Safety and Efficacy of Teduglutide in Pediatric Patients With Intestinal Failure due to Short Bowel Syndrome: A 24-Week, Phase III Study

Samuel A. Kocoshis, Russell J. Merritt, Susan Hill, Susan Protheroe, Beth A. Carter, Simon Horslen, Simin Hu, Stuart S. Kaufman, David F. Mercer, Mikko P. Pakarinen, Robert S. Venick, Paul W. Wales, Andrew A. Grimm

Research output: Contribution to journalArticle

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Abstract

Background: This study evaluated the safety and efficacy of teduglutide in pediatric patients with short bowel syndrome–associated intestinal failure (SBS-IF). Methods: A 24-week, phase III trial with 2 randomized, double-blind teduglutide dose groups and a nonblinded standard of care (SOC) arm was used; patients received 0.025 mg/kg or 0.05 mg/kg teduglutide once daily. Safety end points included treatment-emergent adverse events (TEAEs) and growth parameters. The primary efficacy/pharmacodynamic end point was the number of patients who achieved a ≥20% reduction in parenteral support (PS) from baseline at week 24. Results: All 59 enrolled patients completed the study (0.025 mg/kg, n = 24; 0.05 mg/kg, n = 26; SOC, n = 9). Baseline demographics and disease characteristics were comparable among groups. TEAEs were reported by 98% and 100% of patients in the teduglutide and SOC groups, respectively. The most common TEAEs in the teduglutide-treated groups were pyrexia and vomiting. The primary end point was achieved by 13 (54.2%), 18 (69.2%), and 1 (11.1%) patients who received 0.025 mg/kg teduglutide, 0.05 mg/kg teduglutide, and SOC, respectively (P < 0.05 vs SOC). Both 0.025-mg/kg and 0.05-mg/kg teduglutide groups showed clinically significant reductions in PS volume (P < 0.05 vs SOC), PS calories, days per week and hours per day of PS infusions, and increases in enteral nutrition and plasma citrulline at week 24 compared with baseline. Two (8.3%, 0.025 mg/kg teduglutide) and 3 patients (11.5%, 0.05 mg/kg teduglutide) achieved enteral autonomy. Conclusion: The safety profile of teduglutide was similar to that reported previously in children and adults. Treatment with teduglutide was associated with significant reductions in PS for pediatric patients with SBS-IF over 24 weeks.

Original languageEnglish (US)
JournalJournal of Parenteral and Enteral Nutrition
DOIs
StateAccepted/In press - Jan 1 2019

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Short Bowel Syndrome
Pediatrics
Safety
Standard of Care
teduglutide
Parenteral Infusions
Citrulline
Enteral Nutrition
Therapeutics
Small Intestine
Vomiting

Keywords

  • gastroenterology
  • parenteral nutrition
  • pediatrics
  • short bowel syndrome

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

Cite this

Safety and Efficacy of Teduglutide in Pediatric Patients With Intestinal Failure due to Short Bowel Syndrome : A 24-Week, Phase III Study. / Kocoshis, Samuel A.; Merritt, Russell J.; Hill, Susan; Protheroe, Susan; Carter, Beth A.; Horslen, Simon; Hu, Simin; Kaufman, Stuart S.; Mercer, David F.; Pakarinen, Mikko P.; Venick, Robert S.; Wales, Paul W.; Grimm, Andrew A.

In: Journal of Parenteral and Enteral Nutrition, 01.01.2019.

Research output: Contribution to journalArticle

Kocoshis, SA, Merritt, RJ, Hill, S, Protheroe, S, Carter, BA, Horslen, S, Hu, S, Kaufman, SS, Mercer, DF, Pakarinen, MP, Venick, RS, Wales, PW & Grimm, AA 2019, 'Safety and Efficacy of Teduglutide in Pediatric Patients With Intestinal Failure due to Short Bowel Syndrome: A 24-Week, Phase III Study', Journal of Parenteral and Enteral Nutrition. https://doi.org/10.1002/jpen.1690
Kocoshis, Samuel A. ; Merritt, Russell J. ; Hill, Susan ; Protheroe, Susan ; Carter, Beth A. ; Horslen, Simon ; Hu, Simin ; Kaufman, Stuart S. ; Mercer, David F. ; Pakarinen, Mikko P. ; Venick, Robert S. ; Wales, Paul W. ; Grimm, Andrew A. / Safety and Efficacy of Teduglutide in Pediatric Patients With Intestinal Failure due to Short Bowel Syndrome : A 24-Week, Phase III Study. In: Journal of Parenteral and Enteral Nutrition. 2019.
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abstract = "Background: This study evaluated the safety and efficacy of teduglutide in pediatric patients with short bowel syndrome–associated intestinal failure (SBS-IF). Methods: A 24-week, phase III trial with 2 randomized, double-blind teduglutide dose groups and a nonblinded standard of care (SOC) arm was used; patients received 0.025 mg/kg or 0.05 mg/kg teduglutide once daily. Safety end points included treatment-emergent adverse events (TEAEs) and growth parameters. The primary efficacy/pharmacodynamic end point was the number of patients who achieved a ≥20{\%} reduction in parenteral support (PS) from baseline at week 24. Results: All 59 enrolled patients completed the study (0.025 mg/kg, n = 24; 0.05 mg/kg, n = 26; SOC, n = 9). Baseline demographics and disease characteristics were comparable among groups. TEAEs were reported by 98{\%} and 100{\%} of patients in the teduglutide and SOC groups, respectively. The most common TEAEs in the teduglutide-treated groups were pyrexia and vomiting. The primary end point was achieved by 13 (54.2{\%}), 18 (69.2{\%}), and 1 (11.1{\%}) patients who received 0.025 mg/kg teduglutide, 0.05 mg/kg teduglutide, and SOC, respectively (P < 0.05 vs SOC). Both 0.025-mg/kg and 0.05-mg/kg teduglutide groups showed clinically significant reductions in PS volume (P < 0.05 vs SOC), PS calories, days per week and hours per day of PS infusions, and increases in enteral nutrition and plasma citrulline at week 24 compared with baseline. Two (8.3{\%}, 0.025 mg/kg teduglutide) and 3 patients (11.5{\%}, 0.05 mg/kg teduglutide) achieved enteral autonomy. Conclusion: The safety profile of teduglutide was similar to that reported previously in children and adults. Treatment with teduglutide was associated with significant reductions in PS for pediatric patients with SBS-IF over 24 weeks.",
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author = "Kocoshis, {Samuel A.} and Merritt, {Russell J.} and Susan Hill and Susan Protheroe and Carter, {Beth A.} and Simon Horslen and Simin Hu and Kaufman, {Stuart S.} and Mercer, {David F.} and Pakarinen, {Mikko P.} and Venick, {Robert S.} and Wales, {Paul W.} and Grimm, {Andrew A.}",
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T1 - Safety and Efficacy of Teduglutide in Pediatric Patients With Intestinal Failure due to Short Bowel Syndrome

