{
    "info": {
        "nct_id": "NCT04366648",
        "official_title": "Study on the Safety, Tolerability and Pharmacokinetics of Single and Multiple Administration of Injectable PEG-Irinotecan (JK-1201I) in Patients with Malignant Solid Tumor",
        "inclusion_criteria": "1. 18 to 70 years of age (inclusive)；\n2. Body mass index (BMI) within the range of 19-30 (inclusive)\n3. Patient with a malignant solid tumor that has been confirmed by histopathology and/or cytology to be ineffective in conventional treatment or lack effective treatment。 Primary tumors include colorectal cancer, gastric cancer, esophageal cancer, pancreatic cancer and advanced breast cancer patients with brain metastases\n4. More than 4 weeks after the completion of previous anti-tumor therapy (including chemotherapy/radiotherapy, surgical treatment, targeted therapy, immunotherapy, Chinese herbal medicine therapy, endocrine therapy or other anti-tumor therapy), And it has recovered from the adverse reactions of previous treatments (treatment-related toxicity grade ≤1);\n5. At least one measurable or evaluable lesion was identified using RECIST 1.1;\n6. Physical state score (ECOG PS score) 0~1\n7. Estimated survival time ≥ 3 months\n8. Both standard blood tests and Blood Biochemistry tests are within normal range.\n9. All subjects and their partners have no plan to have children from screening to 6 month after the trial, and those who agree to use effective non-drug contraceptive methods during the trial period (e.g., condoms， etc.), those already have permanent contraceptive measures, such as bilateral tubal ligation, vasectomy, etc.\n10. Voluntarily participate in clinical research and sign informed consent\nHealthy volunteers allowed\nMust have minimum age of 18 Years\nMust have maximum age of 70 Years",
        "exclusion_criteria": "1. Patients with previous allergy history and known severe allergy to injectable PEG-Irinotecan or any excipient of the product;\n2. Have received HCl-Irinotecan (CPY-11) treatment in the past\n3. With active brain metastasis;\n4. Have other malignant tumors within 5 years before enrollment, except for previously treated with the purpose of radical cure such as carcinoma in situ of the cervix, squamous cell carcinoma or basal cell carcinoma\n5. Large amount of thorax and ascites that need treatment\n6. Serious cardiovascular disease, including grade II and above cardiac dysfunction (NYHA standard)\n7. Active hepatitis b (HBsAg and/or HBCAb positive, peripheral blood HBV DNA titer test ≥1×103 IU/mL, or hepatitis c patients; or testing positive for syphilis or human immunodeficiency virus (HIV);\n8. Subject is participating in other clinical studies or the presumed first time of drug administration is less than 4 weeks from the end of the previous clinical study (last administration or 5 half-lives of the previous study drug);\n9. Subjects who have been treated with anti-tumor vaccines or other anti-tumor drugs (interferon, interleukin, etc.) with immune-stimulatory effects within 28 days before the assumed first medication\n10. Subjects who had a severe infection within 4 weeks before the first medication， including but not limited to complications of infection, bacteremia, severe pneumonia and others requiring hospital stays;\n11. Patient has electrolyte disorder with clinically significance\n12. Subject has clinically severe gastrointestinal disorders, (positive fecal occult blood with severe gastrointestinal bleeding, gastrointestinal infection, obstruction or diarrhea of grade 1 or above on endoscopic examination (the number of stool increases ≥4 times per day))\n13. Patients with bleeding tendency or receiving thrombolytic or anticoagulant therapy\n14. Within 14 days before receiving the study drug treatment subject have used a strong CYP3A4 inducer (Phenytoin or Carbamazepine, Barbiturates, Rifampicin or Rifabutin, Hypericum perforatum, etc.);\n15. Within 7 days prior drug treatment, patients have used strong CYP3A4 inhibitors (Clarithromycin, Ketoconazole or Itraconazole, Indinavir, Lopinavir, Nafazodone, Nelfinavir, Ritonavir, Saquinavir, Trapavir, Voriconazole, etc.)\n16. Within 7 days before receiving study drug treatment, subject has used strong UGT1A1 inhibitors (Atazanavir, Gemfibrozil, etc.)\n17. Clear history of neuropathy or mental disorders (including epilepsy or dementia)\n18. Persons with a history of alcohol or drug abuse\n19. Pregnant or lactating women\n20. Investigator considered the subject who are not suitable to participate in this study",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "1. 18 to 70 years of age (inclusive)；",
            "criterions": [
                {
                    "exact_snippets": "18 to 70 years of age (inclusive)",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 18,
                                        "unit": "years"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 70,
                                        "unit": "years"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Body mass index (BMI) within the range of 19-30 (inclusive)",
            "criterions": [
                {
                    "exact_snippets": "Body mass index (BMI) within the range of 19-30 (inclusive)",
                    "criterion": "body mass index (BMI)",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 19,
                                        "unit": "N/A"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 30,
                                        "unit": "N/A"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Patient with a malignant solid tumor that has been confirmed by histopathology and/or cytology to be ineffective in conventional treatment or lack effective treatment。 Primary tumors include colorectal cancer, gastric cancer, esophageal cancer, pancreatic cancer and advanced breast cancer patients with brain metastases",
            "criterions": [
                {
                    "exact_snippets": "malignant solid tumor",
                    "criterion": "malignant solid tumor",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "confirmed by histopathology and/or cytology",
                    "criterion": "confirmation by histopathology and/or cytology",
                    "requirements": [
                        {
                            "requirement_type": "confirmation",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "ineffective in conventional treatment or lack effective treatment",
                    "criterion": "effectiveness of conventional treatment",
                    "requirements": [
                        {
