An open-label study to determine the pharmacokinetics and safety of migalastat HCl in subjects with impaired renal function and healthy subjects with normal renal function.

ABSTRACT

OBJECTIVES: Renal function may progressively decline in patients with Fabry disease. This study assessed pharmacokinetics, safety, and tolerability of a single oral dose of migalastat HCl 150 mg in subjects with normal or mildly, moderately, or severely impaired renal function. METHODS: Volunteers were enrolled into two cohorts stratified for renal function calculated using the Cockcroft-Gault equation for creatinine clearance. Pharmacokinetic parameters determined were area under the concentration-time curve (AUC) from time zero to the last measurable concentration postdose (AUC0-t ) and extrapolated to infinity (AUC0-∞ ), maximum observed concentration (Cmax ), time to Cmax (tmax ), concentration at 48 hours postdose (C48h ), terminal elimination half-life (t1/2 ), oral clearance (CL/F), and apparent terminal elimination rate constant (λz) (ClinicalTrials.gov registration NCT01730469). RESULTS: Thirty-two subjects enrolled and completed the study (Cohort 1 n = 24; Cohort 2 n = 8). Migalastat clearance decreased with increasing renal impairment, resulting in increases in migalastat HCl plasma t1/2 , AUC0-∞ , and C48h compared with subjects with normal renal function. Incidence of adverse events was comparable across all renal function groups. CONCLUSIONS: Plasma migalastat clearance decreased as degree of renal impairment increased. Data from the migalastat HCl clinical program will guide dosing and intervals for patients with Fabry disease with renal impairment.