Ixazomib is the first oral proteasome inhibitor to be investigated in the 
clinic. This clinical study assessed whether the pharmacokinetics of ixazomib 
would be altered if administered after a high-calorie, high-fat meal. In a 
2-period, 2-sequence, crossover study design, adult patients with advanced solid 
tumors or lymphoma received a 4-mg oral dose of ixazomib as immediate-release 
capsules on day 1 without food (fasted, administered following an overnight 
fast) or with food (fed, following consumption of a high-calorie, high-fat 
meal), followed by another dose on day 15 in the alternate food intake condition 
(fasted to fed or fed to fasted). Twenty-four patients were enrolled; of these, 
15 were included in the pharmacokinetic-evaluable population. Administration of 
ixazomib after a high-fat meal reduced both the rate and extent of absorption of 
ixazomib. Under fed conditions, the median time to peak plasma concentration 
(Tmax ) of ixazomib was delayed by approximately 3 hours compared with 
administration in the fasted state (1.02 hours vs 4.0 hours), and there was a 
28% reduction in total systemic exposure (area under the curve, AUC) and a 69% 
reduction in peak plasma concentration (Cmax ). Together, the results support 
the administration of ixazomib on an empty stomach, at least 1 hour before or at 
least 2 hours after food. These recommendations are reflected in the United 
States Prescribing Information for ixazomib (clinicaltrials.gov identifier 
NCT01454076).