<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/NCT04464551</url>
  </required_header>
  <id_info>
    <org_study_id>IBIO-105</org_study_id>
    <nct_id>NCT04464551</nct_id>
  </id_info>
  <brief_title>The Absorption, Metabolism and Excretion of [14C]D-0316 in Human</brief_title>
  <official_title>A Single-center, Open-label, Single-dose Phase I Study to Investigate the Absorption, Metabolism and Excretion of [14C]D-0316 After a Single Oral 75mg/50µCi Dose in Healthy Chinese Male Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Betta Pharmaceuticals Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Betta Pharmaceuticals 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>
      This is a single-center, open-label, single-dose phase I study to investigate the absorption,&#xD;
      metabolism and excretion of [14C] D-0316 in healthy Chinese male subjects. The study will be&#xD;
      conducted into two steps：Firstly, 2 subjects are enrolled in to participate in the pilot&#xD;
      study to grope for the completion date of plasma, urine and feces sampling on the 3rd day&#xD;
      post-dose and onwards. Then, the collection time of blood and excreta samples (urine and&#xD;
      feces) from the subsequent 2-4 subjects will be adjusted according to the pilot study&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Subjects who had signed informed consent and meet inclusion criteria and no exclusion&#xD;
      criteria are admitted to Phase I Clinical Unit two days prior to dosing (D-2). On the morning&#xD;
      of Day 1 before dosing, subjects will be transferred to nuclear medical ward. And after an&#xD;
      overnight fast of at least 10 h, subjects will receive a single oral dose of 75 mg (50 μCi)&#xD;
      of [14C]D-0316 as an oral suspension. Then, after two days of the dosing, subjects will be&#xD;
      transferred back to Phase I Clinical Unit ward and confined to this unit until blood or&#xD;
      excreta sampling and safety monitoring at the designated time points or intervals are&#xD;
      complete&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">December 5, 2020</start_date>
  <completion_date type="Anticipated">August 2021</completion_date>
  <primary_completion_date type="Anticipated">August 2021</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>Radioactivity concentration of each plasma sample</measure>
    <time_frame>Day 1-Day85</time_frame>
    <description>Use liquid scintillation counter or accelerator mass spectrometry to evaluate radioactivity concentration of each plasma（DPM/ml) sample</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Radioactivity concentration of each urine samples</measure>
    <time_frame>Day-1-Day85</time_frame>
    <description>Use liquid scintillation counter or accelerator mass spectrometry to evaluate radioactivity concentration of each urine（DPM/ml) sample</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Radioactivity concentration of each feces sample</measure>
    <time_frame>Day-1-Day85</time_frame>
    <description>Use liquid scintillation counter or accelerator mass spectrometry to evaluate radioactivity concentration of each feces（DPM/ml) sample</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Total recovery of radioactivity in urine and feces</measure>
    <time_frame>Day-1-Day85</time_frame>
    <description>Calculate the total radioactivity in urine and feces based on the radioactivity concentration of each sample</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Identification of metabolites in plasma, urine and fecal samples</measure>
    <time_frame>Day-1-Day85</time_frame>
    <description>LC-MS/MS was used to identify the main metabolites in plasma, urine and feces, and finally to provide the main biotransformation pathway of CM082 in human body</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic parameters of unlabeled D-0316 and metabolite D-0865</measure>
    <time_frame>Day-1-Day85</time_frame>
    <description>To determine the plasma concentrations of D-0316 with validated LC-MS/MS method for obtaining its pharmacokinetics parameters</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with treatment-related adverse events as assessed by CTCAE v4.03</measure>
    <time_frame>Day-14-Day85</time_frame>
    <description>According to CTCAE v4.03, the number and frequency of adverse events after a single dose of test drug were assessed</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">4</enrollment>
  <condition>Advanced or Metastatic Non-small Cell Lung</condition>
  <arm_group>
    <arm_group_label>[14C]D-0316</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>To investigate the absorption properties, as well as to evaluate the mass balance and elucidate the pathways of biotransformation after a single oral dose (75mg, 50µCi) of [14C]D-0316 to healthy Chinese male subjects</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>[14C]D-0316 suspension</intervention_name>
