Migalastat HCl is an investigational, oral treatment for Fabry disease, an X-linked lysosomal storage disorder. Four Phase 1 studies were conducted to determine the pharmacokinetics, pharmacodynamics, safety, and tolerability of migalastat. Healthy volunteers (N = 124), 18-55 years old, received migalastat HCl single (25 mg-2000 mg) or twice-daily doses (50 mg, 150 mg) for 7 days in a double-blind, placebo-controlled fashion. Migalastat pharmacokinetics were dose-proportional (AUC∞ range: 1129-72 838 ng h/mL, Cmax range: 200.5-13 844 ng/mL, t1/2 3-4 hours). Steady state was achieved by Day 7. Up to 67% of the dose was excreted as unchanged drug in urine. Increased α-Gal A activity was dose related. No abnormal cardiac effects, including prolonged QTc intervals, were observed. The pharmacokinetics of migalastat were well characterized in these Phase 1 studies conducted healthy volunteers. The 150 mg dose of migalastat HCl administered BID for 7 days was generally safe and well tolerated. A TQT study demonstrated lack of a positive signal at therapeutic and supra-therapeutic doses. Increases in α-Gal A enzyme activity for the 150 mg dose observed in healthy subjects suggested a successful proof of mechanism for further investigations.
Keywords: Fabry disease; enzyme replacement therapy; lysosomal storage disorders; pharmacokinetics; pharmacological chaperone.
© The Author(s) 2013.