Hoch, Matthias, Bebrevska, Lidiya, Singh, Namrata and Hourcade-Potelleret, Florence (2023) Relative Bioavailability and Food Effect of Asciminib Pediatric Mini-tablet Formulation Compared to the Reference Tablet Formulation in Healthy Adult Participants. Clinical Pharmacology in Drug Development.

Abstract

Asciminib, a first-in-class allosteric BCR::ABL1 inhibitor that works by specifically targeting the ABL myristoyl pocket (STAMP), is used in the treatment of chronic myeloid leukemia (CML). This was a randomized, single dose, open-label, four-period cross-over study in healthy adult participants (N=24) which evaluated the relative bioavailability of a single 40 mg dose of asciminib pediatric formulation (1 mg mini-tablets) compared with the reference adult tablet, under fasting conditions. In addition, the effect of food on the bioavailability of the mini-tablet formulation was evaluated. Under fasting conditions, asciminib exposure was similar for both formulations (geometric mean [Gmean] area under the concentration-time curve from time 0 to infinity [AUCinf] 5970 ng·h/mL 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 (CI)]: 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). Both formulations were well tolerated. The mini-tablets were assessed to be easy to ingest with good palatability. Results gained from this study will be utilized in physiologically-based pharmacokinetic (PBPK) modelling to define asciminib starting doses in a pivotal pediatric clinical trial.

Item Type:	Article
Date Deposited:	31 Jan 2023 00:45
Last Modified:	31 Jan 2023 00:45
URI:	https://oak.novartis.com/id/eprint/48426