Outcomes from a 12-Week, Open-Label, Multicenter Clinical Trial of Teduglutide in Pediatric Short Bowel Syndrome

J Pediatr. 2017 Feb:181:102-111.e5. doi: 10.1016/j.jpeds.2016.10.027. Epub 2016 Nov 15.

Abstract

Objective: To determine safety and pharmacodynamics/efficacy of teduglutide in children with intestinal failure associated with short bowel syndrome (SBS-IF).

Study design: This 12-week, open-label study enrolled patients aged 1-17 years with SBS-IF who required parenteral nutrition (PN) and showed minimal or no advance in enteral nutrition (EN) feeds. Patients enrolled sequentially into 3 teduglutide cohorts (0.0125 mg/kg/d [n = 8], 0.025 mg/kg/d [n = 14], 0.05 mg/kg/d [n = 15]) or received standard of care (SOC, n = 5). Descriptive summary statistics were used.

Results: All patients experienced ≥1 treatment-emergent adverse event; most were mild or moderate. No serious teduglutide-related treatment-emergent adverse events occurred. Between baseline and week 12, prescribed PN volume and calories (kcal/kg/d) changed by a median of -41% and -45%, respectively, with 0.025 mg/kg/d teduglutide and by -25% and -52% with 0.05 mg/kg/d teduglutide. In contrast, PN volume and calories changed by 0% and -6%, respectively, with 0.0125 mg/kg/d teduglutide and by 0% and -1% with SOC. Per patient diary data, EN volume increased by a median of 22%, 32%, and 40% in the 0.0125, 0.025, and 0.05 mg/kg/d cohorts, respectively, and by 11% with SOC. Four patients achieved independence from PN, 3 in the 0.05 mg/kg/d cohort and 1 in the 0.025 mg/kg/d cohort. Study limitations included its short-term, open-label design, and small sample size.

Conclusions: Teduglutide was well tolerated in pediatric patients with SBS-IF. Teduglutide 0.025 or 0.05 mg/kg/d was associated with trends toward reductions in PN requirements and advancements in EN feeding in children with SBS-IF.

Trial registration: ClinicalTrials.gov:NCT01952080; EudraCT: 2013-004588-30.

Keywords: glucagon-like peptide 2; intestinal failure; pediatric short bowel syndrome; short gut syndrome.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Age Factors
  • Child
  • Child, Preschool
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Enteral Nutrition / methods*
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Patient Safety
  • Peptides / administration & dosage*
  • Peptides / adverse effects
  • Prospective Studies
  • Risk Assessment
  • Severity of Illness Index
  • Sex Factors
  • Short Bowel Syndrome / diagnosis
  • Short Bowel Syndrome / drug therapy*
  • Short Bowel Syndrome / therapy
  • Treatment Outcome

Substances

  • Peptides
  • teduglutide

Associated data

  • ClinicalTrials.gov/NCT01952080