Daily Oral Linaclotide Significantly Improves Frequent Constipation in Pediatric Patients Through 12 Weeks

Published on: 

Findings from the pivotal phase 3 trial that which supported linaclotide's FDA approval show significant benefit in bowel movement and stool consistency.

A once-daily dose of 72 mg linaclotide (Linzess) was associated with significant reduction to the frequency of spontaneous bowel movements and improved stool consistency in patients with functional constipation, according to new late-stage data.

Pivotal phase 3 trial data presented in an abstract at the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) 2023 Annual Meeting in San Diego this week, showed pediatric patients receiving the constipation-indicated therapy reported significantly improved disease management and a safety profile consistent with that of previously treated adult patients.

The findings add to the robust portfolio for linaclotide in the treatment of differing subtypes of chronic constipation across both adult and pediatric patients.

Investigators led by Carlo Di Lorenzo, MD, chief of the division of pediatric gastroenterology, hepatology and nutrition at the Nationwide Children’s Hospital, conducted the randomized, controlled phase 3 trial to observe the efficacy and safety of linaclotide versus placebo in patients with functional constipation aged 6 - 17 years old. The guanylate cyclase-C agonist therapy was approved by the US Food and Drug Administration (FDA) for the indication in June2; it was additionally approved to treat irritable bowel syndrome with constipation in 2021.3

The trial included pediatric participants who met modified Rome III criteria for functional constipation. Patients were stratified by younger (6 - 11 years) and older (12 - 17 years) age cohorts and randomized 1:1 to receive either the daily 72 mg oral linaclotide dose or placebo for 12 weeks. Di Lorenzo and colleagues sought a primary efficacy endpoint of change from baseline in weekly spontaneous bowel movements; the key secondary endpoint was change from baseline in stool consistency per the Bristol Stool Form Scale (BSFS).

The team used the age groups as fixed factors and participants’ baseline values as covariate. They additionally assessed for adverse events, laboratory values, and electrocardiograms.

The final analysis included 328 patients who received ≥1 dose of either linaclotide (n = 164) or placebo (n = 164). Mean patient age was 11 years old; a majority of patients were female 55.2%. At 12 weeks, 148 (90.2%) patients in the linaclotide arm and 145 (88.4%) patients in the placebo arm had completed the full treatment duration.

Patients who received linaclotide reported a mean reduction of 2.22 spontaneous bowel movements weekly, versus 1.05 among patients receiving placebo, at 12 weeks (P <.0001). Treated patients additionally reported significantly improved mean BSFS scores (1.11) versus placebo (0.69) at 12 weeks (P = .0001).

The most common treatment-emergent adverse events reported by the linaclotide arm included diarrhea (4.3%) and COVID-19 (2.4%). Overall, 17% of patients receiving linaclotide reported a treatment-emergent adverse event 1.2% reported a serious adverse event—consistent with the placebo arm rates (21% and 1.2%, respectively). Just 1.2% of patients receiving linaclotide discontinued therapy due to a treatment-emergent adverse event.

“Linaclotide 72 mg once daily demonstrated significant improvement in the spontaneous bowel movement frequency rate and stool consistency in pediatric patients with frequent constipation and exhibited a favorable safety profile consistent with prior adult data and a prior pediatric phase 2 frequent constipation study,” investigators concluded.


  1. Di Lorenzo C, Nurko S, Rodriguez G, Xie W, 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. Paper presented at: North American Society for Pediatric Gastroenterology, Hepatology and Nutrition 2023 Annual Meeting; October 4 - 7; San Diego, CA. Accessed October 5, 2023.
  2. Walter K. FDA Approves Linaclotide for Pediatric Patients With Functional Constipation. HCPLive. Published June 12, 2023.
  3. Walter K. FDA Approves Linaclotide as a Generic Drug to Treat IBS-C. HCPLive. Published February 10, 2021.