<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/NCT03804541</url>
  </required_header>
  <id_info>
    <org_study_id>BTP-44316</org_study_id>
    <nct_id>NCT03804541</nct_id>
  </id_info>
  <brief_title>The Absorption, Metabolism and Excretion of [14C]Ensartinib 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]Ensartinib (X-396) After a Single Oral 200mg (100µCi) 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>Yes</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] Ensartinib in healthy Chinese male subjects. The study will&#xD;
      be 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]Ensartinib as an oral suspension. Then, after two days of the dosing, subjects will&#xD;
      be 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>Recruiting</last_known_status>
  <start_date type="Actual">December 28, 2018</start_date>
  <completion_date type="Anticipated">October 2019</completion_date>
  <primary_completion_date type="Anticipated">June 2019</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <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>Day1-Day15</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>Day1-Day15</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>Day1-Day15</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>Day1-Day15</time_frame>
    <description>Calculate the total radioactivity in urine and feces based on the radioactivity concentration of each sample.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Plasma drug concentrations</measure>
    <time_frame>Day1-Day15</time_frame>
    <description>To determine the plasma concentrations of Ensartinib 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>Day1-Day15</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="Anticipated">6</enrollment>
  <condition>ALK-POSITIVE NSCLC</condition>
  <arm_group>
    <arm_group_label>[14C]Ensartinib</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]Ensartinib to healthy Chinese male subjects。</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ensartinib</intervention_name>
    <description>A novel, potent ALK inhibitor.The ALK inhibitor ensartinib has been validated in potency and selectivity assays indicating that it is more selective and up to 10 times more potent than competitive ALK inhibitors. Ensartinib has been active in animal models of non-small cell lung cancer (NSCLC) and neuroblastoma, a childhood cancer. Importantly, ensartinib has shown activity in models with ALK mutations that confer resistance to other small molecule ALK inhibitors.</description>
    <arm_group_label>[14C]Ensartinib</arm_group_label>
    <other_name>X-396</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        A subject will be eligible for study participation if he meets the following criteria:&#xD;
&#xD;
          1. healthy male volunteers between the ages of 18 to 50 years old, inclusive;&#xD;
&#xD;
          2. Body weight &gt;=50 kg, Body mass index (body weight(kg)/hight2(m2)) between 19 and 26&#xD;
             kg/m2 (inclusive);&#xD;
&#xD;
          3. Normal physical findings, clinical laboratory values, vital signs and 12-lead ECG, or&#xD;
             any abnormality that is non-clinically significant;&#xD;
&#xD;
          4. 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;
          5. Must understand, and voluntarily sign the informed consent, comply with the&#xD;
             requirements of the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        A subject will not be eligible for study participation if he meets any of the exclusion&#xD;
        criteria:&#xD;
&#xD;
          1. 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;
          2. Positive test for HBsAg, HBeAg, anti-HCV, anti-HIV or syphilis antibody;&#xD;
&#xD;
          3. History of clinically significant disease or infection within 1 month before entering&#xD;
             the study;&#xD;
&#xD;
          4. 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;
          5. 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;
          6. 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,CRE,ALT,AST,BIL,BUN, GLU value, and is judged as clinically&#xD;
                  significant by the investigator;&#xD;
&#xD;
          7. Received any drug within 14 days before taking the investigational drug, including any&#xD;
             prescription drug, OTC drug or herbal drug, except for vitamins and paracetamol;&#xD;
&#xD;
          8. 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;
          9. Chronic constipation or diarrhea, irritable bowel syndrome, inflammatory bowel&#xD;
             disease;&#xD;
&#xD;
         10. Hemorrhoids or perianal disease with regular/perianal bleeding;&#xD;
&#xD;
         11. Allergies, have allergies to two or more drugs or foods; or have known allergies to&#xD;
             the components of the drug (microcrystalline cellulose, stearic acid, hydroxypropyl&#xD;
             methylcellulose);&#xD;
&#xD;
         12. Have donated 500ml or more of blood or plasma 2 months prior to the study drug&#xD;
             administration, or more than 50ml within 2 weeks prior to administration;&#xD;
&#xD;
         13. Vaccination was administered within 6 months prior to screening or during screening;&#xD;
&#xD;
         14. History of drug or alcohol abuse;&#xD;
&#xD;
         15. Smoking (&gt; 10 cigarette / day), drinking (&gt; 15 g, pure alcohol / day, equivalent to&#xD;
             450 ml beer, 150 ml wine or 50 ml low-alcohol liquor), or abusing drugs(MOP, METmAMP,&#xD;
             MTD, THC, AMP positive) within last 3 months;&#xD;
&#xD;
         16. Subject with mentally ill and could not understand the property, scope and possible&#xD;
