<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/NCT04426708</url>
  </required_header>
  <id_info>
    <org_study_id>HMM0109</org_study_id>
    <nct_id>NCT04426708</nct_id>
  </id_info>
  <brief_title>A Clinical Study to Access the Pharmacokinetics of HMS5552 in Hepatic Impaired Subjects and Healthy Volunteers</brief_title>
  <official_title>An Open-Label, Paralleled Study of the Pharmacokinetics of HMS5552 Following a Single Oral Dose in Mild and Moderate Hepatic Impaired Subjects and Matched Healthy Volunteers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hua Medicine Limited</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hua Medicine 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>
      The objectives of this study is to access the pharmacokinetics and safety of HMS5552 in&#xD;
      single dose in mild and moderate hepatic impaired subjects and matched healthy adult&#xD;
      subjects.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is an open-label and paralleled study with single oral dose of HMS5552 given to hepatic&#xD;
      impaired subjects and matched healthy volunteers.&#xD;
&#xD;
      The primary objective is to access the pharmacokinetic profiles of HMS5552 in 25 mg dose in&#xD;
      hepatic impaired subjects and (gender, age and BMI) matched healthy adult subjects.&#xD;
&#xD;
      The secondary objective is to characterize the safety profiles of HMS5552 in single dose in&#xD;
      hepatic impaired subjects.&#xD;
&#xD;
      The subjects include mild hepatic impaired subjects (A group), moderate hepatic impaired&#xD;
      subjects (B group), and healthy subjects (C Group) matched with hepatic impaired subjects in&#xD;
      gender, age and BMI. The number of subjects in each group was no less than 8, and no less&#xD;
      than 3 subjects in each gender.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 18, 2019</start_date>
  <completion_date type="Actual">July 3, 2020</completion_date>
  <primary_completion_date type="Actual">July 3, 2020</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The single dose pharmacokinetics of HMS5552 will be described by estimating parameters of Cmax;</measure>
    <time_frame>Up to 72 hours post-dose</time_frame>
    <description>Plasma will be collected at predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hour post-dose.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The single dose pharmacokinetics of HMS5552 will be described by estimating parameters of AUClast;</measure>
    <time_frame>Up to 72 hours post-dose</time_frame>
    <description>Plasma will be collected at predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hour post-dose.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The single dose pharmacokinetics of HMS5552 will be described by estimating parameters of AUCinf;</measure>
    <time_frame>Up to 72 hours post-dose</time_frame>
    <description>Plasma will be collected at predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hour post-dose.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The single dose pharmacokinetics of HMS5552 will be described by estimating parameters of Cmax,u</measure>
    <time_frame>Up to 72 hours post-dose</time_frame>
    <description>Plasma will be collected at predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hour post-dose.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The single dose pharmacokinetics of HMS5552 will be described by estimating parameters of AUClast,u</measure>
    <time_frame>Up to 72 hours post-dose</time_frame>
    <description>Plasma will be collected at predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hour post-dose.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The single dose pharmacokinetics of HMS5552 will be described by estimating parameters of AUCinf,u</measure>
    <time_frame>Up to 72 hours post-dose</time_frame>
    <description>Plasma will be collected at predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hour post-dose.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The single dose pharmacokinetics of HMS5552 will be described by estimating parameters of Tmax ;</measure>
    <time_frame>Up to 72 hours post-dose</time_frame>
    <description>Plasma will be collected at predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hour post-dose.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The single dose pharmacokinetics of HMS5552 will be described by estimating parameters of T1/2;</measure>
    <time_frame>Up to 72 hours post-dose</time_frame>
    <description>Plasma will be collected at predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hour post-dose.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The single dose pharmacokinetics of HMS5552 will be described by estimating parameters of CL/F;</measure>
    <time_frame>Up to 72 hours post-dose</time_frame>
    <description>Plasma will be collected at predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hour post-dose.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The single dose pharmacokinetics of HMS5552 will be described by estimating parameters of Vz/F;</measure>
    <time_frame>Up to 72 hours post-dose</time_frame>
    <description>Plasma will be collected at predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hour post-dose.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The single dose pharmacokinetics of HMS5552 will be described by estimating parameters of fu;</measure>
    <time_frame>Up to 72 hours post-dose</time_frame>
    <description>Plasma will be collected at predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hour post-dose.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">25</enrollment>
  <condition>Type 2 Diabetes Mellitus</condition>
  <arm_group>
    <arm_group_label>Mild hepatic impaired subjects (A)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Mild hepatic impaired subjects: to receive a single dose of HMS5552 ( 25mg ) tablet orally</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Moderate hepatic impaired subjects (B)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Moderate hepatic impaired subjects: to receive a single dose of HMS5552 ( 25mg ) tablet orally</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Healthy volunteers (C)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Matched healthy volunteers: to receive a single dose of HMS5552 ( 25mg ) tablet orally</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>HMS5552</intervention_name>
