Linaclotide Safety and Efficacy in Pediatric Functional Constipation

In children with functional constipation, no clear improvement over placebo was observed for linaclotide; however, a trend for improved efficacy was observed at higher doses.

SAN ANTONIO — In children with functional constipation, no clear improvement was observed for linaclotide over placebo, although a trend toward improved efficacy was observed at higher doses, according to research presented at the ACG Annual Scientific Meeting, held October 25 to 30, 2019, in San Antonio, Texas.

Functional constipation, also known as chronic idiopathic constipation, is a common issue that severely impacts quality of life, and there are currently no approved therapies for children with this problem. This multicenter, randomized, double-blind, placebo-controlled, parallel-group safety and efficacy study evaluated a range of linaclotide doses for treatment of functional constipation in children ages 6 to 17. Participants were grouped by age (6 to 11 and 12 to 17) and treated for 4 weeks.

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The primary end point was change from baseline in overall spontaneous bowel movement (SBM) frequency rate, and secondary end points included change from baseline in daytime bloating and abdominal pain, straining severity, stool consistency, overall rate of complete SBM frequency, and daytime fecal incontinence. Safety was also assessed, including adverse events (AEs), treatment-emergent AEs (TEAEs), serious AEs (SAEs), causality, and severity.

Of the total of 173 children randomly assigned to placebo or linaclotide, 52% (n=90) were age 6 to 11 and 48% (n=83) were age 12 to 17. For the primary end point and the secondary efficacy end points, none of the linaclotide doses showed a clear improvement over placebo (P ≥.1502), although at high doses of linaclotide, a trend for improved efficacy was observed for the primary end point, straining severity, and stool consistency versus placebo. Results were similar between age groups. TEAEs were reported in 16.7% of the low-dose linaclotide group, in 29.3% of the medium-dose group, in 38.5% of the high-dose group, in 22.0% of the placebo group, and in 25% of the 145-μg group. The most common TEAE was diarrhea, with most cases being mild and none being severe. No AEs or SAEs reported in participants 6 to 11 led to treatment discontinuation, but among participants 12 to 17, there were 2 SAEs not considered treatment-related: vomiting and suicidal ideation.

Study investigators concluded, “In children with [functional constipation], no clear improvement over [placebo] was observed for [linaclotide]; however, a trend for improved efficacy was observed at higher doses. [Linaclotide] was well tolerated with a safety profile consistent with studies in adults with chronic idiopathic constipation.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Di Lorenzo C, Nurko S, Hyams JS, et al. Linaclotide safety and efficacy in children aged 6 to 17 years with functional constipation. Poster presented at: ACG Annual Scientific Meeting; October 25-30, 2019; San Antonio, TX. Abstract #P1689