xml: <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/NCT06012578</url>
    </required_header>
    <id_info>
      <org_study_id>ISM5411-101</org_study_id>
      <nct_id>NCT06012578</nct_id>
    </id_info>
    <brief_title>Study Evaluating ISM5411 Administered Orally to Healthy Volunteers</brief_title>
    <official_title>A Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose, Multiple Ascending Dose and Food Effect Study to Evaluate Safety, Tolerability, Pharmacokinetics and Food Effect of ISM5411 in Healthy Subjects</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>InSilico Medicine Hong Kong Limited</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>InSilico Medicine Hong Kong Limited</source>
    <oversight_info>
      <has_dmc>Yes</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 goal of this clinical trial is to learn about ISM5411 in healthy subjects. The primary&#xD;
        objective is to evaluate the safety and tolerability of single and multiple oral doses of&#xD;
        ISM5411 in healthy subjects.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 2023</start_date>
    <completion_date type="Anticipated">September 2024</completion_date>
    <primary_completion_date type="Anticipated">September 2024</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>Double (Participant, Investigator)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Number of participants with Adverse Events (AEs) after single or multiple doses of ISM5411.</measure>
      <time_frame>Up to 7 days after last dose.</time_frame>
      <description>The number of participants with treatment related AEs as assessed by CTCAE v5.0. will be monitored.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Number of participants with clinically significant changes in vital signs</measure>
      <time_frame>Up to 7 days after last dose.</time_frame>
      <description>The number of participants with clinically significant changes in vital signs will be monitored based on the assessment of blood pressure, heart rate, respiration and body temperature before and after administration.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Number of participants with clinically significant changes in in chemistry laboratory values</measure>
      <time_frame>Up to 7 days after last dose</time_frame>
      <description>The number of participants with clinically significant changes in blood routine, blood biochemistry, urine routine, coagulation function, etc. will be monitored before and after administration.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Number of participants with clinically significant changes in 12-lead Electrocardiogram (ECG) readings</measure>
      <time_frame>Up to 7 days after last dose</time_frame>
      <description>The number of participants with clinically significant changes in 12-lead Electrocardiogram (ECG) readings will be monitored based on changes in cardiovascular system function (change in QTC parameters) as a criterion of safety and tolerability variables.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Number of participants with clinically significant changes in physical examinations</measure>
      <time_frame>Up to 7 days after last dose</time_frame>
      <description>Complete physical examination should include the head and face, skin system, lymph nodes, eyes, ears, nose and throat, mouth, respiratory system, cardiovascular system, abdomen, musculoskeletal system, nervous system and mental status.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Maximum plasma concentration (Cmax) of ISM5411</measure>
      <time_frame>Day 1 through Day 17</time_frame>
      <description>To evaluate the pharmacokinetics (PK) characteristics of ISM5411 in healthy subjects.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time at which the maximum plasma concentration occurred (tmax) of ISM5411</measure>
      <time_frame>Day 1 through Day 17</time_frame>
      <description>To evaluate the pharmacokinetics (PK) characteristics of ISM5411 in healthy subjects.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Area under the plasma concentration-time curve from time zero to infinity (AUC0-inf) of ISM5411</measure>
      <time_frame>Day 1 through Day 17</time_frame>
      <description>To evaluate the pharmacokinetics (PK) characteristics of ISM5411 in healthy subjects.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Area under the plasma concentration-time curve from time zero to time with last measurable concentration t (AUC0-t) of ISM5411</measure>
      <time_frame>Day 1 through Day 17</time_frame>
      <description>To evaluate the pharmacokinetics (PK) characteristics of ISM5411 in healthy subjects.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Elimination rate constant (λz) of ISM5411</measure>
      <time_frame>Day 1 through Day 17</time_frame>
      <description>To evaluate the pharmacokinetics (PK) characteristics of ISM5411 in healthy subjects.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Elimination half-life (t1/2) of ISM5411</measure>
      <time_frame>Day 1 through Day 17</time_frame>
