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Relative Bioavailability and Food Effect Evaluation for 2 Tablet Formulations of Asciminib in a 2‐Arm, Crossover, Randomized, Open‐Label Study in Healthy Volunteers
Author(s) -
Menssen Hans D.,
Quinlan Michelle,
Kemp Charisse,
Tian Xianbin
Publication year - 2019
Publication title -
clinical pharmacology in drug development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.711
H-Index - 22
eISSN - 2160-7648
pISSN - 2160-763X
DOI - 10.1002/cpdd.602
Subject(s) - bioavailability , medicine , cmax , crossover study , meal , capsule , pharmacokinetics , adverse effect , bioequivalence , pharmacology , botany , alternative medicine , pathology , biology , placebo
Asciminib (ABL001) is an orally administered allosteric inhibitor of the BCR‐ABL tyrosine kinase. The current study evaluated the relative bioavailability of its 2 tablet variants, AAA and NXA, compared with the capsule CSF and assessed the impact of food in healthy participants in a 2‐arm, randomized, open‐label, 4‐way crossover design. The primary pharmacokinetic parameters analyzed were area under the plasma concentration‐time curve (AUC) from time 0 to the time of last measurable concentration (AUC last ), AUC from time 0 to infinity (AUC inf ), and peak concentration (C max ). Forty‐five healthy volunteers were enrolled, 22 in the AAA arm and 23 in the NXA arm. Under fasting conditions, the AUC inf , AUC last , and C max of the AAA tablet were similar to those of the capsule, but slightly higher (∼20%) for NXA and decreased with a high‐fat meal (∼65%) and a low‐fat meal (∼30%) for both tablet formulations. Overall, 20 participants (9 in the AAA arm; 11 in the NXA arm) experienced at least 1 adverse event, the most common in both arms being headache. The study showed that under fasting conditions, tablet AAA had bioavailability similar to that in the capsule CSF. The bioavailability of both tablet formulations decreased with food, with a more pronounced effect observed with a high‐fat meal.