CuraGen and TopoTarget have announced updated interim Phase I data on PXD101,
a small-molecule histone deacetylase inhibitor being developed for the treatment
of solid and hematologic tumors.
The ongoing open-label study was designed to determine the safety, maximum-tolerated dose, pharmacokinetics, and pharmacodynamics of intravenously administered PXD101. PXD101 was administered as a single-agent to patients with advanced solid tumors whose disease was refractory to standard therapy or for whom no standard therapy existed.
The most common adverse events were fatigue, nausea, vomiting and phlebitis. No significant hematological toxicities were noted. Clinical investigators described toxicities as mild with no Grade 4 toxicity observed. Histone hyperacteylation, a biomarker of the activity of PXD101 on its target, was noted to increase proportionally with dose escalation, and lasted from six to 24 hours after administration. Initial pharmacokinetic assessment of orally administered PXD101 showed that PXD101 had an oral bioavailability of approximately 33 percent with PXD101 plasma concentrations exceeding levels required for in vitro activity.