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Safety and efficacy of linaclotide in children aged 2–5 years with functional constipation: Phase 2, randomized study
Open accessAbstract
Objectives: Linaclotide, a guanylate cyclase‐C agonist, was recently approved in the United States for the treatment of children 6–17 years of age with functional constipation (FC). This study evaluated the dose‐response, safety, and efficacy of 4 weeks of linaclotide compared with placebo in children 2–5 years of age with FC. Methods: In this phase 2, randomized, double‐blind, placebo‐controlled, multidose study, 35 children with FC (based on Rome III criteria) were randomized 3:1 to receive linaclotide (18, 36, or 72 μg, for groups 1, 2, and 3, respectively) and 5:1 to receive linaclotide 9, 18, 36, or 72 μg (group 4), or matching placebo. Key endpoints were the changes from baseline in overall spontaneous bowel movement (SBM) frequency (SBMs/week), stool consistency, and straining, as well as the proportion of days with fecal incontinence during the study intervention period. Adverse events (AEs) were recorded. Results: Of the randomized patients, 34 (97.1%) completed the treatment period and 33 (94.3%) completed the posttreatment period. Mean change from baseline over the treatment period for three of the four key efficacy endpoints showed greater improvement in the linaclotide 72 μg group versus placebo. A dose‐response trend was seen for stool consistency in patients receiving linaclotide. Four patients randomized to linaclotide experienced treatment‐emergent AEs, one of which was treatment‐related (mild diarrhea). All AEs were mild or moderate and none were severe. Conclusions: Linaclotide was well tolerated in this pediatric population and an efficacy trend was seen with linaclotide 72 μg versus placebo.
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Almost all domains of the included linaclotide trials were assessed as low risk of bias, except for performance bias and other bias in one study which were assessed as unclear risk.
“Almost all domains of the included trials were assessed as low risk of bias, except for performance bias and other bias in one study, 67 which were assessed as unclear risk.”
In children aged 2-5 years, there is only data available from a phase 2 trial including 35 children for linaclotide.
“In children aged 2–5 years, there is only data available from a phase 2 trial including 35 children. 67”
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Metadata
- Authors
- Di Lorenzo, C., Robert, J., Rodriguez‐Araujo, G., Shakhnovich, V., Xie, W., Nurko, S., & Saps, M.
- Affiliations
- Division of Pediatric Gastroenterology, Hepatology and Nutrition Nationwide Children's Hospital Columbus Ohio USA
- HealthStar Research Hot Springs Arkansas USA
- AbbVie (United States) (US)
- Ironwood Pharmaceuticals (United States) (US)
- Boston Children's Hospital (US)
- University of Miami (US)
- Venue
- Journal of Pediatric Gastroenterology and Nutrition
- Publisher
- Wiley
- Published
- 2024-07-04
- Volume
- 79
- Issue
- 3
- Pages
- 510-518
- ISSN
- 0277-2116 (ISSN-L)
- 1536-4801
- OpenAlex
- W4400325964
- Cited by
- 7
- References
- 27
- Citations by year
- 2026: 2 · 2025: 5
- FWCI
- 3.12
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Pediatric Gastroenterology and Nutrition (publishedVersion)
- PubMed (publishedVersion)
- Funders
- AbbVie
- Ironwood Pharmaceuticals, Incorporated
- Allergan
- Topics
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Health Sciences › Medicine › Urology › Pelvic floor disorders treatments
- Health Sciences › Medicine › Surgery › Congenital gastrointestinal and neural anomalies
- Keywords
- linaclotide, functional constipation, pediatric constipation, guanylate cyclase-C agonist, dose-response relationship, stool consistency, straining, fecal incontinence, drug safety, adverse events
- MeSH terms
- Guanylyl Cyclase C Agonists, Child, Preschool, Constipation, Defecation, Dose-Response Relationship, Drug, Double-Blind Method, Fecal Incontinence, Female, Humans, Male, Peptides, Treatment Outcome
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