    <description>Before administration, the drug preparation was placed at room temperature, and 40ml drinking water was added into each bottle to prepare suspension for the subjects to take. 40ml pure water was injected again. After washing the container, the subjects took orally. Repeat the previous step, and then used 160ml purified water. After the administration container was moistened for several times, the subjects took all the moistening lotion. Pay attention not to splash the liquid during mixing outside the bottle</description>
    <arm_group_label>[14C]D-0316</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  healthy male volunteers between the ages of 18 to 50 years old；&#xD;
&#xD;
          -  Body weight &gt;=50 kg, Body mass index (body weight(kg)/hight2(m2)) between 19 and 26&#xD;
             kg/m2；&#xD;
&#xD;
          -  Normal physical findings, clinical laboratory values, vital signs and 12-lead ECG, or&#xD;
             any abnormality that is non-clinically significant;&#xD;
&#xD;
          -  Male subjects of reproductive potential with partners will be instructed to, and must&#xD;
             be willing to practice a highly effective method of birth control for the duration of&#xD;
             the study and continuing 1 year after discontinuing treatment with the investigational&#xD;
             product. Highly effective methods of birth control include using condom, contraceptive&#xD;
             sponge, contraceptive gel, contraceptive film, intrauterine device, oral or injectable&#xD;
             contraceptive pill, hypodermic implants or others；&#xD;
&#xD;
          -  Must understand, and voluntarily sign the informed consent, comply with the&#xD;
             requirements of the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of or current clinically significant cardio, pulmonary, endocrine, metabolism,&#xD;
             renal, hepatic, gastrointestinal, dermatology, infection, hematology, neurological,&#xD;
             mental disease or disorder;&#xD;
&#xD;
          -  Positive test for HBsAg, HBeAg, anti-HCV, anti-HIV or syphilis antibody;&#xD;
&#xD;
          -  History of syncope / needle syncope and intolerable intravenous indwelling needle;&#xD;
&#xD;
          -  History of clinically significant disease or infection within 1 month before entering&#xD;
             the study;&#xD;
&#xD;
          -  Abnormality in blood pressure, including hypertensive BP (SBP&gt;=140 mmHg, or DBP &gt;=90&#xD;
             mmHg), or hypotensive BP(SBP&lt;90 mmHg, or DBP &lt;=55 mmHg), Pulse rate&lt;55 bpm or &gt;100&#xD;
             bpm;&#xD;
&#xD;
          -  Long-QT syndrome or family history of it, or QTcB interval &gt; 450 ms; intraventricular&#xD;
             blocks or left/right bundle branch block or QRS&gt;120ms; frequent ventricular ectopic&#xD;
             beats (any 10s ECG ventricular premature beat &gt;= 1 in screening period); or abnormal&#xD;
             resting heart rate (&gt; 100 bpm);&#xD;
&#xD;
          -  Received any drug within 14 days before taking the investigational drug, including any&#xD;
             prescription drug, OTC drug, herbal drug or health care products, except for vitamins&#xD;
             and paracetamol；&#xD;
&#xD;
          -  History of or current swallowing disorder, active gastrointestinal diseases, or other&#xD;
             diseases that significantly affect absorption, distribution, metabolism and excretion&#xD;
             of drugs;&#xD;
&#xD;
          -  Chronic constipation or diarrhea, irritable bowel syndrome, inflammatory bowel&#xD;
             disease;&#xD;
&#xD;
          -  Hemorrhoids or perianal disease with regular/perianal bleeding;&#xD;
&#xD;
          -  Allergies, have allergies to two or more drugs or foods; or have known allergies to&#xD;
             the components of the drug;&#xD;
&#xD;
          -  Participated in other clinical trials within 3 months before screening;&#xD;
&#xD;
          -  The subjects participated in the clinical trial of radioactive labeling within one&#xD;
             year before taking the medicine;&#xD;
&#xD;
          -  Significant radiation exposure within one year prior to drug administration (more than&#xD;
             one exposure from chest X-ray, CT scan, or barium meal examination and&#xD;
             radiation-related occupations);&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Feng Shao, Ph D</last_name>
    <role>Principal Investigator</role>
    <affiliation>Jiangsu Province Hospital Affiliated to Nanjing Madical University of Medicine</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Wei Liu, M.A</last_name>
    <role>Principal Investigator</role>
    <affiliation>Jiangsu Province Hospital Affiliated to Nanjing Madical University of Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Jiangsu Province Hospital Affiliated to Nanjing Madical University of Medicine</name>
      <address>
