<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/NCT04472819</url>
  </required_header>
  <id_info>
    <org_study_id>SHR2285-104</org_study_id>
    <nct_id>NCT04472819</nct_id>
  </id_info>
  <brief_title>The Single, Multiple Dose and Food Effect Study of SHR2285 Tablets on Pharmacokinetics and Pharmacodynamics in Healthy Subjects</brief_title>
  <official_title>A Phase I, Randomized, Double -Blinded, Placebo-Controlled, Single and Multiple Dose and Food Effect Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of SHR2285 Tablets in Healthy Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Jiangsu HengRui Medicine Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Jiangsu HengRui Medicine Co., Ltd.</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>
      The study is a randomized, doubled-blinded, placebo-controlled, Phase I trials. The study is&#xD;
      divided into two parts. The first part is a single-dose escalated study (SAD,part 1A ) and&#xD;
      food effect study (SAD, part 1B ) in healthy subjects. The second part is a multi-dose&#xD;
      escalated study (MAD) in healthy subjects.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 28, 2020</start_date>
  <completion_date type="Actual">May 31, 2021</completion_date>
  <primary_completion_date type="Actual">May 31, 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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of subjects with adverse events and severity of adverse events.</measure>
    <time_frame>Part 1: Pre-dose to day 7 after single dose administration and Part 2: Pre-dose to day 14after multiple dose administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum observed serum concentration (Cmax) for Food Effect of SHR2285 on pharmacokinetics parameters in healthy subjects.</measure>
    <time_frame>Part 1A: Pre-dose to day 7 after single dose administration and Part 1B: Pre-dose to day 7 after single dose administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Time to maximum observed serum concentration (Tmax) for Food Effect of SHR2285 on pharmacokinetics parameters in healthy subjects.</measure>
    <time_frame>Part 1A: Pre-dose to day 7 after single dose administration and Part 1B: Pre-dose to day 7 after single dose administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Time to elimination half-life (T1/2) for Food Effect of SHR2285 on pharmacokinetics parameters in healthy subjects.</measure>
    <time_frame>Part 1A: Pre-dose to day 7 after single dose administration and Part 1B: Pre-dose to day 7 after single dose administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Area under the plasma concentration versus time curve (AUC0-last) for Food Effect of SHR2285 on pharmacokinetics parameters in healthy subjects.</measure>
    <time_frame>Part 1A: Pre-dose to day 7 after single dose administration and Part 1B: Pre-dose to day 7 after single dose administration</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Maximum observed serum concentration (Cmax) for single dose of SHR2285.</measure>
    <time_frame>Part 1:Pre-dose to day 3 after single dose administration and Part 2:Pre-dose to day 9 after multiple dose administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to maximum observed serum concentration (Tmax) for single dose of SHR2285.</measure>
    <time_frame>Part 1:Pre-dose to day 3 after single dose administration and Part 2:Pre-dose to day 9 after multiple dose administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to elimination half-life (T1/2) for single dose of SHR2285.</measure>
    <time_frame>Part 1:Pre-dose to day 3 after single dose administration and Part 2:Pre-dose to day 9 after multiple dose administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the plasma concentration versus time curve (AUC0-last) for single dose of SHR2285.</measure>
    <time_frame>Part 1:Pre-dose to day 3 after single dose administration and Part 2:Pre-dose to day 9 after multiple dose administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Steady-state peak concentration (Cmax，ss) for multiple dose of SHR2285.</measure>
    <time_frame>Pre-dose to day 9 after multiple dose administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Steady state valley concentration (Ctrough，ss) for multiple dose of SHR2285.</measure>
    <time_frame>Pre-dose to day 9 after multiple dose administration.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Accumulation ratio (Racc) for multiple dose of SHR2285.</measure>
    <time_frame>Pre-dose to day 9 after multiple dose administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clotting factor XI (FXI) activity .</measure>
    <time_frame>Part 1:Pre-dose to day 7 after single dose administration and Part 2:Pre-dose to day 14 after multiple dose administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of activated partial thromboplastin time (APTT) from baseline.</measure>
    <time_frame>Part 1:Pre-dose to day 7 after single dose administration and Part 2:Pre-dose to day 14 after multiple dose administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of prothrombin time (PT) from baseline.</measure>
    <time_frame>Part 1:Pre-dose to day 7 after single dose administration and Part 2:Pre-dose to day 14 after multiple dose administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of international normalization ratio (INR) from baseline.</measure>
