<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04404790</url>
  </required_header>
  <id_info>
    <org_study_id>ZK-APT-201803</org_study_id>
    <nct_id>NCT04404790</nct_id>
  </id_info>
  <brief_title>Antiplatelet Thrombolysin (Anfibatide) Phase 1 Clinical Trial in Healthy Volunteers</brief_title>
  <official_title>Phase I Clinical Trial of the Tolerance and Pharmacokinetics of Anfibatide in Health Volunteer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Lee's Pharmaceutical Limited</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Lee's Pharmaceutical Limited</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a phase 1, dose-escalation, and multidose study, aiming to investigate the&#xD;
      tolerability, safety and pharmacokinetics of Anfibatate in healthy subjects. The study is&#xD;
      divided into 2 intravenous single groups and 3 continuous administration groups. The dose of&#xD;
      Anfibatate from 5 IU/60kg to 7 IU/60kg in intravenous single groups. The dose of Anfibatate&#xD;
      from 0.002 IU/kg/h, 0.004 IU/kg/h to 0.008 IU/kg/h in continuous administration groups.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Suspended</overall_status>
  <why_stopped>
    Optimization of protocol&#xD;
  </why_stopped>
  <start_date type="Anticipated">September 2020</start_date>
  <completion_date type="Anticipated">May 2021</completion_date>
  <primary_completion_date type="Anticipated">March 2021</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Bleeding events</measure>
    <time_frame>7 days after drug administration</time_frame>
    <description>Bleeding events are judged according to Bleeding Academic Research Consortium Definition for Bleeding criteria.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cmax</measure>
    <time_frame>7 days after drug administration</time_frame>
    <description>Peak concentration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tmax</measure>
    <time_frame>7 days after drug administration</time_frame>
    <description>Peak time</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC(0-t)</measure>
    <time_frame>7 days after drug administration</time_frame>
    <description>Area under curve 0-t</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC(0-∞)</measure>
    <time_frame>7 days after drug administration</time_frame>
    <description>Area under curve 0-∞</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>T1/2</measure>
    <time_frame>7 days after drug administration</time_frame>
    <description>Half life</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Inhibition of platelet aggregation</measure>
    <time_frame>7 days after drug administration</time_frame>
    <description>Inhibition rate of platelet aggregation is measured by chrono-log700.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>corrected QT interval</measure>
    <time_frame>7 days after drug administration</time_frame>
    <description>Corrected QT interval is measured by 12-lead ECG.</description>
  </secondary_outcome>
  <number_of_arms>8</number_of_arms>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Antiplatelet Drug</condition>
  <arm_group>
    <arm_group_label>Anfibatide 5 IU/60kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ten subjects will injected with the dose of 5 IU/60kg of Anfibatide with 5 minutes.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Anfibatide 5 IU/60kg+0.002 IU/kg/h</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Anfibatide 5 IU/60kg+0.004 IU/kg/h</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Anfibatide 5 IU/60kg+0.008 IU/kg/h</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Anfibatide 7 IU/60kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ten subjects will injected with the dose of 7 IU/60kg of Anfibatide with 5 minutes.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Anfibatide 7 IU/60kg+0.002 IU/kg/h</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Anfibatide 7 IU/60kg+0.004 IU/kg/h</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Anfibatide 7 IU/60kg+0.008 IU/kg/h</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Anfibatide 5 IU/60kg</intervention_name>
    <description>5 IU/60kg IV administration of Anfibatide with 5 minutes</description>
    <arm_group_label>Anfibatide 5 IU/60kg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Anfibatide 5 IU/60kg +0.002 IU/kg/h</intervention_name>
    <description>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</description>
    <arm_group_label>Anfibatide 5 IU/60kg+0.002 IU/kg/h</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Anfibatide 5 IU/60kg +0.004 IU/kg/h</intervention_name>
    <description>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</description>
    <arm_group_label>Anfibatide 5 IU/60kg+0.004 IU/kg/h</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Anfibatide 5 IU/60kg +0.008 IU/kg/h</intervention_name>
    <description>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</description>
    <arm_group_label>Anfibatide 5 IU/60kg+0.008 IU/kg/h</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Anfibatide 7 IU/60kg</intervention_name>
    <description>7 IU/60kg IV administration of Anfibatide with 5 minutes</description>
    <arm_group_label>Anfibatide 7 IU/60kg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Anfibatide 7 IU/60kg +0.002 IU/kg/h</intervention_name>
    <description>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</description>
