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, Jon S Thompson, Charles Vanderpool, Juliana F. Vaughan, Benjamin Li, Nader N. Youssef, Robert S. VenickSamuel A. Kocoshis

Research output: Contribution to journalArticle

38 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)102-111.e5
JournalJournal of Pediatrics
Volume181
DOIs
StatePublished - Feb 1 2017

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Short Bowel Syndrome
Multicenter Studies
Clinical Trials
Pediatrics
Parenteral Nutrition
Enteral Nutrition
Nutritional Requirements
teduglutide
Standard of Care
Sample Size
Safety

Keywords

  • glucagon-like peptide 2
  • intestinal failure
  • pediatric short bowel syndrome
  • short gut syndrome

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Carter, B. A., Cohran, V. C., Cole, C. R., Corkins, M. R., Dimmitt, R. A., Duggan, C., ... Kocoshis, S. A. (2017). Outcomes from a 12-Week, Open-Label, Multicenter Clinical Trial of Teduglutide in Pediatric Short Bowel Syndrome. Journal of Pediatrics, 181, 102-111.e5. https://doi.org/10.1016/j.jpeds.2016.10.027

Outcomes from a 12-Week, Open-Label, Multicenter Clinical Trial of Teduglutide in Pediatric Short Bowel Syndrome. / Carter, Beth A.; Cohran, Valeria C.; Cole, Conrad R.; Corkins, Mark R.; Dimmitt, Reed A.; Duggan, Christopher; Hill, Susan; Horslen, Simon; Lim, Joel D.; Mercer, David F; Merritt, Russell J.; Nichol, Peter F.; Sigurdsson, Luther; Teitelbaum, Daniel H.; Thompson, Jon S; Vanderpool, Charles; Vaughan, Juliana F.; Li, Benjamin; Youssef, Nader N.; Venick, Robert S.; Kocoshis, Samuel A.

In: Journal of Pediatrics, Vol. 181, 01.02.2017, p. 102-111.e5.

Research output: Contribution to journalArticle

Carter, BA, Cohran, VC, Cole, CR, Corkins, MR, Dimmitt, RA, Duggan, C, Hill, S, Horslen, S, Lim, JD, Mercer, DF, Merritt, RJ, Nichol, PF, Sigurdsson, L, Teitelbaum, DH, Thompson, JS, Vanderpool, C, Vaughan, JF, Li, B, Youssef, NN, Venick, RS & Kocoshis, SA 2017, 'Outcomes from a 12-Week, Open-Label, Multicenter Clinical Trial of Teduglutide in Pediatric Short Bowel Syndrome', Journal of Pediatrics, vol. 181, pp. 102-111.e5. https://doi.org/10.1016/j.jpeds.2016.10.027
Carter, Beth A. ; Cohran, Valeria C. ; Cole, Conrad R. ; Corkins, Mark R. ; Dimmitt, Reed A. ; Duggan, Christopher ; Hill, Susan ; Horslen, Simon ; Lim, Joel D. ; Mercer, David F ; Merritt, Russell J. ; Nichol, Peter F. ; Sigurdsson, Luther ; Teitelbaum, Daniel H. ; Thompson, Jon S ; Vanderpool, Charles ; Vaughan, Juliana F. ; Li, Benjamin ; Youssef, Nader N. ; Venick, Robert S. ; Kocoshis, Samuel A. / Outcomes from a 12-Week, Open-Label, Multicenter Clinical Trial of Teduglutide in Pediatric Short Bowel Syndrome. In: Journal of Pediatrics. 2017 ; Vol. 181. pp. 102-111.e5.
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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.",
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author = "Carter, {Beth A.} and Cohran, {Valeria C.} and Cole, {Conrad R.} and Corkins, {Mark R.} and Dimmitt, {Reed A.} and Christopher Duggan and Susan Hill and Simon Horslen and Lim, {Joel D.} and Mercer, {David F} and Merritt, {Russell J.} and Nichol, {Peter F.} and Luther Sigurdsson and Teitelbaum, {Daniel H.} and Thompson, {Jon S} and Charles Vanderpool and Vaughan, {Juliana F.} and Benjamin Li and Youssef, {Nader N.} and Venick, {Robert S.} and Kocoshis, {Samuel A.}",
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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, Jon S

AU - Vanderpool, Charles

AU - Vaughan, Juliana F.

AU - Li, Benjamin

AU - Youssef, Nader N.

AU - Venick, Robert S.

AU - Kocoshis, Samuel A.

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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