<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/NCT04428086</url>
  </required_header>
  <id_info>
    <org_study_id>HR-APTN-I-010</org_study_id>
    <nct_id>NCT04428086</nct_id>
  </id_info>
  <brief_title>A Pharmacokinetic Interaction Study Between Apatinib and Rosuvastatin or Metformin in Solid Tumor Subjects.</brief_title>
  <official_title>Open-Label, Fixed-Sequence Study in Solid Tumor Subjects to Investigate the Pharmacokinetic Interaction Between Apatinib and Transporter Substrates Rosuvastatin and Metformin.</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>
      The primary objective of the study was to assess investigate the pharmacokinetic effects of&#xD;
      Apatinib on Rosuvastatin or Metformin.&#xD;
&#xD;
      The secondary objective of the study was to assess the safety of Apatinib alone or&#xD;
      Rosuvastatin/Metformin alone or concomitant medication.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 27, 2020</start_date>
  <completion_date type="Actual">August 22, 2021</completion_date>
  <primary_completion_date type="Actual">August 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>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Two arms Assignment</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum Observed Plasma Concentration (Cmax)</measure>
    <time_frame>Up to Day 10</time_frame>
    <description>The Cmax is the maximum observed concentration</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Time (AUC [0-last])</measure>
    <time_frame>Up to Day 10</time_frame>
    <description>The AUC (0-last) is the area under the plasma concentration-time curve from time zero to last quantifiable time.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity])</measure>
    <time_frame>Up to Day 10</time_frame>
    <description>The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of participants with treatment-related adverse events as assessed by CTCAE v5.0</measure>
    <time_frame>through study completion, an average of 35 or 37 days in two groups.</time_frame>
    <description>An adverse event is any untoward medical occurrence in a patient or clinical study participant criteria</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">19</enrollment>
  <condition>Solid Tumor, Adult</condition>
  <arm_group>
    <arm_group_label>Assess PK effects of Apatinib on Rosuvastatin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participant will be administered a single oral dose of rosuvastatin 10 milligram (mg) on Day 1 and Day 7 and Apatinib at a dose of 250 mg once daily from Day 4 until Day 9.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Assess PK effects of Apatinib on Metformin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participant will be administered a single oral dose of metformin 500 milligram (mg) on Day 1 and Day 6 and Apatinib at a dose of 250 mg once daily from Day 3 until Day 7.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Apatinib in arm1</intervention_name>
    <description>Apatinib will be administered at a dose of 250 mg once daily from Day 4 to Day 9.</description>
    <arm_group_label>Assess PK effects of Apatinib on Rosuvastatin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rosuvastatin</intervention_name>
    <description>Rosuvastatin will be administered as a single oral 10 milligram (mg) dose on Day 1 and Day 7.</description>
    <arm_group_label>Assess PK effects of Apatinib on Rosuvastatin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Apatinib in arm2</intervention_name>
    <description>Apatinib will be administered at a dose of 250 mg once daily from Day 3 to Day 7.</description>
    <arm_group_label>Assess PK effects of Apatinib on Metformin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Metformin</intervention_name>
    <description>Metformin will be administered as a single oral 500 mg on Day 1 and Day 6.</description>
    <arm_group_label>Assess PK effects of Apatinib on Metformin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Subjects must meet all of the following criteria to enter the study:&#xD;
&#xD;
          1. Age: 18-70 years old (Include both values);&#xD;
&#xD;
          2. Patients with histopathologically or cytologically confirmed advanced solid&#xD;
             tumor(except primary gastrointestinal tumors or metastatic gastrointestinal tumors and&#xD;
             primary hepatocellular tumors) , not necessary to have measurable lesions;&#xD;
&#xD;
          3. The standard systemic treatment plan for tumors is ineffective, or intolerable, or&#xD;
             there is no recurrence and metastasis after adjuvant chemotherapy and radiotherapy&#xD;
             after surgery;&#xD;
&#xD;
          4. ECOG PS score: 0-1;&#xD;
