Beth A Carter1, Valeria C Cohran2, Conrad R Cole3, Mark R Corkins4, Reed A Dimmitt5, Christopher Duggan6, Susan Hill7, Simon Horslen8, Joel D Lim9, David F Mercer10, Russell J Merritt11, Peter F Nichol12, Luther Sigurdsson13, Daniel H Teitelbaum14, John Thompson15, Charles Vanderpool16, Juliana F Vaughan17, Benjamin Li18, Nader N Youssef19, Robert S Venick20, Samuel A Kocoshis3. 1. Department of Pediatric Medicine, Gastroenterology, Hepatology and Nutrition, Texas Children's Hospital and Baylor College of Medicine, Houston, TX. Electronic address: bac@bcm.edu. 2. Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL. 3. Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH. 4. Pediatric Gastroenterology, LeBonheur Children's Hospital and University of Tennessee Health Science Center, Memphis, TN. 5. Division of Pediatric Gastroenterology, Hepatology and Nutrition, University of Alabama at Birmingham and Children's of Alabama, Birmingham, AL. 6. Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, MA. 7. Gastroenterology Department, Great Ormond Street Hospital for Children, London, United Kingdom. 8. Hepatobiliary and Intestinal Failure Programs, Seattle Children's Hospital, Seattle, WA. 9. Intestinal Rehabilitation Center, Children's Mercy Hospitals & Clinics, Kansas City, MO. 10. Intestinal Rehabilitation Program, Nebraska Medical Center, Omaha, NE. 11. Gastroenterology, Hepatology and Nutrition, Children's Hospital Los Angeles and Keck School of Medicine, University of Southern California, Los Angeles, CA. 12. Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI. 13. Division of Pediatric Gastroenterology, University of Wisconsin School of Medicine and Public Health, Madison, WI. 14. Pediatric Surgery, CS Mott Children's Hospital, Ann Arbor, MI. 15. Division of Pediatric Gastroenterology and Nutrition, Children's Hospital at Montefiore, New York, NY. 16. Division of Pediatric Gastroenterology, Hepatology & Nutrition, Riley Hospital for Children and Indiana University School of Medicine, Indianapolis, IN. 17. Gastroenterology, Nutrition, and Hepatology, Arkansas Children's Hospital, Little Rock, AR. 18. Department of Statistics, NPS Pharmaceuticals, Inc., Lexington, MA. 19. Department of Clinical Research and Development, NPS Pharmaceuticals, Inc., Lexington, MA. 20. Departments of Pediatrics and Surgery, Mattel Children's Hospital UCLA, Los Angeles, CA.
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.
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.
Authors: Sen Lin; Barbara Stoll; Jason Robinson; Jose J Pastor; Juan C Marini; Ignacio R Ipharraguerre; Bolette Hartmann; Jens J Holst; Stephanie Cruz; Patricio Lau; Oluyinka Olutoye; Zhengfeng Fang; Douglas G Burrin Journal: Am J Physiol Gastrointest Liver Physiol Date: 2019-03-28 Impact factor: 4.052
Authors: Patrick J Javid; Assaf P Oron; Christopher P Duggan; Robert H Squires; Simon P Horslen Journal: J Pediatr Surg Date: 2017-09-05 Impact factor: 2.545