Drug-Drug Interaction Study of Pacritinib and CYP450,Transporter Substrates, and CYP450 3A4 in Healthy Male Subjects

This is a Phase 1, open-label, fixed-sequence, 2-part DDI study. Part 1 will evaluate the effect of 14 days of pacritinib 200 mg BID at steady state on the systemic exposure of a cocktail of single doses of cytochrome P450 (caffeine, midazolam, omeprazole) and transporter substrates (digoxin, rosuvastatin, metformin) in 18 healthy male subjects who will participate in 2 treatment periods sequentially separated by a washout period. Part 2 will evaluate the effect of a CYP450 3A4 inducer (bosentan BID) for 7 days and the effect of a CYP450 3A4 inhibitor (fluconazole QD) for 7 days, on the PK of multiple doses of pacritinib 200 mg BID in 36 healthy male subjects. Safety and tolerability will be assessed by AEs, clinical laboratory tests, vital signs, ECGs, and physical examinations.