Pharmacokinetic results
Results from Module 1A demonstrated a half-life for samuraciclib of approximately 75 h after single dosing, supporting OD dosing. Samuraciclib had moderate to high apparent clearance and was extensively distributed. Dose proportionality in exposure (120–480 mg) was observed after single and multiple dosing. Samuraciclib PK appeared time independent, although this was based on a small sample size. Steady state was achieved between 8 and 15 days of dosing (Supplementary Figs. Results from Module 1B-1 demonstrated that steady state was achieved by Cycle 1 Day 8 and PK trough levels then remained consistent throughout the study module following multiple dosing. The geometric mean trough plasma concentration was 39.22 ng/mL.Analysis of the trough PK samuraciclib data from Module 2A, along with Module 1A trough PK and fulvestrant trough PK data and previously reported data