<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/NCT03015948</url>
  </required_header>
  <id_info>
    <org_study_id>SHR4640-101-AUS</org_study_id>
    <nct_id>NCT03015948</nct_id>
  </id_info>
  <brief_title>A Single Dose Study of SHR4640 in Healthy Male Volunteers</brief_title>
  <official_title>A Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Dose of SHR4640 in Healthy Male Volunteers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Atridia Pty Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Atridia Pty 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>
      This is a single-center, randomized, double-blind, placebo-controlled, single ascending-dose&#xD;
      Phase I trial.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study includes screening (Days -16 to -3), check-in (Day -2), enrollment (Day -1),&#xD;
      dosing (Day 1), observational period (Days 2 to 3), discharge day (Day 4), and safety&#xD;
      follow-up visit (Day 8). Forty eligible subjects will be enrolled into 4 dose cohorts (10 for&#xD;
      each cohort), and every 10 subjects will be randomized in a 4:1 ratio to receive a single&#xD;
      dose of either SHR4640 (n=8) or placebo (n=2).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 22, 2016</start_date>
  <completion_date type="Actual">November 23, 2016</completion_date>
  <primary_completion_date type="Actual">November 23, 2016</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>Other</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Assess safety and tolerability of SHR 4640 over 11days including AEs, laboratory safety variables (including hematology, creatinine kinase (CK), biochemistry, and urinalysis), physical examinations, vital signs, and 12-lead electrocardiograms (ECGs)</measure>
    <time_frame>11 days</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Assess Pharmacokinetics (PK) Plasma parameter Area under the concentration-time curve (AUC) from zero to 24 and 72 hours postdose and from zero to infinity.</measure>
    <time_frame>from time of dosing to 72 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess Pharmacokinetics (PK) Plasma parameter Time to maximum concentration.</measure>
    <time_frame>from time of dosing to 72 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess Pharmacokinetics (PK) Plasma parameter Maximum concentration.</measure>
    <time_frame>from time of dosing to 72 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess Pharmacokinetics (PK) Plasma parameter Terminal elimination half-life (T1/2).</measure>
    <time_frame>from time of dosing to 72 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess Pharmacodynamics (PD) parameter Actual and percent changes in serum uric acid (sUA )from baseline.</measure>
    <time_frame>from time of dosing to 72 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess Pharmacodynamics (PD) parameter urinary uric acid concentration (uUA): actual and percent changes from baseline.</measure>
    <time_frame>from time of dosing to 72 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess Pharmacodynamics (PD) parameter urinary uric acid excretion (eUA): actual and percent changes from baseline.</measure>
    <time_frame>from time of dosing to 72 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess Pharmacodynamics (PD) parameter Uric acid renal clearance (UaCl): actual and percent changes from baseline</measure>
    <time_frame>from time of dosing to 72 hours</time_frame>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>Gout</condition>
  <arm_group>
    <arm_group_label>2.5mg SHR4640</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>10 subjects will be randomized in a 4:1 ratio to receive a single dose of either 2.5 mg SHR4640 (n=8) or placebo (n=2)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>10mg SHR4640</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>10 subjects will be randomized in a 4:1 ratio to receive a single dose of either 10mg SHR4640 (n=8) or placebo (n=2) 10mg.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>20mg SHR4640</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>10 subjects will be randomized in a 4:1 ratio to receive a single dose of either 20mg SHR4640 (n=8) or placebo (n=2) .</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>For each dose cohort, 10 subjects will be randomized in a 4:1 ratio to receive a single dose of either SHR4640 (n=8) or placebo (n=2)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>5mg SHR4640</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>10 subjects will be randomized in a 4:1 ratio to receive a single dose of either 5 mg SHR4640 (n=8) or placebo (n=2)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>SHR4640</intervention_name>
    <description>a single dose of SHR4640 (n=8) for each dose cohort</description>
    <arm_group_label>10mg SHR4640</arm_group_label>
    <arm_group_label>2.5mg SHR4640</arm_group_label>
    <arm_group_label>20mg SHR4640</arm_group_label>
    <arm_group_label>5mg SHR4640</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>a single dose of placebo (n=2) for each dose cohort .</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male, aged between 18 and 55 years, inclusive.&#xD;
&#xD;
          2. Body weight ≥ 50 kg and body mass index between 18.0 to 30.0 kg/m2, inclusive.&#xD;
&#xD;
          3. Screening sUA level from 0.24 to 0.42 mmol/L, inclusive.&#xD;
