The single-center, Phase Ib trial examined the safety, tolerability and pharmacokinetics of intravenous bolus plus infusion dosing of NU172, in 24 healthy male volunteers. Volunteers were given a 2mg/kg bolus dose followed by escalating infusion doses of NU172 for four hours.
In all four cohorts, NU172 produced dose-dependent increases in anticoagulation, measured by activated clotting time (ACT), prothrombin time (PT) and activated partial thromboplastin time (aPTT). The highest infusion dose rate tested, 6mg/kg/hr, resulted in an average ACT per subject ranging from 373 to 414 seconds and an increase of approximately three times baseline.
Average PT values per subject ranged from 56 to 92 seconds and had an increase of approximately five times baseline. Average aPTT values per subject ranged from 130 to 178 seconds and had an increase of approximately five times baseline. All measurements were maintained stably throughout the four-hour infusion.
Once the infusion ended, the ACT and other coagulation parameters showed a rapid return toward baseline, consistent with the short plasma half-life of NU172 observed in the Phase Ia trial. In addition, NU172 was well-tolerated with no serious adverse events.
Ted Love, chairman and CEO of Nuvelo, said: “In addition to supporting our previous proof-of-concept data, the Phase Ib study shows that anticoagulation with NU172 can be maintained for four hours, which is longer than a typical coronary artery bypass graft procedure. We are on track to launch a Phase II study evaluating NU172 in the fourth quarter of 2008 or the first quarter of 2009.”