Hoch, Matthias, Weis, Wendy, Huth, Felix, Seshulatha, Jamalapuram, Quinlan, Michelle, Amarnath, Bandaru, Bellibas, Al, Mirkou, Asmae, Kapoor, Shruti and Kakar, Shefali (2025) Assessment of pharmacokinetic drug interaction of asciminib with atorvastatin in healthy participants. Journal of Clinical Pharmacology.

Abstract

Asciminib is the first BCR::ABL1 inhibitor that Specifically Targets the ABL Myristoyl Pocket (STAMP) in patients with chronic myeloid leukemia. This phase I, two-treatment-period, drug-drug interaction study evaluated the effect of steady-state asciminib on the pharmacokinetics of atorvastatin. A single dose of atorvastatin (20 mg) was administered on day 1 (period 1: days 14). On days 511 (period 2: days 512), 80 mg asciminib was administered once daily, with a single dose of atorvastatin co-administered on day 9. Pharmacokinetic sampling for atorvastatin was performed on days 14 in period 1 and days 912 in period 2. Twenty-two healthy participants were enrolled. Twenty participants completed the study, and two discontinued due to adverse events (AEs). Asciminib increased the adjusted geometric mean (Gmean) of maximum plasma concentration (Cmax), the area under the curve (AUC) from zero to the last quantifiable concentration (AUClast), and the AUC from zero to infinity (AUCinf) of atorvastatin by 24%, 16%, and 14%, respectively, and did not affect these parameters for its active metabolites, o-hydroxy-atorvastatin and p-hydroxy-atorvastatin. Plasma concentrations of coproporphyrin-1 (CP-1), an endogenous substrate of the atorvastatin transporter OATP1B, were not affected by asciminib. Thirteen participants reported at least one AE, all being grade 1/2, except for one grade 3 AE (increased alanine aminotransferase). No serious AEs were reported. In conclusion, concomitant administration of steady-state asciminib and atorvastatin resulted in a small, clinically irrelevant increase in atorvastatin exposure and no change in CP-1 concentrations. Both drugs were well tolerated. These data support co-administration of asciminib and atorvastatin.

Item Type:	Article
Date Deposited:	20 Jan 2026 00:46
Last Modified:	20 Jan 2026 00:46
URI:	https://oak.novartis.com/id/eprint/57740