&#xD;
          4. Considered generally healthy upon completion of medical history, full physical&#xD;
             examination, vital signs, laboratory parameters (including thyroid function,&#xD;
             coagulation and serological tests, hematology, creatinine kinase, biochemistry, and&#xD;
             urinalysis), 12-lead ECG, and abdominal ultrasound, as judged by the Investigator.&#xD;
&#xD;
          5. Agrees to use a highly effective method of contraception, i.e. condom and suitable&#xD;
             contraception for your female partner e.g. diaphragm (double barrier), oral&#xD;
             contraceptive or intrauterine contraceptive device during heterosexual intercourse or&#xD;
             be non-heterosexually active, or practice sexual abstinence throughout the study&#xD;
             period and for 30 days following study drug dosing, and must agree to refrain from&#xD;
             sperm donation from Day -2 until at least 30 days following study drug dosing.&#xD;
&#xD;
          6. Negative drug screen (including alcohol) at screening and on admission to clinical&#xD;
             site.&#xD;
&#xD;
          7. Able to understand the study procedures and the risks involved and must be willing to&#xD;
             provide written informed consent before any study-related activity.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. History of hypersensitivity to SHR4640 or its analogues.&#xD;
&#xD;
          2. Screening sCr above upper limit of normal.&#xD;
&#xD;
          3. Screening alanine aminotransferase, aspartate aminotransferase, total bilirubin, or&#xD;
             gamma glutamyl transferase &gt; 1.5 × upper limit of normal.&#xD;
&#xD;
          4. Positive result for HIV.&#xD;
&#xD;
          5. Positive result for hepatitis B surface antigen or hepatitis C virus antibody.&#xD;
&#xD;
          6. History or presence of kidney stones.&#xD;
&#xD;
          7. Acute or chronic illness that, in the opinion of the Investigator, might confound the&#xD;
             results of the trial or pose risk in administering the trial product to the subject.&#xD;
&#xD;
          8. Undergone major surgery within 3 months of Day 1.&#xD;
&#xD;
          9. Donated any blood or plasma in the past month or more than 400 mL within 3 months of&#xD;
             Day 1.&#xD;
&#xD;
         10. Has poor venous access and is unable to donate blood.&#xD;
&#xD;
         11. Use of tobacco products within 30 days of Day 1.&#xD;
&#xD;
         12. Heavy caffeine drinker (more than 5 cups or glasses of caffeinated beverages per day).&#xD;
&#xD;
         13. History of drug and/or alcohol abuse in the last year.&#xD;
&#xD;
         14. Consumes more than 14 drinks of alcohol per week (eg, 1 drink = 5 oz [150 mL] of wine,&#xD;
             12 oz of beer, or 1.5 oz of hard liquor).&#xD;
&#xD;
         15. Consumes grapefruit and/or poppy seed within 5 days of Day 1.&#xD;
&#xD;
         16. Cannot refrain from heavy exercises, tobacco products, alcohol, grapefruit, and/or&#xD;
             poppy seed from Day -2 to Day 4.&#xD;
&#xD;
         17. Use of any of the following, unless agreed as nonclinically relevant by the&#xD;
             Investigator and the Sponsor:&#xD;
&#xD;
        1) Prescription medication within 2 weeks of Day 1. 2) Over-the-counter medication within 1&#xD;
        week of Day 1. 3) Use of any over the-counter, nutraceuticals, or prescription medications&#xD;
        that might interfere with the absorption, distribution, metabolism, or excretion of SHR4640&#xD;
        (proton-pump inhibitor, fluconazole, indomethacin, ranitidine, flurbiprofen, probenecid,&#xD;
        aprepitant, etc.) within 1 month of Day 1.&#xD;
&#xD;
        18. Received the last dose of a study drug (or treatment with a medical device) within 30&#xD;
        days or 5 T1/2 (whichever is longer) of the study drug of Day 1 or are currently&#xD;
        participating in another study of a study drug (or medical device).&#xD;
&#xD;
        19. Any other medical or psychological condition, which in the opinion of the Investigator,&#xD;
        might create undue risk to the subject or interfere with the subject's ability to comply&#xD;
        with the protocol requirements or to complete the study.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sam Salman, B.Sc,BMBS</last_name>
    <role>Principal Investigator</role>
    <affiliation>Linear Clinical Research</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Atridia Pty Limited</name>
      <address>
        <city>Sydney</city>
        <state>New South Wales</state>
        <zip>2000</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
  </location_countries>
  <verification_date>July 2018</verification_date>
  <study_first_submitted>September 20, 2016</study_first_submitted>
  <study_first_submitted_qc>January 9, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 10, 2017</study_first_posted>
  <last_update_submitted>July 2, 2018</last_update_submitted>
  <last_update_submitted_qc>July 2, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">July 3, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <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/NCT03015948
org study id: SHR4640-101-AUS
nct id: NCT03015948
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This is a single-center, randomized, double-blind, placebo-controlled, single ascending-dose
      Phase I trial.
