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The linaclotide group had significant improvements from baseline in the 12 week SBM frequency rate and 12-week stool consistency.
A team, led by Carlo Di Lorenzo, MD, Nationwide Children’s Hospital, assessed the efficacy and safety of linaclotide compared to placebo in pediatric patients with functional constipation aged 6-17 years.
Functional constipation is common for pediatric patients, severely impacting their quality of life. However, currently there are no prescription treatments for this patient population approved by the US Food and Drug Administration (FDA).
Currently, there is an option for adults in linaclotide, a guanylate cyclase-C agonist to treat chronic idiopathic constipation and constipation-predominant irritable bowel syndrome.
In the phase 3, randomized, double-blind, placebo-controlled study, the investigators enrolled patients with met the modified Rome III criteria for functional constipation.
The study included 328 patients with a mean age of 11 years.
The patients were stratified by age group at 6-11 years or 12-17 years and were treated by either linaclotide 72 μg (n = 164) or placebo (n = 164) once daily for 12 weeks.
The investigators sought primary efficacy endpoints of the change from baseline in 12-week spontaneous bowel movement (SBM) frequency rate in SBMs per week.
There were also key secondary efficacy endpoint, including the change from baseline in 12-week stool consistency based on the Bristol Stool Form Scale. The investigators also made comparisons between the 2 groups for efficacy endpoints using an analysis of covariance (ANCOVA) model with study intervention, with age group as fixed factors and baseline value as a covariate.
They also monitored adverse events, laboratory values, vital signs, and electrocardiograms.
A total of 145 patients (88.4%) in the placebo group completed the study, compared to 90.2% (n = 148) in the treatment group. Both groups were similar in baseline stool frequency (mean SBMs/week; linaclotide, 1.16 [0.83]; placebo, 1.28 [0.87]).
After conducting sensitivity analyses and analyses of age subgroups, the investigators found these figures were consistent with the primary analyses.
In the safety analysis, the investigators found treatment-emergent adverse events, including diarrhea (linaclotide, 4.3%; placebo, 1.8%) and COVID-19 (linaclotide, 2.4%; placebo, 3.0%) in more than 2% of patients.
There were also similar proportions of adverse events (1.2% for both), and treatment-emergent adverse events leading to study treatment discontinuation (linaclotide, 1.2%; placebo, 1.8%).
There was also 1 adverse event of special interest of diarrhea found in in a 17-year old. However, it was not considered related to linaclotide and was resolved within a day without sequelae.
“Linaclotide 72 μg once daily demonstrated significant improvement in the SBM frequency rate and stool consistency in pediatric patients with functional constipation and exhibited a favorable safety profile consistent with prior adult data and a prior pediatric phase 2 functional constipation study,” the authors wrote.
Di Lorenzo C, Nurko S, Rodriguez-Araujo G, Xie W, Huh S, Hyams, Khlevner J, Saps M, et al. EFFICACY AND SAFETY OF LINACLOTIDE IN TREATING FUNCTIONAL CONSTIPATION IN PEDIATRIC PATIENTS AGED 6-17 YEARS: A PHASE 3 PIVOTAL RANDOMIZED PLACEBO-CONTROLLED TRIAL
Abstract presented at Digestive Disease Week (DDW) 2023 Annual Meeting. Chicago, IL. May 6-10, 2023.