Effect of Itraconazole and Rifampin on the Pharmacokinetics of Olaparib Tablet Formulation in Patients with Advanced Solid Tumours: Phase I Open-Label Studies.

2565 Background: The metabolism of olaparib (Lynparza) is mediated predominantly by CYP3A4/5 enzymes. Two Phase I studies are reported here investigating pharmacokinetic interactions between olaparib (tablet formulation) and itraconazole, a potent CYP3A4 inhibitor (Study 1, NCT01900028), and rifampin, a potent CYP3A4 inducer (Study 2, NCT01929603). Methods: In Study 1, 59 eligible patients (pts) received a single oral dose of olaparib 100 mg on Day 1 and olaparib 100 mg plus itraconazole 200 mg on Day 9; itraconazole 200 mg was administered once daily (qd) on Days 5–11. In Study 2, 22 pts received a single oral dose of olaparib 300 mg on Day 1 and single oral dose olaparib 300 mg plus rifampin 600 mg on Day 14; rifampin 600 mg qd was administered on Days 5–17. Results: Co-administration with itraconazole in Study 1 resulted in a significant increase in mean Cmax (treatment ratio 1.42; 90% CI: 1.33, 1.52) and mean AUC (treatment ratio 2.70; CI: 2.44, 2.97) compared with olaparib alone. Olaparib absorption ...