title: An open-label study to determine the pharmacokinetics and safety of migalastat HCl in subjects with impaired renal function and healthy subjects with normal renal function.
abstract: Renal function may progressively decline in patients with Fabry disease. This study assessed pharmacokinetics, safety, and tolerability of a single oral dose of migalastat HCl 150 mg in subjects with normal or mildly, moderately, or severely impaired renal function.
  
  
  
  Volunteers were enrolled into two cohorts stratified for renal function calculated using the Cockcroft-Gault equation for creatinine clearance. Pharmacokinetic parameters determined were: area under the concentration-time curve (AUC) from time zero to the last measurable concentration postdose (AUC0-t ) and extrapolated to infinity (AUC0-∞ ), maximum observed concentration (Cmax ), time to Cmax (tmax ), concentration at 48 hours postdose (C48h ), terminal elimination half-life (t1/2 ), oral clearance (CL/F), and apparent terminal elimination rate constant (λz) (ClinicalTrials.gov registration: NCT01730469).
  
  
  
  Thirty-two subjects enrolled and completed the study (Cohort 1: n = 24; Cohort 2: n = 8). Migalastat clearance decreased with increasing renal impairment, resulting in increases in migalastat HCl plasma t1/2 , AUC0-∞ , and C48h compared with subjects with normal renal function. Incidence of adverse events was comparable across all renal function groups.
  
  
  
  Plasma migalastat clearance decreased as degree of renal impairment increased. Data from the migalastat HCl clinical program will guide dosing and intervals for patients with Fabry disease with renal impairment.
authors.affiliation: Amicus Therapeutics, Cranbury, NJ, USA.
authors.forename: Franklin K
authors.initials: FK
authors.lastname: Johnson
authors.affiliation: GlaxoSmithKline, Research Triangle Park, NC, USA.
authors.forename: Paul N
authors.initials: PN
authors.lastname: Mudd
authors.affiliation: GlaxoSmithKline, Research Triangle Park, NC, USA.
authors.forename: Tara
authors.initials: T
authors.lastname: DiMino
authors.affiliation: Amicus Therapeutics, Cranbury, NJ, USA.
authors.forename: Jennie
authors.initials: J
authors.lastname: Vosk
authors.affiliation: Amicus Therapeutics, Cranbury, NJ, USA.
authors.forename: Sheela
authors.initials: S
authors.lastname: Sitaraman
authors.affiliation: Amicus Therapeutics, Cranbury, NJ, USA.
authors.forename: Pol
authors.initials: P
authors.lastname: Boudes
authors.affiliation: GlaxoSmithKline, Research Triangle Park, NC, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: France
authors.affiliation: Amicus Therapeutics, Cranbury, NJ, USA.
authors.forename: Carrolee
authors.initials: C
authors.lastname: Barlow
mesh_terms: D017485:1-Deoxynojirimycin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D005260:Female; D065089:Glycoside Hydrolase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000503:physiopathology*; D007674:Kidney Diseases / Q000097:blood / Q000175:diagnosis / Q000503:physiopathology*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008954:Models, Biological; D012720:Severity of Illness Index; D014481:United States; D055815:Young Adult
chemical_list: D065089:Glycoside Hydrolase Inhibitors; D017485:1-Deoxynojirimycin; C090092:migalastat
keywords: Fabry disease; kidney; migalastat HCl; pharmacokinetics; renal impairment