{
    "info": {
        "nct_id": "NCT02540291",
        "official_title": "An Open-Label Multicenter Phase 1 Study of E7046 in Subjects With Selected Advanced Malignancies",
        "inclusion_criteria": "1. Age greater than or equal to 18 years\n2. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1\n3. Life expectancy greater than or equal to 12 weeks\n4. Participants must have any of the following tumor types, confirmed by available pathology records or current biopsy, that is advanced, nonresectable, or recurrent and progressing since last antitumor therapy, and for which no alternative standard therapy exists: pancreatic adenocarcinoma, renal clear cell carcinoma, SCCHN (squamous cell carcinoma of head and neck), NSCLC (non-small cell lung cancer), colorectal cancer (CRC), hepatocellular carcinoma (HCC), ovarian serous epithelial cancer, bladder transitional cancer, cervical cancer, and triple-negative breast cancer\n5. Prior chemotherapy or immunotherapy (tumor vaccine, cytokine, or growth factor given to control the cancer) must have been completed at least 4 weeks before study drug administration, and all adverse events (AEs) have either returned to baseline or stabilized\n6. Prior definitive radiation therapy must have been completed at least 6 weeks before study drug administration and the irradiated lesions should show evidence of progression if they are intended to be considered target lesions. Prior palliative radiotherapy must be completed at least 2 weeks before study drug administration. The radiotherapy-related side effects must have resolved before the study entry. No radiopharmaceuticals (strontium, samarium) will be allowed within 8 weeks before study drug administration.\n7. Participants must have accessible tumors and consent to repeated biopsy for performance of correlative tissue studies\n8. Must have at least one measurable lesion per irRECIST (immune-related Response Evaluation Criteria Criteria in Solid Tumors):\n\n   * At least 1 lesion of greater than or equal to 10 mm in the longest diameter for a non-lymph node or greater than or equal to 15 mm in the short-axis diameter for a lymph node that is serially measurable according to irRECIST using computerized tomography/magnetic resonance imaging (CT/MRI)\n   * Lesions that have had definitive external beam radiotherapy or locoregional therapies such as radiofrequency (RF) ablation or brachytherapy must show evidence of progressive disease to be deemed a target lesion\n9. Prior treated brain or meningeal metastases must be without evidence of progression (confirmed by MRI) for at least 8 weeks and off immunosuppressive doses of systemic steroids (greater than 10 mg/day prednisone or equivalent) for at least 4 weeks before study drug administration\n10. Immunosuppressive doses of systemic medications, such as steroids or absorbed topical steroids (doses greater than 7.5 to 10 mg/day prednisone or equivalent) must be discontinued at least 2 weeks before study drug administration.\n11. Participants with prior Hepatitis B or C are eligible on the condition that participants have adequate liver function as defined by Inclusion Criterion number 16 and Exclusion Criterion number 5\n12. Left ventricular ejection fraction (LVEF) greater than 50% on echocardiography or multiple gated acquisition (MUGA) scan\n13. Adequate renal function defined as serum creatinine less than 1.5 X ULN (upper limit of normal) or use SI units or calculated creatinine clearance greater than or equal to 50 mL/min per the Cockcroft and Gault formula\n14. Adequate bone marrow function:\n\n    * Absolute neutrophil count (ANC) greater than or equal to 1500/mm3 (greater than or equal to 1.5 X 103/ul)\n    * Platelets greater than or equal to 100,000/mm3 (greater than or equal to 100 X 109/L)\n    * Hemoglobin greater than or equal to 9.0 g/dL\n15. Adequate liver function:\n\n    * Total bilirubin less than or equal to 1.5 X ULN except for unconjugated hyperbilirubinemia of Gilbert's syndrome\n    * Alkaline phosphatase, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) less than or equal to 3 X ULN (less than or equal to 5 X ULN if participant has liver metastases). If alkaline phosphatase is greater than 3 X ULN (in absence of liver metastases) or greater than 5 X ULN (in presence of liver metastases) AND the participant also is known to have bone metastases, the liver-specific alkaline phosphatase must be separated from the total and used to assess the liver function instead of total alkaline phosphatase\n16. Adequate blood coagulation function as evidenced by an International Normalized Ratio (INR) less than or equal to 1.5\n17. Willing and able to comply with all aspects of the protocol\n18. Provide written informed consent prior to any study-specific screening procedures\n19. Females must not be lactating or pregnant at screening or baseline (as documented by a negative beta-human chorionic gonadotropin [B-hCG] test with a minimum sensitivity of 25 IU/L or equivalent units of B-hCG). A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug. All females will be considered to be of childbearing potential unless they are postmenopausal (at least 12 months consecutive amenorrheic, in the appropriate age group, and without other known or suspected cause) or have been sterilized surgically (ie, bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing). Females of childbearing potential must not have had unprotected sexual intercourse within 30 days prior to study entry and must agree to use a highly effective method of contraception, from the last menstrual period prior to initiation of treatment, during Treatment Cycles, and for 30 days after the final dose of study treatment, and have a male partner who uses a condom. Highly effective contraception includes:\n\n    * Double barrier methods of contraception such as condom plus diaphragm or cervical/vault cap with spermicide\n    * Placement of an intrauterine device\n    * Established hormonal contraceptive methods: oral, injectable, or implant. Females who are using hormonal contraceptives must have been on a stable dose of the same hormonal contraceptive product for at least 4 weeks prior to dosing and must continue to use the same contraceptive during the study and for 30 days after study drug discontinuation. Female participants exempt from this requirement are participants who practice total abstinence or have a male partner who is vasectomized with confirmed azoospermia. If currently abstinent, the participant must agree to use a double barrier method as described above if they become sexually active during the Treatment Cycles, and for 30 days after study drug discontinuation\n20. Male participants must have had a successful vasectomy (confirmed azoospermia) or they and their female partners must meet the criteria above (ie, not of childbearing potential or practicing highly effective contraception and use a condom throughout the study period and for 90 days after study drug discontinuation)\nHealthy volunteers allowed\nMust have minimum age of 18 Years\nMust have maximum age of 99 Years",
