<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/NCT04455100</url>
  </required_header>
  <id_info>
    <org_study_id>SHR1459-I-106</org_study_id>
    <nct_id>NCT04455100</nct_id>
  </id_info>
  <brief_title>A Phase I Study of SHR1459 in Healthy Subjects</brief_title>
  <official_title>Open-Label, Single-Center, Single-arm, Fixed Sequence Study on the Effect of Itraconazole on the Pharmacokinetics of SHR1459 in Health Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Jiangsu HengRui Medicine Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </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>
      Following a 10-hour overnight fast, subjects will be administered one dose of SHR1459 orally&#xD;
      with 240 mL of ambient temperature water on Day 1. D2-D3 was the cleaning period.&#xD;
      Itraconazole will be administered orally 200 mg/time/day form D4 to D8 after meal. On D7&#xD;
      following a 10-hour overnight fast, subjects will be administered SHR1459 and itraconazole&#xD;
      200 mg with 240 mL of ambient temperature water.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 17, 2020</start_date>
  <completion_date type="Actual">August 14, 2020</completion_date>
  <primary_completion_date type="Actual">August 14, 2020</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pharmacokinetics parameter: Cmax of SHR1459</measure>
    <time_frame>from Day 1 to Day 9</time_frame>
    <description>Peak Plasma Concentration (Cmax) of SHR1459</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetics parameter: AUC of SHR1459</measure>
    <time_frame>from Day 1 to Day 9</time_frame>
    <description>Area under the plasma concentration versus time curve (AUC) of SHR1459</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics parameter: Tmax of SHR1459</measure>
    <time_frame>from Day 1 to Day 9</time_frame>
    <description>Time of maximum observed concentration (Tmax) of SHR1459</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics parameter: T1/2 of SHR1459</measure>
    <time_frame>from Day 1 to Day 9</time_frame>
    <description>Half time (T1/2) of SHR1459</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics parameter: CL/F of SHR1459</measure>
    <time_frame>from Day 1 to Day 9</time_frame>
    <description>Apparent clearance of SHR1459</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics parameter: Vz/F of SHR1459</measure>
    <time_frame>from Day 1 to Day 9</time_frame>
    <description>Apparent volume of distribution of SHR1459</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Health, Subjective</condition>
  <arm_group>
    <arm_group_label>SHR1459</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Following a 10-hour overnight fast, subjects will be administered one dose of SHR1459 orally with 240 mL of ambient temperature water on Day 1. D2-D3 was the cleaning period. Itraconazole will be administered orally 200 mg/time/day form D4 to D8 after meal. On D7 following a 10-hour overnight fast, subjects will be administered SHR1459 and itraconazole 200 mg with 240 mL of ambient temperature water.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>SHR1459/Itraconazole</intervention_name>
    <description>SHR1459 will be administered on Day 1 and Day 7. Itraconazole will be administered on Day 4 to Day 8</description>
    <arm_group_label>SHR1459</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Sign the informed consent before the trial and fully understand the content, process&#xD;
             and possible adverse of the trial;&#xD;
&#xD;
          2. Able and willing to complete research according to the requirements of the trial;&#xD;
&#xD;
          3. Age at the date of signing informed consent 18 to 55 years old (inclusive), male and&#xD;
             female;&#xD;
&#xD;
          4. Male body weight ≥50 kg, female body weight ≥45 kg, body mass index (BMI) between&#xD;
             ≥18.0 and ≤26.0 kg/m2, inclusive;&#xD;
&#xD;
          5. Health status: lack of medical history of heart, liver, kidney, digestive tract,&#xD;
             nervous system, mental disorders and metabolic abnormalities;&#xD;
&#xD;
          6. Comprehensive physical examination (vital signs, physical examination), routine&#xD;
             laboratory examination (blood routine, blood biochemistry, urine routine, etc.),&#xD;
             X-chest radiograph, abdominal ultrasound (liver, gallbladder, bile duct, spleen,&#xD;
