<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/NCT04434326</url>
  </required_header>
  <id_info>
    <org_study_id>CM082-CA-I-109</org_study_id>
    <nct_id>NCT04434326</nct_id>
  </id_info>
  <brief_title>The Absorption, Metabolism and Excretion of [14C]CM082 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]CM082 After a Single Oral 200mg/100µCi Dose in Healthy Chinese Male Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AnewPharma</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>AnewPharma</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] CM082 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 4-6 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 200 mg (100 μCi)&#xD;
      of [14C]CM082 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>Completed</overall_status>
  <start_date type="Actual">July 5, 2021</start_date>
  <completion_date type="Actual">October 22, 2021</completion_date>
  <primary_completion_date type="Actual">October 22, 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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Radioactivity concentration of each plasma sample</measure>
    <time_frame>Day 1-Day6</time_frame>
    <description>Use liquid scintillation counter 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-Day11</time_frame>
    <description>Use liquid scintillation counter 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-Day11</time_frame>
    <description>Use liquid scintillation counter to evaluate Radioactivity concentration of each feces（DPM/g） sample</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Total recovery of radioactivity in urine and feces</measure>
    <time_frame>Day-1-Day11</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-Day11</time_frame>
    <description>LC-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>Plasma drug concentrations</measure>
    <time_frame>Day-1-Day11</time_frame>
    <description>To determine the plasma concentrations of CMO82 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-Day11</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 Solid Tumor</condition>
  <arm_group>
    <arm_group_label>[14C]CM082</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 (200mg, 100µCi) of [14C]CM082 to healthy Chinese male subjects</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>[14]CM082 suspension</intervention_name>
    <description>Before administration, the solid powder for administration was placed at room temperature. 40 ml drinking water was added into the drug container to prepare the suspension for the subjects to take. After that, 200 ml drinking water was used to repeatedly rinse the drug container for many times, and the subjects continued to take the lotion. Take care not to spill the liquid out of the bottle when shaking</description>
    <arm_group_label>[14C]CM082</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  1.healthy male volunteers between the ages of 18 to 50 years old; 2.Body weight &gt;=50&#xD;
             kg, Body mass index (body weight(kg)/hight2(m2)) between 19 and 26 kg/m2; 3.Normal&#xD;
             physical findings, clinical laboratory values, vital signs and 12-lead ECG, or any&#xD;
             abnormality that is non-clinically significant; 4.Male subjects of reproductive&#xD;
             potential with partners will be instructed to, and must be willing to practice a&#xD;
             highly effective method of birth control for the duration of the study and continuing&#xD;
             1 year after discontinuing treatment with the investigational product. Highly&#xD;
             effective methods of birth control include using condom, contraceptive sponge,&#xD;
             contraceptive gel, contraceptive film, intrauterine device, oral or injectable&#xD;
             contraceptive pill, hypodermic implants or others; 5. Must understand, and voluntarily&#xD;
             sign the informed consent, comply with the requirements of the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  1.History of or current clinically significant cardio, pulmonary, endocrine,&#xD;
             metabolism, renal, hepatic, gastrointestinal, dermatology, infection, hematology,&#xD;
             neurological, mental disease or disorder; 2.Positive test for HBsAg, HBeAg, anti-HCV,&#xD;
             anti-HIV or syphilis antibody; 3.History of syncope / needle syncope and intolerable&#xD;
             intravenous indwelling needle; 4.History of clinically significant disease or&#xD;
             infection within 1 month before entering the study; 5.Abnormality in blood pressure,&#xD;
             including hypertensive BP (SBP&gt;=140 mmHg, or DBP &gt;=90 mmHg), or hypotensive BP(SBP&lt;90&#xD;
             mmHg, or DBP &lt;=55 mmHg), Pulse rate&lt;55 bpm or &gt;100 bpm; 6.Long-QT syndrome or family&#xD;
             history of it, or QTcB interval &gt; 450 ms; intraventricular blocks or left/right bundle&#xD;
             branch block or QRS&gt;120ms; frequent ventricular ectopic beats (any 10s ECG ventricular&#xD;
             premature beat &gt;= 1 in screening period); or abnormal resting heart rate (&gt; 100 bpm);&#xD;
             7.The following abnormal clinical laboratory values&#xD;
&#xD;
               1. HGB &lt; LLN, and is judged as clinically significant by the investigator；&#xD;
&#xD;
               2. Abnormal ALP, ALB,TP,Cr,ALT,AST,BIL,Urea, GLU value, and is judged as clinically&#xD;