        "exclusion_criteria": "1. Other malignancy active within the previous 2 years except for basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix or breast that has completed curative therapy\n2. Participants with any active autoimmune disease (Appendix 2) or a documented history of autoimmune disease, poorly controlled asthma or history of syndrome that required systemic steroids or immunosuppressive medications, except for participants with vitiligo or resolved childhood asthma/atopy. Participants with asthma who require intermittent use of bronchodilators (such as albuterol) will not be excluded from this study.\n3. Participants with inflammatory bowel disease\n4. Known human immunodeficiency virus (HIV) infection\n5. Active infection requiring therapy, including known positive tests for Hepatitis B surface antigen and hepatitis C virus (HCV) RNA\n6. Major surgery within 4 weeks before the first dose of study drug\n7. Concurrent medical condition requiring the use of immunosuppressive medications, or immunosuppressive doses of systemic or absorbable topical corticosteroids except inhaled or intranasal corticosteroids (with minimal systemic absorption)\n8. Inability to take oral medication, or malabsorption syndrome or any other uncontrolled gastrointestinal condition (eg, nausea, diarrhea, or vomiting) that might impair the bioavailability of E7046\n9. Any other major illness that, in the investigator's judgment, will substantially increase the risk associated with the participant's participation in this study\n10. Use of other investigational drugs within 28 days or at least 5 half-lives (whichever is shorter) before study drug administration\n11. Prior exposure to drugs that are antagonists of colony stimulating factor-1 receptor (CSF1R) like but not limited to emactuzumab (RG7155) (Roche), PLX3397 (Plexicon), and JNJ40346627 (J & J)\n12. Use of any live vaccines (eg, intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella, and TY21a typhoid vaccines) within 28 days\n13. Prolongation of corrected QT [QTcF (Fridericia's corrected QT interval)] interval to greater than 480 msec when electrolytes balance is normal\n14. Significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II, uncontrolled arterial hypertension, unstable angina, myocardial infarction, or stroke within 6 months of the first dose of study drug; or cardiac arrhythmia requiring medical treatment (including oral anticoagulation)\n15. Females who are pregnant (positive urine test) or breastfeeding\n16. Any history of a medical condition or a concomitant medical condition that, in the opinion of the investigator, would compromise the subject's ability to safely complete the study",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "1. Age greater than or equal to 18 years",
            "criterions": [
                {
                    "exact_snippets": "Age greater than or equal to 18 years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1",
            "criterions": [
                {
                    "exact_snippets": "Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1",
                    "criterion": "ECOG Performance Status",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": [
                                "0",
                                "1"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Life expectancy greater than or equal to 12 weeks",
            "criterions": [
                {
                    "exact_snippets": "Life expectancy greater than or equal to 12 weeks",
                    "criterion": "life expectancy",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 12,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Participants must have any of the following tumor types, confirmed by available pathology records or current biopsy, that is advanced, nonresectable, or recurrent and progressing since last antitumor therapy, and for which no alternative standard therapy exists: pancreatic adenocarcinoma, renal clear cell carcinoma, SCCHN (squamous cell carcinoma of head and neck), NSCLC (non-small cell lung cancer), colorectal cancer (CRC), hepatocellular carcinoma (HCC), ovarian serous epithelial cancer, bladder transitional cancer, cervical cancer, and triple-negative breast cancer",
            "criterions": [
                {
                    "exact_snippets": "Participants must have any of the following tumor types",
                    "criterion": "tumor type",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": [
                                "pancreatic adenocarcinoma",
                                "renal clear cell carcinoma",
                                "SCCHN",
                                "NSCLC",
                                "colorectal cancer",
                                "hepatocellular carcinoma",
                                "ovarian serous epithelial cancer",
                                "bladder transitional cancer",
                                "cervical cancer",
                                "triple-negative breast cancer"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "confirmed by available pathology records or current biopsy",
                    "criterion": "confirmation of tumor type",
                    "requirements": [
                        {
                            "requirement_type": "method",
                            "expected_value": [
                                "available pathology records",
                                "current biopsy"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "that is advanced, nonresectable, or recurrent and progressing since last antitumor therapy",
                    "criterion": "tumor status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": [
                                "advanced",
                                "nonresectable",
                                "recurrent and progressing since last antitumor therapy"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "for which no alternative standard therapy exists",
                    "criterion": "availability of alternative standard therapy",
                    "requirements": [
                        {
                            "requirement_type": "availability",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Prior chemotherapy or immunotherapy (tumor vaccine, cytokine, or growth factor given to control the cancer) must have been completed at least 4 weeks before study drug administration, and all adverse events (AEs) have either returned to baseline or stabilized",
            "criterions": [
                {
                    "exact_snippets": "Prior chemotherapy or immunotherapy ... must have been completed at least 4 weeks before study drug administration",
                    "criterion": "prior chemotherapy or immunotherapy",
                    "requirements": [
                        {
                            "requirement_type": "completion time",
                            "expected_value": {
                                "operator": ">=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "all adverse events (AEs) have either returned to baseline or stabilized",
                    "criterion": "adverse events (AEs)",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": [
                                "returned to baseline",
                                "stabilized"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Prior definitive radiation therapy must have been completed at least 6 weeks before study drug administration and the irradiated lesions should show evidence of progression if they are intended to be considered target lesions. Prior palliative radiotherapy must be completed at least 2 weeks before study drug administration. The radiotherapy-related side effects must have resolved before the study entry. No radiopharmaceuticals (strontium, samarium) will be allowed within 8 weeks before study drug administration.",
            "criterions": [
                {
                    "exact_snippets": "Prior definitive radiation therapy must have been completed at least 6 weeks before study drug administration",
                    "criterion": "prior definitive radiation therapy",
                    "requirements": [
                        {
                            "requirement_type": "completion time",
                            "expected_value": {
                                "operator": ">=",
