PMID- 30740733
OWN - NLM
STAT- MEDLINE
DCOM- 20200401
LR  - 20220408
IS  - 1573-2665 (Electronic)
IS  - 0141-8955 (Print)
IS  - 0141-8955 (Linking)
VI  - 42
IP  - 1
DP  - 2019 Jan
TI  - Results from a 78-week, single-arm, open-label phase 2 study to evaluate UX007 in 
      pediatric and adult patients with severe long-chain fatty acid oxidation 
      disorders (LC-FAOD).
PG  - 169-177
LID - 10.1002/jimd.12038 [doi]
AB  - Long-chain fatty acid oxidation disorders (LC-FAOD) are rare disorders 
      characterized by acute crises of energy metabolism and severe energy deficiency 
      that may present with cardiomyopathy, hypoglycemia, and/or rhabdomyolysis, which 
      can lead to frequent hospitalizations and early death. An open-label Phase 2 
      study evaluated the efficacy of UX007, an investigational odd-carbon medium-chain 
      triglyceride, in 29 subjects with severe LC-FAOD. UX007 was administered over 
      78 weeks at a target dose of 25-35% total daily caloric intake (mean 27.5%). The 
      frequency and duration of major clinical events (hospitalizations, emergency room 
      visits, and emergency home interventions due to rhabdomyolysis, hypoglycemia, and 
      cardiomyopathy) occurring during 78 weeks of UX007 treatment was compared with 
      the frequency and duration of events captured retrospectively from medical 
      records for 78 weeks before UX007 initiation. The mean annualized event rates 
      decreased from 1.69 to 0.88 events/year following UX007 initiation (p = 0.021; 
      48.1% reduction). The mean annualized duration rate decreased from 5.96 to 
      2.96 days/year (p = 0.028; 50.3% reduction). Hospitalizations due to 
      rhabdomyolysis, the most common event, decreased from 1.03 to 0.63 events/year (p 
      = 0.104; 38.7% reduction). Initiation of UX007 eliminated hypoglycemia events 
      leading to hospitalization (from 11 pre-UX007 hospitalizations, 0.30 events/year 
      vs. 0; p = 0.067) and intensive care unit (ICU) care (from 2 pre-UX007 ICU 
      admissions, 0.05 events/year vs. 0; p = 0.161) and reduced cardiomyopathy events 
      (3 events vs. 1 event; 0.07 to 0.02 events/year; 69.7% decrease). The majority of 
      treatment-related adverse events (AEs) were mild to moderate gastrointestinal 
      symptoms, including diarrhea, vomiting, and abdominal or gastrointestinal pain, 
      which can be managed with smaller, frequent doses mixed with food.
CI  - (c) 2018 The Authors. Journal of Inherited Metabolic Disease published by John 
      Wiley & Sons Ltd on behalf of SSIEM.
FAU - Vockley, Jerry
AU  - Vockley J
AD  - School of Medicine and Graduate School of Public Health, University of 
      Pittsburgh, Pittsburgh, Pennsylvania, USA.
AD  - Children's Hospital of Pittsburgh, UPMC, 4401 Penn Avenue, Pittsburgh, 
      Pennsylvania, 15224, USA.
FAU - Burton, Barbara
AU  - Burton B
AD  - Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA.
FAU - Berry, Gerard T
AU  - Berry GT
AD  - Boston Children's Hospital, Boston, Massachusetts, USA.
FAU - Longo, Nicola
AU  - Longo N
AD  - University of Utah, Salt Lake City, Utah, USA.
FAU - Phillips, John
AU  - Phillips J
AD  - Vanderbilt University Medical Center, Nashville, Tennessee, USA.
FAU - Sanchez-Valle, Amarilis
AU  - Sanchez-Valle A
AD  - USF Health, Morsani College of Medicine, Tampa, Florida, USA.
FAU - Tanpaiboon, Pranoot
AU  - Tanpaiboon P
AD  - Children's National Health System, Washington, District of Columbia, USA.
FAU - Grunewald, Stephanie
AU  - Grunewald S
AD  - Great Ormond Street, UCL Institute of Child Health, London, UK.
FAU - Murphy, Elaine
AU  - Murphy E
AD  - National Hospital for Neurology and Neurosurgery, London, UK.
FAU - Bowden, Alexandra
AU  - Bowden A
AD  - Ultragenyx Pharmaceutical Inc., Novato, California, USA.
FAU - Chen, Wencong
AU  - Chen W
AD  - Ultragenyx Pharmaceutical Inc., Novato, California, USA.
FAU - Chen, Chao-Yin
AU  - Chen CY
AD  - Ultragenyx Pharmaceutical Inc., Novato, California, USA.
FAU - Cataldo, Jason
AU  - Cataldo J
AD  - Ultragenyx Pharmaceutical Inc., Novato, California, USA.
FAU - Marsden, Deborah
AU  - Marsden D
AD  - Ultragenyx Pharmaceutical Inc., Novato, California, USA.
FAU - Kakkis, Emil
AU  - Kakkis E
AD  - Ultragenyx Pharmaceutical Inc., Novato, California, USA.
LA  - eng
GR  - R01 DK078775/DK/NIDDK NIH HHS/United States
GR  - UL1 TR001102/TR/NCATS NIH HHS/United States
GR  - UL1 TR002538/TR/NCATS NIH HHS/United States
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Inherit Metab Dis
JT  - Journal of inherited metabolic disease
JID - 7910918
RN  - 0 (Fatty Acids)
RN  - 0 (Triglycerides)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Cardiomyopathies/metabolism
MH  - Child
MH  - Child, Preschool
MH  - Fatty Acids/*metabolism
MH  - Female
MH  - Humans
MH  - Hypoglycemia/metabolism
MH  - Infant
MH  - Infant, Newborn
MH  - Lipid Metabolism, Inborn Errors/*drug therapy/metabolism
MH  - Male
MH  - Middle Aged
MH  - Oxidation-Reduction/*drug effects
MH  - Retrospective Studies
MH  - Rhabdomyolysis/metabolism
MH  - Triglycerides/*administration & dosage
MH  - Young Adult
PMC - PMC6348052
MID - NIHMS1004062
EDAT- 2019/02/12 06:00
MHDA- 2020/04/02 06:00
PMCR- 2020/01/01
CRDT- 2019/02/12 06:00
PHST- 2019/02/12 06:00 [entrez]
PHST- 2019/02/12 06:00 [pubmed]
PHST- 2020/04/02 06:00 [medline]
PHST- 2020/01/01 00:00 [pmc-release]
AID - 10.1002/jimd.12038 [doi]
PST - ppublish
SO  - J Inherit Metab Dis. 2019 Jan;42(1):169-177. doi: 10.1002/jimd.12038.