&#xD;
          5. Expected survival ≥ 3 months;&#xD;
&#xD;
          6. Adverse reactions caused by the subject receiving other treatments have recovered&#xD;
             (recovered to ≤ grade 1 according to NCI-CTCAE 5.0, except for hair loss), more than 4&#xD;
             weeks after receiving radiotherapy or surgery or receiving other cytotoxic drugs or&#xD;
             cell growth inhibitor.&#xD;
&#xD;
          7. Major organs must function normally, meeting the following criteria:&#xD;
&#xD;
             I. Haematology (no blood transfusion or blood products within the last 14 days, not&#xD;
             corrected with G-CSF or other hematopoietic colony-stimulating factors):&#xD;
&#xD;
               1. HB≥100 g/L;&#xD;
&#xD;
               2. ANC≥1.5×109/L;&#xD;
&#xD;
               3. PLT≥90×109/L;&#xD;
&#xD;
             II. Blood biochemistry:&#xD;
&#xD;
               1. TBIL≤ 1.25×ULN;&#xD;
&#xD;
               2. ALT and AST≤2.5×ULN;&#xD;
&#xD;
               3. ALP≤2.5×ULN;&#xD;
&#xD;
               4. Serum Cr ≤ 1.5 × ULN or endogenous CrCl ≥ 60 mL/min (Cockcroft-Gault formula);&#xD;
&#xD;
               5. Albumin &gt; 30 g/L;&#xD;
&#xD;
             III. Urine protein inspection:&#xD;
&#xD;
             a. Urinary routines suggest that urine protein &lt;++. If urinary protein ≥ ++, the&#xD;
             quantification of urinary protein in 24 hours should be ≤1.5 g;&#xD;
&#xD;
          8. Agree to abstinence or take effective contraception during the study and for at least&#xD;
             8 weeks after the last study drug administration&#xD;
&#xD;
          9. Sign the ICF voluntarily, have good compliance, corporate with follow-up visits, and&#xD;
             follow the study requirements.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Subjects meeting any one of the followings will be excluded in this study:&#xD;
&#xD;
          1. Patients with gastrointestinal diseases that affect the use or absorption of drugs,&#xD;
             such as gastric cancer or intestinal cancer, unable to swallow, chronic diarrhea,&#xD;
             intestinal obstruction, large stomach or total gastrectomy, or within 6 months before&#xD;
             the first medication Patients with abdominal fistula, gastrointestinal perforation or&#xD;
             abdominal abscess;&#xD;
&#xD;
          2. Active (without medical control) brain metastases, cancerous meningitis, spinal cord&#xD;
             compression patients, or imaging CT or MRI examination at screening to find diseases&#xD;
             of the brain or pia mater&#xD;
&#xD;
          3. Presence of clinically symptomatic third space fluid (e.g. large pleural fluid or&#xD;
             ascites) that cannot be controlled by drainage or other methods;&#xD;
&#xD;
          4. Patients with hypertension, or patients with a history of hypertension&#xD;
&#xD;
          5. Patients with NYHA Class III-IV cardiac insufficiency or left ventricular ejection&#xD;
             fraction (LVEF) &lt; 50% by echocardiography; uncontrolled arrhythmias (QTc interval ≥&#xD;
             450 ms in males and ≥ 470 ms in females);&#xD;
&#xD;
          6. During the study period, patients should be used drugs that may lead to prolonged QTc&#xD;
             interval (such as antiarrhythmic drugs, quinidine, disopyramide, procainamide,&#xD;
             sotalol, amiodarone, etc.)&#xD;
&#xD;
          7. Patients with abnormal coagulation function (INR &gt; 1.5 or prothrombin time (PT) &gt; ULN&#xD;
             + 4 s or APTT &gt; 1.5 ULN)&#xD;
&#xD;
          8. Patients with clinically significant bleeding or clear bleeding tendency within 3&#xD;
             months prior to the first dose, such as coughing up blood, hemoptysis, GI bleeding,&#xD;
             hemorrhagic gastric ulcer, or baseline fecal occult blood (FOB) ++ and above.&#xD;
             Gastroscopy is required for patients with FOB (+) and no surgical resection of primary&#xD;
             gastric tumor. In case of ulcerative gastric cancer, patients are not enrolled due to&#xD;
             a risk of acute gastrointestinal hemorrhage;&#xD;
&#xD;
          9. Events of arterial/venous thrombosis within 6 months prior to the first dose, such as&#xD;
             cerebrovascular accidents (including transient ischemic attacks, cerebral hemorrhage,&#xD;
             brain infarction), deep vein thrombosis, and pulmonary embolism;&#xD;
&#xD;
         10. Known hereditary or acquired hemorrhage and thrombophilia (such as hemophilia,&#xD;
             coagulopathy, thrombocytopenia, hypersplenism, etc.);&#xD;
&#xD;
         11. Patients treated with anticoagulants or vitamin K antagonists such as warfarin,&#xD;
             heparin or similar drugs;&#xD;
