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

• Status: Terminated
• Trial end date: 2012-10-01
• Target enrollment: 0
• Participant gender: Male

Summary

Single-chain urokinase-type plasminogen activator (pro-urokinase) is a highly effective thrombolytic drug. At pharmacologic concentrations however, pro-urokinase is converted to urokinase - a non specific thrombolytic, limiting its therapeutic use. Mutant pro-urokinase (M5) is more stable and its conversion to urokinase is inhibited by C1-inhibitor.

The primary objectives of the study are:

• To assess the overall safety and tolerability related to systemic plasminogen activation of single doses of M5 over a wide dose range (study part I).

• To assess the effect of single doses of C1-inhibitor on the overall safety and tolerability of single doses of M5 and its effect on M5-induced coagulation changes (study part II).

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: TSI, LLC

Criteria

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.