             pancreas, kidney), etc, normal or abnormal and no clinical significance;&#xD;
&#xD;
          7. 12-lead ECG is normal, QTcF for men &lt;430 ms, QTcF for women &lt;450 ms, and heart rate&#xD;
             &gt;60;&#xD;
&#xD;
          8. Creatinine clearance (CLCr) ≥80 mL/min, and creatinine is less than or equal to the&#xD;
             upper limit of normal value;&#xD;
&#xD;
          9. A negative pregnancy test for females of childbearing potential;&#xD;
&#xD;
         10. Consent to abstinence or use of effective nondrug contraception during the study&#xD;
             period and for at least 3 months after the last study drug administration (for women,&#xD;
             abstinence or use of effective nondrug contraception during the two weeks prior to&#xD;
             study entry is also required).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Blood donation or loss of more than 200 mL of blood within 1 month of screening; or&#xD;
             blood donation or loss of more than 400 mL of blood within 3 months of screening; or&#xD;
             received blood&#xD;
&#xD;
          2. Allergic constitution, including severe drug allergy or history of drug allergy;&#xD;
             history of allergy to SHR1459, itraconazole, or its accessories;&#xD;
&#xD;
          3. Subject has a history of drug abuse in past 5 years or drug abuse in past 3 months, or&#xD;
             is positive for drugs of abuse (eg, morphine/methamphetamine/ketamine/&#xD;
             tetrahydrocannabinolic acid /methylenedioxyethylamphetamine );&#xD;
&#xD;
          4. History of regular alcohol and smoke consumption( exceeding or equal an average weekly&#xD;
             intake of 14 standard drinks; 1 drink=150 mL of wine or 360 mL of beer or 45 mL of&#xD;
             hard liquor; smoke more than or equal to 5 cigarettes per day)or will not refrain from&#xD;
             smoking and drinking during the study;&#xD;
&#xD;
          5. History of cardiovascular dysfunction, myocarditis, coronary heart disease,&#xD;
             pathological arrhythmia, stroke and other cardiovascular diseases;&#xD;
&#xD;
          6. Lung diseases, including invasive lung disease, pneumonia, dyspnea, etc;&#xD;
&#xD;
          7. History of chronic kidney disease, renal insufficiency, renal anemia;&#xD;
&#xD;
          8. History of dysphagia or any gastrointestinal disease that affects drug absorption;&#xD;
&#xD;
          9. Any uncontrolled peptic ulcer, colitis, pancreatitis, etc;&#xD;
&#xD;
         10. Had a surgery within 6 months of screening;&#xD;
&#xD;
         11. Important organ diseases such as nervous system, cardiovascular system, urinary&#xD;
             system, digestive system, respiratory system, metabolism and skeletal muscle system&#xD;
             (such as uncontrolled diabetes, hypertension, etc.), in the investigator's judgment it&#xD;
             is not suitable to participate in this trial;&#xD;
&#xD;
         12. Have taken hepatotoxic drugs for a long period of time (more than 2 consecutive weeks)&#xD;
             (such as acetaminophen, statin lipid-lowering drugs, azithromycin, dapsone,&#xD;
             clarithromycin, fluconazole, ketoconazole) before the screening;&#xD;
&#xD;
         13. Participated in other clinical trials or used drugs related to this trial within 3&#xD;
             months before screening;&#xD;
&#xD;
         14. Have taken any drugs that alter the activity of liver enzymes 28 days before or during&#xD;
             the study;&#xD;
&#xD;
         15. Have taken any prescription or over-the-counter medicine 14 days before study drug&#xD;
             administration;&#xD;
&#xD;
         16. Have taken any vitamin products or herbs 14 days before study drug administration;&#xD;
&#xD;
         17. Evidence of clinically significant or other clinical findings show the following&#xD;
             diseases (including but not limited to gastrointestinal tract, kidney, liver, nerve,&#xD;
             blood, endocrine, tumor, lung, immune, mental or cardio-cerebrovascular diseases);&#xD;
&#xD;
         18. Combine with other viral infections (anti-HCV, anti-HIV positive, HBsAg positive) or&#xD;
             syphilis infection;&#xD;
&#xD;
         19. Have ingested grapefruit or products containing grapefruit, dragon fruit, mango, lime,&#xD;
             carambola, or food or beverage prepared therefrom 48 hours before taking the study&#xD;
             drug;, food or beverage containing caffeine, xanthine or alcohol (Including chocolate,&#xD;