                  significant by the investigator; 8.Received any drug within 14 days before taking&#xD;
                  the investigational drug, including any prescription drug, OTC drug, herbal drug&#xD;
                  or health care products, except for vitamins and paracetamol； 9.History of or&#xD;
                  current swallowing disorder, active gastrointestinal diseases, or other diseases&#xD;
                  that significantly affect absorption, distribution, metabolism and excretion of&#xD;
                  drugs; 10.Chronic constipation or diarrhea, irritable bowel syndrome,&#xD;
                  inflammatory bowel disease; 11.Hemorrhoids or perianal disease with&#xD;
                  regular/perianal bleeding; 12.Allergies, have allergies to two or more drugs or&#xD;
                  foods; or have known allergies to the components of the drug (Mannitol, sodium&#xD;
                  bicarbonate, sodium dodecyl citrate, sodium carboxymethylcellulose, povidone,&#xD;
                  silica, magnesium stearate); 13.Have donated 500ml or more of blood or plasma 2&#xD;
                  months prior to the study drug administration, or more than 50ml within 2 weeks&#xD;
                  prior to administration; 14.Vaccination was administered within 6 months prior to&#xD;
                  screening or during screening; 15.History of drug or alcohol abuse; 16.Smoking (&gt;&#xD;
                  10 cigarette / day), drinking (&gt; 15 g, pure alcohol / day, equivalent to 450 ml&#xD;
                  beer, 150 ml wine or 50 ml low-alcohol liquor), or abusing drugs(MOP, METmAMP,&#xD;
                  MTD, THC, AMP positive) within last 3 months; 17.Subject with mentally ill and&#xD;
                  could not understand the property, scope and possible consequences of the study;&#xD;
                  18.subject in prison or whose freedom is restricted by administrative or legal&#xD;
                  issues; 19.Failure to comply with clinical study protocols, such as&#xD;
                  non-cooperation, follow-up visit and completion of entire study; 20.Investigator,&#xD;
                  pharmacist, CRC or research associate; 21.Participated in other clinical trials&#xD;
                  within 3 months before screening; 22.The subjects participated in the clinical&#xD;
                  trial of radioactive labeling within one year before taking the medicine;&#xD;
                  23.Significant radiation exposure within one year prior to drug administration&#xD;
                  (more than one exposure from chest X-ray, CT scan, or barium meal examination and&#xD;
                  radiation-related occupations); 24.Investigators think that subjects are not&#xD;
                  suitable to participate in the study.&#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>November 2021</verification_date>
  <study_first_submitted>June 12, 2020</study_first_submitted>
  <study_first_submitted_qc>June 12, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 16, 2020</study_first_posted>
  <last_update_submitted>November 10, 2022</last_update_submitted>
  <last_update_submitted_qc>November 10, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 14, 2022</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>Vorolanib</mesh_term>
  </intervention_browse>
  <!-- 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/NCT04434326
org study id: CM082-CA-I-109
nct id: NCT04434326
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] CM082 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 4-6 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 200 mg (100 μCi)
      of [14C]CM082 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: Treatment
masking: None (Open Label)
measure: Radioactivity concentration of each plasma sample
time frame: Day 1-Day6
description: Use liquid scintillation counter to evaluate Radioactivity concentration of each plasma（DPM/ml) sample
measure: Radioactivity concentration of each urine samples
time frame: Day-1-Day11
description: Use liquid scintillation counter to evaluate Radioactivity concentration of each urine（DPM/ml） sample
measure: Radioactivity concentration of each feces sample
time frame: Day-1-Day11
description: Use liquid scintillation counter to evaluate Radioactivity concentration of each feces（DPM/g） sample
measure: Total recovery of radioactivity in urine and feces
time frame: Day-1-Day11
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-Day11
description: LC-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: Plasma drug concentrations
time frame: Day-1-Day11
description: To determine the plasma concentrations of CMO82 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-Day11
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]CM082
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 (200mg, 100µCi) of [14C]CM082 to healthy Chinese male subjects
intervention type: Drug
intervention name: [14]CM082 suspension
description: Before administration, the solid powder for administration was placed at room temperature. 40 ml drinking water was added into the drug container to prepare the suspension for the subjects to take. After that, 200 ml drinking water was used to repeatedly rinse the drug container for many times, and the subjects continued to take the lotion. Take care not to spill the liquid out of the bottle when shaking
arm group label: [14C]CM082
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
mesh term: Vorolanib