title: Relative bioavailability and the effect of meal type and timing on the pharmacokinetics of migalastat in healthy volunteers.
abstract: Migalastat HCl is an investigational, pharmacological chaperone for mutant α-galactosidase A, which is responsible for Fabry disease, an X-linked, lysosomal storage disorder. Two Phase I studies evaluated relative bioavailability, effect of meal type and timing on pharmacokinetics, safety, and tolerability of migalastat HCl in healthy volunteers. Study 1 (N = 15, 19-55 years): single 100-mg doses of migalastat HCl capsule and solution formulations were bioequivalent. The ratios of LSM (90% CIs) for Cmax were 97.1% (86.8-109) and AUC0-inf 97.9% (88.8-108) under fasted conditions. Single 100-mg doses of migalastat HCl capsules administered with a high-fat meal decreased Cmax by 40% and AUC0-inf by 37%. A high-fat meal delayed tmax by approximately 1 hour. Study 2 (N = 20, 18-65 years): A high-fat or light meal up to 1 hour before or after administration of single 150 mg doses of migalastat HCl capsules decreased Cmax and AUC0-inf up to 40%, but had no apparent effect on tmax (range of medians with food: 1.5-3 hours, median fasted: 3 hours). A 50-g glucose drink co-administered with migalastat HCL did not result in clinically significant changes in migalastat absorption. No serious safety or tolerability issues were identified.
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, Stockley Park, Uxbridge, UK.
authors.forename: Salim G
authors.initials: SG
authors.lastname: Janmohamed
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; D001682:Biological Availability; D002214:Capsules; D018592:Cross-Over Studies; D004041:Dietary Fats / Q000008:administration & dosage; D004334:Drug Administration Schedule; D004339:Drug Compounding; D005215:Fasting / Q000097:blood; D005260:Female; D018565:Food-Drug Interactions; D006207:Half-Life; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D062407:Meals; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D019999:Pharmaceutical Solutions; D019518:Postprandial Period; D013781:Texas; D013810:Therapeutic Equivalency; D055815:Young Adult
chemical_list: D002214:Capsules; D004041:Dietary Fats; D019999:Pharmaceutical Solutions; D017485:1-Deoxynojirimycin; C090092:migalastat
keywords: Fabry disease; food effect; migalastat HCl; pharmacokinetics