                                "value": 6,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "the irradiated lesions should show evidence of progression if they are intended to be considered target lesions",
                    "criterion": "irradiated lesions",
                    "requirements": [
                        {
                            "requirement_type": "progression",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Prior palliative radiotherapy must be completed at least 2 weeks before study drug administration",
                    "criterion": "prior palliative radiotherapy",
                    "requirements": [
                        {
                            "requirement_type": "completion time",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "The radiotherapy-related side effects must have resolved before the study entry",
                    "criterion": "radiotherapy-related side effects",
                    "requirements": [
                        {
                            "requirement_type": "resolution",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "No radiopharmaceuticals (strontium, samarium) will be allowed within 8 weeks before study drug administration",
                    "criterion": "radiopharmaceuticals (strontium, samarium)",
                    "requirements": [
                        {
                            "requirement_type": "usage",
                            "expected_value": false
                        },
                        {
                            "requirement_type": "time since last use",
                            "expected_value": {
                                "operator": ">=",
                                "value": 8,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Participants must have accessible tumors and consent to repeated biopsy for performance of correlative tissue studies",
            "criterions": [
                {
                    "exact_snippets": "Participants must have accessible tumors",
                    "criterion": "tumor accessibility",
                    "requirements": [
                        {
                            "requirement_type": "accessibility",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "consent to repeated biopsy",
                    "criterion": "consent for repeated biopsy",
                    "requirements": [
                        {
                            "requirement_type": "consent",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. Must have at least one measurable lesion per irRECIST (immune-related Response Evaluation Criteria Criteria in Solid Tumors):",
            "criterions": [
                {
                    "exact_snippets": "at least one measurable lesion per irRECIST",
                    "criterion": "measurable lesion",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1,
                                "unit": "lesion"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* At least 1 lesion of greater than or equal to 10 mm in the longest diameter for a non-lymph node or greater than or equal to 15 mm in the short-axis diameter for a lymph node that is serially measurable according to irRECIST using computerized tomography/magnetic resonance imaging (CT/MRI)",
            "criterions": [
                {
                    "exact_snippets": "At least 1 lesion of greater than or equal to 10 mm in the longest diameter for a non-lymph node",
                    "criterion": "non-lymph node lesion",
                    "requirements": [
                        {
                            "requirement_type": "size",
                            "expected_value": {
                                "operator": ">=",
                                "value": 10,
                                "unit": "mm"
                            }
                        },
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1,
                                "unit": "lesion"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "greater than or equal to 15 mm in the short-axis diameter for a lymph node",
                    "criterion": "lymph node lesion",
                    "requirements": [
                        {
                            "requirement_type": "size",
                            "expected_value": {
                                "operator": ">=",
                                "value": 15,
                                "unit": "mm"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "that is serially measurable according to irRECIST using computerized tomography/magnetic resonance imaging (CT/MRI)",
                    "criterion": "lesion measurability",
                    "requirements": [
                        {
                            "requirement_type": "method",
                            "expected_value": "irRECIST using CT/MRI"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Lesions that have had definitive external beam radiotherapy or locoregional therapies such as radiofrequency (RF) ablation or brachytherapy must show evidence of progressive disease to be deemed a target lesion",
            "criterions": [
                {
                    "exact_snippets": "Lesions that have had definitive external beam radiotherapy or locoregional therapies such as radiofrequency (RF) ablation or brachytherapy",
                    "criterion": "lesions with prior treatment",
                    "requirements": [
                        {
                            "requirement_type": "treatment history",
                            "expected_value": [
                                "external beam radiotherapy",
                                "radiofrequency (RF) ablation",
                                "brachytherapy"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "must show evidence of progressive disease",
                    "criterion": "progressive disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "9. Prior treated brain or meningeal metastases must be without evidence of progression (confirmed by MRI) for at least 8 weeks and off immunosuppressive doses of systemic steroids (greater than 10 mg/day prednisone or equivalent) for at least 4 weeks before study drug administration",
            "criterions": [
                {
                    "exact_snippets": "Prior treated brain or meningeal metastases must be without evidence of progression (confirmed by MRI) for at least 8 weeks",
                    "criterion": "brain or meningeal metastases",
                    "requirements": [
                        {
                            "requirement_type": "treatment status",
                            "expected_value": "prior treated"
                        },
                        {
                            "requirement_type": "progression evidence",
                            "expected_value": false
                        },
                        {
                            "requirement_type": "confirmation method",
                            "expected_value": "MRI"
                        },
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 8,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "off immunosuppressive doses of systemic steroids (greater than 10 mg/day prednisone or equivalent) for at least 4 weeks",
                    "criterion": "systemic steroid use",
                    "requirements": [
                        {
                            "requirement_type": "dose",
                            "expected_value": {
                                "operator": "<=",
                                "value": 10,
                                "unit": "mg/day prednisone or equivalent"
                            }
                        },
