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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2012 by TSI, LLC
Sponsor:
Information provided by (Responsible Party):
TSI, LLC
ClinicalTrials.gov Identifier:
NCT01694381
First received: September 24, 2012
Last updated: NA
Last verified: September 2012
History: No changes posted
  Purpose

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
Acute Ischemic Stroke

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Phase 1 Trial of Mutant proUK, M5, and Its Inhibitor, C1-inhibitor

Resource links provided by NLM:


Further study details as provided by TSI, LLC:

Biospecimen Retention:   Samples Without DNA

plasma samples.


Estimated Enrollment: 50
Study Start Date: September 2012
Estimated Study Completion Date: January 2013
Estimated Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Groups/Cohorts
mutant pro-urokinase (M5) alone
Mutant pro-urokinase (M5) and its inhibitor, C1 inhibitor

  Eligibility

Ages Eligible for Study:   18 Years to 35 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Community sample

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01694381

Contacts
Contact: Koos Burggraaf, MD, PhD +31 71 5246 400

Locations
Netherlands
Center for Human Drug Research Recruiting
Leiden, Netherlands, 2333
Contact: Koos Burggraaf, MD; PhD    +31 71 5246 400      
Sponsors and Collaborators
TSI, LLC
Investigators
Principal Investigator: Koos Burggraaf, MD, PhD Center for Human Drug Research
  More Information

No publications provided

Responsible Party: TSI, LLC
ClinicalTrials.gov Identifier: NCT01694381     History of Changes
Other Study ID Numbers: TS01-01, 2012-002225-30
Study First Received: September 24, 2012
Last Updated: September 24, 2012
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by TSI, LLC:
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

Additional relevant MeSH terms:
Ischemia
Stroke
Pathologic Processes
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Cardiovascular Agents
Saruplase
Fibrinolytic Agents
Molecular Mechanisms of Pharmacological Action
Therapeutic Uses
Pharmacologic Actions
Fibrin Modulating Agents
Hematologic Agents

ClinicalTrials.gov processed this record on August 20, 2014