             consequences of the study;&#xD;
&#xD;
         17. subject in prison or whose freedom is restricted by administrative or legal issues;&#xD;
&#xD;
         18. Failure to comply with clinical study protocols, such as non-cooperation, follow-up&#xD;
             visit and completion of entire study;&#xD;
&#xD;
         19. Investigator, pharmacist, CRC or research associate;&#xD;
&#xD;
         20. Investigators think that subjects are not suitable to participate in the study;&#xD;
&#xD;
         21. Subjects who have participated in radiolabeled clinical study prior to drug&#xD;
             administration;&#xD;
&#xD;
         22. 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</last_name>
    <role>Principal Investigator</role>
    <affiliation>Jiangsu Province Hospital Affiliated to Nanjing Madical University of Medicine</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Feng Shao</last_name>
    <phone>+8613851691161</phone>
    <email>shaofengnj@163.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Sufeng Zhou</last_name>
    <phone>+8615952052032</phone>
    <email>zhousfhappy@163.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Jiangsu Province Hospital Affiliated to Nanjing Madical University of Medicine</name>
      <address>
        <city>Nanjing</city>
        <state>Jiangsu Provence</state>
        <zip>210005</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Feng Shao，Associate Professor, PhD</last_name>
      <phone>+8613851691161</phone>
      <email>shaofengnj@163.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <link>
    <url>http://edocket.access.gpo.gov/cfr_2008/aprqtr/pdf/21cfr36.</url>
    <description>[6] CFR 361.1 Radioactive Drugs for Certain Research Uses.</description>
  </link>
  <reference>
    <citation>Nijenhuis CM, Schellens JH, Beijnen JH. Regulatory aspects of human radiolabeled mass balance studies in oncology: concise review. Drug Metab Rev. 2016 May;48(2):266-80. doi: 10.1080/03602532.2016.1181081. Epub 2016 May 17.</citation>
    <PMID>27186889</PMID>
  </reference>
  <reference>
    <citation>Penner N, Klunk LJ, Prakash C. Human radiolabeled mass balance studies: objectives, utilities and limitations. Biopharm Drug Dispos. 2009 May;30(4):185-203. doi: 10.1002/bdd.661.</citation>
    <PMID>19544285</PMID>
  </reference>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>December 26, 2018</study_first_submitted>
  <study_first_submitted_qc>January 14, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 15, 2019</study_first_posted>
  <last_update_submitted>January 14, 2019</last_update_submitted>
  <last_update_submitted_qc>January 14, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 15, 2019</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>Ensartinib</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/NCT03804541
org study id: BTP-44316
nct id: NCT03804541
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
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] Ensartinib 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]Ensartinib 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: Day1-Day15
description: Use liquid scintillation counter to evaluate Radioactivity concentration of each plasma（DPM/ml) sample
measure: Radioactivity concentration of each urine samples
time frame: Day1-Day15
description: Use liquid scintillation counter to evaluate Radioactivity concentration of each urine（DPM/ml） sample
measure: Radioactivity concentration of each feces sample
time frame: Day1-Day15
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: Day1-Day15
description: Calculate the total radioactivity in urine and feces based on the radioactivity concentration of each sample.
measure: Plasma drug concentrations
time frame: Day1-Day15
description: To determine the plasma concentrations of Ensartinib 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: Day1-Day15
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]Ensartinib
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]Ensartinib to healthy Chinese male subjects。
intervention type: Drug
intervention name: Ensartinib
description: A novel, potent ALK inhibitor.The ALK inhibitor ensartinib has been validated in potency and selectivity assays indicating that it is more selective and up to 10 times more potent than competitive ALK inhibitors. Ensartinib has been active in animal models of non-small cell lung cancer (NSCLC) and neuroblastoma, a childhood cancer. Importantly, ensartinib has shown activity in models with ALK mutations that confer resistance to other small molecule ALK inhibitors.
arm group label: [14C]Ensartinib
other name: X-396
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Feng Shao
role: Principal Investigator
affiliation: Jiangsu Province Hospital Affiliated to Nanjing Madical University of Medicine
last name: Feng Shao
phone: +8613851691161
email: shaofengnj@163.com
last name: Sufeng Zhou
phone: +8615952052032
email: zhousfhappy@163.com
facility: 
status: Recruiting
contact: 
country: China
url: http://edocket.access.gpo.gov/cfr_2008/aprqtr/pdf/21cfr36.
description: [6] CFR 361.1 Radioactive Drugs for Certain Research Uses.
citation: Nijenhuis CM, Schellens JH, Beijnen JH. Regulatory aspects of human radiolabeled mass balance studies in oncology: concise review. Drug Metab Rev. 2016 May;48(2):266-80. doi: 10.1080/03602532.2016.1181081. Epub 2016 May 17.
PMID: 27186889
citation: Penner N, Klunk LJ, Prakash C. Human radiolabeled mass balance studies: objectives, utilities and limitations. Biopharm Drug Dispos. 2009 May;30(4):185-203. doi: 10.1002/bdd.661.
PMID: 19544285
responsible party type: Sponsor
mesh term: Ensartinib
sharing ipd: Undecided