Antiplatelet Thrombolysin (Anfibatide) Phase 1 Clinical Trial in Healthy Volunteers

Study Overview
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Brief Summary
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This is a phase 1, dose-escalation, and multidose study, aiming to investigate the tolerability, safety and pharmacokinetics of Anfibatate in healthy subjects. The study is divided into 2 intravenous single groups and 3 continuous administration groups. The dose of Anfibatate from 5 IU/60kg to 7 IU/60kg in intravenous single groups. The dose of Anfibatate from 0.002 IU/kg/h, 0.004 IU/kg/h to 0.008 IU/kg/h in continuous administration groups.

Official Title
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Phase I Clinical Trial of the Tolerance and Pharmacokinetics of Anfibatide in Health Volunteer

Conditions
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Antiplatelet Drug

Intervention / Treatment
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* Drug: Anfibatide 5 IU/60kg
* Drug: Anfibatide 5 IU/60kg +0.002 IU/kg/h
* Drug: Anfibatide 5 IU/60kg +0.004 IU/kg/h
* Drug: Anfibatide 5 IU/60kg +0.008 IU/kg/h
* Drug: Anfibatide 7 IU/60kg
* Drug: Anfibatide 7 IU/60kg +0.002 IU/kg/h
* Drug: Anfibatide 7 IU/60kg +0.004 IU/kg/h
* Drug: Anfibatide 7 IU/60kg +0.008 IU/kg/h


