<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/NCT02981108</url>
  </required_header>
  <id_info>
    <org_study_id>HS-10296-12-01</org_study_id>
    <nct_id>NCT02981108</nct_id>
  </id_info>
  <brief_title>A Study to Evaluate Safety, PK and Efficacy of HS-10296 in Patients With NSCLC</brief_title>
  <official_title>A Phase 1/2, Open-label, Multicenter Study to Evaluate Safety, Tolerability, Pharmacokinetics and Efficacy of HS-10296 in Patients With Locally Advanced or Metastatic Non-Small-Cell Lung Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Jiangsu Hansoh Pharmaceutical Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Jiangsu Hansoh Pharmaceutical Co., Ltd.</source>
  <oversight_info>
    <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 Phase 1/2, open-label, multicenter study of HS-10296 with dose escalation, dose&#xD;
      expansion and extension cohorts in locally advanced or metastatic non-small-cell lung cancer&#xD;
      (NSCLC) patients who have progressed following prior therapy with an epidermal growth factor&#xD;
      receptor(EGFR) tyrosine kinase inhibitor (TKI) agent. The study is designed to evaluate&#xD;
      safety, tolerability, pharmacokinetics (PK), and anti-tumor activity of once-daily and orally&#xD;
      (PO) administered HS-10296. The overall study design is shown in the flow chart below, which&#xD;
      consists of 3 phases: dose escalation, dose expansion and extension cohort.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">May 8, 2017</start_date>
  <completion_date type="Anticipated">March 31, 2023</completion_date>
  <primary_completion_date type="Actual">January 5, 2019</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With Dose Limiting Toxicity (DLT) Phase I Part</measure>
    <time_frame>21 days</time_frame>
    <description>DLT is defined as one of the following HS-10296 related adverse event (AE) ：(1) Hematological toxicity ≥ Grade 4 neutropenia lasting more than 5 days, febrile neutropenia of any duration (absolute neutrophil count [ANC]) &lt; 1.0 × 109/L and fever ≥ 38.5°C), Grade 4 thrombocytopenia, Grade 3 thrombocytopenia with bleeding, any requirement for platelet transfusion, Grade 4 anemia (unexplained by underlying disease); (2)Non-hematological toxicity ≥ CTCAE Grade 3 including Infection (including febrile neutropenia), confirmed prolongation of QT interval corrected with Fridericia's (QTcF) (&gt; 500 ms absolute or &gt; 60 ms above Baseline) and cardiac toxicity greater than Grade 3；(3)Any other toxicity that is greater than that at Baseline (clinically significant and/or unacceptable, and judged to be a DLT by the SRC), meets a protocol-defined stopping criteria (i.e., confirmed corneal ulceration), or results in a disruption of dosing schedule of more than 7 days.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Overall Response Rate (ORR) Phase II Part</measure>
    <time_frame>From the date of first dose until the date of disease progression or withdrawal from study, approximately 15 months</time_frame>
    <description>ORR is defined as the percentage of patients with a complete response (CR) or partial response (PR) that was confirmed at a subsequent scan at least 6 weeks later, as assessed according to RECIST (Response Evaluation Criteria In Solid Tumors Criteria) version 1.1 for target lesions and assessed by CT/MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), &gt;=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence and Severity of Adverse Events (AEs) Phase I Part</measure>
    <time_frame>From the screening period to 28 days after treatment completion, approximately 16 months</time_frame>
    <description>An AE is the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition can be symptoms (e.g., nausea, chest pain), signs (e.g., tachycardia, enlarged liver), or the abnormal results of an investigation (e.g., laboratory findings, ECG). Any deterioration of the disease under study and associated symptoms or findings should not be regarded as an AE as far as the deterioration can be anticipated. The AE was graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Area Under the Plasma Concentration Versus Time Curve (AUC) of HS-10296 and HAS-719 From Zero to the 24-Hour Sampling Time (AUC0-24) After Single Dose of HS-10296</measure>
    <time_frame>From pre-dose to 24 hours after single dose on Day 1 of Cycle 0</time_frame>
    <description>Area under the plasma concentration versus time curve from time zero to the 24-hour sampling time at which the concentration was at or above the lower limit of quantification (LLQ). AUC0-24 was to be calculated according to the mixed log-linear trapezoidal rule.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Elimination Half-life(T1/2) of HS-10296 and HAS-719</measure>
    <time_frame>From pre-dose to 120 hours after single dose on Day 1 of Cycle 0</time_frame>
    <description>Elimination half-life is the time measured for the concentration to decrease by one half. Half-life calculated by natural log 2 divided by λz.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Css Max of HS-10296 and HAS-719 After Multiple Dose</measure>
    <time_frame>From pre-dose to 21 days after multiple dose on Day 1 of Cycle 2</time_frame>
    <description>Observed maximum plasma concentration (Css max) after multiple dose of HS-10296 and HAS-719</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUCss of HS-10296 and HAS-719 After Multiple Dose of HS-10296</measure>
    <time_frame>From pre-dose to 21 days after multiple dose on Day 1 of Cycle 2</time_frame>
    <description>Area Under the Plasma Concentration Versus Time Curve at steady state (AUCss) of HS-10296 and HAS-719 after multiple dose of HS-10296</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Response Rate (Phase I Part)</measure>
    <time_frame>From the date of first dose until the date of disease progression or withdrawal from study, approximately 15 months</time_frame>
    <description>ORR is defined as the percentage of patients with a complete response (CR) or partial response (PR) that was confirmed at a subsequent scan at least 6 weeks later, as assessed according to RECIST (Response Evaluation Criteria In Solid Tumors Criteria) version 1.1 for target lesions and assessed by CT/MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), &gt;=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free Survival (PFS)</measure>
    <time_frame>From the date of enrollment until the date of disease progression or death from any cause, approximately 15 months</time_frame>
    <description>The PFS is defined as the time from date of first dosing until the date of objective disease progression as defined by Response Evaluation Criteria in Solid Tumors （RECIST） v1.1 or death (by any cause in the absence of progression) regardless of whether the patients withdraws from HS-10296 therapy or receives another anti-cancer therapy prior to progression. Progression is defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease Control Rate (DCR)</measure>
    <time_frame>From the date of first dose until the date of disease progression or withdrawal from study, approximately 15 months</time_frame>
    <description>Objective response is assessed by RECIST 1.1 thereby to evaluate disease control rate. The DCR is defined as the proportion of patients with a best overall response of CR, PR, or SD (stable disease).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS) Phase II Part</measure>
    <time_frame>From the date of enrollment until the date of death from any cause, approximately 48 months</time_frame>
    <description>Overall survival will be assessed based on the date of first dose and survival status at the time of analysis. Overall survival is defined as the time from date of first dose until the documentation of death from any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Depth of Response (DepOR)</measure>
    <time_frame>From the date of enrollment until the date of disease progression or death, approximately 15 months</time_frame>
    <description>Depth of Response (DepOR) Only in part II dose-extention phase. DepOR is defined as the percentage change in tumor size, based on longest diameter or reconstructed volume, observed at the lowest point compared with baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DoR)</measure>
    <time_frame>From the date of enrollment until the date of disease progression or death, approximately 18 months</time_frame>
    <description>Duration of response (DoR) is defined as the time from the date of first documented response until the date of documented progression or death in the absence of disease progression. The end of response should coincide with the date of progression or death from any cause used for the PFS endpoint. The time of the initial response will be defined as the latest of the dates contributing towards the first visit response of PR or CR. If a patient does not progress following a response, then DoR will be used as the PFS censoring time.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence and Severity of AEs Phase II Part</measure>
    <time_frame>From the screening period to 28 days after treatment completion, approximately 16 months</time_frame>
    <description>An AE is the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition can be symptoms (e.g., nausea, chest pain), signs (e.g., tachycardia, enlarged liver), or the abnormal results of an investigation (e.g., laboratory findings, ECG). Any deterioration of the disease under study and associated symptoms or findings should not be regarded as an AE as far as the deterioration can be anticipated. The AE was graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0.</description>
  </secondary_outcome>
  <number_of_arms>8</number_of_arms>
  <enrollment type="Actual">364</enrollment>
  <condition>Nonsmall Cell Lung Cancer</condition>
  <arm_group>
    <arm_group_label>Escalation Cohort 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Oral Once-Daily Administration of HS-10296 55mg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Escalation Cohort 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Oral Once-Daily Administration of HS-10296 110mg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Escalation Cohort 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Oral Once-Daily Administration of HS-10296 220mg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Escalation Cohort 4</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Oral Once-Daily Administration of HS-10296 260mg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Expansion Cohort 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Oral Once-Daily Administration of HS-10296 55mg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Expansion Cohort 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Oral Once-Daily Administration of HS-10296 110mg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Expansion Cohort 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Oral Once-Daily Administration of HS-10296 220mg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase 2 Extension</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Oral Once-Daily Administration of HS-10296 110mg (RP2D)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>HS-10296</intervention_name>
    <description>HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
    <arm_group_label>Escalation Cohort 1</arm_group_label>
    <arm_group_label>Escalation Cohort 2</arm_group_label>
    <arm_group_label>Escalation Cohort 3</arm_group_label>
    <arm_group_label>Escalation Cohort 4</arm_group_label>
    <arm_group_label>Expansion Cohort 1</arm_group_label>
    <arm_group_label>Expansion Cohort 2</arm_group_label>
    <arm_group_label>Expansion Cohort 3</arm_group_label>
    <arm_group_label>Phase 2 Extension</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Provision of signed and dated written informed consent prior to any study-specific&#xD;
             procedures, sampling, and analyses. If a patient declines to participate in any&#xD;
             voluntary exploratory research and/or genetic component of the study, there will be no&#xD;
             penalty or loss of benefit to the patient and he/she will not be excluded from other&#xD;
             aspects of the study.&#xD;
&#xD;
          2. Age at least 18 years.&#xD;
&#xD;
          3. Histological or cytological confirmation diagnosis of NSCLC.&#xD;
&#xD;
          4. Radiological documentation of disease progression while on a previous continuous&#xD;
             treatment with an EGFR TKI, e.g., gefitinib or erlotinib. In addition, other lines of&#xD;
             therapy may have been given. All patients must have documented radiological&#xD;
             progression on the last treatment administered, prior to enrolling in the study.&#xD;
&#xD;
          5. Patients must fulfill one of the following:&#xD;
&#xD;
               -  Confirmation that the tumor harbors an EGFR mutation known to be associated with&#xD;
                  EGFR TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q) OR must&#xD;
                  have experienced clinical benefit from EGFR TKI, according to the Jackman&#xD;
                  criteria (followed by systemic objective progression (RECIST or World Health&#xD;
                  Organization [WHO]) while on continuous treatment with an EGFR TKI.&#xD;
&#xD;
          6. For the dose expansion and extension cohorts, patients also must have confirmation of&#xD;
             tumor T790M+ mutation status from a biopsy sample taken after disease progression on&#xD;
             the most recent treatment regimen with an EGFR TKI.&#xD;
&#xD;
             Prior to entry, a result from the central analysis of the patient's T790M mutation&#xD;
             status must be obtained.&#xD;
&#xD;
          7. World Health Organization (WHO) performance status equal to 0-1 with no deterioration&#xD;
             over the previous 2 weeks and a minimum life expectancy of 12 weeks.&#xD;
&#xD;
          8. At least 1 lesion that has not previously been irradiated, that has not been chosen&#xD;
