This two-sequence, three-period study (NCT04645940) was designed to evaluate the effect of food and concomitant rabeprazole, a proton pump inhibitor, on the pharmacokinetics (PK) and safety of fruquintinib and its metabolite M11 after a single oral dose of fruquintinib 5 mg in healthy subjects. In the food effect treatment periods, 14 subjects were randomized in a 1:1 ratio utilizing a two-sequence (fed/fasted vs. fasted/fed), two-period, cross-over design. Fruquintinib was administered on Day 1 (Period 1) and Day 15 (Period 2). In the drug-interaction period (Period 3), all subjects received rabeprazole 40 mg 1 h prior to fruquintinib under fasted conditions, following a 6-day lead-in of rabeprazole 40 mg once daily. PK samples to measure fruquintinib and M11 were collected pre-dose and over 168 h after fruquintinib dosing. Administration of fruquintinib with a high-fat meal resulted in similar systemic exposure compared with fasted conditions. In addition, coadministration of fruquintinib with rabeprazole resulted in similar exposure compared with fruquintinib alone. For both evaluations, 90% confidence intervals for the ratio of geometric least square mean of the area under the curve and peak concentration for fruquintinib and M11 were entirely within 80%-125% bounds. The study results showed no effects of food or rabeprazole on fruquintinib PK, and support that fruquintinib can be taken without regard to food or concurrent gastric acid-reducing agents.