Positive Ph Ib data for Nuevelo anticoagulant

California, USA-based Nuvelo has announced positive results from the Phase Ib proof-of-concept trial of NU172, demonstrating that the direct thrombin inhibitor rapidly produced and maintained anticoagulation with a rapid return toward baseline after the infusion ended with a favorable safety profile.

"NU172 has the potential to address many of the limitations of currently-available anticoagulants given the profile we have seen to date in preclinical and Phase I testing, including its ability to produce rapid and predictable onset and offset of anticoagulation without the need for an antidote, its potential ability to work in stagnant blood, its predominately non-renal clearance, and the option to stop and restart anticoagulation as needed during or after surgery," said Michael Lincoff, vice chairman of the department of cardiovascular medicine and an interventional cardiologist at the Cleveland Clinic. "Because of these characteristics, NU172 could potentially offer an improved approach to anticoagulation for procedures such as coronary artery bypass graft (CABG) surgery, kidney dialysis, and percutaneous coronary intervention (PCI)," he added.

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. Subjects were given a 2mg/kg bolus dose followed by escalating infusion doses of NU172 for four hours. In all four cohorts, the agent produced dose-dependent increases in anticoagulation, measured by activated clotting time, prothrombin time and activated partial thromboplastin time (aPTT). The highest infusion dose rate tested, 6.0mg/kg/hr, resulted in an average ACT per subject ranging from 373 to 414 seconds and an increase of around three 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.