The effect of food and acid‐reducing agents on the pharmacokinetic profile of capivasertib: Results from a randomized, crossover study
Claire Prener Miller, Roberto Sommavilla, Donal B. Murphy, Thomas Morris, Mahmuda Khatun, Marie Cullberg
Abstract
Abstract Aims This two‐part, adaptive study assessed the effect of food and an acid‐reducing agent (rabeprazole) on the pharmacokinetics (PK) and safety of capivasertib, a potent AKT inhibitor, in clinical development for cancer treatment. Methods In Part 1, healthy participants (n = 24) were randomized to receive single‐dose capivasertib after overnight fasting, a high‐fat, high‐calorie meal and with rabeprazole postovernight fasting in one of six treatment sequences. Based on Part 1 results, a new group of participants (n = 24) were randomized (Part 2) to receive capivasertib after overnight fasting, a low‐fat, low‐calorie meal and modified fasting (food restricted from 2 h before dosing to 1 h postdose) in one of six treatment sequences. Blood samples were collected for PK analyses. Results Following a high‐fat, high‐calorie meal, capivasertib exposure increased versus overnight fasting (geometric mean ratio [GMR] [90% confidence interval (CI)]: area under the concentration‐time curve [AUC inf ] 1.32 [1.22, 1.43], maximum concentration [ C max ] 1.23 [1.08, 1.41]), but was comparable to that postmodified fasting (GMR: AUC inf 1.13 [0.99, 1.29], C max 0.85 [0.70, 1.04]). AUC inf was similar and C max was lower with/without rabeprazole (GMR: AUC inf 0.94 [0.87, 1.02]), C max 0.73 [0.64, 0.84]). Capivasertib exposure was similar after a low‐fat, low‐calorie meal versus overnight fasting (GMR: AUC inf 1.14 [1.05, 1.25], C max 1.21 [0.99, 1.48]) or modified fasting (GMR: AUC inf 0.96 [0.88, 1.05], C max 0.86 [0.70, 1.06]). Safety was consistent with that in larger trials. Conclusions This study demonstrates that administering capivasertib with food or acid‐reducing agents does not lead to clinically relevant PK or safety profile changes.