PMID- 28699267
OWN - NLM
STAT- MEDLINE
DCOM- 20190514
LR  - 20220409
IS  - 1532-6535 (Electronic)
IS  - 0009-9236 (Linking)
VI  - 103
IP  - 4
DP  - 2018 Apr
TI  - Lucerastat, an Iminosugar for Substrate Reduction Therapy: Tolerability, 
      Pharmacodynamics, and Pharmacokinetics in Patients With Fabry Disease on Enzyme 
      Replacement.
PG  - 703-711
LID - 10.1002/cpt.790 [doi]
AB  - Lucerastat is a glucosylceramide synthase inhibitor aimed at reducing production 
      of glycosphingolipids (GSLs), including those accumulating in Fabry disease. The 
      safety, tolerability, pharmacodynamics, and pharmacokinetics of oral lucerastat 
      were evaluated in an exploratory study in patients with Fabry disease. In this 
      single-center, open-label, randomized study, 10 patients received lucerastat 
      1,000 mg b.i.d. for 12 weeks in addition to enzyme replacement therapy (ERT; the 
      lucerastat group). Four patients with Fabry disease received ERT only. Eight 
      patients reported 17 adverse events (AEs) in the lucerastat group. No clinically 
      relevant safety abnormalities were observed. The mean (SD) levels of the plasma 
      GSLs, glucosylceramide, lactosylceramide, and globotriaosylceramide, were 
      significantly decreased from baseline in the lucerastat group (-49.0% (16.5%), 
      -32.7% (13.0%), and -55.0% (10.4%), respectively). Lucerastat 1,000 mg b.i.d. was 
      well tolerated in patients with Fabry disease over 12 weeks. A marked decrease in 
      plasma GSLs was observed, suggesting clinical potential for lucerastat in 
      patients with Fabry disease.
CI  - (c) 2017 American Society for Clinical Pharmacology and Therapeutics.
FAU - Guerard, Nicolas
AU  - Guerard N
AD  - Department of Global Clinical Pharmacology, Idorsia Pharmaceuticals Ltd, 
      Allschwil, Switzerland.
FAU - Oder, Daniel
AU  - Oder D
AD  - Fabry Center for Interdisciplinary Therapy (FAZiT), Comprehensive Heart Failure 
      Center (CHFC), and Department of Internal Medicine I, Divisions of Cardiology and 
      Nephrology, University Hospital Wurzburg, Wurzburg, Germany.
FAU - Nordbeck, Peter
AU  - Nordbeck P
AD  - Fabry Center for Interdisciplinary Therapy (FAZiT), Comprehensive Heart Failure 
      Center (CHFC), and Department of Internal Medicine I, Divisions of Cardiology and 
      Nephrology, University Hospital Wurzburg, Wurzburg, Germany.
FAU - Zwingelstein, Christian
AU  - Zwingelstein C
AD  - Department of Clinical Pharmacology, Actelion Pharmaceuticals Ltd, Allschwil, 
      Switzerland.
FAU - Morand, Olivier
AU  - Morand O
AD  - Department of Global Clinical Science, Idorsia Pharmaceuticals Ltd, Allschwil, 
      Switzerland.
FAU - Welford, Richard W D
AU  - Welford RWD
AD  - DD Biology, Translational Science, Idorsia Pharmaceuticals Ltd, Allschwil, 
      Switzerland.
FAU - Dingemanse, Jasper
AU  - Dingemanse J
AD  - Department of Global Clinical Pharmacology, Idorsia Pharmaceuticals Ltd, 
      Allschwil, Switzerland.
FAU - Wanner, Christoph
AU  - Wanner C
AD  - Fabry Center for Interdisciplinary Therapy (FAZiT), Comprehensive Heart Failure 
      Center (CHFC), and Department of Internal Medicine I, Divisions of Cardiology and 
      Nephrology, University Hospital Wurzburg, Wurzburg, Germany.
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20170828
PL  - United States
TA  - Clin Pharmacol Ther
JT  - Clinical pharmacology and therapeutics
JID - 0372741
RN  - 0 (Enzyme Inhibitors)
RN  - 19130-96-2 (1-Deoxynojirimycin)
RN  - C4XNY919FW (migalastat)
RN  - EC 2.4.1.- (Glucosyltransferases)
RN  - EC 2.4.1.80 (ceramide glucosyltransferase)
RN  - EC 3.2.1.22 (alpha-Galactosidase)
SB  - IM
MH  - 1-Deoxynojirimycin/administration & dosage/*analogs & 
      derivatives/pharmacokinetics
MH  - Administration, Oral
MH  - Adult
MH  - Drug Monitoring/methods
MH  - Enzyme Inhibitors/administration & dosage/pharmacokinetics
MH  - Enzyme Replacement Therapy/*methods
MH  - Fabry Disease/*drug therapy
MH  - Female
MH  - Glucosyltransferases/antagonists & inhibitors
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Treatment Outcome
MH  - alpha-Galactosidase/*metabolism
EDAT- 2017/07/13 06:00
MHDA- 2019/05/15 06:00
CRDT- 2017/07/13 06:00
PHST- 2017/05/09 00:00 [received]
PHST- 2017/06/23 00:00 [revised]
PHST- 2017/06/29 00:00 [accepted]
PHST- 2017/07/13 06:00 [pubmed]
PHST- 2019/05/15 06:00 [medline]
PHST- 2017/07/13 06:00 [entrez]
AID - 10.1002/cpt.790 [doi]
PST - ppublish
SO  - Clin Pharmacol Ther. 2018 Apr;103(4):703-711. doi: 10.1002/cpt.790. Epub 2017 Aug 
      28.