Healthy volunteers [occlusive thrombotic diseases
Conditions
Interventions
Single dose of HisproUK or placebo, with (part 2) or without (part 1) a
preceding single dose of tPA
Sponsors
Thrombolytic Science International
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: To be eligible for inclusion a volunteer must meet all of the following criteria: 1. 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. 2. 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. 3. Have normal endogenous C1-inhibitor, *2-antiplasmin, and fibrinogen levels. 4. Have a negative serology for HIV, HBsAg, and HCV. 5. Have a negative test for alcohol and drugs of abuse at screening and on study day -1. 6. Be capable of understanding and willing to comply with the conditions and restrictions of the protocol. 7. Have read, understood and provided written informed consent.
Exclusion criteria
Exclusion criteria: A volunteer will not be included if he fulfils one or more of the following criteria: 1. 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. 2. 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: a. Has undergone major (internal) surgery or trauma within the last three months of the anticipated dosing day; b. Has an intestinal or cerebral vascular malformation; c. Has participated in high impact contact sports, such as kick-boxing, within two weeks of the anticipated dosing day. 3. 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. 4. 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. 5. Has received blood or plasma derivatives in the year preceding the administration day. 6. Has lost blood or plasma outside the limits of the local blood donation service (i.c. Sanquin) three months prior to dosing. 7. Has a known hypersensitivity to any of the investigational material or related compounds. 8. Has a history of severe hypersensitivity or of an allergy with severe reactions. 9. Has a history of substance abuse tobacco, or alcohol. 10. 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. 11. Is mentally or legally incapacitated to provide informed consent.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| * The maximum degree of fibrinogen degradation per dose levels of HisproUK with and without tPA; * The maximum degree of plasminogen consumption per dose levels of HisproUK with and without tPA; * The maximum degree of *2-antiplasmin decrease per dose levels of HisproUK with and without tPA; * The effect of HisproUK on circulating cytokines (TNFa, IL-6, IL-8 and IL-1b), with or without tPA. * Nature, frequency, and severity of adverse events; * Changes to vital signs, routine safety laboratory results, or ECG-findings. | — |
Secondary
| Measure | Time frame |
|---|---|
| * The pharmacokinetic profile of HisproUK (with or without exogenous tPA); the following parameters * Maximum plasma concentration (Cmax) * Time of maximum plasma concentration (tmax) * Area under the plasma concentration time curve from time 0 to the last quantifiable point (AUCt) * Area under the plasma concentration time curve from time 0 to infinity (AUC*) * Apparent terminal phase rate constant (*z) * Apparent elimination half-life (t1/2) * Mean residence time (MRT); | — |
Countries
Netherlands
Outcome results
None listed