This study includes screening (Days -16 to -3), check-in (Day -2), enrollment (Day -1),
      dosing (Day 1), observational period (Days 2 to 3), discharge day (Day 4), and safety
      follow-up visit (Day 8). Forty eligible subjects will be enrolled into 4 dose cohorts (10 for
      each cohort), and every 10 subjects will be randomized in a 4:1 ratio to receive a single
      dose of either SHR4640 (n=8) or placebo (n=2).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: Triple (Participant, Care Provider, Investigator)
measure: Assess safety and tolerability of SHR 4640 over 11days including AEs, laboratory safety variables (including hematology, creatinine kinase (CK), biochemistry, and urinalysis), physical examinations, vital signs, and 12-lead electrocardiograms (ECGs)
time frame: 11 days
measure: Assess Pharmacokinetics (PK) Plasma parameter Area under the concentration-time curve (AUC) from zero to 24 and 72 hours postdose and from zero to infinity.
time frame: from time of dosing to 72 hours
measure: Assess Pharmacokinetics (PK) Plasma parameter Time to maximum concentration.
time frame: from time of dosing to 72 hours
measure: Assess Pharmacokinetics (PK) Plasma parameter Maximum concentration.
time frame: from time of dosing to 72 hours
measure: Assess Pharmacokinetics (PK) Plasma parameter Terminal elimination half-life (T1/2).
time frame: from time of dosing to 72 hours
measure: Assess Pharmacodynamics (PD) parameter Actual and percent changes in serum uric acid (sUA )from baseline.
time frame: from time of dosing to 72 hours
measure: Assess Pharmacodynamics (PD) parameter urinary uric acid concentration (uUA): actual and percent changes from baseline.
time frame: from time of dosing to 72 hours
measure: Assess Pharmacodynamics (PD) parameter urinary uric acid excretion (eUA): actual and percent changes from baseline.
time frame: from time of dosing to 72 hours
measure: Assess Pharmacodynamics (PD) parameter Uric acid renal clearance (UaCl): actual and percent changes from baseline
time frame: from time of dosing to 72 hours
arm group label: 2.5mg SHR4640
arm group type: Experimental
description: 10 subjects will be randomized in a 4:1 ratio to receive a single dose of either 2.5 mg SHR4640 (n=8) or placebo (n=2)
arm group label: 10mg SHR4640
arm group type: Experimental
description: 10 subjects will be randomized in a 4:1 ratio to receive a single dose of either 10mg SHR4640 (n=8) or placebo (n=2) 10mg.
arm group label: 20mg SHR4640
arm group type: Experimental
description: 10 subjects will be randomized in a 4:1 ratio to receive a single dose of either 20mg SHR4640 (n=8) or placebo (n=2) .
arm group label: Placebo
arm group type: Experimental
description: For each dose cohort, 10 subjects will be randomized in a 4:1 ratio to receive a single dose of either SHR4640 (n=8) or placebo (n=2)
arm group label: 5mg SHR4640
arm group type: Experimental
description: 10 subjects will be randomized in a 4:1 ratio to receive a single dose of either 5 mg SHR4640 (n=8) or placebo (n=2)
intervention type: Drug
intervention name: SHR4640
description: a single dose of SHR4640 (n=8) for each dose cohort
arm group label: 10mg SHR4640
arm group label: 2.5mg SHR4640
arm group label: 20mg SHR4640
arm group label: 5mg SHR4640
intervention type: Drug
intervention name: Placebo
description: a single dose of placebo (n=2) for each dose cohort .
arm group label: Placebo
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Sam Salman, B.Sc,BMBS
role: Principal Investigator
affiliation: Linear Clinical Research
facility: 
country: Australia
responsible party type: Sponsor
sharing ipd: No