Relative Bioavailability and Food Effect of Asciminib Pediatric Mini-tablet Formulation Compared to the Reference Tablet Formulation in Healthy Adult Participants.

ABSTRACT

Asciminib, a first-in-class allosteric BCRABL1 inhibitor that works by Specifically Targeting the ABL Myristoyl Pocket (STAMP) is used in the treatment of chronic myeloid leukemia. We describe a randomized, single-dose, open-label, four-period crossover study in healthy adult participants (N = 24) which evaluated the relative bioavailability of a single 40-mg dose of asciminib in pediatric formulation (1-mg mini-tablets) compared with the reference adult tablet under fasted conditions. Additionally, the effect of food on the bioavailability of the mini-tablet formulation was evaluated. Under fasted conditions, asciminib exposure was similar for both formulations (geometric mean [Gmean ] area under the concentration-time curve from time 0 to infinity [AUCinf ] 5970 and 5700 ng ×h/mL, respectively). Food decreased the AUCinf and maximum plasma concentration (Cmax ) of the asciminib mini-tablets; this effect was more pronounced with a high-fat meal (Gmean ratios [90% confidence interval] fasted/low-fat meal, 0.42 [0.38-047], 0.32 [0.28-0.37], respectively; fasted/high-fat meal, 0.30 [0.27-0.34], 0.22 [0.19-0.25], respectively). The mini-tablets were assessed to be easy to ingest with good palatability. Asciminib doses for a pivotal pediatric clinical trial will be defined using physiologically based pharmacokinetic modeling, which will consider the age and the higher food effect observed with the mini-tablets.