      <description>To evaluate the pharmacokinetics (PK) characteristics of ISM5411 in healthy subjects.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Apparent volume of distribution (Vz/F) of ISM5411</measure>
      <time_frame>Day 1 through Day 17</time_frame>
      <description>To evaluate the pharmacokinetics (PK) characteristics of ISM5411 in healthy subjects.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Apparent total plasma clearance (CL/F) of ISM5411</measure>
      <time_frame>Day 1 through Day 17</time_frame>
      <description>To evaluate the pharmacokinetics (PK) characteristics of ISM5411 in healthy subjects.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Mean residence time (MRT) of ISM5411</measure>
      <time_frame>Day 1 through Day 17</time_frame>
      <description>To evaluate the pharmacokinetics (PK) characteristics of ISM5411 in healthy subjects.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Renal clearance rate (CLR) of ISM5411</measure>
      <time_frame>Day 1 through Day 17</time_frame>
      <description>To evaluate the pharmacokinetics (PK) characteristics of ISM5411 in healthy subjects.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Accumulative excretion (Ae) of ISM5411</measure>
      <time_frame>Day 1 through Day 17</time_frame>
      <description>To evaluate the pharmacokinetics (PK) characteristics of ISM5411 in healthy subjects.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Fractional excretion (fe) of ISM5411</measure>
      <time_frame>Day 1 through Day 17</time_frame>
      <description>To evaluate the pharmacokinetics (PK) characteristics of ISM5411 in healthy subjects.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Relative bioavailability (fed/fasted) of ISM5411</measure>
      <time_frame>Day 1 through Day 17</time_frame>
      <description>To evaluate the pharmacokinetics (PK) characteristics of ISM5411 in healthy subjects.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">76</enrollment>
    <condition>Healthy Subjects</condition>
    <arm_group>
      <arm_group_label>ISM5411</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <arm_group>
      <arm_group_label>Placebo</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>ISM5411</intervention_name>
      <description>Investigational Drug</description>
      <arm_group_label>ISM5411</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Placebo</intervention_name>
      <description>ISM5411 Matching Placebo</description>
      <arm_group_label>Placebo</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Subjects who have signed the informed consent form (ICF) prior to the study, fully&#xD;
               understand the content, procedures and possible adverse reactions of the study, and&#xD;
               are able to complete the study in accordance with the protocol requirements.&#xD;
  &#xD;
            2. Subjects (including their partners) who have no plan to become pregnant and&#xD;
               voluntarily use effective contraception as described in section 8.1 from screening to&#xD;
               3 months after the last dose.&#xD;
  &#xD;
            3. Male and female subjects aged 18-55 years (inclusive).&#xD;
  &#xD;
            4. Body weight ≥50 kg for males and ≥45 kg for females, with a body mass index (BMI =&#xD;
               weight (kg)/height2 (m2)) of 18 ~ 32 kg/m2 (inclusive).&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Allergy to the IP or any of its ingredients, or allergic constitution (allergy to more&#xD;
               than 1 drugs and food).&#xD;
  &#xD;
            2. History of dysphagia or any gastrointestinal surgery (appendicectomy and&#xD;
               cholecystectomy are excluded) or disease that affects drug absorption and/or&#xD;
               elimination.&#xD;
  &#xD;
            3. Presence of clinically relevant diseases evidenced by clinical findings, which are&#xD;
               making implementation of the protocol or interpretation of the study results&#xD;
               difficult, or that would put the subject at risk by participating in the study in the&#xD;
               opinion of the investigator, including but not limited to gastrointestinal, renal,&#xD;
               hepatic, neurological, hematological, endocrine, oncological, pulmonary,&#xD;
               immunological, psychiatric or cardiovascular and cerebrovascular diseases).&#xD;
  &#xD;
            4. Presence of abnormal and clinically significant medical history, physical examination,&#xD;
               vital signs, 12-lead ECG, clinical laboratory tests, abdominal color Doppler&#xD;
               ultrasound, or other investigations at screening (Repeat testing will be allowed by&#xD;
               the investigator discretion).&#xD;
  &#xD;
            5. Positive human immunodeficiency virus antibody (HIV-Ab), hepatitis B surface antigen&#xD;
               (HBsAg) and hepatitis C antibody (HCV-Ab) in the viral serology testing at screening.&#xD;
  &#xD;
            6. Smoking &gt; 5 cigarettes or an equivalent amount of tobacco per day, or consuming ≥ 14&#xD;
               units of alcohol per week (1 unit of alcohol ≈ 25 mL of spirits/100 mL of wine/285 mL&#xD;