             for biopsy during the study Screening period,and that can be accurately measured at&#xD;
             Baseline as ≥ 10mm in the longest diameter (except lymph nodes which must have short&#xD;
             axis ≥ 15mm) with computerized tomography (CT) or magnetic resonance imaging (MRI),&#xD;
             which is suitable for accurately repeated measurements.&#xD;
&#xD;
          9. Females of child-bearing potential should be using adequate contraceptive measures&#xD;
             throughout the study, should not be breast feeding at the time of screening, during&#xD;
             the study and until 3 months after completion of study, and must have a negative&#xD;
             pregnancy test prior to start of dosing if of child-bearing potential or must have&#xD;
             evidence of non-child-bearing potential by fulfilling 1 of the following criteria at&#xD;
             screening:&#xD;
&#xD;
               -  Post-menopausal defined as age more than 50 years and amenorrheic for at least 12&#xD;
                  months following cessation of all exogenous hormonal treatments.&#xD;
&#xD;
               -  Women under 50 years old would be considered postmenopausal if they have been&#xD;
                  amenorrheic for 12 months or more, following cessation of exogenous hormonal&#xD;
                  treatments, and with luteinizing hormone (LH) and follicle-stimulating hormone&#xD;
                  (FSH) levels in the post-menopausal range for the laboratory.&#xD;
&#xD;
               -  Documentation of irreversible surgical sterilization by hysterectomy, bilateral&#xD;
                  oophorectomy, or bilateral salpingectomy, but not by tubal ligation.&#xD;
&#xD;
         10. Male patients should be willing to use barrier contraception (i.e., condoms).&#xD;
&#xD;
         11. For the dose expansion paired biopsy cohort:&#xD;
&#xD;
               -  Presence of at least 1 non-target lesion suitable for multiple biopsies while on&#xD;
                  treatment.&#xD;
&#xD;
         12. For inclusion in optional genetic research, the patient must provide a written&#xD;
             informed consent for genetic research.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Treatment with any of the following:&#xD;
&#xD;
               -  An EGFR TKI (e.g., erlotinib, gefitinib, or osimertinib) within 8 days or&#xD;
                  approximately 5 times the half-life of the specific drug, whichever is longer, of&#xD;
                  the first dose of study treatment. (If sufficient wash-out time has not occurred&#xD;
                  due to scheduling or PK properties, an alternative appropriate wash-out time&#xD;
                  based on known duration and time to reversibility of drug-related adverse events&#xD;
                  must be agreed upon by Hansoh and the Investigator).&#xD;
&#xD;
               -  Any cytotoxic chemotherapy, investigational agents, or anticancer drugs for&#xD;
                  advanced NSCLC used for a previous treatment regimen or clinical study within 14&#xD;
                  days of the first dose of study treatment.&#xD;
&#xD;
               -  Major surgery (excluding placement of vascular access) within 4 weeks of the&#xD;
                  first dose of study treatment.&#xD;
&#xD;
               -  Radiotherapy with a limited field of radiation for palliation within 1 week of&#xD;
                  the first dose of study treatment, with the exception of patients receiving&#xD;
                  radiation to more than 30% of the bone marrow or with a wide field of radiation&#xD;
                  which must be completed within 4 weeks of the first dose of study treatment.&#xD;
&#xD;
          2. Previously untreated NSCLC patients. To be eligible for this study, patients must have&#xD;
             received and progressed on EGFR TKI therapy.&#xD;
&#xD;
          3. Any unresolved toxicities from prior therapy greater than Common Terminology Criteria&#xD;
             for Adverse Events (CTCAE), Grade 1, at the time of starting study treatment with the&#xD;
             exception of alopecia and Grade 2, prior platinum-therapy related neuropathy.&#xD;
&#xD;
          4. Spinal cord compression or brain metastases unless asymptomatic, stable, and not&#xD;
             requiring steroids for at least 4 weeks prior to start of study treatment.&#xD;
&#xD;
          5. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled&#xD;
             hypertension or active bleeding diatheses, which, in the Investigator's opinion, makes&#xD;
             it undesirable for the patient to participate in the trial OR which would jeopardize&#xD;
             compliance with the protocol such as active infection (e.g., hepatitis B, hepatitis C&#xD;
             or human immunodeficiency virus [HIV]). Screening for chronic conditions is not&#xD;
             required.&#xD;
&#xD;
          6. Any of the following cardiac criteria:&#xD;
&#xD;
               -  Mean resting corrected QT interval (QTc) &gt; 470 msec obtained from 3&#xD;
                  electrocardiograms (ECGs), using the Screening clinic ECG machine and&#xD;
                  Fridericia's formula for QT interval correction.&#xD;
&#xD;
               -  Any clinically important abnormalities in rhythm, conduction, or morphology of&#xD;
                  the resting ECG (e.g., complete left bundle branch block, third-degree heart&#xD;
                  block, second-degree heart block, PR interval &gt;250msec).&#xD;
&#xD;
               -  Any factors that increase the risk of QTc prolongation or risk of arrhythmic&#xD;
                  events such as heart failure, hypokalemia, congenital long QT syndrome, family&#xD;
                  history of long QT syndrome or unexplained sudden death under 40 years of age in&#xD;
                  first degree relatives or any concomitant medication known to prolong the QT&#xD;
                  interval.&#xD;
&#xD;
          7. Past medical history of interstitial lung disease, drug-induced interstitial lung&#xD;
             disease, radiation pneumonitis which required steroid treatment, or any evidence of&#xD;
             clinically active interstitial lung disease.&#xD;
&#xD;
          8. Inadequate bone marrow reserve or organ function as demonstrated by any of the&#xD;
             following laboratory values:&#xD;
&#xD;
               -  Absolute neutrophil count &lt; 1.5 x 109/L.&#xD;
&#xD;
               -  Platelet count &lt; 100 x 109/L.&#xD;
&#xD;
               -  Hemoglobin &lt; 90 g/L (&lt; 9 g/dL).&#xD;
&#xD;
               -  Alanine aminotransferase &gt; 2.5 times the upper limit of normal (ULN) if no&#xD;
                  demonstrable liver metastases or &gt; 5 times the ULN in the presence of liver&#xD;
                  metastases.&#xD;
&#xD;
               -  Aspartate aminotransferase &gt; 2.5 times the ULN if no demonstrable liver&#xD;
                  metastases or &gt; 5 times the ULN in the presence of liver metastases.&#xD;
&#xD;
               -  Total bilirubin &gt; 1.5 times the ULN if no liver metastases or &gt; 3 times the ULN&#xD;
                  in the presence of documented Gilbert's Syndrome (unconjugated&#xD;
                  hyperbilirubinemia) or liver metastases.&#xD;
&#xD;
               -  Creatinine &gt; 1.5 times the ULN concurrent with creatinine clearance &lt; 50 mL/min&#xD;
                  (measured or calculated by the Cockcroft - Gault equation); confirmation of&#xD;
                  creatinine clearance is only required when creatinine is &gt; 1.5 times the ULN.&#xD;
&#xD;
          9. Refractory nausea, vomiting, or chronic gastrointestinal diseases, inability to&#xD;
             swallow the study medication, or previous significant bowel resection that would&#xD;
             preclude adequate absorption of HS-10296.&#xD;
&#xD;
         10. History of hypersensitivity to any active or inactive ingredient of HS-10296 or to a&#xD;
             drug with a similar chemical structure or class to HS-10296.&#xD;
&#xD;
         11. Women who are breast feeding.&#xD;
&#xD;
         12. Involvement in study planning and conduct (i.e., Hansoh staff or staff at the study&#xD;
             site).&#xD;
&#xD;
         13. Judgment by the Investigator that the patient should not participate in the study if&#xD;
             the patient is unlikely to comply with study procedures, restrictions, and&#xD;
             requirements.&#xD;
&#xD;
         14. Any disease or condition that, in the opinion of the Investigator, would compromise&#xD;
             the safety of the patient or interfere with study assessments.&#xD;
&#xD;
         15. The following are considered criteria for exclusion from the exploratory genetic&#xD;
             research:&#xD;
&#xD;
               -  Previous allogenic bone marrow transplant.&#xD;
&#xD;
               -  Non-leukocyte leukocyte-depleted whole blood transfusion within 120 days of the&#xD;
                  date of the genetic sample collection.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Pacific Cancer Medical Center, Inc.</name>
      <address>
        <city>Anaheim</city>
        <state>California</state>
        <zip>92801</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Beverly Hills Cancer Center</name>
      <address>
        <city>Beverly Hills</city>
        <state>California</state>
        <zip>90211</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California San Diego Medical Center Moores Cancer Center</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92093</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Colorado-1775 Aurora Court</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sylvester Comprehensive Cancer Center</name>
      <address>
        <city>Deerfield Beach</city>
        <state>Florida</state>
        <zip>33442</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Cancer &amp; Blood Center, LLC</name>
      <address>
        <city>Athens</city>
        <state>Georgia</state>
        <zip>30607</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baptist Healthcare Systems Inc. Baptist Health Floyd</name>
      <address>
        <city>New Albany</city>
        <state>Indiana</state>
        <zip>47150</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dartmouth-Hitchcock Medical Center</name>
      <address>
        <city>Hanover</city>
        <state>New Hampshire</state>
        <zip>03755</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas Medical Branch at Galveston</name>
      <address>
        <city>Galveston</city>
        <state>Texas</state>
        <zip>77550</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MultiCare Institute for Research and Innovation</name>
      <address>
        <city>Tacoma</city>
        <state>Washington</state>
        <zip>98405</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2022</verification_date>
  <study_first_submitted>November 28, 2016</study_first_submitted>
  <study_first_submitted_qc>November 30, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 2, 2016</study_first_posted>
  <results_first_submitted>September 2, 2022</results_first_submitted>
  <results_first_submitted_qc>December 27, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">January 23, 2023</results_first_posted>
  <last_update_submitted>December 27, 2022</last_update_submitted>
  <last_update_submitted_qc>December 27, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">January 23, 2023</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>Lung Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Non-Small-Cell Lung</mesh_term>
  </condition_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>August 29, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/08/NCT02981108/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>A total of 364 patients were enrolled at 47 centers in 2 countries.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Escalation Cohort 1</title>
          <description>Oral Once-Daily Administration of HS-10296 55mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
        </group>
        <group group_id="P2">
          <title>Escalation Cohort 2</title>
          <description>Oral Once-Daily Administration of HS-10296 110mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
        </group>
        <group group_id="P3">
          <title>Escalation Cohort 3</title>
          <description>Oral Once-Daily Administration of HS-10296 220mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
        </group>
        <group group_id="P4">
          <title>Escalation Cohort 4</title>
          <description>Oral Once-Daily Administration of HS-10296 260mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
        </group>
        <group group_id="P5">
          <title>Expansion Cohort 1</title>
          <description>Oral Once-Daily Administration of HS-10296 55mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
        </group>
        <group group_id="P6">
          <title>Expansion Cohort 2</title>
          <description>Oral Once-Daily Administration of HS-10296 110mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
        </group>
        <group group_id="P7">
          <title>Expansion Cohort 3</title>
          <description>Oral Once-Daily Administration of HS-10296 220mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
        </group>
        <group group_id="P8">
          <title>Phase 2 Extension</title>
          <description>Oral Once-Daily Administration of HS-10296 (MTD or RP2D)&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="8"/>
                <participants group_id="P4" count="6"/>
                <participants group_id="P5" count="30"/>
                <participants group_id="P6" count="33"/>
                <participants group_id="P7" count="31"/>
                <participants group_id="P8" count="244"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="7"/>
                <participants group_id="P4" count="6"/>
                <participants group_id="P5" count="21"/>
                <participants group_id="P6" count="15"/>
