Three phase 1 studies of eliglustat tartrate (Genz-112638), an oral inhibitor of 
glucosylceramide synthase under development for treating Gaucher disease type 1 
(GD1), evaluated the safety, tolerability, and pharmacokinetics in healthy 
volunteers after escalating single doses (n = 99), escalating multiple doses (n 
= 36), and food (n = 24). Eliglustat tartrate was well tolerated at single doses 
≤ 20 mg/kg and multiple doses ≤ 200 mg bid, with 50 mg bid producing plasma 
concentrations in the predicted therapeutic range. No serious adverse events 
occurred. Mild to moderate events of nausea, dizziness, and vomiting increased 
in frequency with escalating single and multiple doses. Single doses ≥ 10 mg/kg 
caused mild increases in electrocardiogram PR, QRS, and QT/QTc intervals. 
Single-dose pharmacokinetics showed dose linearity but not proportionality. 
Maximum plasma concentrations occurred at ~2 hours, followed by a monophasic 
decline with a ~6-hour terminal half-life. Unchanged drug in 8-hour urine 
collections was <1.5% of administered doses. Food did not significantly affect 
the rate or extent of absorption. Multiple-dose pharmacokinetics was nonlinear, 
showing higher than expected plasma drug concentrations. Steady state was 
reached ~60 hours after bid dosing. Higher drug exposure occurred in slower 
CYP2D6 metabolizers. Based on favorable results in healthy participants, a phase 
2 trial of eliglustat tartrate was initiated in GD1 patients.