               of beer) within 1 months prior to screening or unwilling to abstain from smoking or&#xD;
               drinking during the study.&#xD;
  &#xD;
            7. Subjects who are positive for urine drug testing at screening or Day-1, or have a&#xD;
               history of drug abuse or narcotic use in the past five years (Repeat testing will be&#xD;
               allowed by the investigator discretion).&#xD;
  &#xD;
            8. Subjects who have donated blood or lost a significant amount of blood (&gt;400 mL) within&#xD;
               1 months prior to screening, or who plan to donate blood during the study or within 1&#xD;
               month after the end of the study.&#xD;
  &#xD;
            9. Subjects who have undergone major surgical procedures (major visceral, organ, or bone&#xD;
               surgeries) that may affect the study in the judgment of the investigator within 3&#xD;
               months prior to screening, or who intend to have such procedures during the study.&#xD;
  &#xD;
           10. Intolerance to vein puncture, or presence of a history of blood phobia or&#xD;
               trypanophobia.&#xD;
  &#xD;
           11. Use of any prescription drugs within 14 days prior to the admission. Use of counter&#xD;
               medication / vitamins / supplements within 7 days prior to admission (with the&#xD;
               exception of contraception, occasional paracetamol, and standard dose of&#xD;
               multivitamins).&#xD;
  &#xD;
           12. Subjects who have receipt of any study drug or participated in any medical device&#xD;
               clinical studies within 1 month (or 5 half-lives, whichever is longer) prior to&#xD;
               screening.&#xD;
  &#xD;
           13. Vaccination with any live or attenuated vaccine within 1 month prior to screening.&#xD;
  &#xD;
           14. Any acute disease or acute attack of any chronic disease within 28 days prior to&#xD;
               screening.&#xD;
  &#xD;
           15. Consumption of any caffeinated food or beverages (such as coffee, strong tea, cola,&#xD;
               chocolate, etc.), xanthine-rich food (such as anchovies, sardines, bovine liver,&#xD;
               bovine kidney, etc.), food that induces or inhibits liver metabolizing enzymes (such&#xD;
               as dragon fruits, mango, grapefruit, pomegranate, etc.) and beverages made thereof, or&#xD;
               food or beverages containing alcohol, or presence of other factors that may affect the&#xD;
               absorption, distribution, metabolism or excretion of the drug (such as strenuous&#xD;
               exercise) within 48 hours prior to IP.&#xD;
  &#xD;
           16. Female subjects who are in lactation or positive for serum pregnancy test during the&#xD;
               screening period or study course.&#xD;
  &#xD;
           17. Subjects who, in the judgment of the investigator, are not suitable for participation&#xD;
               in the study.&#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>
    <overall_contact>
      <last_name>Yichen Liu</last_name>
      <phone>+86 18817554306</phone>
      <email>Insilico-Clinicaltrial@insilico.ai</email>
    </overall_contact>
    <location>
      <facility>
        <name>Nucleus Network</name>
        <address>
          <city>Melbourne</city>
          <state>Victoria</state>
          <zip>3004</zip>
          <country>Australia</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>Australia</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 17, 2023</study_first_submitted>
    <study_first_submitted_qc>August 22, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 25, 2023</study_first_posted>
    <last_update_submitted>August 22, 2023</last_update_submitted>
    <last_update_submitted_qc>August 22, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 25, 2023</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>
  
  
text: 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/NCT06012578
  org study id: ISM5411-101
  nct id: NCT06012578
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  The goal of this clinical trial is to learn about ISM5411 in healthy subjects. The primary
        objective is to evaluate the safety and tolerability of single and multiple oral doses of
        ISM5411 in healthy subjects.
  allocation: Randomized
  intervention model: Sequential Assignment
  primary purpose: Treatment
  masking: Double (Participant, Investigator)
  measure: Number of participants with Adverse Events (AEs) after single or multiple doses of ISM5411.
  time frame: Up to 7 days after last dose.
  description: The number of participants with treatment related AEs as assessed by CTCAE v5.0. will be monitored.
  measure: Number of participants with clinically significant changes in vital signs
  time frame: Up to 7 days after last dose.
  description: The number of participants with clinically significant changes in vital signs will be monitored based on the assessment of blood pressure, heart rate, respiration and body temperature before and after administration.
