BACKGROUND: ARC1779 is a therapeutic aptamer antagonist of the A1 domain of von 
Willebrand Factor (vWF), the ligand for receptor glycoprotein 1b on platelets. 
ARC1779 is being developed as a novel antithrombotic agent for use in patients 
with acute coronary syndromes.
METHODS AND RESULTS: This was a randomized, double-blind, placebo-controlled 
study in 47 healthy volunteers of doses of ARC1779 from 0.05 to 1.0 mg/kg. 
Pharmacodynamic effects were measured by an ELISA for free vWF A1 binding sites 
and by a platelet function analyzer. In terms of pharmacokinetics, the 
concentration-time profile of ARC1779 appeared monophasic. The observed 
concentration and area under the curve were dose proportional. The mean apparent 
elimination half-life was approximately 2 hours, and mean residence time was 
approximately 3 hours. The mean apparent volumes of distribution (at steady 
state and during terminal phase) were approximately one half the blood volume, 
suggesting that ARC1779 distribution is in the central compartment. The mean 
clearance ranged from approximately 10% to approximately 21% of the glomerular 
filtration rate, suggesting that renal filtration may not be a major mechanism 
of clearance of ARC1779. Inhibition of vWF A1 binding activity was achieved with 
an EC(90) value of 2.0 mug/mL (151 nmol/L) and of platelet function with an 
EC(90) value of 2.6 mug/mL (196 nmol/L). ARC1779 was generally well tolerated, 
and no bleeding was observed. Adverse events tended to be minor and not dose 
related.
CONCLUSIONS: This is the first-in-human evaluation of a novel aptamer antagonist 
of vWF. ARC1779 produced dose- and concentration-dependent inhibition of vWF 
activity and platelet function with duration of effect suitable for the intended 
clinical use in acute coronary syndromes.