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "10. Immunosuppressive doses of systemic medications, such as steroids or absorbed topical steroids (doses greater than 7.5 to 10 mg/day prednisone or equivalent) must be discontinued at least 2 weeks before study drug administration.",
            "criterions": [
                {
                    "exact_snippets": "Immunosuppressive doses of systemic medications, such as steroids or absorbed topical steroids ... must be discontinued at least 2 weeks before study drug administration.",
                    "criterion": "immunosuppressive doses of systemic medications",
                    "requirements": [
                        {
                            "requirement_type": "discontinuation",
                            "expected_value": "at least 2 weeks before study drug administration"
                        }
                    ]
                },
                {
                    "exact_snippets": "doses greater than 7.5 to 10 mg/day prednisone or equivalent",
                    "criterion": "steroid dose",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">",
                                        "value": 7.5,
                                        "unit": "mg/day prednisone or equivalent"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 10,
                                        "unit": "mg/day prednisone or equivalent"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "11. Participants with prior Hepatitis B or C are eligible on the condition that participants have adequate liver function as defined by Inclusion Criterion number 16 and Exclusion Criterion number 5",
            "criterions": [
                {
                    "exact_snippets": "prior Hepatitis B or C",
                    "criterion": "prior Hepatitis B or C",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "adequate liver function",
                    "criterion": "liver function",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "12. Left ventricular ejection fraction (LVEF) greater than 50% on echocardiography or multiple gated acquisition (MUGA) scan",
            "criterions": [
                {
                    "exact_snippets": "Left ventricular ejection fraction (LVEF) greater than 50%",
                    "criterion": "left ventricular ejection fraction (LVEF)",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">",
                                "value": 50,
                                "unit": "%"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "echocardiography or multiple gated acquisition (MUGA) scan",
                    "criterion": "imaging method for LVEF",
                    "requirements": [
                        {
                            "requirement_type": "method",
                            "expected_value": [
                                "echocardiography",
                                "multiple gated acquisition (MUGA) scan"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "13. Adequate renal function defined as serum creatinine less than 1.5 X ULN (upper limit of normal) or use SI units or calculated creatinine clearance greater than or equal to 50 mL/min per the Cockcroft and Gault formula",
            "criterions": [
                {
                    "exact_snippets": "Adequate renal function defined as serum creatinine less than 1.5 X ULN",
                    "criterion": "serum creatinine",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<",
                                "value": 1.5,
                                "unit": "X ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "calculated creatinine clearance greater than or equal to 50 mL/min per the Cockcroft and Gault formula",
                    "criterion": "creatinine clearance",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">=",
                                "value": 50,
                                "unit": "mL/min"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "14. Adequate bone marrow function:",
            "criterions": [
                {
                    "exact_snippets": "Adequate bone marrow function",
                    "criterion": "bone marrow function",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Absolute neutrophil count (ANC) greater than or equal to 1500/mm3 (greater than or equal to 1.5 X 103/ul)",
            "criterions": [
                {
                    "exact_snippets": "Absolute neutrophil count (ANC) greater than or equal to 1500/mm3 (greater than or equal to 1.5 X 103/ul)",
                    "criterion": "absolute neutrophil count (ANC)",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1500,
                                "unit": "mm3"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Platelets greater than or equal to 100,000/mm3 (greater than or equal to 100 X 109/L)",
            "criterions": [
                {
                    "exact_snippets": "Platelets greater than or equal to 100,000/mm3 (greater than or equal to 100 X 109/L)",
                    "criterion": "platelets",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 100000,
                                        "unit": "mm3"
                                    },
                                    {
                                        "operator": ">=",
                                        "value": 100,
                                        "unit": "X 109/L"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Hemoglobin greater than or equal to 9.0 g/dL",
            "criterions": [
                {
                    "exact_snippets": "Hemoglobin greater than or equal to 9.0 g/dL",
                    "criterion": "hemoglobin",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">=",
                                "value": 9.0,
                                "unit": "g/dL"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "15. Adequate liver function:",
            "criterions": [
                {
                    "exact_snippets": "Adequate liver function",
                    "criterion": "liver function",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Total bilirubin less than or equal to 1.5 X ULN except for unconjugated hyperbilirubinemia of Gilbert's syndrome",
            "criterions": [
                {
                    "exact_snippets": "Total bilirubin less than or equal to 1.5 X ULN",
                    "criterion": "total bilirubin",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "X ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "unconjugated hyperbilirubinemia of Gilbert's syndrome",
                    "criterion": "unconjugated hyperbilirubinemia of Gilbert's syndrome",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "16. Adequate blood coagulation function as evidenced by an International Normalized Ratio (INR) less than or equal to 1.5",
            "criterions": [
                {
                    "exact_snippets": "Adequate blood coagulation function ... International Normalized Ratio (INR) less than or equal to 1.5",
                    "criterion": "blood coagulation function",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "INR",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "N/A"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "17. Willing and able to comply with all aspects of the protocol",
            "criterions": [
                {
                    "exact_snippets": "Willing and able to comply with all aspects of the protocol",
                    "criterion": "compliance with protocol",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "18. Provide written informed consent prior to any study-specific screening procedures",
            "criterions": [
                {
                    "exact_snippets": "written informed consent",