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female healthy subjects between the ages of 18 to 40 years（including）. The body mass index（BMI）， in the range of 19   24 (including). Medical history without heart, liver, kidney, digestive tract, nervous system, metabolic, ulcer, obvious bleeding, and history of drug allergy or postural hypotension. According to the medical history, physical examination, vital signs, chest radiograph, 12-lead ECG, coagulation routine, stool routine and occult blood test, as well as the laboratory results of blood and urine, the subjects are healthy. The subjects do not take any medicine in the past two weeks. Willingness to participate the study and sign the written Informed Consent Form. Non-lactating women willingness to use adequate contraceptive measures (including abstinence, intrauterine device, diaphragm and spermicide) during the study (screening period to 1 week after administration). Men are willing to use approved methods of contraception (including condoms and spermicides or oral, implanted or injectable contraceptives by their partners, intrauterine device, diaphragms and spermicides). Subjects do not plan to donate sperm or eggs within two weeks after drug administration. Exclusion Criteria: Abnormal with the safety evaluation is considered to be clinical significance in screening period as judged by the researcher. Subjects with history of hepatitis B virus, hepatitis C virus, human immunodeficiency virus and syphilis virus infection; Excessive smoking (>5 cigarettes/day) or do not interrupt smoke during the study. Intake of more than 25g of alcohol per day (equivalent to 750 mL of beer or 250 mL of wine, or 75 mL of white wine of 38 °, or 50 mL of white wine of ≥40 ° ). Subject who are positive for alcohol breath test or cannot stop drinking during the study. Women with pregnant, lactating or menstruating. History of previous hemoptysis, blood stool, skin mucosal bleeding points, etc., or bleeding tendency (patients with gingival, nasal, skin, mucosal bleeding, hemoptysis). History of active bleeding (peptic ulcer, hemorrhoids, active tuberculosis, subacute bacterial endocarditis, etc.). The examination show arteriovenous malformation, hemangioma and other vascular abnormalities. The examination show that there is hemorrhage in the fundus. The platelet count is less than 150×109/L. History of trauma (craniocerebral trauma, etc.) within 1 year. History of unexplained syncope or convulsions. History of autoimmune diseases, such as systemic lupus erythematosus. History of organic or mental illnesses or disabilities. According to the judgment by the researchers, subjects with low possibility of enrollment (such as weak body, etc.). Donation of blood in the last 3 months or participation in other clinical trials in the last 3 months. Previously recruited into other clinical studies of the product. Mental, psychological, or language disorders that prevent understanding or cooperation. Unwilling or unable to comply with the study schedule or procedure. Unfit to participate in the study for any other reason.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Anfibatide 5 IU/60kg<br>Ten subjects will injected with the dose of 5 IU/60kg of Anfibatide with 5 minutes. | Drug: Anfibatide 5 IU/60kg<br>* 5 IU/60kg IV administration of Anfibatide with 5 minutes<br>|
| Experimental: Anfibatide 5 IU/60kg+0.002 IU/kg/h<br>Four or fourteen subjects will injected with the dose of 5 IU/60kg of Anfibatide with 5 minutes follow by the dose of 0.002 IU/kg/h continuous intravenous infusion with 48 hours. | Drug: Anfibatide 5 IU/60kg +0.002 IU/kg/h<br>* 5 IU/60kg IV administration of Anfibatide with 5 minutes follow by the dose of 0.002 IU/kg/h continuous intravenous infusion with 48 hours<br>|
| Experimental: Anfibatide 5 IU/60kg+0.004 IU/kg/h<br>Four or fourteen subjects will injected with the dose of 5 IU/60kg of Anfibatide with 5 minutes follow by the dose of 0.004 IU/kg/h continuous intravenous infusion with 48 hours. | Drug: Anfibatide 5 IU/60kg +0.004 IU/kg/h<br>* 5 IU/60kg IV administration of Anfibatide with 5 minutes follow by the dose of 0.004 IU/kg/h continuous intravenous infusion with 48 hours<br>|
| Experimental: Anfibatide 5 IU/60kg+0.008 IU/kg/h<br>Four or fourteen subjects will injected with the dose of 5 IU/60kg of Anfibatide with 5 minutes follow by the dose of 0.008 IU/kg/h continuous intravenous infusion with 48 hours. | Drug: Anfibatide 5 IU/60kg +0.008 IU/kg/h<br>* 5 IU/60kg IV administration of Anfibatide with 5 minutes follow by the dose of 0.008 IU/kg/h continuous intravenous infusion with 48 hours<br>|
| Experimental: Anfibatide 7 IU/60kg<br>Ten subjects will injected with the dose of 7 IU/60kg of Anfibatide with 5 minutes. | Drug: Anfibatide 7 IU/60kg<br>* 7 IU/60kg IV administration of Anfibatide with 5 minutes<br>|
| Experimental: Anfibatide 7 IU/60kg+0.002 IU/kg/h<br>Four or fourteen subjects will injected with the dose of 7 IU/60kg of Anfibatide with 5 minutes follow by the dose of 0.002 IU/kg/h continuous intravenous infusion with 48 hours. | Drug: Anfibatide 7 IU/60kg +0.002 IU/kg/h<br>* 7 IU/60kg IV administration of Anfibatide with 5 minutes follow by the dose of 0.002 IU/kg/h continuous intravenous infusion with 48 hours<br>|
| Experimental: Anfibatide 7 IU/60kg+0.004 IU/kg/h<br>Four or fourteen subjects will injected with the dose of 7 IU/60kg of Anfibatide with 5 minutes follow by the dose of 0.004 IU/kg/h continuous intravenous infusion with 48 hours. | Drug: Anfibatide 7 IU/60kg +0.004 IU/kg/h<br>* 7 IU/60kg IV administration of Anfibatide with 5 minutes follow by the dose of 0.004 IU/kg/h continuous intravenous infusion with 48 hours<br>|
| Experimental: Anfibatide 7 IU/60kg+0.008 IU/kg/h<br>Four or fourteen subjects will injected with the dose of 7 IU/60kg of Anfibatide with 5 minutes follow by the dose of 0.008 IU/kg/h continuous intravenous infusion with 48 hours. | Drug: Anfibatide 7 IU/60kg +0.008 IU/kg/h<br>* 7 IU/60kg IV administration of Anfibatide with 5 minutes follow by the dose of 0.008 IU/kg/h continuous intravenous infusion with 48 hours<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bleeding events | Bleeding events are judged according to Bleeding Academic Research Consortium Definition for Bleeding criteria. | 7 days after drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | Peak concentration | 7 days after drug administration | 
| Tmax | Peak time | 7 days after drug administration | 
| AUC(0-t) | Area under curve 0-t | 7 days after drug administration | 
| AUC(0-∞) | Area under curve 0-∞ | 7 days after drug administration | 
| T1/2 | Half life | 7 days after drug administration | 
| Inhibition of platelet aggregation | Inhibition rate of platelet aggregation is measured by chrono-log700. | 7 days after drug administration | 
| corrected QT interval | Corrected QT interval is measured by 12-lead ECG. | 7 days after drug administration |