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

• Published in: Clinical pharmacology in drug development Vol. 12; no. 5; pp. 484 - 492
• Main Authors: Hoch, Matthias, Bebrevska, Lidiya, Singh, Namrata, Hourcade‐Potelleret, Florence
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.05.2023
• Subjects: Adult; asciminib; Bioavailability; Biological Availability; Child; chronic myeloid leukemia; Cross-Over Studies; Food; food effect; Humans; pediatric formulation; Pediatrics; Pyrazoles - pharmacokinetics; Tablets; chronic myeloid leukemia; food effect; bioavailability; pediatric formulation; asciminib
• ISSN: 2160-763X; 2160-7648; 2160-7648
• DOI: 10.1002/cpdd.1213

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. 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.