    <arm_group_label>Anfibatide 7 IU/60kg+0.002 IU/kg/h</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Anfibatide 7 IU/60kg +0.004 IU/kg/h</intervention_name>
    <description>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</description>
    <arm_group_label>Anfibatide 7 IU/60kg+0.004 IU/kg/h</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Anfibatide 7 IU/60kg +0.008 IU/kg/h</intervention_name>
    <description>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</description>
    <arm_group_label>Anfibatide 7 IU/60kg+0.008 IU/kg/h</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female healthy subjects between the ages of 18 to 40 years（including）.&#xD;
&#xD;
          2. The body mass index（BMI）， in the range of 19 ~ 24 (including).&#xD;
&#xD;
          3. Medical history without heart, liver, kidney, digestive tract, nervous system,&#xD;
             metabolic, ulcer, obvious bleeding, and history of drug allergy or postural&#xD;
             hypotension.&#xD;
&#xD;
          4. According to the medical history, physical examination, vital signs, chest radiograph,&#xD;
             12-lead ECG, coagulation routine, stool routine and occult blood test, as well as the&#xD;
             laboratory results of blood and urine, the subjects are healthy.&#xD;
&#xD;
          5. The subjects do not take any medicine in the past two weeks.&#xD;
&#xD;
          6. Willingness to participate the study and sign the written Informed Consent Form.&#xD;
&#xD;
          7. Non-lactating women willingness to use adequate contraceptive measures (including&#xD;
             abstinence, intrauterine device, diaphragm and spermicide) during the study (screening&#xD;
             period to 1 week after administration). Men are willing to use approved methods of&#xD;
             contraception (including condoms and spermicides or oral, implanted or injectable&#xD;
             contraceptives by their partners, intrauterine device, diaphragms and spermicides).&#xD;
             Subjects do not plan to donate sperm or eggs within two weeks after drug&#xD;
             administration.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Abnormal with the safety evaluation is considered to be clinical significance in&#xD;
             screening period as judged by the researcher.&#xD;
&#xD;
          2. Subjects with history of hepatitis B virus, hepatitis C virus, human immunodeficiency&#xD;
             virus and syphilis virus infection;&#xD;
&#xD;
          3. Excessive smoking (&gt;5 cigarettes/day) or do not interrupt smoke during the study.&#xD;
&#xD;
          4. Intake of more than 25g of alcohol per day (equivalent to 750 mL of beer or 250 mL of&#xD;
             wine, or 75 mL of white wine of 38 °, or 50 mL of white wine of ≥40 ° ). Subject who&#xD;
             are positive for alcohol breath test or cannot stop drinking during the study.&#xD;
&#xD;
          5. Women with pregnant, lactating or menstruating.&#xD;
&#xD;
          6. History of previous hemoptysis, blood stool, skin mucosal bleeding points, etc., or&#xD;
             bleeding tendency (patients with gingival, nasal, skin, mucosal bleeding, hemoptysis).&#xD;
&#xD;
          7. History of active bleeding (peptic ulcer, hemorrhoids, active tuberculosis, subacute&#xD;
             bacterial endocarditis, etc.).&#xD;
&#xD;
          8. The examination show arteriovenous malformation, hemangioma and other vascular&#xD;
             abnormalities.&#xD;
&#xD;
          9. The examination show that there is hemorrhage in the fundus.&#xD;
&#xD;
         10. The platelet count is less than 150×109/L.&#xD;
&#xD;
         11. History of trauma (craniocerebral trauma, etc.) within 1 year.&#xD;
&#xD;
         12. History of unexplained syncope or convulsions.&#xD;
&#xD;
         13. History of autoimmune diseases, such as systemic lupus erythematosus.&#xD;
&#xD;
         14. History of organic or mental illnesses or disabilities.&#xD;
&#xD;
         15. According to the judgment by the researchers, subjects with low possibility of&#xD;
             enrollment (such as weak body, etc.).&#xD;
&#xD;
         16. Donation of blood in the last 3 months or participation in other clinical trials in&#xD;
             the last 3 months.&#xD;
&#xD;
         17. Previously recruited into other clinical studies of the product.&#xD;
&#xD;
         18. Mental, psychological, or language disorders that prevent understanding or&#xD;
             cooperation.&#xD;
&#xD;
         19. Unwilling or unable to comply with the study schedule or procedure.&#xD;
&#xD;
         20. Unfit to participate in the study for any other reason.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ningru Zhang</last_name>
    <role>Study Director</role>
    <affiliation>Bengbu Medical College First Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Bengbu Medical College First Hospital</name>
      <address>
        <city>Bengbu</city>
        <state>Anhui</state>
        <zip>233004</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>May 2020</verification_date>
  <study_first_submitted>May 26, 2020</study_first_submitted>
  <study_first_submitted_qc>May 26, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 28, 2020</study_first_posted>
  <last_update_submitted>May 26, 2020</last_update_submitted>
  <last_update_submitted_qc>May 26, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">May 28, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04404790
org study id: ZK-APT-201803
nct id: NCT04404790
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
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.
