<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/NCT03245307</url>
  </required_header>
  <id_info>
    <org_study_id>HR-APTN-DDI-01</org_study_id>
    <nct_id>NCT03245307</nct_id>
  </id_info>
  <brief_title>A Study To Test The Effect Of Apatinib On P450 Enzymes</brief_title>
  <official_title>A Single-center, Open-Label, Drug Interaction Study to Determine the Effects of Apatinib on the Metabolism of CYP3A4/5 and CYP2C9 Probe Drugs in Patients With Solid Tumors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Jiangsu HengRui Medicine Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </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>
      Apatinib, an oral inhibitor of vascular endothelial growth factor receptor 2（VEGFR-2）,&#xD;
      inhibits multiple cytochrome P450 (CYP450) enzymes in vitro. This study in patients with&#xD;
      advanced cancer evaluated the effect of Apatinib on CYP450 function by comparing the&#xD;
      pharmacokinetics of CYP-specific probe drugs in the presence and absence of Apatinib. The&#xD;
      probes used included Nifedipine (CYP3A specific), warfarin (CYP2C9 specific).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This open-label study consists of a drug interaction phase that (part A) and a&#xD;
      drug-continuation phase (part B). Patients will receive CYP450-probe drugs, and PK&#xD;
      assessments will be performed before apatinib-administration and aſter once-daily&#xD;
      administration of apatinib for 5 days (the predicted time point when steady-state plasma&#xD;
      apatinib concentrations will have been achieved).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">August 22, 2017</start_date>
  <completion_date type="Anticipated">September 30, 2018</completion_date>
  <primary_completion_date type="Anticipated">April 30, 2018</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>Area under the plasma concentration versus time curve (AUC) of warfarin or nifedipine</measure>
    <time_frame>1 year</time_frame>
    <description>AUC0~t of warfarin and nifedipine in the absence or in presence of apatinib will be defined</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of participants with treatment-related adverse events as assessed by CTCAE v4.0</measure>
    <time_frame>Day 1 to 21 ( Phase A）</time_frame>
    <description>to assess safety and tolerability of apatinib combined with warfarin or nifedipine in patients with advanced solid tumors. The vital signs, ECG, laboratory values and adverse events (AE and SAE) were judged according to NCI-CTCAE V4.0 criteria</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Cytochrome P450 Interaction</condition>
  <arm_group>
    <arm_group_label>Treament</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In phase A, subjects receiving a single 30 mg oral dose of Nifedipine controlled-release tablets and wash-out for 2 days,a single 3 mg oral dose of warfarin tablets and wash-out for 12 days, then apatinib 750 mg once daily with a single 30 mg oral dose of Nifedipine controlled-release tablets co-administered on day 6 ,a a single 3 mg oral dose of warfarin tablets co-administered on day 9.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Apatinib</intervention_name>
    <description>Apatinib at a dosage of 750mg will be administered daily from day 9 of phase A</description>
    <arm_group_label>Treament</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nifedipine GTIS</intervention_name>
    <description>Nifedipine at a dosage of 30mg will be administered at day 1 and day 14 of phase A</description>
    <arm_group_label>Treament</arm_group_label>
    <other_name>Nifedipine</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Warfarin Potassium</intervention_name>
    <description>Nifedipine at a dosage of 3mg will be administered at day 3 and day 16 of phase A</description>
    <arm_group_label>Treament</arm_group_label>
    <other_name>warfarin</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically or cytologically confirmed diagnosis of advanced solid tumors.&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.&#xD;
&#xD;
          -  Adequate bone marrow, renal, lung, and liver function.&#xD;
&#xD;
          -  A female subject must not be pregnant and will agree not to become pregnant during the&#xD;
             trial&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Primary carcinoma of liver&#xD;
&#xD;
