Venetoclax is a selective, first-in-class, B-cell lymphoma-2 inhibitor that has demonstrated clinical efficacy in several hematological malignancies. Two studies evaluated the relative bioavailability of venetoclax in healthy subjects: (1) a bioequivalence study to compare the bioavailability of the film-coated tablet with that of an earlier uncoated tablet and (2) a food effect study to evaluate the effect of food on venetoclax pharmacokinetics. Both studies were open-label, single-dose, crossover studies. In the bioequivalence study, 15 subjects received a single dose of venetoclax 50 mg under nonfasting conditions, in each of 2 periods; one period used the uncoated tablet, and the other used the film-coated tablet. In the food effect study, 24 subjects received a single dose of venetoclax film-coated 100-mg tablet under fasting conditions, after a low-fat breakfast or after a high-fat breakfast in different periods. The venetoclax film-coated tablet was bioequivalent to the uncoated tablet, which indicates that the film coating does not affect bioavailability. The median Tmax of venetoclax was delayed by about 2 hours when administered with food. Compared with fasting conditions, Cmax and AUC increased by approximately 3.4-fold following a low-fat breakfast. High-fat meals increased Cmax and AUC by approximately 50% relative to low-fat meals. The mean terminal half-life was comparable between the high-fat meal and fasting conditions (19.1 versus 16.1 hours). Based on these results and the venetoclax exposure-response profile, venetoclax should be administered with food and without specific recommendations for fat content to ensure adequate and consistent bioavailability.
Keywords: BCL-2; CLL; NHL; bioavailability; fat; food effect; pharmacokinetics; venetoclax.
© 2016, The American College of Clinical Pharmacology.