        <city>Nanjing</city>
        <state>Jiangsu</state>
        <zip>210029</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>May 2021</verification_date>
  <study_first_submitted>July 3, 2020</study_first_submitted>
  <study_first_submitted_qc>July 3, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 9, 2020</study_first_posted>
  <last_update_submitted>May 31, 2021</last_update_submitted>
  <last_update_submitted_qc>May 31, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">June 2, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <!-- 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/NCT04464551
org study id: IBIO-105
nct id: NCT04464551
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This is a single-center, open-label, single-dose phase I study to investigate the absorption,
      metabolism and excretion of [14C] D-0316 in healthy Chinese male subjects. The study will be
      conducted into two steps：Firstly, 2 subjects are enrolled in to participate in the pilot
      study to grope for the completion date of plasma, urine and feces sampling on the 3rd day
      post-dose and onwards. Then, the collection time of blood and excreta samples (urine and
      feces) from the subsequent 2-4 subjects will be adjusted according to the pilot study
Subjects who had signed informed consent and meet inclusion criteria and no exclusion
      criteria are admitted to Phase I Clinical Unit two days prior to dosing (D-2). On the morning
      of Day 1 before dosing, subjects will be transferred to nuclear medical ward. And after an
      overnight fast of at least 10 h, subjects will receive a single oral dose of 75 mg (50 μCi)
      of [14C]D-0316 as an oral suspension. Then, after two days of the dosing, subjects will be
      transferred back to Phase I Clinical Unit ward and confined to this unit until blood or
      excreta sampling and safety monitoring at the designated time points or intervals are
      complete
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Other
masking: None (Open Label)
measure: Radioactivity concentration of each plasma sample
time frame: Day 1-Day85
description: Use liquid scintillation counter or accelerator mass spectrometry to evaluate radioactivity concentration of each plasma（DPM/ml) sample
measure: Radioactivity concentration of each urine samples
time frame: Day-1-Day85
description: Use liquid scintillation counter or accelerator mass spectrometry to evaluate radioactivity concentration of each urine（DPM/ml) sample
measure: Radioactivity concentration of each feces sample
time frame: Day-1-Day85
description: Use liquid scintillation counter or accelerator mass spectrometry to evaluate radioactivity concentration of each feces（DPM/ml) sample
measure: Total recovery of radioactivity in urine and feces
time frame: Day-1-Day85
description: Calculate the total radioactivity in urine and feces based on the radioactivity concentration of each sample
measure: Identification of metabolites in plasma, urine and fecal samples
time frame: Day-1-Day85
description: LC-MS/MS was used to identify the main metabolites in plasma, urine and feces, and finally to provide the main biotransformation pathway of CM082 in human body
measure: Pharmacokinetic parameters of unlabeled D-0316 and metabolite D-0865
time frame: Day-1-Day85
description: To determine the plasma concentrations of D-0316 with validated LC-MS/MS method for obtaining its pharmacokinetics parameters
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.03
time frame: Day-14-Day85
description: According to CTCAE v4.03, the number and frequency of adverse events after a single dose of test drug were assessed
arm group label: [14C]D-0316
arm group type: Experimental
description: To investigate the absorption properties, as well as to evaluate the mass balance and elucidate the pathways of biotransformation after a single oral dose (75mg, 50µCi) of [14C]D-0316 to healthy Chinese male subjects
intervention type: Drug
intervention name: [14C]D-0316 suspension
description: Before administration, the drug preparation was placed at room temperature, and 40ml drinking water was added into each bottle to prepare suspension for the subjects to take. 40ml pure water was injected again. After washing the container, the subjects took orally. Repeat the previous step, and then used 160ml purified water. After the administration container was moistened for several times, the subjects took all the moistening lotion. Pay attention not to splash the liquid during mixing outside the bottle
arm group label: [14C]D-0316
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Feng Shao, Ph D
role: Principal Investigator
affiliation: Jiangsu Province Hospital Affiliated to Nanjing Madical University of Medicine
last name: Wei Liu, M.A
role: Principal Investigator
affiliation: Jiangsu Province Hospital Affiliated to Nanjing Madical University of Medicine
facility: 
country: China
responsible party type: Sponsor