Pharmacokinetics and Safety of Migalastat HCl and Effects on Agalsidase Activity in Healthy Volunteers

摘要: Migalastat HCl is an investigational, oral treatment for Fabry disease, 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 single (25 mg-2000 mg) or twice-daily doses (50 mg, 150 7 days in a double-blind, placebo-controlled fashion. pharmacokinetics dose-proportional (AUC∞ range: 1129-72 838 ng h/mL, Cmax 200.5-13 844 ng/mL, t1/2 3-4 hours). Steady state was achieved by Day 7. Up 67% dose excreted as unchanged drug urine. Increased α-Gal A activity related. No abnormal cardiac effects, including prolonged QTc intervals, observed. The well characterized these healthy volunteers. mg administered BID generally safe tolerated. TQT study demonstrated lack positive signal at therapeutic supra-therapeutic doses. Increases enzyme observed subjects suggested successful proof mechanism further investigations.