The effect of food and acid-reducing agents on the pharmacokinetic profile of capivasertib: Results from a randomised, cross-over study.

Abstract

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. In Part 1, healthy participants (n=24) were randomised to receive single-dose capivasertib after overnight fasting, a high-fat, high-calorie meal and with rabeprazole post-overnight fasting in one of six treatment sequences. Based on Part 1 results, a new group of participants (n=24) were randomised (Part 2) to receive capivasertib after overnight fasting, a low-fat, low-calorie meal and modified fasting (food restricted from 2 hours before dosing to 1 hour post-dose) in one of six treatment sequences. Blood samples were collected for PK analyses. Following a high-fat, high-calorie meal, capivasertib exposure increased versus overnight fasting (geometric mean ratio [GMR 90% CI]: area under the concentration-time curve [AUCinf ] 1.32 [1.22, 1.43]; maximum concentration [Cmax ] 1.23 [1.08, 1.41]), but was comparable to that post-modified fasting (GMR: AUCinf 1.13 [0.99, 1.29]; Cmax 0.85 [0.70, 1.04]). AUCinf was similar and Cmax was lower with/without rabeprazole (GMR: AUCinf 0.94 [0.87, 1.02]); Cmax 0.73 [0.64, 0.84]). Capivasertib exposure was similar after a low-fat, low-calorie meal versus overnight fasting (GMR: AUCinf 1.14 [1.05, 1.25]; Cmax 1.21 [0.99, 1.48]) or modified fasting (GMR: AUCinf 0.96 [0.88, 1.05]; Cmax 0.86 [0.70, 1.06]). Safety was consistent with that in larger trials. This study demonstrates that administering capivasertib with food or acid-reducing agents does not lead to clinically relevant PK or safety profile changes.