ticagrelor

Primary Objectives: To demonstrate that the antiplatelet effect of ticagrelor can be reversed after initiation of intravenous PB2452 in patients who experience uncontrolled massive/life-threatening bleeding or require urgent surgery/invasive procedures after ticagrelor treatment using the VerifyNow™ PRUTest™ (VerifyNow™, 2016) platelet reactivity assay; To demonstrate the effect of PB2452 in achieving effective hemostasis after administration of PB2452 in patients who experience uncontrolled massive/life-threatening bleeding or require urgent surgery/invasive procedures after ticagrelor treatment Secondary Objectives: To demonstrate that the antiplatelet effect of ticagrelor can be reversed after intravenous PB2452 in patients who experience uncontrolled massive/life-threatening bleeding or require urgent surgery/invasive procedures after ticagrelor treatment using the PRU and platelet reactivity index (PRI) measured using the vasodilator stimulated phosphoprotein (VASP) assay Other Prespecified Objectives: To evaluate the efficacy of all enrolled patients receiving PB2452 Clinical outcomes of platelet function; evaluate the pharmacokinetic (PK) profile of intravenously administered PB2452, ticagrelor, and ticagrelor active metabolite (TAM); evaluate the reversal effect of ticagrelor on P-selectin and optionally other platelet function-related biomarkers Safety Objectives: To evaluate the safety, tolerability, and immunogenicity of PB2452 in patients receiving ticagrelor.

The primary objectives of this study were to evaluate the safety and tolerability of PB2452 given as single escalating doses intravenously (IV) with or without ticagrelor in Chinese subjects and to assess the effect of single escalating doses of PB2452 on the antiplatelet activity of ticagrelor as measured by the VerifyNow P2Y12 assay, P2Y12 response units (PRUs).