    <time_frame>Part 1:Pre-dose to day 7 after single dose administration and Part 2:Pre-dose to day 14 after multiple dose administration</time_frame>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">104</enrollment>
  <condition>Thrombosis</condition>
  <arm_group>
    <arm_group_label>SHR2285 Part 1A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participant received one of 7 dose levels of SHR2285 tablet as single-dose oral administration</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo Part 1A</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Single ascending doses of placebo orally</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SHR2285 Part 1B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participant received one dose of SHR2285 tablet as single-dose oral administration</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo Part 1B</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Single doses of placebo orally</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SHR2285 Part 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participant received one of 4 dose levels of SHR2285 tablet as multi-dose oral administration</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo Part 2</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Multiple ascending doses of placebo orally</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>SHR2285 tablet</intervention_name>
    <description>single dose or multi-dose</description>
    <arm_group_label>SHR2285 Part 1A</arm_group_label>
    <arm_group_label>SHR2285 Part 1B</arm_group_label>
    <arm_group_label>SHR2285 Part 2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>single dose or multi-dose</description>
    <arm_group_label>Placebo Part 1A</arm_group_label>
    <arm_group_label>Placebo Part 1B</arm_group_label>
    <arm_group_label>Placebo Part 2</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Healthy subjects, aged 18-55 (including boundary);&#xD;
&#xD;
          2. Body mass index (BMI) between 18 to 28 kg/m2 (including boundary), male body weight&#xD;
             ≥50 kg and &lt;90 kg , female body weight ≥45kg and &lt;90kg;&#xD;
&#xD;
          3. Participant with no clinically significant findings in vital signs, physical&#xD;
             examination, 12-lead ECG ,X-ray and laboratory parameters.&#xD;
&#xD;
          4. Understand the study procedures and methods, voluntary to participate in the study and&#xD;
             signed the informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) or total&#xD;
             bilirubin/direct bilirubin &gt; upper limit of normal (ULN) during screening/baseline.&#xD;
&#xD;
          2. Serum creatinine&gt; ULN during screening/baseline.&#xD;
&#xD;
          3. Positive faecal occult blood&#xD;
&#xD;
          4. Abnormal coagulation function.&#xD;
&#xD;
          5. A clinical history of coagulation dysfunction; subjects with adverse reaction of&#xD;
             antiplatelet drugs or anticoagulant drugs.&#xD;
&#xD;
          6. Subjects with severe head trauma or head surgery within 2 years or surgery within 3&#xD;
             months prior to the screening.&#xD;
&#xD;
          7. Blood donation or blood loss within 1 month≥200 mLor≥400 mL within 3 months before&#xD;
             administration.&#xD;
&#xD;
          8. Human immunodeficiency virus antibody, syphilis serological examination, hepatitis b&#xD;
             virus surface antigen, hepatitis c virus antibody were positive.&#xD;
&#xD;
        9.3 months prior to screening involved in any drug or medical device clinical studies or&#xD;
        within 5 half-life of drugs before screening.&#xD;
&#xD;
        10.Female subjects who did not receive contraception at least 30 days before administration&#xD;
        and etc.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Peking University First Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100034</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Third Xiangya Hospital of Central South University</name>
      <address>
        <city>Changsha</city>
        <state>Hunan</state>
        <zip>410006</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>September 2021</verification_date>
  <study_first_submitted>July 9, 2020</study_first_submitted>
  <study_first_submitted_qc>July 12, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 15, 2020</study_first_posted>
  <last_update_submitted>September 26, 2021</last_update_submitted>
  <last_update_submitted_qc>September 26, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">September 28, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Thrombosis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT04472819
org study id: SHR2285-104
nct id: NCT04472819
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The study is a randomized, doubled-blinded, placebo-controlled, Phase I trials. The study is
      divided into two parts. The first part is a single-dose escalated study (SAD,part 1A ) and
      food effect study (SAD, part 1B ) in healthy subjects. The second part is a multi-dose
      escalated study (MAD) in healthy subjects.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Number of subjects with adverse events and severity of adverse events.
time frame: Part 1: Pre-dose to day 7 after single dose administration and Part 2: Pre-dose to day 14after multiple dose administration
measure: Maximum observed serum concentration (Cmax) for Food Effect of SHR2285 on pharmacokinetics parameters in healthy subjects.