                    "criterion": "informed consent",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "19. Females must not be lactating or pregnant at screening or baseline (as documented by a negative beta-human chorionic gonadotropin [B-hCG] test with a minimum sensitivity of 25 IU/L or equivalent units of B-hCG). A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug. All females will be considered to be of childbearing potential unless they are postmenopausal (at least 12 months consecutive amenorrheic, in the appropriate age group, and without other known or suspected cause) or have been sterilized surgically (ie, bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing). Females of childbearing potential must not have had unprotected sexual intercourse within 30 days prior to study entry and must agree to use a highly effective method of contraception, from the last menstrual period prior to initiation of treatment, during Treatment Cycles, and for 30 days after the final dose of study treatment, and have a male partner who uses a condom. Highly effective contraception includes:",
            "criterions": [
                {
                    "exact_snippets": "Females must not be lactating",
                    "criterion": "lactation status",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Females must not be ... pregnant at screening or baseline",
                    "criterion": "pregnancy status",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "negative beta-human chorionic gonadotropin [B-hCG] test with a minimum sensitivity of 25 IU/L",
                    "criterion": "beta-human chorionic gonadotropin (B-hCG) test",
                    "requirements": [
                        {
                            "requirement_type": "result",
                            "expected_value": "negative"
                        },
                        {
                            "requirement_type": "sensitivity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 25,
                                "unit": "IU/L"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "All females will be considered to be of childbearing potential unless they are postmenopausal",
                    "criterion": "menopausal status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "postmenopausal"
                        }
                    ]
                },
                {
                    "exact_snippets": "postmenopausal (at least 12 months consecutive amenorrheic, in the appropriate age group, and without other known or suspected cause)",
                    "criterion": "postmenopausal status",
                    "requirements": [
                        {
                            "requirement_type": "amenorrhea duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 12,
                                "unit": "months"
                            }
                        },
                        {
                            "requirement_type": "age group",
                            "expected_value": "appropriate"
                        },
                        {
                            "requirement_type": "cause",
                            "expected_value": "without other known or suspected cause"
                        }
                    ]
                },
                {
                    "exact_snippets": "have been sterilized surgically (ie, bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing)",
                    "criterion": "surgical sterilization",
                    "requirements": [
                        {
                            "requirement_type": "procedure",
                            "expected_value": [
                                "bilateral tubal ligation",
                                "total hysterectomy",
                                "bilateral oophorectomy"
                            ]
                        },
                        {
                            "requirement_type": "time since surgery",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1,
                                "unit": "month"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Females of childbearing potential must not have had unprotected sexual intercourse within 30 days prior to study entry",
                    "criterion": "unprotected sexual intercourse",
                    "requirements": [
                        {
                            "requirement_type": "time since last occurrence",
                            "expected_value": {
                                "operator": ">=",
                                "value": 30,
                                "unit": "days"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "must agree to use a highly effective method of contraception, from the last menstrual period prior to initiation of treatment, during Treatment Cycles, and for 30 days after the final dose of study treatment",
                    "criterion": "contraception use",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "duration",
                            "expected_value": "from the last menstrual period prior to initiation of treatment, during Treatment Cycles, and for 30 days after the final dose of study treatment"
                        }
                    ]
                },
                {
                    "exact_snippets": "have a male partner who uses a condom",
                    "criterion": "partner's condom use",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Double barrier methods of contraception such as condom plus diaphragm or cervical/vault cap with spermicide",
            "criterions": [
                {
                    "exact_snippets": "Double barrier methods of contraception such as condom plus diaphragm or cervical/vault cap with spermicide",
                    "criterion": "contraception method",
                    "requirements": [
                        {
                            "requirement_type": "type",
                            "expected_value": [
                                "condom plus diaphragm",
                                "cervical/vault cap with spermicide"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Placement of an intrauterine device",
            "criterions": [
                {
                    "exact_snippets": "Placement of an intrauterine device",
                    "criterion": "intrauterine device",
                    "requirements": [
                        {
                            "requirement_type": "placement",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Established hormonal contraceptive methods: oral, injectable, or implant. Females who are using hormonal contraceptives must have been on a stable dose of the same hormonal contraceptive product for at least 4 weeks prior to dosing and must continue to use the same contraceptive during the study and for 30 days after study drug discontinuation. Female participants exempt from this requirement are participants who practice total abstinence or have a male partner who is vasectomized with confirmed azoospermia. If currently abstinent, the participant must agree to use a double barrier method as described above if they become sexually active during the Treatment Cycles, and for 30 days after study drug discontinuation",
            "criterions": [
                {
                    "exact_snippets": "Established hormonal contraceptive methods: oral, injectable, or implant.",
                    "criterion": "hormonal contraceptive method",
                    "requirements": [
                        {
                            "requirement_type": "type",
                            "expected_value": [
