PMID- 32885845
OWN - NLM
STAT- MEDLINE
DCOM- 20211223
LR  - 20211223
IS  - 1573-2665 (Electronic)
IS  - 0141-8955 (Print)
IS  - 0141-8955 (Linking)
VI  - 44
IP  - 1
DP  - 2021 Jan
TI  - Effects of triheptanoin (UX007) in patients with long-chain fatty acid oxidation 
      disorders: Results from an open-label, long-term extension study.
PG  - 253-263
LID - 10.1002/jimd.12313 [doi]
AB  - Long-chain fatty acid oxidation disorders (LC-FAOD) are autosomal recessive 
      conditions that impair conversion of long-chain fatty acids into energy, leading 
      to significant clinical symptoms. Triheptanoin is a highly purified, 7-carbon 
      chain triglyceride approved in the United States as a source of calories and 
      fatty acids for treatment of pediatric and adult patients with molecularly 
      confirmed LC-FAOD. CL202 is an open-label, long-term extension study evaluating 
      triheptanoin (Dojolvi) safety and efficacy in patients with LC-FAOD. Patients 
      rolled over from the CL201 triheptanoin clinical trial (rollover); were 
      triheptanoin-naive (naive); or had participated in investigator-sponsored 
      trials/expanded access programs (IST/other). Results focus on rollover and naive 
      groups, as pretreatment data allow comparison. Primary outcomes were annual rate 
      and duration of major clinical events (MCEs; rhabdomyolysis, hypoglycemia, and 
      cardiomyopathy events). Seventy-five patients were enrolled (24 rollover, 20 
      naive, 31 IST/other). Mean study duration was 23.0 months for rollover, 15.7 
      months for naive, and 34.7 months for IST/other. In the rollover group, mean 
      annualized MCE rate decreased from 1.76 events/year pre-triheptanoin to 0.96 
      events/year with triheptanoin (P = .0319). Median MCE duration was reduced by 
      66%. In the naive group, median annualized MCE rate decreased from 2.33 
      events/year pre-triheptanoin to 0.71 events/year with triheptanoin (P = .1072). 
      Median MCE duration was reduced by 80%. The most common related adverse events 
      (AEs) were diarrhea, abdominal pain/discomfort, and vomiting, most mild to 
      moderate. Three patients had serious AEs (diverticulitis, ileus, rhabdomyolysis) 
      possibly related to drug; all resolved. Two patients had AEs leading to death; 
      neither drug related. Triheptanoin reduced rate and duration of MCEs. Safety was 
      consistent with previous observations.
CI  - (c) 2020 The Authors. Journal of Inherited Metabolic Disease published by John 
      Wiley & Sons Ltd on behalf of SSIEM.
FAU - Vockley, Jerry
AU  - Vockley J
AUID- ORCID: 0000-0002-8180-6457
AD  - University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
FAU - Burton, Barbara
AU  - Burton B
AD  - Ann & Robert H. Lurie Children's Hospital, Chicago, Illinois, USA.
FAU - Berry, Gerard
AU  - Berry G
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 - Chapman, Kimberly
AU  - Chapman K
AD  - Children's National Health System, Washington, District of Columbia, 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 Hospital and Institute of Child Health, NIHR Biomedical 
      Research Center (BRC), UCL, London, UK.
FAU - Murphy, Elaine
AU  - Murphy E
AD  - National Hospital for Neurology and Neurosurgery, London, UK.
FAU - Lu, Xiaoxiao
AU  - Lu X
AD  - Ultragenyx Pharmaceutical Inc., Novato, California, USA.
FAU - Cataldo, Jason
AU  - Cataldo J
AD  - Ultragenyx Pharmaceutical Inc., Novato, California, USA.
LA  - eng
GR  - R01 DK078775/DK/NIDDK NIH HHS/United States
GR  - UL1 TR002538/TR/NCATS NIH HHS/United States
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20200914
PL  - United States
TA  - J Inherit Metab Dis
JT  - Journal of inherited metabolic disease
JID - 7910918
RN  - 0 (Fatty Acids)
RN  - 0 (Triglycerides)
RN  - 2P6O7CFW5K (triheptanoin)
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  - Lipid Metabolism, Inborn Errors/*drug therapy/metabolism
MH  - Male
MH  - Middle Aged
MH  - Oxidation-Reduction/*drug effects
MH  - Rhabdomyolysis/metabolism
MH  - Triglycerides/*administration & dosage
MH  - United Kingdom
MH  - United States
MH  - Young Adult
PMC - PMC7891391
OTO - NOTNLM
OT  - cardiomyopathy
OT  - long-chain fatty acid oxidation disorders (LC-FAOD)
OT  - rhabdomyolysis
OT  - triheptanoin (UX007)
COIS- J. C. and X. L. are an employee and shareholder of Ultragenyx Pharmaceutical Inc. 
      J. V., B. B., G. B., N. L., J. P., A. S.-V., K. C., P. T., S. G., and E. M. have 
      served as a clinical investigator in clinical trials with the product 
      manufactured by Ultragenyx Pharmaceutical Inc.
EDAT- 2020/09/05 06:00
MHDA- 2021/12/24 06:00
PMCR- 2021/02/18
CRDT- 2020/09/05 06:00
PHST- 2020/01/27 00:00 [received]
PHST- 2020/08/31 00:00 [revised]
PHST- 2020/09/01 00:00 [accepted]
PHST- 2020/09/05 06:00 [pubmed]
PHST- 2021/12/24 06:00 [medline]
PHST- 2020/09/05 06:00 [entrez]
PHST- 2021/02/18 00:00 [pmc-release]
AID - JIMD12313 [pii]
AID - 10.1002/jimd.12313 [doi]
PST - ppublish
SO  - J Inherit Metab Dis. 2021 Jan;44(1):253-263. doi: 10.1002/jimd.12313. Epub 2020 
      Sep 14.