Outcomes from a 12-Week, Open-Label, Multicenter Clinical Trial of Teduglutide in Pediatric Short Bowel Syndrome
Beth A Carter, Valeria C Cohran, Conrad R Cole, Mark R Corkins, Reed A Dimmitt, Christopher Duggan, Susan Hill, Simon Horslen, Joel D Lim, David F Mercer, Russell J Merritt, Peter F Nichol, Luther Sigurdsson, Daniel H Teitelbaum, John Thompson, Charles Vanderpool, Juliana F Vaughan, Benjamin Li, Nader N Youssef, Robert S Venick, Samuel A Kocoshis, Beth A Carter, Valeria C Cohran, Conrad R Cole, Mark R Corkins, Reed A Dimmitt, Christopher Duggan, Susan Hill, Simon Horslen, Joel D Lim, David F Mercer, Russell J Merritt, Peter F Nichol, Luther Sigurdsson, Daniel H Teitelbaum, John Thompson, Charles Vanderpool, Juliana F Vaughan, Benjamin Li, Nader N Youssef, Robert S Venick, Samuel A Kocoshis
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.
Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
Source: PubMed