                                "oral",
                                "injectable",
                                "implant"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "Females who are using hormonal contraceptives must have been on a stable dose of the same hormonal contraceptive product for at least 4 weeks prior to dosing",
                    "criterion": "hormonal contraceptive stability",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "must continue to use the same contraceptive during the study and for 30 days after study drug discontinuation",
                    "criterion": "hormonal contraceptive continuation",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": "during the study and for 30 days after study drug discontinuation"
                        }
                    ]
                },
                {
                    "exact_snippets": "Female participants exempt from this requirement are participants who practice total abstinence",
                    "criterion": "total abstinence",
                    "requirements": [
                        {
                            "requirement_type": "practice",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "or have a male partner who is vasectomized with confirmed azoospermia",
                    "criterion": "male partner vasectomy",
                    "requirements": [
                        {
                            "requirement_type": "azoospermia confirmation",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "If currently abstinent, the participant must agree to use a double barrier method as described above if they become sexually active during the Treatment Cycles, and for 30 days after study drug discontinuation",
                    "criterion": "double barrier method",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": "if they become sexually active during the Treatment Cycles, and for 30 days after study drug discontinuation"
                        }
                    ]
                }
            ]
        },
        {
            "line": "20. Male participants must have had a successful vasectomy (confirmed azoospermia) or they and their female partners must meet the criteria above (ie, not of childbearing potential or practicing highly effective contraception and use a condom throughout the study period and for 90 days after study drug discontinuation)",
            "criterions": [
                {
                    "exact_snippets": "Male participants must have had a successful vasectomy (confirmed azoospermia)",
                    "criterion": "vasectomy",
                    "requirements": [
                        {
                            "requirement_type": "success",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "azoospermia",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "they and their female partners must meet the criteria above (ie, not of childbearing potential",
                    "criterion": "childbearing potential",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "not of childbearing potential"
                        }
                    ]
                },
                {
                    "exact_snippets": "practicing highly effective contraception",
                    "criterion": "contraception",
                    "requirements": [
                        {
                            "requirement_type": "effectiveness",
                            "expected_value": "highly effective"
                        }
                    ]
                },
                {
                    "exact_snippets": "use a condom throughout the study period and for 90 days after study drug discontinuation",
                    "criterion": "condom use",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": "throughout the study period and for 90 days after study drug discontinuation"
                        }
                    ]
                }
            ]
        },
        {
            "line": "Healthy volunteers allowed",
            "criterions": [
                {
                    "exact_snippets": "Healthy volunteers allowed",
                    "criterion": "volunteer health status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "healthy"
                        }
                    ]
                }
            ]
        },
        {
            "line": "Must have minimum age of 18 Years",
            "criterions": [
                {
                    "exact_snippets": "minimum age of 18 Years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "Years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "Must have maximum age of 99 Years",
            "criterions": [
                {
                    "exact_snippets": "maximum age of 99 Years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "maximum",
                            "expected_value": {
                                "operator": "<=",
                                "value": 99,
                                "unit": "Years"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "exclusion_lines": [
        {
            "line": "1. Other malignancy active within the previous 2 years except for basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix or breast that has completed curative therapy",
            "criterions": [
                {
                    "exact_snippets": "Other malignancy active within the previous 2 years",
                    "criterion": "other malignancy",
                    "requirements": [
                        {
                            "requirement_type": "activity",
                            "expected_value": false
                        },
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2,
                                "unit": "years"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "except for basal or squamous cell skin cancer",
                    "criterion": "basal or squamous cell skin cancer",
                    "requirements": [
                        {
                            "requirement_type": "exception",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "except for ... superficial bladder cancer",
                    "criterion": "superficial bladder cancer",
                    "requirements": [
                        {
                            "requirement_type": "exception",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "except for ... carcinoma in situ of the cervix or breast that has completed curative therapy",
                    "criterion": "carcinoma in situ of the cervix or breast",
                    "requirements": [
                        {
                            "requirement_type": "exception",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "curative therapy completion",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Participants with any active autoimmune disease (Appendix 2) or a documented history of autoimmune disease, poorly controlled asthma or history of syndrome that required systemic steroids or immunosuppressive medications, except for participants with vitiligo or resolved childhood asthma/atopy. Participants with asthma who require intermittent use of bronchodilators (such as albuterol) will not be excluded from this study.",
            "criterions": [
                {
                    "exact_snippets": "Participants with any active autoimmune disease",
                    "criterion": "active autoimmune disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "documented history of autoimmune disease",
                    "criterion": "history of autoimmune disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "poorly controlled asthma",
                    "criterion": "poorly controlled asthma",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": "poorly controlled"
