Pharmacokinetics of the Akt Serine/Threonine Protein Kinase Inhibitor, Capivasertib, Administered to Healthy Volunteers in the Presence and Absence of the CYP3A4 Inhibitor Itraconazole.

Capivasertib is a potent, selective inhibitor of all 3 Akt isoforms (Akt1/2/3), and it is currently being tested in Phase III trials for the treatment of prostate and breast cancer. To investigate the effect of a cytochrome P450 3A4 (CYP3A4) inhibitor on the pharmacokinetics of capivasertib, a Phase I drug-drug interaction study of capivasertib and itraconazole was conducted in 11 healthy volunteers (median age, 54 years). The 8-day study had 3 stages: Participants received a single dose of capivasertib 80 mg in Stage 1, 4 doses of itraconazole 200 mg over 3 days in Stage 2, and a final dose of capivasertib 80 mg coadministered with itraconazole 200 mg in Stage 3. Capivasertib pharmacokinetics were examined in Stages 1 and 3. Itraconazole coadministration increased the maximum plasma concentration of capivasertib and total capivasertib exposure (area under the concentration-time curve from time of administration to infinity) by 1.70-fold (90% confidence interval, 1.56-1.86) and 1.95-fold (90% confidence interval, 1.82-2.10), respectively.
(© 2023 AstraZeneca. Clinical Pharmacology in Drug Development published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.)