    <description>single dose of HMS5552 25mg</description>
    <arm_group_label>Healthy volunteers (C)</arm_group_label>
    <arm_group_label>Mild hepatic impaired subjects (A)</arm_group_label>
    <arm_group_label>Moderate hepatic impaired subjects (B)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  For hepatic impaired subjects:&#xD;
&#xD;
               1. Male and female subjects between ages of 18 and 65 years, no less than 3 subjects&#xD;
                  in each gender.&#xD;
&#xD;
               2. Body weight≥50kg for male and ≥45kg for female； BMI: 18.5~30 kg/m2&#xD;
&#xD;
               3. ALT&gt;2×normal upper limit (ULN), or TBiL&gt;1.5×ULN, or diagnosed cirrhosis. The&#xD;
                  related clinical manifestations have been stable for 4-12 weeks, and Child-Pugh&#xD;
                  score is in grade A or B:&#xD;
&#xD;
                  A= mild liver damage (Group A): Child-Pugh 5-6; B= moderate liver damage (Group&#xD;
                  B): Child-Pugh 7-9;&#xD;
&#xD;
               4. Willing to sign the informed consent form (ICF) and take reliable contraceptive&#xD;
                  measures within 6 months after taking the last dose of study drug;&#xD;
&#xD;
               5. Willing to adhere to the protocol requirement.&#xD;
&#xD;
          -  For healthy volunteers:&#xD;
&#xD;
               1. Male and female subjects between ages of 18 and 65 years, no less than 3 subjects&#xD;
                  in each gender;&#xD;
&#xD;
               2. Body weight≥50kg for male and ≥45kg for female； BMI: 18.5~30 kg/m2;&#xD;
&#xD;
               3. Gender, age (±5 years) and BMI (±15%) matched with corresponding subject in&#xD;
                  hepatic impaired group;&#xD;
&#xD;
               4. Normal physical conditions, vital signs,12 lead ECG and laboratory recording;&#xD;
&#xD;
               5. Willing to sign the informed consent form (ICF) and take reliable contraceptive&#xD;
                  measures within 6 months after taking the last dose of study drug;&#xD;
&#xD;
               6. Willing to adhere to the protocol requirement.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects with impaired hepatic function cannot be enrolled if they meet one of the&#xD;
             following criteria:&#xD;
&#xD;
               1. Liver cancer, liver transplantation, liver failure, autoimmune liver disease,&#xD;
                  biliary cirrhosis, or drug-induced liver damage;&#xD;
&#xD;
               2. History of allergy;&#xD;
&#xD;
               3. Investigators adjudicate subjects have surgery that may affect drug absorption,&#xD;
                  distribution, metabolism or excretion;&#xD;
&#xD;
               4. In addition to diseases and complications of impaired hepatic function,&#xD;
                  investigator adjudicate subjects have clinically meaningful or unstable diseases&#xD;
                  or complications of central nervous system, cardiovascular system, digestive&#xD;
                  system, endocrine system, respiratory system, urinary system, blood system,&#xD;
                  mental disease, or malignant tumor, etc;&#xD;
&#xD;
               5. Abnormal of ECG performance or laboratory recording during screening;&#xD;
&#xD;
               6. Family history of QT prolongation syndrome;&#xD;
&#xD;
               7. History of hepatic encephalopathy or hepatic coma within 6 months before&#xD;
                  screening;&#xD;
&#xD;
               8. More than 5 cigarettes per day within 3 months before screening;&#xD;
&#xD;
               9. Alcohol addicts;&#xD;
&#xD;
              10. History of drug abuse&#xD;
&#xD;
          -  Healthy subjects cannot be enrolled if they meet one of the following criteria:&#xD;
&#xD;
               1. History of allergy;&#xD;
&#xD;
               2. Investigators adjudicate subjects have surgery that may affect drug absorption,&#xD;
                  distribution, metabolism or excretion;&#xD;
&#xD;
               3. Investigator adjudicate subjects have clinically meaningful or unstable diseases&#xD;
                  or complications of central nervous system, cardiovascular system, digestive&#xD;
                  system, endocrine system, respiratory system, urinary system, blood system,&#xD;
                  mental disease, or malignant tumor, etc;&#xD;
&#xD;
               4. Abnormal of ECG performance or laboratory recording during screening;&#xD;
&#xD;
               5. Family history of QT prolongation syndrome;&#xD;
&#xD;
               6. Severe infection, severe trauma or major surgery judged by investigator within 3&#xD;
                  months before screening;&#xD;
&#xD;
               7. More than 5 cigarettes per day within 3 months before screening;&#xD;
&#xD;
               8. Alcohol addicts;&#xD;
&#xD;
               9. History of drug abuse&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>West China Hospital of Sichuan University</name>
      <address>
        <city>Chengdu</city>
        <state>Sichuan</state>
        <zip>610000</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>June 8, 2020</study_first_submitted>
  <study_first_submitted_qc>June 8, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 11, 2020</study_first_posted>
  <last_update_submitted>November 28, 2022</last_update_submitted>
  <last_update_submitted_qc>November 28, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 29, 2022</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>Diabetes Mellitus, Type 2</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/NCT04426708
org study id: HMM0109
nct id: NCT04426708
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The objectives of this study is to access the pharmacokinetics and safety of HMS5552 in
      single dose in mild and moderate hepatic impaired subjects and matched healthy adult
      subjects.