          -  Any major surgery, chemotherapy, hormone therapy, investigational drugs, or&#xD;
             radiotherapy within the last 28 days.&#xD;
&#xD;
          -  Poorly controlled hypertension.&#xD;
&#xD;
          -  A prior history of cardiovascular disease, arrhythmias, or significant ECG&#xD;
             abnormalities, and corrected QT (QTc) prolongation defined as a QTc interval greater&#xD;
             than or equal to 450 msec(male) or 470 msec(female).&#xD;
&#xD;
          -  Arterial or venous thrombi (including cerebrovascular accident).&#xD;
&#xD;
          -  Current use of therapeutic anticoagulation (low molecular weight heparin, oral&#xD;
             anticoagulant agents).&#xD;
&#xD;
          -  Active brain metastases.&#xD;
&#xD;
          -  A history of bleeding problems.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Chinese Medical University First Hospital</name>
      <address>
        <city>Shenyang</city>
        <state>Liaoning</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Yunpeng Liu</last_name>
      <phone>86024-83282802</phone>
      <email>cmu_trial@163.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>July 2017</verification_date>
  <study_first_submitted>July 17, 2017</study_first_submitted>
  <study_first_submitted_qc>August 7, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 10, 2017</study_first_posted>
  <last_update_submitted>February 6, 2018</last_update_submitted>
  <last_update_submitted_qc>February 6, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">February 7, 2018</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>Apatinib</mesh_term>
    <mesh_term>Nifedipine</mesh_term>
    <mesh_term>Warfarin</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/NCT03245307
org study id: HR-APTN-DDI-01
nct id: NCT03245307
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Apatinib, an oral inhibitor of vascular endothelial growth factor receptor 2（VEGFR-2）,
      inhibits multiple cytochrome P450 (CYP450) enzymes in vitro. This study in patients with
      advanced cancer evaluated the effect of Apatinib on CYP450 function by comparing the
      pharmacokinetics of CYP-specific probe drugs in the presence and absence of Apatinib. The
      probes used included Nifedipine (CYP3A specific), warfarin (CYP2C9 specific).
This open-label study consists of a drug interaction phase that (part A) and a
      drug-continuation phase (part B). Patients will receive CYP450-probe drugs, and PK
      assessments will be performed before apatinib-administration and aſter once-daily
      administration of apatinib for 5 days (the predicted time point when steady-state plasma
      apatinib concentrations will have been achieved).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Area under the plasma concentration versus time curve (AUC) of warfarin or nifedipine
time frame: 1 year
description: AUC0~t of warfarin and nifedipine in the absence or in presence of apatinib will be defined
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
time frame: Day 1 to 21 ( Phase A）
description: to assess safety and tolerability of apatinib combined with warfarin or nifedipine in patients with advanced solid tumors. The vital signs, ECG, laboratory values and adverse events (AE and SAE) were judged according to NCI-CTCAE V4.0 criteria
arm group label: Treament
arm group type: Experimental
description: In phase A, subjects receiving a single 30 mg oral dose of Nifedipine controlled-release tablets and wash-out for 2 days,a single 3 mg oral dose of warfarin tablets and wash-out for 12 days, then apatinib 750 mg once daily with a single 30 mg oral dose of Nifedipine controlled-release tablets co-administered on day 6 ,a a single 3 mg oral dose of warfarin tablets co-administered on day 9.
intervention type: Drug
intervention name: Apatinib
description: Apatinib at a dosage of 750mg will be administered daily from day 9 of phase A
arm group label: Treament
intervention type: Drug
intervention name: Nifedipine GTIS
description: Nifedipine at a dosage of 30mg will be administered at day 1 and day 14 of phase A
arm group label: Treament
other name: Nifedipine
intervention type: Drug
intervention name: Warfarin Potassium
description: Nifedipine at a dosage of 3mg will be administered at day 3 and day 16 of phase A
arm group label: Treament
other name: warfarin
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Sponsor
mesh term: Apatinib
mesh term: Nifedipine
mesh term: Warfarin
sharing ipd: Undecided