time frame: Part 1A: Pre-dose to day 7 after single dose administration and Part 1B: Pre-dose to day 7 after single dose administration
measure: Time to maximum observed serum concentration (Tmax) for Food Effect of SHR2285 on pharmacokinetics parameters in healthy subjects.
time frame: Part 1A: Pre-dose to day 7 after single dose administration and Part 1B: Pre-dose to day 7 after single dose administration
measure: Time to elimination half-life (T1/2) for Food Effect of SHR2285 on pharmacokinetics parameters in healthy subjects.
time frame: Part 1A: Pre-dose to day 7 after single dose administration and Part 1B: Pre-dose to day 7 after single dose administration
measure: Area under the plasma concentration versus time curve (AUC0-last) for Food Effect of SHR2285 on pharmacokinetics parameters in healthy subjects.
time frame: Part 1A: Pre-dose to day 7 after single dose administration and Part 1B: Pre-dose to day 7 after single dose administration
measure: Maximum observed serum concentration (Cmax) for single dose of SHR2285.
time frame: Part 1:Pre-dose to day 3 after single dose administration and Part 2:Pre-dose to day 9 after multiple dose administration
measure: Time to maximum observed serum concentration (Tmax) for single dose of SHR2285.
time frame: Part 1:Pre-dose to day 3 after single dose administration and Part 2:Pre-dose to day 9 after multiple dose administration
measure: Time to elimination half-life (T1/2) for single dose of SHR2285.
time frame: Part 1:Pre-dose to day 3 after single dose administration and Part 2:Pre-dose to day 9 after multiple dose administration
measure: Area under the plasma concentration versus time curve (AUC0-last) for single dose of SHR2285.
time frame: Part 1:Pre-dose to day 3 after single dose administration and Part 2:Pre-dose to day 9 after multiple dose administration
measure: Steady-state peak concentration (Cmax，ss) for multiple dose of SHR2285.
time frame: Pre-dose to day 9 after multiple dose administration
measure: Steady state valley concentration (Ctrough，ss) for multiple dose of SHR2285.
time frame: Pre-dose to day 9 after multiple dose administration.
measure: Accumulation ratio (Racc) for multiple dose of SHR2285.
time frame: Pre-dose to day 9 after multiple dose administration
measure: Clotting factor XI (FXI) activity .
time frame: Part 1:Pre-dose to day 7 after single dose administration and Part 2:Pre-dose to day 14 after multiple dose administration
measure: Change of activated partial thromboplastin time (APTT) from baseline.
time frame: Part 1:Pre-dose to day 7 after single dose administration and Part 2:Pre-dose to day 14 after multiple dose administration
measure: Change of prothrombin time (PT) from baseline.
time frame: Part 1:Pre-dose to day 7 after single dose administration and Part 2:Pre-dose to day 14 after multiple dose administration
measure: Change of international normalization ratio (INR) from baseline.
time frame: Part 1:Pre-dose to day 7 after single dose administration and Part 2:Pre-dose to day 14 after multiple dose administration
arm group label: SHR2285 Part 1A
arm group type: Experimental
description: Participant received one of 7 dose levels of SHR2285 tablet as single-dose oral administration
arm group label: Placebo Part 1A
arm group type: Placebo Comparator
description: Single ascending doses of placebo orally
arm group label: SHR2285 Part 1B
arm group type: Experimental
description: Participant received one dose of SHR2285 tablet as single-dose oral administration
arm group label: Placebo Part 1B
arm group type: Placebo Comparator
description: Single doses of placebo orally
arm group label: SHR2285 Part 2
arm group type: Experimental
description: Participant received one of 4 dose levels of SHR2285 tablet as multi-dose oral administration
arm group label: Placebo Part 2
arm group type: Placebo Comparator
description: Multiple ascending doses of placebo orally
intervention type: Drug
intervention name: SHR2285 tablet
description: single dose or multi-dose
arm group label: SHR2285 Part 1A
arm group label: SHR2285 Part 1B
arm group label: SHR2285 Part 2
intervention type: Drug
intervention name: Placebo
description: single dose or multi-dose
arm group label: Placebo Part 1A
arm group label: Placebo Part 1B
arm group label: Placebo Part 2
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
facility: 
country: China
responsible party type: Sponsor
mesh term: Thrombosis
sharing ipd: No