TY - JOUR
T1 - Outcomes from a 12-Week, Open-Label, Multicenter Clinical Trial of Teduglutide in Pediatric Short Bowel Syndrome
AU - Carter, Beth A.
AU - Cohran, Valeria C.
AU - Cole, Conrad R.
AU - Corkins, Mark R.
AU - Dimmitt, Reed A.
AU - Duggan, Christopher
AU - Hill, Susan
AU - Horslen, Simon
AU - Lim, Joel D.
AU - Mercer, David F.
AU - Merritt, Russell J.
AU - Nichol, Peter F.
AU - Sigurdsson, Luther
AU - Teitelbaum, Daniel H.
AU - Thompson, John
AU - Vanderpool, Charles
AU - Vaughan, Juliana F.
AU - Li, Benjamin
AU - Youssef, Nader N.
AU - Venick, Robert S.
AU - Kocoshis, Samuel A.
N1 - Publisher Copyright:
© 2016 The Authors
PY - 2017/2/1
Y1 - 2017/2/1
N2 - 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.
AB - 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.
KW - glucagon-like peptide 2
KW - intestinal failure
KW - pediatric short bowel syndrome
KW - short gut syndrome
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U2 - 10.1016/j.jpeds.2016.10.027
DO - 10.1016/j.jpeds.2016.10.027
M3 - Article
C2 - 27855998
AN - SCOPUS:85006835291
SN - 0022-3476
VL - 181
SP - 102-111.e5
JO - Journal of Pediatrics
JF - Journal of Pediatrics
ER -