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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01694381
Recruitment Status : Suspended
First Posted : September 27, 2012
Last Update Posted : January 13, 2015
Information provided by (Responsible Party):

Brief 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).

Condition or disease
Acute Ischemic Stroke

Study Type : Observational
Estimated Enrollment : 50 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Phase 1 Trial of Mutant proUK, M5, and Its Inhibitor, C1-inhibitor
Study Start Date : September 2015
Estimated Primary Completion Date : December 2015
Estimated Study Completion Date : December 2015

mutant pro-urokinase (M5) alone
Mutant pro-urokinase (M5) and its inhibitor, C1 inhibitor

Primary Outcome Measures :
  1. Changes to vital signs, routine safety laboratory results, or ECG-findings [ Time Frame: -42d, -14h, -15', 15', 30', 45',60', 90', 10h, 24h, 48h, 7d ]

Biospecimen Retention:   Samples Without DNA
plasma samples.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 35 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Community sample

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01694381

Center for Human Drug Research
Leiden, Netherlands, 2333
Sponsors and Collaborators
Principal Investigator: Koos Burggraaf, MD, PhD Center for Human Drug Research

Responsible Party: TSI, LLC Identifier: NCT01694381     History of Changes
Other Study ID Numbers: TS01-01
2012-002225-30 ( EudraCT Number )
First Posted: September 27, 2012    Key Record Dates
Last Update Posted: January 13, 2015
Last Verified: January 2015

Keywords provided by TSI, LLC:
Acute Ischemic Stroke
Mutant pro-urokinase
C1 inhibitor
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

Additional relevant MeSH terms:
Molecular Mechanisms of Pharmacological Action
Fibrinolytic Agents
Fibrin Modulating Agents