Abstract 80: The Experimental Neuroprotective Drug Na1 Does Not Interfere With the Fibrinolytic Activities of Alteplase or Tenecteplase

Introduction: Tissue plasminogen activator (Alteplase; tPA) is the most commonly used thrombolytic medication for treatment of acute ischemic stroke, and recent research suggests that Tenecteplase (TNKase) is also effective. NA-1 is a novel neuroprotective drug intended to reduce disability when administered after stroke that is currently being studied in two late stage clinical trials, FRONTIER (NCT02315443) and ESCAPE-NA1 (NCT02930018). Given the overlap in the patient populations and the likelihood that subjects receiving NA-1 could receive thrombolysis, studies were performed to evaluate the effects of NA-1 on the fibrinolytic activity of tPA and TNKase. Methods: A spectrophotometric method of measuring clot formation and lysis in citrated human plasma was developed and used to assess the fibrinolytic activity of tPA and of TNKase. Aprotinin, a known protease inhibitor capable of blocking tPA and TNKase activity, was used as a positive control to demonstrate that the assay system was appropriately sensitive to detect inhibition of thrombolytic activity. Varying concentrations of NA-1 were added to the reaction to assess whether NA-1 could affect the rate of clot formation or the rate of clot lysis in the presence of tPA or TNKase. Results: The sensitivity of this assay system was demonstrated to enable detection of small changes in the fibrinolytic activity of tPA and TNKase on human plasma in the presence of thrombin. NA-1 did not display any fibrinolytic activity on its own nor did it affect the rate of clot formation in the system. NA-1 also did not affect the rate of clot formation or of fibrinolysis in the presence of tPA or TNKase. Conclusions: NA-1 has no intrinsic fibrinolytic activity and does not modulate the fibrinolytic activity of tPA or TNKase. Therefore, NA-1 can be given safely to stroke victims receiving tPA or TNKase without negatively impacting the potential benefit of thrombolysis. This method could also be used to assess other drugs that may have the potential to interact with or be concurrently administered to patients receiving thrombolytic medications.