Research Into the Effect of a Clot-dissolving Agent and Its Inhibitor

This is an interventional treatment trial for Acute Ischemic Stroke focused on measuring Acute Ischemic Stroke, TS01, Mutant pro-urokinase, M5, C1 inhibitor, Safety, Stroke, Tolerability, Ischemia, Cerebral Infarction, Cerebrovascular Disorders, Vascular Diseases, Cardiovascular Diseases, Brain Infarction, Brain Ischemia, Fibrinolytic Agents, Thrombolytic Agents, Molecular Mechanisms of Pharmacological Action, Pharmacologic Actions, Cardiovascular Agents, Therapeutic Uses, Hematologic Agents Read More

Inclusion Criteria:

• Be male, aged between 18 and 35 years inclusive, and with a body weight of at least 60 kg and a body mass index (BMI) between 18.5 and 25 kg/m2 inclusive.
• Be without clinical significant abnormalities according to the investigator's judgment, based on a detailed medical history, a complete physical examination (including vital signs), a standard 12-lead electrocardiogram, urinalysis, and routine clinical laboratory tests.
• Have endogenous C1-inhibitor, α2-antiplasmin, fibrinogen, and plasminogen levels within the laboratory's reference range.
• Have a negative serology for HIV, HBsAg, and HCV.
• Have a negative test for alcohol and drugs of abuse at screening and on study day -1.
• Be capable of understanding and willing to comply with the conditions and restrictions of the protocol.
• Have read, understood and provided written informed consent.

Exclusion Criteria:

• Has a known or suspected inherited, congenital, or acquired disease or condition that affects the haemostatic or coagulation pathways or that is associated with an increased bleeding tendency.
• Has a reasonable chance of developing a clinically significant bleeding event or a bleeding event that may go undetected for a considerable amount of time during the study, for example:
• Has undergone major (internal) surgery or trauma within the last three months of the anticipated dosing day;
• Has an intestinal or cerebral vascular malformation;
• Has participated in high impact contact sports, such as kick-boxing, within two weeks of the anticipated dosing day.
• Has received any systemically absorbed drug or substance (including prescription, over-the-counter, or alternative remedies) that is not permitted by this protocol prior to dosing without undergoing a wash-out period of at least seven times the elimination half-life of the product. For aspirin or other products inhibiting thrombocyte-aggregation the wash-out period must not be less than 28 days.
• Has smoked tobacco in any form within three months of dosing, or has ever smoked more than five cigarettes per day (or equivalent) on average.
• Has received blood or plasma derivatives in the year preceding the administration day.
• Has lost blood or plasma outside the limits of the local blood donation service (i.c. Sanquin) three months prior to dosing.
• Has a known hypersensitivity to any of the investigational material or related compounds.
• Has a history of severe hypersensitivity or of an allergy with severe reactions.
• Has a history of substance abuse, including caffeine, tobacco, and alcohol.
• Has a condition or demonstrates an attitude that in the opinion of the investigator might jeopardise the subject's health or well-being, or the scientific integrity of the study results.
• Is mentally or legally incapacitated to provide informed consent.