile consistent with studies in adults with chronic idiopathic constipation.