allocation: Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Bleeding events
time frame: 7 days after drug administration
description: Bleeding events are judged according to Bleeding Academic Research Consortium Definition for Bleeding criteria.
measure: Cmax
time frame: 7 days after drug administration
description: Peak concentration
measure: Tmax
time frame: 7 days after drug administration
description: Peak time
measure: AUC(0-t)
time frame: 7 days after drug administration
description: Area under curve 0-t
measure: AUC(0-∞)
time frame: 7 days after drug administration
description: Area under curve 0-∞
measure: T1/2
time frame: 7 days after drug administration
description: Half life
measure: Inhibition of platelet aggregation
time frame: 7 days after drug administration
description: Inhibition rate of platelet aggregation is measured by chrono-log700.
measure: corrected QT interval
time frame: 7 days after drug administration
description: Corrected QT interval is measured by 12-lead ECG.
arm group label: Anfibatide 5 IU/60kg
arm group type: Experimental
description: Ten subjects will injected with the dose of 5 IU/60kg of Anfibatide with 5 minutes.
arm group label: Anfibatide 5 IU/60kg+0.002 IU/kg/h
arm group type: Experimental
description: 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.
arm group label: Anfibatide 5 IU/60kg+0.004 IU/kg/h
arm group type: Experimental
description: 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.
arm group label: Anfibatide 5 IU/60kg+0.008 IU/kg/h
arm group type: Experimental
description: 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.
arm group label: Anfibatide 7 IU/60kg
arm group type: Experimental
description: Ten subjects will injected with the dose of 7 IU/60kg of Anfibatide with 5 minutes.
arm group label: Anfibatide 7 IU/60kg+0.002 IU/kg/h
arm group type: Experimental
description: 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.
arm group label: Anfibatide 7 IU/60kg+0.004 IU/kg/h
arm group type: Experimental
description: 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.
arm group label: Anfibatide 7 IU/60kg+0.008 IU/kg/h
arm group type: Experimental
description: 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.
intervention type: Drug
intervention name: Anfibatide 5 IU/60kg
description: 5 IU/60kg IV administration of Anfibatide with 5 minutes
arm group label: Anfibatide 5 IU/60kg
intervention type: Drug
intervention name: Anfibatide 5 IU/60kg +0.002 IU/kg/h
description: 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
arm group label: Anfibatide 5 IU/60kg+0.002 IU/kg/h
intervention type: Drug
intervention name: Anfibatide 5 IU/60kg +0.004 IU/kg/h
description: 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
arm group label: Anfibatide 5 IU/60kg+0.004 IU/kg/h
intervention type: Drug
intervention name: Anfibatide 5 IU/60kg +0.008 IU/kg/h
description: 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
arm group label: Anfibatide 5 IU/60kg+0.008 IU/kg/h
intervention type: Drug
intervention name: Anfibatide 7 IU/60kg
description: 7 IU/60kg IV administration of Anfibatide with 5 minutes
arm group label: Anfibatide 7 IU/60kg
intervention type: Drug
intervention name: Anfibatide 7 IU/60kg +0.002 IU/kg/h
description: 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
arm group label: Anfibatide 7 IU/60kg+0.002 IU/kg/h
intervention type: Drug
intervention name: Anfibatide 7 IU/60kg +0.004 IU/kg/h
description: 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
arm group label: Anfibatide 7 IU/60kg+0.004 IU/kg/h
intervention type: Drug
intervention name: Anfibatide 7 IU/60kg +0.008 IU/kg/h
description: 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
arm group label: Anfibatide 7 IU/60kg+0.008 IU/kg/h
criteria: 
gender: All
minimum age: 18 Years
maximum age: 40 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Ningru Zhang
role: Study Director
affiliation: Bengbu Medical College First Hospital
facility: 
country: China
responsible party type: Sponsor