                <participants group_id="P7" count="13"/>
                <participants group_id="P8" count="62"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="9"/>
                <participants group_id="P6" count="18"/>
                <participants group_id="P7" count="18"/>
                <participants group_id="P8" count="182"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Escalation Cohort 1</title>
          <description>Oral Once-Daily Administration of HS-10296 55mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
        </group>
        <group group_id="B2">
          <title>Escalation Cohort 2</title>
          <description>Oral Once-Daily Administration of HS-10296 110mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
        </group>
        <group group_id="B3">
          <title>Escalation Cohort 3</title>
          <description>Oral Once-Daily Administration of HS-10296 220mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
        </group>
        <group group_id="B4">
          <title>Escalation Cohort 4</title>
          <description>Oral Once-Daily Administration of HS-10296 260mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
        </group>
        <group group_id="B5">
          <title>Expansion Cohort 1</title>
          <description>Oral Once-Daily Administration of HS-10296 55mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
        </group>
        <group group_id="B6">
          <title>Expansion Cohort 2</title>
          <description>Oral Once-Daily Administration of HS-10296 110mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
        </group>
        <group group_id="B7">
          <title>Expansion Cohort 3</title>
          <description>Oral Once-Daily Administration of HS-10296 220mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
        </group>
        <group group_id="B8">
          <title>Phase 2 Extension</title>
          <description>Oral Once-Daily Administration of HS-10296 (MTD or RP2D)&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
        </group>
        <group group_id="B9">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="6"/>
            <count group_id="B2" value="6"/>
            <count group_id="B3" value="8"/>
            <count group_id="B4" value="6"/>
            <count group_id="B5" value="30"/>
            <count group_id="B6" value="33"/>
            <count group_id="B7" value="31"/>
            <count group_id="B8" value="244"/>
            <count group_id="B9" value="364"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                    <measurement group_id="B8" value="0"/>
                    <measurement group_id="B9" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="4"/>
                    <measurement group_id="B5" value="22"/>
                    <measurement group_id="B6" value="16"/>
                    <measurement group_id="B7" value="21"/>
                    <measurement group_id="B8" value="153"/>
                    <measurement group_id="B9" value="228"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="8"/>
                    <measurement group_id="B6" value="17"/>
                    <measurement group_id="B7" value="10"/>
                    <measurement group_id="B8" value="91"/>
                    <measurement group_id="B9" value="136"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="5"/>
                    <measurement group_id="B5" value="19"/>
                    <measurement group_id="B6" value="20"/>
                    <measurement group_id="B7" value="20"/>
                    <measurement group_id="B8" value="142"/>
                    <measurement group_id="B9" value="219"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="11"/>
                    <measurement group_id="B6" value="13"/>
                    <measurement group_id="B7" value="11"/>
                    <measurement group_id="B8" value="102"/>
                    <measurement group_id="B9" value="145"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                    <measurement group_id="B8" value="0"/>
                    <measurement group_id="B9" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="7"/>
                    <measurement group_id="B4" value="5"/>
                    <measurement group_id="B5" value="29"/>
                    <measurement group_id="B6" value="31"/>
                    <measurement group_id="B7" value="31"/>
                    <measurement group_id="B8" value="244"/>
                    <measurement group_id="B9" value="358"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="1"/>
                    <measurement group_id="B7" value="0"/>
                    <measurement group_id="B8" value="0"/>
                    <measurement group_id="B9" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                    <measurement group_id="B8" value="0"/>
                    <measurement group_id="B9" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="1"/>
                    <measurement group_id="B6" value="1"/>
                    <measurement group_id="B7" value="0"/>
                    <measurement group_id="B8" value="0"/>
                    <measurement group_id="B9" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                    <measurement group_id="B8" value="0"/>
                    <measurement group_id="B9" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                    <measurement group_id="B8" value="0"/>
                    <measurement group_id="B9" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="1"/>
                    <measurement group_id="B6" value="2"/>
                    <measurement group_id="B7" value="0"/>
                    <measurement group_id="B8" value="0"/>
                    <measurement group_id="B9" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Taiwan</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="5"/>
                    <measurement group_id="B5" value="13"/>
                    <measurement group_id="B6" value="17"/>
                    <measurement group_id="B7" value="18"/>
                    <measurement group_id="B8" value="55"/>
                    <measurement group_id="B9" value="124"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>China</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="16"/>
                    <measurement group_id="B6" value="14"/>
                    <measurement group_id="B7" value="13"/>
                    <measurement group_id="B8" value="189"/>
                    <measurement group_id="B9" value="233"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Dose Limiting Toxicity (DLT) Phase I Part</title>
        <description>DLT is defined as one of the following HS-10296 related adverse event (AE) ：(1) Hematological toxicity ≥ Grade 4 neutropenia lasting more than 5 days, febrile neutropenia of any duration (absolute neutrophil count [ANC]) &lt; 1.0 × 109/L and fever ≥ 38.5°C), Grade 4 thrombocytopenia, Grade 3 thrombocytopenia with bleeding, any requirement for platelet transfusion, Grade 4 anemia (unexplained by underlying disease); (2)Non-hematological toxicity ≥ CTCAE Grade 3 including Infection (including febrile neutropenia), confirmed prolongation of QT interval corrected with Fridericia's (QTcF) (&gt; 500 ms absolute or &gt; 60 ms above Baseline) and cardiac toxicity greater than Grade 3；(3)Any other toxicity that is greater than that at Baseline (clinically significant and/or unacceptable, and judged to be a DLT by the SRC), meets a protocol-defined stopping criteria (i.e., confirmed corneal ulceration), or results in a disruption of dosing schedule of more than 7 days.</description>
        <time_frame>21 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Escalation Cohort 1</title>
            <description>Oral Once-Daily Administration of HS-10296 55mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
          <group group_id="O2">
            <title>Escalation Cohort 2</title>
            <description>Oral Once-Daily Administration of HS-10296 110mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
          <group group_id="O3">
            <title>Escalation Cohort 3</title>
            <description>Oral Once-Daily Administration of HS-10296 220mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
          <group group_id="O4">
            <title>Escalation Cohort 4</title>
            <description>Oral Once-Daily Administration of HS-10296 260mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Dose Limiting Toxicity (DLT) Phase I Part</title>
          <description>DLT is defined as one of the following HS-10296 related adverse event (AE) ：(1) Hematological toxicity ≥ Grade 4 neutropenia lasting more than 5 days, febrile neutropenia of any duration (absolute neutrophil count [ANC]) &lt; 1.0 × 109/L and fever ≥ 38.5°C), Grade 4 thrombocytopenia, Grade 3 thrombocytopenia with bleeding, any requirement for platelet transfusion, Grade 4 anemia (unexplained by underlying disease); (2)Non-hematological toxicity ≥ CTCAE Grade 3 including Infection (including febrile neutropenia), confirmed prolongation of QT interval corrected with Fridericia's (QTcF) (&gt; 500 ms absolute or &gt; 60 ms above Baseline) and cardiac toxicity greater than Grade 3；(3)Any other toxicity that is greater than that at Baseline (clinically significant and/or unacceptable, and judged to be a DLT by the SRC), meets a protocol-defined stopping criteria (i.e., confirmed corneal ulceration), or results in a disruption of dosing schedule of more than 7 days.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="8"/>
                <count group_id="O4" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Overall Response Rate (ORR) Phase II Part</title>
        <description>ORR is defined as the percentage of patients with a complete response (CR) or partial response (PR) that was confirmed at a subsequent scan at least 6 weeks later, as assessed according to RECIST (Response Evaluation Criteria In Solid Tumors Criteria) version 1.1 for target lesions and assessed by CT/MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), &gt;=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.</description>
        <time_frame>From the date of first dose until the date of disease progression or withdrawal from study, approximately 15 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Phase 2 Extension</title>
            <description>Oral Once-Daily Administration of HS-10296 (MTD or RP2D)&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Response Rate (ORR) Phase II Part</title>
          <description>ORR is defined as the percentage of patients with a complete response (CR) or partial response (PR) that was confirmed at a subsequent scan at least 6 weeks later, as assessed according to RECIST (Response Evaluation Criteria In Solid Tumors Criteria) version 1.1 for target lesions and assessed by CT/MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), &gt;=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.</description>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="244"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="65.6" lower_limit="59.2" upper_limit="71.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Incidence and Severity of Adverse Events (AEs) Phase I Part</title>
        <description>An AE is the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition can be symptoms (e.g., nausea, chest pain), signs (e.g., tachycardia, enlarged liver), or the abnormal results of an investigation (e.g., laboratory findings, ECG). Any deterioration of the disease under study and associated symptoms or findings should not be regarded as an AE as far as the deterioration can be anticipated. The AE was graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0.</description>
        <time_frame>From the screening period to 28 days after treatment completion, approximately 16 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Escalation Cohort 1</title>
            <description>Oral Once-Daily Administration of HS-10296 55mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
          <group group_id="O2">
            <title>Escalation Cohort 2</title>
            <description>Oral Once-Daily Administration of HS-10296 110mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
          <group group_id="O3">
            <title>Escalation Cohort 3</title>
            <description>Oral Once-Daily Administration of HS-10296 220mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
          <group group_id="O4">
            <title>Escalation Cohort 4</title>
            <description>Oral Once-Daily Administration of HS-10296 260mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
          <group group_id="O5">
            <title>Expansion Cohort 1</title>
            <description>Oral Once-Daily Administration of HS-10296 55mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
          <group group_id="O6">
            <title>Expansion Cohort 2</title>
            <description>Oral Once-Daily Administration of HS-10296 110mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
          <group group_id="O7">
            <title>Expansion Cohort 3</title>
            <description>Oral Once-Daily Administration of HS-10296 220mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence and Severity of Adverse Events (AEs) Phase I Part</title>
          <description>An AE is the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition can be symptoms (e.g., nausea, chest pain), signs (e.g., tachycardia, enlarged liver), or the abnormal results of an investigation (e.g., laboratory findings, ECG). Any deterioration of the disease under study and associated symptoms or findings should not be regarded as an AE as far as the deterioration can be anticipated. The AE was graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="8"/>
                <count group_id="O4" value="6"/>
                <count group_id="O5" value="30"/>
                <count group_id="O6" value="33"/>
                <count group_id="O7" value="31"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>At least one adverse event</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="6"/>