             tea, coffee, cola, etc.); strenuous exercise, or other factors that affect the&#xD;
             absorption, distribution, metabolism, excretion of drugs, etc;&#xD;
&#xD;
         20. According to the screening chest X-ray and abdominal ultrasound (liver, gallbladder,&#xD;
             bile duct, spleen, pancreas, kidney) examination items confirmed abnormal and&#xD;
             clinically significant;&#xD;
&#xD;
         21. Vaccination recipients within 4 weeks before screening;&#xD;
&#xD;
         22. Cannot tolerate venous puncture or have a history of halo acupuncture;&#xD;
&#xD;
         23. Lactose intolerant;&#xD;
&#xD;
         24. Required special dietary and refuse the unified diet;&#xD;
&#xD;
         25. Subjects with acute illness from screening to pre-dose;&#xD;
&#xD;
         26. In the investigator's judgment subjects are not suitable to participate in this trial;&#xD;
&#xD;
             In addition to the above requirements, female volunteers who meet the following&#xD;
             conditions should also be excluded:&#xD;
&#xD;
         27. Have taken contraceptives within 30 days before screening (interview);&#xD;
&#xD;
         28. Used long-acting estrogen or progesterone injections (including progesterone&#xD;
             intrauterine devices) or implants within 6 months before screening;&#xD;
&#xD;
         29. Subjects had unprotected sex with their partner within 14 days before screening;&#xD;
&#xD;
         30. Female subjects are during in period of lactating.&#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>Shanghai General Hospital</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200080</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>June 27, 2020</study_first_submitted>
  <study_first_submitted_qc>July 1, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 2, 2020</study_first_posted>
  <last_update_submitted>October 9, 2021</last_update_submitted>
  <last_update_submitted_qc>October 9, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">October 18, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Itraconazole</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT04455100
org study id: SHR1459-I-106
nct id: NCT04455100
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Following a 10-hour overnight fast, subjects will be administered one dose of SHR1459 orally
      with 240 mL of ambient temperature water on Day 1. D2-D3 was the cleaning period.
      Itraconazole will be administered orally 200 mg/time/day form D4 to D8 after meal. On D7
      following a 10-hour overnight fast, subjects will be administered SHR1459 and itraconazole
      200 mg with 240 mL of ambient temperature water.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Other
masking: None (Open Label)
measure: Pharmacokinetics parameter: Cmax of SHR1459
time frame: from Day 1 to Day 9
description: Peak Plasma Concentration (Cmax) of SHR1459
measure: Pharmacokinetics parameter: AUC of SHR1459
time frame: from Day 1 to Day 9
description: Area under the plasma concentration versus time curve (AUC) of SHR1459
measure: Pharmacokinetics parameter: Tmax of SHR1459
time frame: from Day 1 to Day 9
description: Time of maximum observed concentration (Tmax) of SHR1459
measure: Pharmacokinetics parameter: T1/2 of SHR1459
time frame: from Day 1 to Day 9
description: Half time (T1/2) of SHR1459
measure: Pharmacokinetics parameter: CL/F of SHR1459
time frame: from Day 1 to Day 9
description: Apparent clearance of SHR1459
measure: Pharmacokinetics parameter: Vz/F of SHR1459
time frame: from Day 1 to Day 9
description: Apparent volume of distribution of SHR1459
arm group label: SHR1459
arm group type: Experimental
description: Following a 10-hour overnight fast, subjects will be administered one dose of SHR1459 orally with 240 mL of ambient temperature water on Day 1. D2-D3 was the cleaning period. Itraconazole will be administered orally 200 mg/time/day form D4 to D8 after meal. On D7 following a 10-hour overnight fast, subjects will be administered SHR1459 and itraconazole 200 mg with 240 mL of ambient temperature water.
intervention type: Drug
intervention name: SHR1459/Itraconazole
description: SHR1459 will be administered on Day 1 and Day 7. Itraconazole will be administered on Day 4 to Day 8
arm group label: SHR1459
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: China
responsible party type: Sponsor
mesh term: Itraconazole
sharing ipd: Undecided