                        }
                    ]
                },
                {
                    "exact_snippets": "history of syndrome that required systemic steroids or immunosuppressive medications",
                    "criterion": "history of syndrome requiring systemic steroids or immunosuppressive medications",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Participants with asthma who require intermittent use of bronchodilators (such as albuterol) will not be excluded",
                    "criterion": "asthma requiring intermittent use of bronchodilators",
                    "requirements": [
                        {
                            "requirement_type": "exclusion",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Participants with inflammatory bowel disease",
            "criterions": [
                {
                    "exact_snippets": "Participants with inflammatory bowel disease",
                    "criterion": "inflammatory bowel disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Known human immunodeficiency virus (HIV) infection",
            "criterions": [
                {
                    "exact_snippets": "Known human immunodeficiency virus (HIV) infection",
                    "criterion": "HIV infection",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Active infection requiring therapy, including known positive tests for Hepatitis B surface antigen and hepatitis C virus (HCV) RNA",
            "criterions": [
                {
                    "exact_snippets": "Active infection requiring therapy",
                    "criterion": "active infection",
                    "requirements": [
                        {
                            "requirement_type": "therapy requirement",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "known positive tests for Hepatitis B surface antigen",
                    "criterion": "Hepatitis B surface antigen",
                    "requirements": [
                        {
                            "requirement_type": "test result",
                            "expected_value": "positive"
                        }
                    ]
                },
                {
                    "exact_snippets": "known positive tests for ... hepatitis C virus (HCV) RNA",
                    "criterion": "hepatitis C virus (HCV) RNA",
                    "requirements": [
                        {
                            "requirement_type": "test result",
                            "expected_value": "positive"
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Major surgery within 4 weeks before the first dose of study drug",
            "criterions": [
                {
                    "exact_snippets": "Major surgery within 4 weeks before the first dose of study drug",
                    "criterion": "major surgery",
                    "requirements": [
                        {
                            "requirement_type": "time since",
                            "expected_value": {
                                "operator": "<",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Concurrent medical condition requiring the use of immunosuppressive medications, or immunosuppressive doses of systemic or absorbable topical corticosteroids except inhaled or intranasal corticosteroids (with minimal systemic absorption)",
            "criterions": [
                {
                    "exact_snippets": "Concurrent medical condition requiring the use of immunosuppressive medications",
                    "criterion": "concurrent medical condition",
                    "requirements": [
                        {
                            "requirement_type": "use of immunosuppressive medications",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Concurrent medical condition requiring the use of ... immunosuppressive doses of systemic or absorbable topical corticosteroids",
                    "criterion": "concurrent medical condition",
                    "requirements": [
                        {
                            "requirement_type": "use of immunosuppressive doses of systemic or absorbable topical corticosteroids",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "except inhaled or intranasal corticosteroids (with minimal systemic absorption)",
                    "criterion": "inhaled or intranasal corticosteroids",
                    "requirements": [
                        {
                            "requirement_type": "systemic absorption",
                            "expected_value": "minimal"
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. Inability to take oral medication, or malabsorption syndrome or any other uncontrolled gastrointestinal condition (eg, nausea, diarrhea, or vomiting) that might impair the bioavailability of E7046",
            "criterions": [
                {
                    "exact_snippets": "Inability to take oral medication",
                    "criterion": "ability to take oral medication",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "malabsorption syndrome",
                    "criterion": "malabsorption syndrome",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "uncontrolled gastrointestinal condition",
                    "criterion": "uncontrolled gastrointestinal condition",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "nausea",
                    "criterion": "nausea",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "diarrhea",
                    "criterion": "diarrhea",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "vomiting",
                    "criterion": "vomiting",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "9. Any other major illness that, in the investigator's judgment, will substantially increase the risk associated with the participant's participation in this study",
            "criterions": [
                {
                    "exact_snippets": "Any other major illness ... will substantially increase the risk",
                    "criterion": "major illness",
                    "requirements": [
                        {
                            "requirement_type": "risk increase",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "10. Use of other investigational drugs within 28 days or at least 5 half-lives (whichever is shorter) before study drug administration",
            "criterions": [
                {
                    "exact_snippets": "Use of other investigational drugs within 28 days or at least 5 half-lives (whichever is shorter) before study drug administration",
                    "criterion": "use of other investigational drugs",
                    "requirements": [
                        {
                            "requirement_type": "time since last use",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 28,
                                        "unit": "days"
                                    }
                                ]
                            }
                        },
                        {
                            "requirement_type": "time since last use",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 5,
                                        "unit": "half-lives"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "11. Prior exposure to drugs that are antagonists of colony stimulating factor-1 receptor (CSF1R) like but not limited to emactuzumab (RG7155) (Roche), PLX3397 (Plexicon), and JNJ40346627 (J & J)",
            "criterions": [
                {
                    "exact_snippets": "Prior exposure to drugs that are antagonists of colony stimulating factor-1 receptor (CSF1R)",