                    <measurement group_id="O3" value="8"/>
                    <measurement group_id="O4" value="6"/>
                    <measurement group_id="O5" value="30"/>
                    <measurement group_id="O6" value="32"/>
                    <measurement group_id="O7" value="31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At least one adverse event of Grade 3 or greater</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="3"/>
                    <measurement group_id="O4" value="3"/>
                    <measurement group_id="O5" value="6"/>
                    <measurement group_id="O6" value="8"/>
                    <measurement group_id="O7" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At least one serious adverse event</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="2"/>
                    <measurement group_id="O4" value="3"/>
                    <measurement group_id="O5" value="5"/>
                    <measurement group_id="O6" value="6"/>
                    <measurement group_id="O7" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Area Under the Plasma Concentration Versus Time Curve (AUC) of HS-10296 and HAS-719 From Zero to the 24-Hour Sampling Time (AUC0-24) After Single Dose of HS-10296</title>
        <description>Area under the plasma concentration versus time curve from time zero to the 24-hour sampling time at which the concentration was at or above the lower limit of quantification (LLQ). AUC0-24 was to be calculated according to the mixed log-linear trapezoidal rule.</description>
        <time_frame>From pre-dose to 24 hours after single dose on Day 1 of Cycle 0</time_frame>
        <population>Data was collected for only Part 1 dose escalation Arms</population>
        <group_list>
          <group group_id="O1">
            <title>Escalation Cohort 1</title>
            <description>Oral Once-Daily Administration of HS-10296 55mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
          <group group_id="O2">
            <title>Escalation Cohort 2</title>
            <description>Oral Once-Daily Administration of HS-10296 110mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
          <group group_id="O3">
            <title>Escalation Cohort 3</title>
            <description>Oral Once-Daily Administration of HS-10296 220mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
          <group group_id="O4">
            <title>Escalation Cohort 4</title>
            <description>Oral Once-Daily Administration of HS-10296 260mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration Versus Time Curve (AUC) of HS-10296 and HAS-719 From Zero to the 24-Hour Sampling Time (AUC0-24) After Single Dose of HS-10296</title>
          <description>Area under the plasma concentration versus time curve from time zero to the 24-hour sampling time at which the concentration was at or above the lower limit of quantification (LLQ). AUC0-24 was to be calculated according to the mixed log-linear trapezoidal rule.</description>
          <population>Data was collected for only Part 1 dose escalation Arms</population>
          <units>h*ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="8"/>
                <count group_id="O4" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>HS-10296</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1740.1175" spread="917.7303"/>
                    <measurement group_id="O2" value="5250.2364" spread="3345.8348"/>
                    <measurement group_id="O3" value="8174.4312" spread="8126.7012"/>
                    <measurement group_id="O4" value="8038.9348" spread="1648.4566"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>HAS-719</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="298.4934" spread="131.6189"/>
                    <measurement group_id="O2" value="696.4536" spread="293.4756"/>
                    <measurement group_id="O3" value="1152.1150" spread="475.5067"/>
                    <measurement group_id="O4" value="1564.3829" spread="488.6330"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Elimination Half-life(T1/2) of HS-10296 and HAS-719</title>
        <description>Elimination half-life is the time measured for the concentration to decrease by one half. Half-life calculated by natural log 2 divided by λz.</description>
        <time_frame>From pre-dose to 120 hours after single dose on Day 1 of Cycle 0</time_frame>
        <population>Data was collected for only Part 1 dose escalation Arms</population>
        <group_list>
          <group group_id="O1">
            <title>Escalation Cohort 1</title>
            <description>Oral Once-Daily Administration of HS-10296 55mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
          <group group_id="O2">
            <title>Escalation Cohort 2</title>
            <description>Oral Once-Daily Administration of HS-10296 110mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
          <group group_id="O3">
            <title>Escalation Cohort 3</title>
            <description>Oral Once-Daily Administration of HS-10296 220mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
          <group group_id="O4">
            <title>Escalation Cohort 4</title>
            <description>Oral Once-Daily Administration of HS-10296 260mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
        </group_list>
        <measure>
          <title>Elimination Half-life(T1/2) of HS-10296 and HAS-719</title>
          <description>Elimination half-life is the time measured for the concentration to decrease by one half. Half-life calculated by natural log 2 divided by λz.</description>
          <population>Data was collected for only Part 1 dose escalation Arms</population>
          <units>hours</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="8"/>
                <count group_id="O4" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>HS-10296</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="31.29" spread="9.57"/>
                    <measurement group_id="O2" value="30.62" spread="9.34"/>
                    <measurement group_id="O3" value="35.19" spread="13.89"/>
                    <measurement group_id="O4" value="34.81" spread="9.76"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>HAS-719</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="49.75" spread="10.70"/>
                    <measurement group_id="O2" value="55.36" spread="19.95"/>
                    <measurement group_id="O3" value="63.75" spread="29.83"/>
                    <measurement group_id="O4" value="57.79" spread="13.95"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Css Max of HS-10296 and HAS-719 After Multiple Dose</title>
        <description>Observed maximum plasma concentration (Css max) after multiple dose of HS-10296 and HAS-719</description>
        <time_frame>From pre-dose to 21 days after multiple dose on Day 1 of Cycle 2</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Escalation Cohort 1</title>
            <description>Oral Once-Daily Administration of HS-10296 55mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
          <group group_id="O2">
            <title>Escalation Cohort 2</title>
            <description>Oral Once-Daily Administration of HS-10296 110mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
          <group group_id="O3">
            <title>Escalation Cohort 3</title>
            <description>Oral Once-Daily Administration of HS-10296 220mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
          <group group_id="O4">
            <title>Escalation Cohort 4</title>
            <description>Oral Once-Daily Administration of HS-10296 260mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
          <group group_id="O5">
            <title>Expansion Cohort 1</title>
            <description>Oral Once-Daily Administration of HS-10296 55mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
          <group group_id="O6">
            <title>Expansion Cohort 2</title>
            <description>Oral Once-Daily Administration of HS-10296 110mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
          <group group_id="O7">
            <title>Expansion Cohort 3</title>
            <description>Oral Once-Daily Administration of HS-10296 220mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
          <group group_id="O8">
            <title>Phase 2 Extension</title>
            <description>Oral Once-Daily Administration of HS-10296 110mg (RP2D)&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
        </group_list>
        <measure>
          <title>Css Max of HS-10296 and HAS-719 After Multiple Dose</title>
          <description>Observed maximum plasma concentration (Css max) after multiple dose of HS-10296 and HAS-719</description>
          <units>ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="8"/>
                <count group_id="O4" value="6"/>
                <count group_id="O5" value="30"/>
                <count group_id="O6" value="33"/>
                <count group_id="O7" value="31"/>
                <count group_id="O8" value="244"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>HS-10296</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="164.5000" spread="70.6222"/>
                    <measurement group_id="O2" value="352.8333" spread="102.7062"/>
                    <measurement group_id="O3" value="762.0000" spread="231.8888"/>
                    <measurement group_id="O4" value="765.4000" spread="285.2802"/>
                    <measurement group_id="O5" value="197.9308" spread="78.6513"/>
                    <measurement group_id="O6" value="413.2751" spread="194.0200"/>
                    <measurement group_id="O7" value="552.0635" spread="257.9572"/>
                    <measurement group_id="O8" value="352.5111" spread="185.3279"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>HAS-719</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="55.3500" spread="18.1391"/>
                    <measurement group_id="O2" value="118.1333" spread="26.9018"/>
                    <measurement group_id="O3" value="276.1667" spread="42.9391"/>
                    <measurement group_id="O4" value="338.2000" spread="119.3302"/>
                    <measurement group_id="O5" value="62.9535" spread="21.4094"/>
                    <measurement group_id="O6" value="142.1545" spread="49.4867"/>
                    <measurement group_id="O7" value="221.9404" spread="83.6900"/>
                    <measurement group_id="O8" value="118.3758" spread="43.3468"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>AUCss of HS-10296 and HAS-719 After Multiple Dose of HS-10296</title>
        <description>Area Under the Plasma Concentration Versus Time Curve at steady state (AUCss) of HS-10296 and HAS-719 after multiple dose of HS-10296</description>
        <time_frame>From pre-dose to 21 days after multiple dose on Day 1 of Cycle 2</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Escalation Cohort 1</title>
            <description>Oral Once-Daily Administration of HS-10296 55mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
          <group group_id="O2">
            <title>Escalation Cohort 2</title>
            <description>Oral Once-Daily Administration of HS-10296 110mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
          <group group_id="O3">
            <title>Escalation Cohort 3</title>
            <description>Oral Once-Daily Administration of HS-10296 220mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
          <group group_id="O4">
            <title>Escalation Cohort 4</title>
            <description>Oral Once-Daily Administration of HS-10296 260mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
          <group group_id="O5">
            <title>Expansion Cohort 1</title>
            <description>Oral Once-Daily Administration of HS-10296 55mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
          <group group_id="O6">
            <title>Expansion Cohort 2</title>
            <description>Oral Once-Daily Administration of HS-10296 110mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
          <group group_id="O7">
            <title>Expansion Cohort 3</title>
            <description>Oral Once-Daily Administration of HS-10296 220mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
          <group group_id="O8">
            <title>Phase 2 Extension</title>
            <description>Oral Once-Daily Administration of HS-10296 (MTD or RP2D)&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
        </group_list>
        <measure>
          <title>AUCss of HS-10296 and HAS-719 After Multiple Dose of HS-10296</title>
          <description>Area Under the Plasma Concentration Versus Time Curve at steady state (AUCss) of HS-10296 and HAS-719 after multiple dose of HS-10296</description>
          <units>h*ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="8"/>
                <count group_id="O4" value="6"/>
                <count group_id="O5" value="30"/>
                <count group_id="O6" value="33"/>
                <count group_id="O7" value="31"/>
                <count group_id="O8" value="244"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>HS-10296</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2488.0953" spread="439.3443"/>
                    <measurement group_id="O2" value="7000.2498" spread="2832.8180"/>
                    <measurement group_id="O3" value="11994.8801" spread="3839.4164"/>
                    <measurement group_id="O4" value="14101.8608" spread="5294.1409"/>
                    <measurement group_id="O5" value="3550.8674" spread="1451.0173"/>
                    <measurement group_id="O6" value="7098.0738" spread="2826.1228"/>
                    <measurement group_id="O7" value="10185.6761" spread="4862.0070"/>
                    <measurement group_id="O8" value="6602.2491" spread="3482.0499"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>HAS-719</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="983.7103" spread="201.9267"/>