&#xD;
         12. Have undergone major surgery or with severe traumatic injury, fracture, or ulcer&#xD;
             within 4 weeks prior to the first dose; There is no previous wound healing.&#xD;
&#xD;
         13. Use of study drugs in other clinical trials within 4 weeks prior to the first dose;&#xD;
&#xD;
         14. Drugs that is CYP3A inhibitor, or the transporter BCRP or MATE1 inhibitor, or drugs&#xD;
             that affect gastric acid secretion, or Chinese herbal medicines within 2 weeks before&#xD;
             the first dose; use the drug that is metabolic enzyme CYP3A inducer within 4 weeks&#xD;
             before the first dose&#xD;
&#xD;
         15. Infectious disease screening (hepatitis B virus surface antigen, hepatitis C virus&#xD;
             antibody, Treponema pallidum antibody and human immunodeficiency virus antibody)&#xD;
             positive&#xD;
&#xD;
         16. History of immunodeficiency, with acquired, congenital immunodeficiency disease, or&#xD;
             history of organ transplantation&#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>The Fourth Hospital of Hebei Medical University</name>
      <address>
        <city>Shijiazhuang</city>
        <state>Hebei</state>
        <zip>050035</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>July 2022</verification_date>
  <study_first_submitted>May 27, 2020</study_first_submitted>
  <study_first_submitted_qc>June 9, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 11, 2020</study_first_posted>
  <last_update_submitted>July 21, 2022</last_update_submitted>
  <last_update_submitted_qc>July 21, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">July 26, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Metformin</mesh_term>
    <mesh_term>Apatinib</mesh_term>
    <mesh_term>Rosuvastatin Calcium</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/NCT04428086
org study id: HR-APTN-I-010
nct id: NCT04428086
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The primary objective of the study was to assess investigate the pharmacokinetic effects of
      Apatinib on Rosuvastatin or Metformin.

      The secondary objective of the study was to assess the safety of Apatinib alone or
      Rosuvastatin/Metformin alone or concomitant medication.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Two arms Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum Observed Plasma Concentration (Cmax)
time frame: Up to Day 10
description: The Cmax is the maximum observed concentration
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Time (AUC [0-last])
time frame: Up to Day 10
description: The AUC (0-last) is the area under the plasma concentration-time curve from time zero to last quantifiable time.
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity])
time frame: Up to Day 10
description: The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
time frame: through study completion, an average of 35 or 37 days in two groups.
description: An adverse event is any untoward medical occurrence in a patient or clinical study participant criteria
arm group label: Assess PK effects of Apatinib on Rosuvastatin
arm group type: Experimental
description: Participant will be administered a single oral dose of rosuvastatin 10 milligram (mg) on Day 1 and Day 7 and Apatinib at a dose of 250 mg once daily from Day 4 until Day 9.
arm group label: Assess PK effects of Apatinib on Metformin
arm group type: Experimental
description: Participant will be administered a single oral dose of metformin 500 milligram (mg) on Day 1 and Day 6 and Apatinib at a dose of 250 mg once daily from Day 3 until Day 7.
intervention type: Drug
intervention name: Apatinib in arm1
description: Apatinib will be administered at a dose of 250 mg once daily from Day 4 to Day 9.
arm group label: Assess PK effects of Apatinib on Rosuvastatin
intervention type: Drug
intervention name: Rosuvastatin
description: Rosuvastatin will be administered as a single oral 10 milligram (mg) dose on Day 1 and Day 7.
arm group label: Assess PK effects of Apatinib on Rosuvastatin
intervention type: Drug
intervention name: Apatinib in arm2
description: Apatinib will be administered at a dose of 250 mg once daily from Day 3 to Day 7.
arm group label: Assess PK effects of Apatinib on Metformin
intervention type: Drug
intervention name: Metformin
description: Metformin will be administered as a single oral 500 mg on Day 1 and Day 6.
arm group label: Assess PK effects of Apatinib on Metformin
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
facility: 
country: China
responsible party type: Sponsor
mesh term: Neoplasms
mesh term: Metformin
mesh term: Apatinib
mesh term: Rosuvastatin Calcium
sharing ipd: Undecided