  measure: Number of participants with clinically significant changes in in chemistry laboratory values
  time frame: Up to 7 days after last dose
  description: The number of participants with clinically significant changes in blood routine, blood biochemistry, urine routine, coagulation function, etc. will be monitored before and after administration.
  measure: Number of participants with clinically significant changes in 12-lead Electrocardiogram (ECG) readings
  time frame: Up to 7 days after last dose
  description: The number of participants with clinically significant changes in 12-lead Electrocardiogram (ECG) readings will be monitored based on changes in cardiovascular system function (change in QTC parameters) as a criterion of safety and tolerability variables.
  measure: Number of participants with clinically significant changes in physical examinations
  time frame: Up to 7 days after last dose
  description: Complete physical examination should include the head and face, skin system, lymph nodes, eyes, ears, nose and throat, mouth, respiratory system, cardiovascular system, abdomen, musculoskeletal system, nervous system and mental status.
  measure: Maximum plasma concentration (Cmax) of ISM5411
  time frame: Day 1 through Day 17
  description: To evaluate the pharmacokinetics (PK) characteristics of ISM5411 in healthy subjects.
  measure: Time at which the maximum plasma concentration occurred (tmax) of ISM5411
  time frame: Day 1 through Day 17
  description: To evaluate the pharmacokinetics (PK) characteristics of ISM5411 in healthy subjects.
  measure: Area under the plasma concentration-time curve from time zero to infinity (AUC0-inf) of ISM5411
  time frame: Day 1 through Day 17
  description: To evaluate the pharmacokinetics (PK) characteristics of ISM5411 in healthy subjects.
  measure: Area under the plasma concentration-time curve from time zero to time with last measurable concentration t (AUC0-t) of ISM5411
  time frame: Day 1 through Day 17
  description: To evaluate the pharmacokinetics (PK) characteristics of ISM5411 in healthy subjects.
  measure: Elimination rate constant (λz) of ISM5411
  time frame: Day 1 through Day 17
  description: To evaluate the pharmacokinetics (PK) characteristics of ISM5411 in healthy subjects.
  measure: Elimination half-life (t1/2) of ISM5411
  time frame: Day 1 through Day 17
  description: To evaluate the pharmacokinetics (PK) characteristics of ISM5411 in healthy subjects.
  measure: Apparent volume of distribution (Vz/F) of ISM5411
  time frame: Day 1 through Day 17
  description: To evaluate the pharmacokinetics (PK) characteristics of ISM5411 in healthy subjects.
  measure: Apparent total plasma clearance (CL/F) of ISM5411
  time frame: Day 1 through Day 17
  description: To evaluate the pharmacokinetics (PK) characteristics of ISM5411 in healthy subjects.
  measure: Mean residence time (MRT) of ISM5411
  time frame: Day 1 through Day 17
  description: To evaluate the pharmacokinetics (PK) characteristics of ISM5411 in healthy subjects.
  measure: Renal clearance rate (CLR) of ISM5411
  time frame: Day 1 through Day 17
  description: To evaluate the pharmacokinetics (PK) characteristics of ISM5411 in healthy subjects.
  measure: Accumulative excretion (Ae) of ISM5411
  time frame: Day 1 through Day 17
  description: To evaluate the pharmacokinetics (PK) characteristics of ISM5411 in healthy subjects.
  measure: Fractional excretion (fe) of ISM5411
  time frame: Day 1 through Day 17
  description: To evaluate the pharmacokinetics (PK) characteristics of ISM5411 in healthy subjects.
  measure: Relative bioavailability (fed/fasted) of ISM5411
  time frame: Day 1 through Day 17
  description: To evaluate the pharmacokinetics (PK) characteristics of ISM5411 in healthy subjects.
  arm group label: ISM5411
  arm group type: Experimental
  arm group label: Placebo
  arm group type: Placebo Comparator
  intervention type: Drug
  intervention name: ISM5411
  description: Investigational Drug
  arm group label: ISM5411
  intervention type: Drug
  intervention name: Placebo
  description: ISM5411 Matching Placebo
  arm group label: Placebo
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 55 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Yichen Liu
  phone: +86 18817554306
  email: Insilico-Clinicaltrial@insilico.ai
  facility: 
  country: Australia
  responsible party type: Sponsor
  sharing ipd: No