                    "criterion": "prior exposure to CSF1R antagonists",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "12. Use of any live vaccines (eg, intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella, and TY21a typhoid vaccines) within 28 days",
            "criterions": [
                {
                    "exact_snippets": "Use of any live vaccines (eg, intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella, and TY21a typhoid vaccines) within 28 days",
                    "criterion": "use of live vaccines",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "operator": "<=",
                                "value": 28,
                                "unit": "days"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "13. Prolongation of corrected QT [QTcF (Fridericia's corrected QT interval)] interval to greater than 480 msec when electrolytes balance is normal",
            "criterions": [
                {
                    "exact_snippets": "Prolongation of corrected QT [QTcF (Fridericia's corrected QT interval)] interval to greater than 480 msec",
                    "criterion": "corrected QT interval (QTcF)",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">",
                                "value": 480,
                                "unit": "msec"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "when electrolytes balance is normal",
                    "criterion": "electrolytes balance",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "normal"
                        }
                    ]
                }
            ]
        },
        {
            "line": "14. Significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II, uncontrolled arterial hypertension, unstable angina, myocardial infarction, or stroke within 6 months of the first dose of study drug; or cardiac arrhythmia requiring medical treatment (including oral anticoagulation)",
            "criterions": [
                {
                    "exact_snippets": "history of congestive heart failure greater than New York Heart Association (NYHA) Class II",
                    "criterion": "congestive heart failure",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">",
                                "value": 2,
                                "unit": "NYHA Class"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "uncontrolled arterial hypertension",
                    "criterion": "arterial hypertension",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "unstable angina",
                    "criterion": "angina",
                    "requirements": [
                        {
                            "requirement_type": "stability",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "myocardial infarction, or stroke within 6 months of the first dose of study drug",
                    "criterion": "myocardial infarction or stroke",
                    "requirements": [
                        {
                            "requirement_type": "time since event",
                            "expected_value": {
                                "operator": "<=",
                                "value": 6,
                                "unit": "months"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "cardiac arrhythmia requiring medical treatment (including oral anticoagulation)",
                    "criterion": "cardiac arrhythmia",
                    "requirements": [
                        {
                            "requirement_type": "treatment requirement",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "15. Females who are pregnant (positive urine test) or breastfeeding",
            "criterions": [
                {
                    "exact_snippets": "Females who are pregnant (positive urine test)",
                    "criterion": "pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Females who are ... breastfeeding",
                    "criterion": "breastfeeding",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "16. Any history of a medical condition or a concomitant medical condition that, in the opinion of the investigator, would compromise the subject's ability to safely complete the study",
            "criterions": [
                {
                    "exact_snippets": "Any history of a medical condition",
                    "criterion": "history of a medical condition",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "a concomitant medical condition",
                    "criterion": "concomitant medical condition",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [
        {
            "line": "* Alkaline phosphatase, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) less than or equal to 3 X ULN (less than or equal to 5 X ULN if participant has liver metastases). If alkaline phosphatase is greater than 3 X ULN (in absence of liver metastases) or greater than 5 X ULN (in presence of liver metastases) AND the participant also is known to have bone metastases, the liver-specific alkaline phosphatase must be separated from the total and used to assess the liver function instead of total alkaline phosphatase",
            "criterions": [
                {
                    "exact_snippets": "Alkaline phosphatase ... less than or equal to 3 X ULN",
                    "criterion": "alkaline phosphatase",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 3,
                                "unit": "X ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "alanine aminotransferase (ALT) ... less than or equal to 3 X ULN",
                    "criterion": "alanine aminotransferase (ALT)",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 3,
                                "unit": "X ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "aspartate aminotransferase (AST) less than or equal to 3 X ULN",
                    "criterion": "aspartate aminotransferase (AST)",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 3,
                                "unit": "X ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "alkaline phosphatase ... less than or equal to 5 X ULN if participant has liver metastases",
                    "criterion": "alkaline phosphatase with liver metastases",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 5,
                                "unit": "X ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "alkaline phosphatase is greater than 3 X ULN (in absence of liver metastases)",
                    "criterion": "alkaline phosphatase without liver metastases",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">",
                                "value": 3,
                                "unit": "X ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "alkaline phosphatase is greater than 5 X ULN (in presence of liver metastases)",
                    "criterion": "alkaline phosphatase with liver metastases",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">",
                                "value": 5,
                                "unit": "X ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "participant also is known to have bone metastases",
                    "criterion": "bone metastases",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "liver-specific alkaline phosphatase must be separated from the total and used to assess the liver function instead of total alkaline phosphatase",
                    "criterion": "liver-specific alkaline phosphatase",
                    "requirements": [
                        {
                            "requirement_type": "usage",
                            "expected_value": "separated from total and used to assess liver function"
                        }
                    ]
                }
            ]
        }
    ],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}