                    <measurement group_id="O2" value="2691.7220" spread="677.2407"/>
                    <measurement group_id="O3" value="5458.2304" spread="659.3078"/>
                    <measurement group_id="O4" value="8154.0849" spread="1144.0617"/>
                    <measurement group_id="O5" value="1304.4143" spread="429.1216"/>
                    <measurement group_id="O6" value="2852.8083" spread="820.1842"/>
                    <measurement group_id="O7" value="4692.6023" spread="1771.6881"/>
                    <measurement group_id="O8" value="2467.8527" spread="892.5071"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Response Rate (Phase I Part)</title>
        <description>ORR is defined as the percentage of patients with a complete response (CR) or partial response (PR) that was confirmed at a subsequent scan at least 6 weeks later, as assessed according to RECIST (Response Evaluation Criteria In Solid Tumors Criteria) version 1.1 for target lesions and assessed by CT/MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), &gt;=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.</description>
        <time_frame>From the date of first dose until the date of disease progression or withdrawal from study, approximately 15 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Escalation Cohort 1</title>
            <description>Oral Once-Daily Administration of HS-10296 55mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
          <group group_id="O2">
            <title>Escalation Cohort 2</title>
            <description>Oral Once-Daily Administration of HS-10296 110mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
          <group group_id="O3">
            <title>Escalation Cohort 3</title>
            <description>Oral Once-Daily Administration of HS-10296 220mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
          <group group_id="O4">
            <title>Escalation Cohort 4</title>
            <description>Oral Once-Daily Administration of HS-10296 260mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
          <group group_id="O5">
            <title>Expansion Cohort 1</title>
            <description>Oral Once-Daily Administration of HS-10296 55mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
          <group group_id="O6">
            <title>Expansion Cohort 2</title>
            <description>Oral Once-Daily Administration of HS-10296 110mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
          <group group_id="O7">
            <title>Expansion Cohort 3</title>
            <description>Oral Once-Daily Administration of HS-10296 220mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Response Rate (Phase I Part)</title>
          <description>ORR is defined as the percentage of patients with a complete response (CR) or partial response (PR) that was confirmed at a subsequent scan at least 6 weeks later, as assessed according to RECIST (Response Evaluation Criteria In Solid Tumors Criteria) version 1.1 for target lesions and assessed by CT/MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), &gt;=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.</description>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="8"/>
                <count group_id="O4" value="6"/>
                <count group_id="O5" value="30"/>
                <count group_id="O6" value="33"/>
                <count group_id="O7" value="31"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="50.0" lower_limit="11.8" upper_limit="88.2"/>
                    <measurement group_id="O2" value="66.7" lower_limit="22.3" upper_limit="95.7"/>
                    <measurement group_id="O3" value="37.5" lower_limit="8.5" upper_limit="75.5"/>
                    <measurement group_id="O4" value="16.7" lower_limit="0.4" upper_limit="64.1"/>
                    <measurement group_id="O5" value="60.0" lower_limit="40.6" upper_limit="77.3"/>
                    <measurement group_id="O6" value="54.5" lower_limit="36.4" upper_limit="71.9"/>
                    <measurement group_id="O7" value="41.9" lower_limit="24.5" upper_limit="60.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression-free Survival (PFS)</title>
        <description>The PFS is defined as the time from date of first dosing until the date of objective disease progression as defined by Response Evaluation Criteria in Solid Tumors （RECIST） v1.1 or death (by any cause in the absence of progression) regardless of whether the patients withdraws from HS-10296 therapy or receives another anti-cancer therapy prior to progression. Progression is defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.</description>
        <time_frame>From the date of enrollment until the date of disease progression or death from any cause, approximately 15 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Escalation Cohort 1</title>
            <description>Oral Once-Daily Administration of HS-10296 55mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
          <group group_id="O2">
            <title>Escalation Cohort 2</title>
            <description>Oral Once-Daily Administration of HS-10296 110mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
          <group group_id="O3">
            <title>Escalation Cohort 3</title>
            <description>Oral Once-Daily Administration of HS-10296 220mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
          <group group_id="O4">
            <title>Escalation Cohort 4</title>
            <description>Oral Once-Daily Administration of HS-10296 260mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
          <group group_id="O5">
            <title>Expansion Cohort 1</title>
            <description>Oral Once-Daily Administration of HS-10296 55mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
          <group group_id="O6">
            <title>Expansion Cohort 2</title>
            <description>Oral Once-Daily Administration of HS-10296 110mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
          <group group_id="O7">
            <title>Expansion Cohort 3</title>
            <description>Oral Once-Daily Administration of HS-10296 220mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
          <group group_id="O8">
            <title>Phase 2 Extension</title>
            <description>Oral Once-Daily Administration of HS-10296 110mg (RP2D)&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
        </group_list>
        <measure>
          <title>Progression-free Survival (PFS)</title>
          <description>The PFS is defined as the time from date of first dosing until the date of objective disease progression as defined by Response Evaluation Criteria in Solid Tumors （RECIST） v1.1 or death (by any cause in the absence of progression) regardless of whether the patients withdraws from HS-10296 therapy or receives another anti-cancer therapy prior to progression. Progression is defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.</description>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="8"/>
                <count group_id="O4" value="6"/>
                <count group_id="O5" value="30"/>
                <count group_id="O6" value="33"/>
                <count group_id="O7" value="31"/>
                <count group_id="O8" value="244"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.2" lower_limit="3.0" upper_limit="NA">Since the curve that represents the upper confidence limits for the KM survivor function lies above 0.5, thus the upper limits for the median can not be estimated.</measurement>
                    <measurement group_id="O2" value="7.0" lower_limit="5.8" upper_limit="12.5"/>
                    <measurement group_id="O3" value="5.5" lower_limit="1.1" upper_limit="8.4"/>
                    <measurement group_id="O4" value="3.7" lower_limit="0.8" upper_limit="11.0"/>
                    <measurement group_id="O5" value="9.6" lower_limit="6.7" upper_limit="15.1"/>
                    <measurement group_id="O6" value="13.6" lower_limit="6.9" upper_limit="19.2"/>
                    <measurement group_id="O7" value="11.1" lower_limit="8.3" upper_limit="24.8"/>
                    <measurement group_id="O8" value="12.4" lower_limit="9.7" upper_limit="15.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Disease Control Rate (DCR)</title>
        <description>Objective response is assessed by RECIST 1.1 thereby to evaluate disease control rate. The DCR is defined as the proportion of patients with a best overall response of CR, PR, or SD (stable disease).</description>
        <time_frame>From the date of first dose until the date of disease progression or withdrawal from study, approximately 15 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Escalation Cohort 1</title>
            <description>Oral Once-Daily Administration of HS-10296 55mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
          <group group_id="O2">
            <title>Escalation Cohort 2</title>
            <description>Oral Once-Daily Administration of HS-10296 110mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
          <group group_id="O3">
            <title>Escalation Cohort 3</title>
            <description>Oral Once-Daily Administration of HS-10296 220mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
          <group group_id="O4">
            <title>Escalation Cohort 4</title>
            <description>Oral Once-Daily Administration of HS-10296 260mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
          <group group_id="O5">
            <title>Expansion Cohort 1</title>
            <description>Oral Once-Daily Administration of HS-10296 55mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
          <group group_id="O6">
            <title>Expansion Cohort 2</title>
            <description>Oral Once-Daily Administration of HS-10296 110mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
          <group group_id="O7">
            <title>Expansion Cohort 3</title>
            <description>Oral Once-Daily Administration of HS-10296 220mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
          <group group_id="O8">
            <title>Phase 2 Extension</title>
            <description>Oral Once-Daily Administration of HS-10296 110mg (RP2D)&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
        </group_list>
        <measure>
          <title>Disease Control Rate (DCR)</title>
          <description>Objective response is assessed by RECIST 1.1 thereby to evaluate disease control rate. The DCR is defined as the proportion of patients with a best overall response of CR, PR, or SD (stable disease).</description>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="8"/>
                <count group_id="O4" value="6"/>
                <count group_id="O5" value="30"/>
                <count group_id="O6" value="33"/>
                <count group_id="O7" value="31"/>
                <count group_id="O8" value="244"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100.0" lower_limit="54.1" upper_limit="100.0"/>
                    <measurement group_id="O2" value="100.0" lower_limit="54.1" upper_limit="100.0"/>
                    <measurement group_id="O3" value="75.0" lower_limit="34.9" upper_limit="96.8"/>
                    <measurement group_id="O4" value="50.0" lower_limit="11.8" upper_limit="88.2"/>
                    <measurement group_id="O5" value="83.3" lower_limit="65.3" upper_limit="94.4"/>
                    <measurement group_id="O6" value="97.0" lower_limit="84.2" upper_limit="99.9"/>
                    <measurement group_id="O7" value="93.5" lower_limit="78.6" upper_limit="99.2"/>
                    <measurement group_id="O8" value="93.4" lower_limit="89.6" upper_limit="96.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival (OS) Phase II Part</title>
        <description>Overall survival will be assessed based on the date of first dose and survival status at the time of analysis. Overall survival is defined as the time from date of first dose until the documentation of death from any cause.</description>
        <time_frame>From the date of enrollment until the date of death from any cause, approximately 48 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Phase 2 Extension</title>
            <description>Oral Once-Daily Administration of HS-10296 (MTD or RP2D)&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival (OS) Phase II Part</title>
          <description>Overall survival will be assessed based on the date of first dose and survival status at the time of analysis. Overall survival is defined as the time from date of first dose until the documentation of death from any cause.</description>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="244"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="31.5" lower_limit="25.9" upper_limit="35.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Depth of Response (DepOR)</title>
        <description>Depth of Response (DepOR) Only in part II dose-extention phase. DepOR is defined as the percentage change in tumor size, based on longest diameter or reconstructed volume, observed at the lowest point compared with baseline.</description>
        <time_frame>From the date of enrollment until the date of disease progression or death, approximately 15 months</time_frame>
        <population>Based on the ICR evaluation results, DepOR analysis was performed on patients with efficacy evaluation</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 2 Extension</title>
            <description>Oral Once-Daily Administration of HS-10296 (MTD or RP2D)&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
        </group_list>
        <measure>
          <title>Depth of Response (DepOR)</title>
          <description>Depth of Response (DepOR) Only in part II dose-extention phase. DepOR is defined as the percentage change in tumor size, based on longest diameter or reconstructed volume, observed at the lowest point compared with baseline.</description>
          <population>Based on the ICR evaluation results, DepOR analysis was performed on patients with efficacy evaluation</population>