This is an open-label and paralleled study with single oral dose of HMS5552 given to hepatic
      impaired subjects and matched healthy volunteers.

      The primary objective is to access the pharmacokinetic profiles of HMS5552 in 25 mg dose in
      hepatic impaired subjects and (gender, age and BMI) matched healthy adult subjects.

      The secondary objective is to characterize the safety profiles of HMS5552 in single dose in
      hepatic impaired subjects.

      The subjects include mild hepatic impaired subjects (A group), moderate hepatic impaired
      subjects (B group), and healthy subjects (C Group) matched with hepatic impaired subjects in
      gender, age and BMI. The number of subjects in each group was no less than 8, and no less
      than 3 subjects in each gender.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: The single dose pharmacokinetics of HMS5552 will be described by estimating parameters of Cmax;
time frame: Up to 72 hours post-dose
description: Plasma will be collected at predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hour post-dose.
measure: The single dose pharmacokinetics of HMS5552 will be described by estimating parameters of AUClast;
time frame: Up to 72 hours post-dose
description: Plasma will be collected at predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hour post-dose.
measure: The single dose pharmacokinetics of HMS5552 will be described by estimating parameters of AUCinf;
time frame: Up to 72 hours post-dose
description: Plasma will be collected at predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hour post-dose.
measure: The single dose pharmacokinetics of HMS5552 will be described by estimating parameters of Cmax,u
time frame: Up to 72 hours post-dose
description: Plasma will be collected at predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hour post-dose.
measure: The single dose pharmacokinetics of HMS5552 will be described by estimating parameters of AUClast,u
time frame: Up to 72 hours post-dose
description: Plasma will be collected at predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hour post-dose.
measure: The single dose pharmacokinetics of HMS5552 will be described by estimating parameters of AUCinf,u
time frame: Up to 72 hours post-dose
description: Plasma will be collected at predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hour post-dose.
measure: The single dose pharmacokinetics of HMS5552 will be described by estimating parameters of Tmax ;
time frame: Up to 72 hours post-dose
description: Plasma will be collected at predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hour post-dose.
measure: The single dose pharmacokinetics of HMS5552 will be described by estimating parameters of T1/2;
time frame: Up to 72 hours post-dose
description: Plasma will be collected at predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hour post-dose.
measure: The single dose pharmacokinetics of HMS5552 will be described by estimating parameters of CL/F;
time frame: Up to 72 hours post-dose
description: Plasma will be collected at predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hour post-dose.
measure: The single dose pharmacokinetics of HMS5552 will be described by estimating parameters of Vz/F;
time frame: Up to 72 hours post-dose
description: Plasma will be collected at predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hour post-dose.
measure: The single dose pharmacokinetics of HMS5552 will be described by estimating parameters of fu;
time frame: Up to 72 hours post-dose
description: Plasma will be collected at predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hour post-dose.
arm group label: Mild hepatic impaired subjects (A)
arm group type: Experimental
description: Mild hepatic impaired subjects: to receive a single dose of HMS5552 ( 25mg ) tablet orally
arm group label: Moderate hepatic impaired subjects (B)
arm group type: Experimental
description: Moderate hepatic impaired subjects: to receive a single dose of HMS5552 ( 25mg ) tablet orally
arm group label: Healthy volunteers (C)
arm group type: Experimental
description: Matched healthy volunteers: to receive a single dose of HMS5552 ( 25mg ) tablet orally
intervention type: Drug
intervention name: HMS5552
description: single dose of HMS5552 25mg
arm group label: Healthy volunteers (C)
arm group label: Mild hepatic impaired subjects (A)
arm group label: Moderate hepatic impaired subjects (B)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: China
responsible party type: Sponsor
mesh term: Diabetes Mellitus, Type 2
sharing ipd: No