Rexahn Pharmaceuticals, Inc. (REXN)

[MilesTeg]

Rexahn ASCO Abstract--RX-3117

Abstract:
Background: RX-3117 (fluorocyclopentenylcytosine) is a novel antimetabolite, that requires activation by uridine-cytidine kinase (UCK) , a cancer cell specific kinase, that interferes with cancer cell division and nucleic acid synthesis, causes cellular arrest in the G1 phase and induces apoptosis. Methods: This study was a first-in-human, open-label, exploratory pharmacokinetic study of RX-3117. The study duration was 14-15 days (7-day screening period; 3-day treatment period; 4 (+1)-day safety follow-up period). Nine adult male and female subjects with histologically confirmed, solid tumors were enrolled and completed the study. Subjects received RX-3117 (n = 3 subjects per dose) as a single oral dose (50 mg or 100 mg) or a single intravenous dose (20 mg). Results: Pharmacokinetics (PK): The absolute bioavailability (F) for oral RX-3117 was 55.67% and 33.42% for the 50 and 100 mg doses, respectively. The mean Tmax was 2.16 hours and 2.49 hours for the 50 and 100 mg doses, respectively. The mean Cmax was 303.3 ng/mL and 311.43 ng/mL for the 50 and 100 mg doses, respectively. The greater absolute bioavailability and Cmax results of the 50 mg dose compared to the 100 mg dose suggests that oral bioavailability of RX-3117 in plasma may not be dose-proportional or due to the low subject number tested. The t1/2for the 50 mg and 100 mg doses was 13.95 hours and 20.92 hours, respectively, indicating that RX-3117 may show dose proportionality on some parameters but not on others at the doses tested. The plasma PK profile of intravenous RX-3117 differed from the plasma PK profile of oral RX-3117. The 20 mg dose of intravenous RX-3117 recovered rapidly after bolus infusion (Tmax = 0.25 hours). The 20 mg dose of intravenous RX-3117 had a mean Cmaxof 1143.63 ng/mL, which was approximately a 4-fold increase over the peak concentrations of the oral doses. RX-3117 was safe and well-tolerated at the doses tested in all subjects. No AEs, TEAEs or SAEs occurred. Conclusions: This exploratory first-in-human study shows that RX-3117 was orally bioavailable and well-tolerated at the doses tested. The results support the study of higher and multiple doses in a standard Phase 1 study

http://abstracts.asco.org/156/AbstView_156_145747.html