          <units>percentage of change from baseline</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="237"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-47.89" spread="22.333"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Response (DoR)</title>
        <description>Duration of response (DoR) is defined as the time from the date of first documented response until the date of documented progression or death in the absence of disease progression. The end of response should coincide with the date of progression or death from any cause used for the PFS endpoint. The time of the initial response will be defined as the latest of the dates contributing towards the first visit response of PR or CR. If a patient does not progress following a response, then DoR will be used as the PFS censoring time.</description>
        <time_frame>From the date of enrollment until the date of disease progression or death, approximately 18 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Escalation Cohort 1</title>
            <description>Oral Once-Daily Administration of HS-10296 55mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
          <group group_id="O2">
            <title>Escalation Cohort 2</title>
            <description>Oral Once-Daily Administration of HS-10296 110mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
          <group group_id="O3">
            <title>Escalation Cohort 3</title>
            <description>Oral Once-Daily Administration of HS-10296 220mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
          <group group_id="O4">
            <title>Escalation Cohort 4</title>
            <description>Oral Once-Daily Administration of HS-10296 260mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
          <group group_id="O5">
            <title>Expansion Cohort 1</title>
            <description>Oral Once-Daily Administration of HS-10296 55mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
          <group group_id="O6">
            <title>Expansion Cohort 2</title>
            <description>Oral Once-Daily Administration of HS-10296 110mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
          <group group_id="O7">
            <title>Expansion Cohort 3</title>
            <description>Oral Once-Daily Administration of HS-10296 220mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
          <group group_id="O8">
            <title>Phase 2 Extension</title>
            <description>Oral Once-Daily Administration of HS-10296 110mg (RP2D)&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Response (DoR)</title>
          <description>Duration of response (DoR) is defined as the time from the date of first documented response until the date of documented progression or death in the absence of disease progression. The end of response should coincide with the date of progression or death from any cause used for the PFS endpoint. The time of the initial response will be defined as the latest of the dates contributing towards the first visit response of PR or CR. If a patient does not progress following a response, then DoR will be used as the PFS censoring time.</description>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="8"/>
                <count group_id="O4" value="6"/>
                <count group_id="O5" value="30"/>
                <count group_id="O6" value="33"/>
                <count group_id="O7" value="31"/>
                <count group_id="O8" value="244"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.9" lower_limit="1.9" upper_limit="NA">Since the curve that represents the upper confidence limits for the KM survivor function lies above 0.5, thus the upper limits for the median can not be estimated.</measurement>
                    <measurement group_id="O2" value="5.6" lower_limit="4.2" upper_limit="9.5"/>
                    <measurement group_id="O3" value="5.6" lower_limit="4.1" upper_limit="7.0"/>
                    <measurement group_id="O4" value="5.5" lower_limit="NA" upper_limit="NA">Since the curve that represents the upper confidence limits for the KM survivor function lies above 0.5, thus the upper limits for the median can not be estimated.</measurement>
                    <measurement group_id="O5" value="8.3" lower_limit="8.1" upper_limit="16.5"/>
                    <measurement group_id="O6" value="12.5" lower_limit="5.5" upper_limit="22.1"/>
                    <measurement group_id="O7" value="22.1" lower_limit="8.1" upper_limit="35.7"/>
                    <measurement group_id="O8" value="15.1" lower_limit="12.9" upper_limit="16.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Incidence and Severity of AEs Phase II Part</title>
        <description>An AE is the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition can be symptoms (e.g., nausea, chest pain), signs (e.g., tachycardia, enlarged liver), or the abnormal results of an investigation (e.g., laboratory findings, ECG). Any deterioration of the disease under study and associated symptoms or findings should not be regarded as an AE as far as the deterioration can be anticipated. The AE was graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0.</description>
        <time_frame>From the screening period to 28 days after treatment completion, approximately 16 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Phase 2 Extension</title>
            <description>Oral Once-Daily Administration of HS-10296 (MTD or RP2D)&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence and Severity of AEs Phase II Part</title>
          <description>An AE is the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition can be symptoms (e.g., nausea, chest pain), signs (e.g., tachycardia, enlarged liver), or the abnormal results of an investigation (e.g., laboratory findings, ECG). Any deterioration of the disease under study and associated symptoms or findings should not be regarded as an AE as far as the deterioration can be anticipated. The AE was graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="244"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>At least 1 adverse event</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="219"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At least one adverse event of Grade 3 or greater</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="60"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At least one serious adverse event</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Throughout the study, from informed consent until the end of the follow-up period. The follow-up period is defined as 28 ± 3 days after study treatment is discontinued, assessed up to 16 months. Deaths were assessed up to 48 months. Serious and Other (Non-Serious) Adverse Events were assessed up to 16 months.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Escalation Cohort 1</title>
          <description>Oral Once-Daily Administration of HS-10296 55mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
        </group>
        <group group_id="E2">
          <title>Escalation Cohort 2</title>
          <description>Oral Once-Daily Administration of HS-10296 110mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
        </group>
        <group group_id="E3">
          <title>Escalation Cohort 3</title>
          <description>Oral Once-Daily Administration of HS-10296 220mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
        </group>
        <group group_id="E4">
          <title>Escalation Cohort 4</title>
          <description>Oral Once-Daily Administration of HS-10296 260mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
        </group>
        <group group_id="E5">
          <title>Expansion Cohort 1</title>
          <description>Oral Once-Daily Administration of HS-10296 55mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
        </group>
        <group group_id="E6">
          <title>Expansion Cohort 2</title>
          <description>Oral Once-Daily Administration of HS-10296 110mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
        </group>
        <group group_id="E7">
          <title>Expansion Cohort 3</title>
          <description>Oral Once-Daily Administration of HS-10296 220mg&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
        </group>
        <group group_id="E8">
          <title>Phase 2 Extension</title>
          <description>Oral Once-Daily Administration of HS-10296 (MTD or RP2D)&#xD;
HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" subjects_affected="11" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="5" subjects_at_risk="30"/>
                <counts group_id="E6" subjects_affected="6" subjects_at_risk="33"/>
                <counts group_id="E7" subjects_affected="3" subjects_at_risk="31"/>
                <counts group_id="E8" subjects_affected="30" subjects_at_risk="244"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Arrhythmia supraventricular</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="1" subjects_affected="1" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="1" subjects_affected="1" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Pericardial effusion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="1" subjects_affected="1" subjects_at_risk="244"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Bowel obstruction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="1" subjects_affected="1" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Inguinal hernia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="1" subjects_affected="1" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Ileus</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Peripheral swelling</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Chest discomfort</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="1" subjects_affected="1" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Death</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="3" subjects_affected="3" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="2" subjects_affected="2" subjects_at_risk="244"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholecystitis acute</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Pneumonitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="5" subjects_affected="5" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Appendicitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Biliary tract infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Intervertebral discitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Pyelonephritis acute</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Atypical pneumonia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="1" subjects_affected="1" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Bacteraemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="1" subjects_affected="1" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="1" subjects_affected="1" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Cystitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="1" subjects_affected="1" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Empyema</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="1" subjects_affected="1" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Herpes ophthalmic</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="1" subjects_affected="1" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="1" subjects_affected="1" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Tooth infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="1" subjects_affected="1" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="3" subjects_affected="3" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="1" subjects_affected="1" subjects_at_risk="244"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="2" subjects_affected="2" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Femoral neck fracture</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="1" subjects_affected="1" subjects_at_risk="244"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood creatine phosphokinase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="2" subjects_affected="2" subjects_at_risk="31"/>
