Fig 1.
Flow diagram of subject disposition.
Stage 1 was comprised of 3 periods. Period 1 patients received ERT alone on Day 1, Period 2 patients received ERT co-administered with 150 mg migalastat HCl on Day 1, and Period 3 patients received migalastat HCl alone on Day 7 (i.e., 7 days after the previous ERT infusion). A new cohort of patients was recruited for Stage 2. Stage 2 was comprised of 2 periods. Period 1 patients received ERT alone on Day 1 and Period 2 patients received ERT co-administered with 450 mg migalastat HCl on Day 1.
Table 1.
Patient Disposition.
Table 2.
Demographic and Clinical Characteristics Related to Fabry Disease by Study Stage and Overall.
Fig 2.
Two-by-two panel of total plasma α-Gal A activity AUC stick plots for agalsidase alone and co-administered with migalastat HCl.
Upper left and right plots show individual patient changes between agalsidase beta alone and when co-administered with 150 mg migalastat HCl (upper left) or 450 mg migalastat (upper right) for plasma α-Gal activity AUC0-∞. Lower left and right plots show individual patient changes between agalsidase alfa alone and when co-administered with 150 mg migalastat HCl (lower left) or 450 mg migalastat HCl (lower right) for plasma α-Gal activity AUC0-∞. Patients’ actual ID number is blinded with the following code: Treatment and Dose (AB = agalsidase beta, 0.5 = 0.5 mg/kg dose or 1.0 = 1.0 mg/kg dose; AA = agalsidase alfa, 0.2 = 0.2 mg/kg dose)–migalastat HCl dose (150 = 150 mg, 450 = 450 mg)–arbitrary sequential number (1 through 23). Increases in plasma α-Gal activity AUC0-∞ are observed for all patients with the exception of AB1.0-450-14 shown in the upper left plot.
Table 3.
Summary of α-Gal A Activity Pharmacokinetic Parameters by Treatment.
Fig 3.
Mean (SD) total plasma α-Gal A activity-time profile panel for all treatments.
Mean α-Gal A activity increased at all post-dose time points for all treatments after co-administration with migalastat HCl. Increases after co-administration do not appear to be related to migalastat dose.
Table 4.
Summary of α-Gal A Activity Levels in Skin.
Fig 4.
Mean (CV%) change from baseline on Days 2 and 7 for 1.0 mg/kg, 0.5 mg/kg, and 0.2 mg/kg agalsidase alone and agalsidase co-administered with 150 mg or 450 mg migalastat HCl.
Table 5.
Plasma Migalastat PK Summary.
Fig 5.
Mean (SD) plasma migalastat concentration-time profiles following co-administration of agalsidase with 450 mg or 150 mg migalastat HCl, and 150 mg migalastat HCl alone.
Whether co-administered with agalsidase (Stage 1/Period 2) or administered alone (Stage 1/Period 3), plasma migalastat concentrations were similar at all post-dose time points. Mean concentration-time profiles following administration of 450 mg migalastat HCl (Stage 2/Period 2) were approximately dose proportional to 150 mg (Stage 1).