Pharmacokinetic Analyses

Blood samples for plasma analysis were collected pre-dose, and then at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 48 h after dose administration on Day 1. Additional samples were analyzed from follow-up visits on Days 8, 15, 30, 60, and 90. Vupanorsen plasma concentration was measured using a validated electrochemiluminescence method (data on file). PK parameters were determined from plasma concentration–time data using standard noncompartmental methods by an internally validated software system (oNCA version 2.4.33). Vupanorsen plasma PK parameters included overall and dose-normalized AUC, area under the concentration–time curve values (AUC from time 0 to the quantifiable concentration 24 h and 48 h post-dose [AUC_{24 h} and AUC_48h], AUC from time 0 to the time of the last quantifiable concentration [AUC_last], AUC from time 0 extrapolated to infinite time [AUC_inf]), C_max, T_max, t_½, apparent clearance (CL/F), and apparent volume of distribution (Vz/F).