                <counts group_id="E8" events="1" subjects_affected="1" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="2" subjects_affected="2" subjects_at_risk="244"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="1" subjects_affected="1" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Hypoglycaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="1" subjects_affected="1" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Pathological fracture</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Breast cancer</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="1" subjects_affected="1" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Metastases to breast</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="1" subjects_affected="1" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Prostate cancer</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="1" subjects_affected="1" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Presyncope</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="1" subjects_affected="1" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Cerebellar infarction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="1" subjects_affected="1" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Brain oedema</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E8" events="1" subjects_affected="1" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Depressed level of consciousness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="1" subjects_affected="1" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Epilepsy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="1" subjects_affected="1" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Hypoaesthesia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="1" subjects_affected="1" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Spinal cord compression</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="1" subjects_affected="1" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="1" subjects_affected="1" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Vertebrobasilar insufficiency</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="1" subjects_affected="1" subjects_at_risk="244"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="1" subjects_affected="1" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Major depression</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="1" subjects_affected="1" subjects_at_risk="244"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Hydronephrosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="1" subjects_affected="1" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Nephrolithiasis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="1" subjects_affected="1" subjects_at_risk="244"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Interstitial lung disease</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="1" subjects_affected="1" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Respiratory Failure</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Pulmonary embolism</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="8" subjects_affected="8" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Haemoptysis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="2" subjects_affected="2" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Pneumonitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="1" subjects_affected="1" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Pulmonary artery thrombosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="1" subjects_affected="1" subjects_at_risk="244"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Deep vein thrombosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="2" subjects_affected="2" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Deep vein thrombosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Embolism</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="1" subjects_affected="1" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Venous thrombosis limb</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="2" subjects_affected="2" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="1" subjects_affected="1" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Venous thrombosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="1" subjects_affected="1" subjects_at_risk="244"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="6" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="29" subjects_at_risk="30"/>
                <counts group_id="E6" subjects_affected="31" subjects_at_risk="33"/>
                <counts group_id="E7" subjects_affected="29" subjects_at_risk="31"/>
                <counts group_id="E8" subjects_affected="193" subjects_at_risk="244"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Leukopenia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="4" subjects_affected="4" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="11" subjects_affected="11" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Palpitations</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Sinus bradycardia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E6" events="2" subjects_affected="2" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Tachycardia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Ventricular extrasystoles</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="3" subjects_affected="3" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Sudden hearing loss</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Tinnitus</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Vertigo</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Dry eye</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="4" subjects_affected="4" subjects_at_risk="30"/>
                <counts group_id="E6" events="4" subjects_affected="4" subjects_at_risk="33"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E8" events="7" subjects_affected="7" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Glaucoma</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Ocular discomfort</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="2" subjects_affected="2" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Vision blurred</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E7" events="2" subjects_affected="2" subjects_at_risk="31"/>
                <counts group_id="E8" events="5" subjects_affected="5" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Visual impairment</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="2" subjects_affected="2" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Anal fissure</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Ascites</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="3" subjects_affected="3" subjects_at_risk="30"/>
                <counts group_id="E6" events="3" subjects_affected="3" subjects_at_risk="33"/>
                <counts group_id="E7" events="2" subjects_affected="2" subjects_at_risk="31"/>
                <counts group_id="E8" events="20" subjects_affected="20" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="3" subjects_affected="3" subjects_at_risk="30"/>
                <counts group_id="E6" events="5" subjects_affected="5" subjects_at_risk="33"/>
                <counts group_id="E7" events="7" subjects_affected="7" subjects_at_risk="31"/>
                <counts group_id="E8" events="11" subjects_affected="11" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Eructation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Flatulence</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Gastritis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Gastrooesophageal reflux disease</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Haemorrhoidal haemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Mouth ulceration</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" events="3" subjects_affected="3" subjects_at_risk="30"/>
                <counts group_id="E6" events="2" subjects_affected="2" subjects_at_risk="33"/>
                <counts group_id="E7" events="2" subjects_affected="2" subjects_at_risk="31"/>
                <counts group_id="E8" events="10" subjects_affected="10" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E4" events="4" subjects_affected="4" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="4" subjects_affected="4" subjects_at_risk="33"/>
                <counts group_id="E7" events="5" subjects_affected="5" subjects_at_risk="31"/>
                <counts group_id="E8" events="15" subjects_affected="15" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Stomatitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="3" subjects_affected="3" subjects_at_risk="31"/>
                <counts group_id="E8" events="9" subjects_affected="9" subjects_at_risk="244"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Chest pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E6" events="4" subjects_affected="4" subjects_at_risk="33"/>
                <counts group_id="E7" events="3" subjects_affected="3" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Mucosal inflammation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E7" events="2" subjects_affected="2" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="2" subjects_affected="2" subjects_at_risk="33"/>
                <counts group_id="E7" events="3" subjects_affected="3" subjects_at_risk="31"/>
                <counts group_id="E8" events="7" subjects_affected="7" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Xerosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="2" subjects_affected="2" subjects_at_risk="31"/>
                <counts group_id="E8" events="3" subjects_affected="3" subjects_at_risk="244"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Liver injury</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="2" subjects_affected="2" subjects_at_risk="33"/>
                <counts group_id="E7" events="4" subjects_affected="4" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Hypersensitivity</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Acute sinusitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Conjunctivitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="3" subjects_affected="3" subjects_at_risk="33"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Folliculitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Furuncle</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Helicobacter infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Hepatitis B</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Herpes zoster</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Onychomycosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Paronychia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="4" subjects_affected="4" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Skin infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Tonsillitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="6" subjects_affected="6" subjects_at_risk="30"/>
                <counts group_id="E6" events="2" subjects_affected="2" subjects_at_risk="33"/>
                <counts group_id="E7" events="3" subjects_affected="3" subjects_at_risk="31"/>
                <counts group_id="E8" events="32" subjects_affected="32" subjects_at_risk="244"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" events="4" subjects_affected="4" subjects_at_risk="30"/>
                <counts group_id="E6" events="2" subjects_affected="2" subjects_at_risk="33"/>
                <counts group_id="E7" events="5" subjects_affected="5" subjects_at_risk="31"/>
                <counts group_id="E8" events="28" subjects_affected="28" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Alpha hydroxybutyrate dehydrogenase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="2" subjects_affected="2" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase abnormal</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="4" subjects_affected="4" subjects_at_risk="30"/>
                <counts group_id="E6" events="2" subjects_affected="2" subjects_at_risk="33"/>
                <counts group_id="E7" events="7" subjects_affected="7" subjects_at_risk="31"/>
                <counts group_id="E8" events="33" subjects_affected="33" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Blood creatine phosphokinase MB increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="2" subjects_affected="2" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="3" subjects_affected="3" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="2" subjects_affected="2" subjects_at_risk="31"/>
                <counts group_id="E8" events="12" subjects_affected="12" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Blood lactate dehydrogenase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="3" subjects_affected="3" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Blood urea increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E7" events="2" subjects_affected="2" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Electrocardiogram QT prolonged</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E7" events="3" subjects_affected="3" subjects_at_risk="31"/>
                <counts group_id="E8" events="11" subjects_affected="11" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Myoglobin blood increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="2" subjects_affected="2" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="5" subjects_affected="5" subjects_at_risk="30"/>
                <counts group_id="E6" events="3" subjects_affected="3" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="14" subjects_affected="14" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Neutrophil percentage increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="4" subjects_affected="4" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="3" subjects_affected="3" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Weight increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E6" events="2" subjects_affected="2" subjects_at_risk="33"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E8" events="10" subjects_affected="10" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>White blood cell count decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="7" subjects_affected="7" subjects_at_risk="30"/>
                <counts group_id="E6" events="2" subjects_affected="2" subjects_at_risk="33"/>
                <counts group_id="E7" events="2" subjects_affected="2" subjects_at_risk="31"/>
                <counts group_id="E8" events="23" subjects_affected="23" subjects_at_risk="244"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Hyperkalaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Hyperuricaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E8" events="11" subjects_affected="11" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Hypoalbuminaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Hypoproteinaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E7" events="3" subjects_affected="3" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="2" subjects_affected="2" subjects_at_risk="31"/>
                <counts group_id="E8" events="10" subjects_affected="10" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Muscular weakness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Musculoskeletal chest pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Musculoskeletal discomfort</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E6" events="3" subjects_affected="3" subjects_at_risk="33"/>
                <counts group_id="E7" events="3" subjects_affected="3" subjects_at_risk="31"/>
                <counts group_id="E8" events="10" subjects_affected="10" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="3" subjects_affected="3" subjects_at_risk="31"/>
                <counts group_id="E8" events="7" subjects_affected="7" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" events="3" subjects_affected="3" subjects_at_risk="30"/>