T2 - A 24-Week, Phase III Study

AU - Kocoshis, Samuel A.

AU - Merritt, Russell J.

AU - Hill, Susan

AU - Protheroe, Susan

AU - Carter, Beth A.

AU - Horslen, Simon

AU - Hu, Simin

AU - Kaufman, Stuart S.

AU - Mercer, David F.

AU - Pakarinen, Mikko P.

AU - Venick, Robert S.

AU - Wales, Paul W.

AU - Grimm, Andrew A.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background: This study evaluated the safety and efficacy of teduglutide in pediatric patients with short bowel syndrome–associated intestinal failure (SBS-IF). Methods: A 24-week, phase III trial with 2 randomized, double-blind teduglutide dose groups and a nonblinded standard of care (SOC) arm was used; patients received 0.025 mg/kg or 0.05 mg/kg teduglutide once daily. Safety end points included treatment-emergent adverse events (TEAEs) and growth parameters. The primary efficacy/pharmacodynamic end point was the number of patients who achieved a ≥20% reduction in parenteral support (PS) from baseline at week 24. Results: All 59 enrolled patients completed the study (0.025 mg/kg, n = 24; 0.05 mg/kg, n = 26; SOC, n = 9). Baseline demographics and disease characteristics were comparable among groups. TEAEs were reported by 98% and 100% of patients in the teduglutide and SOC groups, respectively. The most common TEAEs in the teduglutide-treated groups were pyrexia and vomiting. The primary end point was achieved by 13 (54.2%), 18 (69.2%), and 1 (11.1%) patients who received 0.025 mg/kg teduglutide, 0.05 mg/kg teduglutide, and SOC, respectively (P < 0.05 vs SOC). Both 0.025-mg/kg and 0.05-mg/kg teduglutide groups showed clinically significant reductions in PS volume (P < 0.05 vs SOC), PS calories, days per week and hours per day of PS infusions, and increases in enteral nutrition and plasma citrulline at week 24 compared with baseline. Two (8.3%, 0.025 mg/kg teduglutide) and 3 patients (11.5%, 0.05 mg/kg teduglutide) achieved enteral autonomy. Conclusion: The safety profile of teduglutide was similar to that reported previously in children and adults. Treatment with teduglutide was associated with significant reductions in PS for pediatric patients with SBS-IF over 24 weeks.

AB - Background: This study evaluated the safety and efficacy of teduglutide in pediatric patients with short bowel syndrome–associated intestinal failure (SBS-IF). Methods: A 24-week, phase III trial with 2 randomized, double-blind teduglutide dose groups and a nonblinded standard of care (SOC) arm was used; patients received 0.025 mg/kg or 0.05 mg/kg teduglutide once daily. Safety end points included treatment-emergent adverse events (TEAEs) and growth parameters. The primary efficacy/pharmacodynamic end point was the number of patients who achieved a ≥20% reduction in parenteral support (PS) from baseline at week 24. Results: All 59 enrolled patients completed the study (0.025 mg/kg, n = 24; 0.05 mg/kg, n = 26; SOC, n = 9). Baseline demographics and disease characteristics were comparable among groups. TEAEs were reported by 98% and 100% of patients in the teduglutide and SOC groups, respectively. The most common TEAEs in the teduglutide-treated groups were pyrexia and vomiting. The primary end point was achieved by 13 (54.2%), 18 (69.2%), and 1 (11.1%) patients who received 0.025 mg/kg teduglutide, 0.05 mg/kg teduglutide, and SOC, respectively (P < 0.05 vs SOC). Both 0.025-mg/kg and 0.05-mg/kg teduglutide groups showed clinically significant reductions in PS volume (P < 0.05 vs SOC), PS calories, days per week and hours per day of PS infusions, and increases in enteral nutrition and plasma citrulline at week 24 compared with baseline. Two (8.3%, 0.025 mg/kg teduglutide) and 3 patients (11.5%, 0.05 mg/kg teduglutide) achieved enteral autonomy. Conclusion: The safety profile of teduglutide was similar to that reported previously in children and adults. Treatment with teduglutide was associated with significant reductions in PS for pediatric patients with SBS-IF over 24 weeks.

KW - gastroenterology

KW - parenteral nutrition

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