Novel Oral Nano-Amorphous Sirolimus Formulation To Exhibit Comparable Exposure To Intravenously Administered Temsirolimus: An Oral Alternative To The Treatment Of Mtor-Responsive Malignancies

e16555Background: Rapamune (Sirolimus) exhibits low bioavailability and high variability following oral administration. Reaching the therapeutic blood concentrations in renal cancer patients was found to be challenging when the marketed drug was administered alone (Cohen et al., 2012). Therefore intravenous delivery of a prodrug of sirolumus, temsirolimus is required to achieve suitable exposures. The PK properties of a novel nano-amorphous oral formulation were investigated in a dose escalation study. The effect of food at the highest dose was also assessed. The objective of the work was to achieve comparable sirolimus exposures to the currently used temsirolimus therapy. Methods: 32 healthy volunteers divided into 4 cohorts received one of the escalating doses (0.5 – 2 – 10 – 40 mg) the novel formulation in the fasted state. To avoid degradation of sirolimus in the acidic environment in the stomach, 40 mg famotidine was administered three hours pre-dose in all regimens. The 40 mg cohort received a secon...