                <counts group_id="E6" events="3" subjects_affected="3" subjects_at_risk="33"/>
                <counts group_id="E7" events="8" subjects_affected="8" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E6" events="2" subjects_affected="2" subjects_at_risk="33"/>
                <counts group_id="E7" events="2" subjects_affected="2" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Muscle spasticity</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Neuralgia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Haematuria</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E6" events="2" subjects_affected="2" subjects_at_risk="33"/>
                <counts group_id="E7" events="2" subjects_affected="2" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Proteinuria</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="4" subjects_affected="4" subjects_at_risk="31"/>
                <counts group_id="E8" events="17" subjects_affected="17" subjects_at_risk="244"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="6" subjects_affected="6" subjects_at_risk="30"/>
                <counts group_id="E6" events="4" subjects_affected="4" subjects_at_risk="33"/>
                <counts group_id="E7" events="7" subjects_affected="7" subjects_at_risk="31"/>
                <counts group_id="E8" events="25" subjects_affected="25" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Hiccups</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="2" subjects_affected="2" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Pneumothorax</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Productive cough</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="2" subjects_affected="2" subjects_at_risk="33"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Pulmonary hypertension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Pulmonary thrombosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Rhinorrhoea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E7" events="2" subjects_affected="2" subjects_at_risk="31"/>
                <counts group_id="E8" events="4" subjects_affected="4" subjects_at_risk="244"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Blister</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Dermatitis acneiform</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Eczema</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="3" subjects_affected="3" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Erythema</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="2" subjects_affected="2" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Palmar-plantar erythrodysaesthesia syndrome</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E6" events="6" subjects_affected="6" subjects_at_risk="33"/>
                <counts group_id="E7" events="4" subjects_affected="4" subjects_at_risk="31"/>
                <counts group_id="E8" events="28" subjects_affected="28" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Pruritus generalised</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="5" subjects_affected="5" subjects_at_risk="30"/>
                <counts group_id="E6" events="6" subjects_affected="6" subjects_at_risk="33"/>
                <counts group_id="E7" events="6" subjects_affected="6" subjects_at_risk="31"/>
                <counts group_id="E8" events="30" subjects_affected="30" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E6" events="2" subjects_affected="2" subjects_at_risk="33"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Seborrhoeic dermatitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Skin exfoliation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Urticaria</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="4" subjects_affected="4" subjects_at_risk="31"/>
                <counts group_id="E8" events="6" subjects_affected="6" subjects_at_risk="244"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hot flush</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Jugular vein thrombosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
              <event>
                <sub_title>Phlebitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="244"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Alison Li</name_or_title>
      <organization>Jiangsu Hansoh Pharmaceutical Group Co., Ltd.</organization>
      <phone>86-21-51211850</phone>
      <email>Alison.li@hspharm.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT02981108
org study id: HS-10296-12-01
nct id: NCT02981108
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
This is a Phase 1/2, open-label, multicenter study of HS-10296 with dose escalation, dose
      expansion and extension cohorts in locally advanced or metastatic non-small-cell lung cancer
      (NSCLC) patients who have progressed following prior therapy with an epidermal growth factor
      receptor(EGFR) tyrosine kinase inhibitor (TKI) agent. The study is designed to evaluate
      safety, tolerability, pharmacokinetics (PK), and anti-tumor activity of once-daily and orally
      (PO) administered HS-10296. The overall study design is shown in the flow chart below, which
      consists of 3 phases: dose escalation, dose expansion and extension cohort.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants With Dose Limiting Toxicity (DLT) Phase I Part
time frame: 21 days
description: DLT is defined as one of the following HS-10296 related adverse event (AE) ：(1) Hematological toxicity ≥ Grade 4 neutropenia lasting more than 5 days, febrile neutropenia of any duration (absolute neutrophil count [ANC]) < 1.0 × 109/L and fever ≥ 38.5°C), Grade 4 thrombocytopenia, Grade 3 thrombocytopenia with bleeding, any requirement for platelet transfusion, Grade 4 anemia (unexplained by underlying disease); (2)Non-hematological toxicity ≥ CTCAE Grade 3 including Infection (including febrile neutropenia), confirmed prolongation of QT interval corrected with Fridericia's (QTcF) (> 500 ms absolute or > 60 ms above Baseline) and cardiac toxicity greater than Grade 3；(3)Any other toxicity that is greater than that at Baseline (clinically significant and/or unacceptable, and judged to be a DLT by the SRC), meets a protocol-defined stopping criteria (i.e., confirmed corneal ulceration), or results in a disruption of dosing schedule of more than 7 days.
measure: Overall Response Rate (ORR) Phase II Part
time frame: From the date of first dose until the date of disease progression or withdrawal from study, approximately 15 months
description: ORR is defined as the percentage of patients with a complete response (CR) or partial response (PR) that was confirmed at a subsequent scan at least 6 weeks later, as assessed according to RECIST (Response Evaluation Criteria In Solid Tumors Criteria) version 1.1 for target lesions and assessed by CT/MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
measure: Incidence and Severity of Adverse Events (AEs) Phase I Part
time frame: From the screening period to 28 days after treatment completion, approximately 16 months
description: An AE is the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition can be symptoms (e.g., nausea, chest pain), signs (e.g., tachycardia, enlarged liver), or the abnormal results of an investigation (e.g., laboratory findings, ECG). Any deterioration of the disease under study and associated symptoms or findings should not be regarded as an AE as far as the deterioration can be anticipated. The AE was graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0.
measure: Area Under the Plasma Concentration Versus Time Curve (AUC) of HS-10296 and HAS-719 From Zero to the 24-Hour Sampling Time (AUC0-24) After Single Dose of HS-10296
time frame: From pre-dose to 24 hours after single dose on Day 1 of Cycle 0
description: Area under the plasma concentration versus time curve from time zero to the 24-hour sampling time at which the concentration was at or above the lower limit of quantification (LLQ). AUC0-24 was to be calculated according to the mixed log-linear trapezoidal rule.
measure: Elimination Half-life(T1/2) of HS-10296 and HAS-719
time frame: From pre-dose to 120 hours after single dose on Day 1 of Cycle 0
description: Elimination half-life is the time measured for the concentration to decrease by one half. Half-life calculated by natural log 2 divided by λz.
measure: Css Max of HS-10296 and HAS-719 After Multiple Dose
time frame: From pre-dose to 21 days after multiple dose on Day 1 of Cycle 2
description: Observed maximum plasma concentration (Css max) after multiple dose of HS-10296 and HAS-719
measure: AUCss of HS-10296 and HAS-719 After Multiple Dose of HS-10296
time frame: From pre-dose to 21 days after multiple dose on Day 1 of Cycle 2
description: Area Under the Plasma Concentration Versus Time Curve at steady state (AUCss) of HS-10296 and HAS-719 after multiple dose of HS-10296
measure: Overall Response Rate (Phase I Part)
time frame: From the date of first dose until the date of disease progression or withdrawal from study, approximately 15 months
description: ORR is defined as the percentage of patients with a complete response (CR) or partial response (PR) that was confirmed at a subsequent scan at least 6 weeks later, as assessed according to RECIST (Response Evaluation Criteria In Solid Tumors Criteria) version 1.1 for target lesions and assessed by CT/MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
measure: Progression-free Survival (PFS)
time frame: From the date of enrollment until the date of disease progression or death from any cause, approximately 15 months
description: The PFS is defined as the time from date of first dosing until the date of objective disease progression as defined by Response Evaluation Criteria in Solid Tumors （RECIST） v1.1 or death (by any cause in the absence of progression) regardless of whether the patients withdraws from HS-10296 therapy or receives another anti-cancer therapy prior to progression. Progression is defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
measure: Disease Control Rate (DCR)
time frame: From the date of first dose until the date of disease progression or withdrawal from study, approximately 15 months
description: Objective response is assessed by RECIST 1.1 thereby to evaluate disease control rate. The DCR is defined as the proportion of patients with a best overall response of CR, PR, or SD (stable disease).
measure: Overall Survival (OS) Phase II Part
time frame: From the date of enrollment until the date of death from any cause, approximately 48 months
description: Overall survival will be assessed based on the date of first dose and survival status at the time of analysis. Overall survival is defined as the time from date of first dose until the documentation of death from any cause.
measure: Depth of Response (DepOR)
time frame: From the date of enrollment until the date of disease progression or death, approximately 15 months
description: Depth of Response (DepOR) Only in part II dose-extention phase. DepOR is defined as the percentage change in tumor size, based on longest diameter or reconstructed volume, observed at the lowest point compared with baseline.
measure: Duration of Response (DoR)
time frame: From the date of enrollment until the date of disease progression or death, approximately 18 months
description: Duration of response (DoR) is defined as the time from the date of first documented response until the date of documented progression or death in the absence of disease progression. The end of response should coincide with the date of progression or death from any cause used for the PFS endpoint. The time of the initial response will be defined as the latest of the dates contributing towards the first visit response of PR or CR. If a patient does not progress following a response, then DoR will be used as the PFS censoring time.
measure: Incidence and Severity of AEs Phase II Part
time frame: From the screening period to 28 days after treatment completion, approximately 16 months
description: An AE is the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition can be symptoms (e.g., nausea, chest pain), signs (e.g., tachycardia, enlarged liver), or the abnormal results of an investigation (e.g., laboratory findings, ECG). Any deterioration of the disease under study and associated symptoms or findings should not be regarded as an AE as far as the deterioration can be anticipated. The AE was graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0.
arm group label: Escalation Cohort 1
arm group type: Experimental
description: Oral Once-Daily Administration of HS-10296 55mg
arm group label: Escalation Cohort 2
arm group type: Experimental
description: Oral Once-Daily Administration of HS-10296 110mg
arm group label: Escalation Cohort 3
arm group type: Experimental
description: Oral Once-Daily Administration of HS-10296 220mg
arm group label: Escalation Cohort 4
arm group type: Experimental
description: Oral Once-Daily Administration of HS-10296 260mg
arm group label: Expansion Cohort 1
arm group type: Experimental
description: Oral Once-Daily Administration of HS-10296 55mg
arm group label: Expansion Cohort 2
arm group type: Experimental
description: Oral Once-Daily Administration of HS-10296 110mg
arm group label: Expansion Cohort 3
arm group type: Experimental
description: Oral Once-Daily Administration of HS-10296 220mg
arm group label: Phase 2 Extension
arm group type: Experimental
description: Oral Once-Daily Administration of HS-10296 110mg (RP2D)
intervention type: Drug
intervention name: HS-10296
description: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.
arm group label: Escalation Cohort 1
arm group label: Escalation Cohort 2
arm group label: Escalation Cohort 3
arm group label: Escalation Cohort 4
arm group label: Expansion Cohort 1
arm group label: Expansion Cohort 2
arm group label: Expansion Cohort 3
arm group label: Phase 2 Extension
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Lung Neoplasms
mesh term: Carcinoma, Non-Small-Cell Lung
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 