Background: Docetaxel has poor oral bioavailability in part due to extrusion by intestinal p-glycoprotein. To improve IV solubility, it is fomulated with the nonionic surfactant polysorbate 80, requiring steroid premedication to manage hypersensitivity type reactions. Oral administration has the potential to improve tolerability, reduce day-stay utilization and improve patient convenience and allows investigation of alternative dosing schedules. Oradoxel is a new combination of oral docetaxel capsules plus the novel gut-selective P-glycoprotein inhibitor encequidar (HM30181A). Methods: Patients with mPC receiving IV docetaxel were enrolled in 3 cohorts with a dose escalation schedule of Oradoxel 75 mg/m² in Cohort 1, 150 mg/m² in Cohort 2, 300mg/m² in Cohort 3. Oradoxel was given 3 weeks before or after IV docetaxel treatment. Intensive PK samples were taken on days 1-5 for Oradoxel and days 1-4 for IV docetaxel. Dose limiting toxicity (DLT) or serious adverse events (SAE) were assessed per CTCAE v4.03. Results: 3 evaluable patients in each Cohort were studied. No DLT, MTD, or drug-related SAE were observed. PK parameters of Oradoxel vs IV docetaxel are summarized in the table below. Mean absolute bioavailability of Oradoxel was 15.9% (range 8-25%). PK became non linear at 300mg/m². Conclusions: Oradoxel was well tolerated. Based on the results of this and related studies, Oradoxel 300mg/m² in divided doses is being further evaluated in phase 2 studies. Clinical trial information: 12616000983404.

Results are in mean ± SD or otherwise specified. ^aMean (range). ^bMedian (range).