                            "requirement_type": "effectiveness",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Primary tumors include colorectal cancer, gastric cancer, esophageal cancer, pancreatic cancer and advanced breast cancer patients with brain metastases",
                    "criterion": "primary tumor type",
                    "requirements": [
                        {
                            "requirement_type": "type",
                            "expected_value": [
                                "colorectal cancer",
                                "gastric cancer",
                                "esophageal cancer",
                                "pancreatic cancer",
                                "advanced breast cancer with brain metastases"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. More than 4 weeks after the completion of previous anti-tumor therapy (including chemotherapy/radiotherapy, surgical treatment, targeted therapy, immunotherapy, Chinese herbal medicine therapy, endocrine therapy or other anti-tumor therapy), And it has recovered from the adverse reactions of previous treatments (treatment-related toxicity grade ≤1);",
            "criterions": [
                {
                    "exact_snippets": "More than 4 weeks after the completion of previous anti-tumor therapy",
                    "criterion": "time since completion of previous anti-tumor therapy",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "it has recovered from the adverse reactions of previous treatments",
                    "criterion": "recovery from adverse reactions of previous treatments",
                    "requirements": [
                        {
                            "requirement_type": "recovery",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "treatment-related toxicity grade ≤1",
                    "criterion": "treatment-related toxicity grade",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1,
                                "unit": "grade"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. At least one measurable or evaluable lesion was identified using RECIST 1.1;",
            "criterions": [
                {
                    "exact_snippets": "At least one measurable or evaluable lesion was identified using RECIST 1.1",
                    "criterion": "lesion",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1,
                                "unit": "lesion"
                            }
                        },
                        {
                            "requirement_type": "identification_method",
                            "expected_value": "RECIST 1.1"
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Physical state score (ECOG PS score) 0~1",
            "criterions": [
                {
                    "exact_snippets": "Physical state score (ECOG PS score) 0~1",
                    "criterion": "ECOG PS score",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 0,
                                        "unit": "N/A"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 1,
                                        "unit": "N/A"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Estimated survival time ≥ 3 months",
            "criterions": [
                {
                    "exact_snippets": "Estimated survival time ≥ 3 months",
                    "criterion": "estimated survival time",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 3,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. Both standard blood tests and Blood Biochemistry tests are within normal range.",
            "criterions": [
                {
                    "exact_snippets": "standard blood tests ... within normal range",
                    "criterion": "standard blood tests",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": "normal"
                        }
                    ]
                },
                {
                    "exact_snippets": "Blood Biochemistry tests ... within normal range",
                    "criterion": "Blood Biochemistry tests",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": "normal"
                        }
                    ]
                }
            ]
        },
        {
            "line": "9. All subjects and their partners have no plan to have children from screening to 6 month after the trial, and those who agree to use effective non-drug contraceptive methods during the trial period (e.g., condoms， etc.), those already have permanent contraceptive measures, such as bilateral tubal ligation, vasectomy, etc.",
            "criterions": [
                {
                    "exact_snippets": "All subjects and their partners have no plan to have children from screening to 6 month after the trial",
                    "criterion": "plan to have children",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "those who agree to use effective non-drug contraceptive methods during the trial period (e.g., condoms， etc.)",
                    "criterion": "use of effective non-drug contraceptive methods",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "those already have permanent contraceptive measures, such as bilateral tubal ligation, vasectomy, etc.",
                    "criterion": "permanent contraceptive measures",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "10. Voluntarily participate in clinical research and sign informed consent",
            "criterions": [
                {
                    "exact_snippets": "Voluntarily participate in clinical research",
                    "criterion": "voluntary participation",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "sign informed consent",
                    "criterion": "informed consent",
                    "requirements": [
                        {
                            "requirement_type": "signed",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "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 70 Years",
            "criterions": [
                {
                    "exact_snippets": "maximum age of 70 Years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "maximum",
                            "expected_value": {
                                "operator": "<=",
                                "value": 70,
                                "unit": "Years"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "exclusion_lines": [
        {
            "line": "1. Patients with previous allergy history and known severe allergy to injectable PEG-Irinotecan or any excipient of the product;",
            "criterions": [
                {
                    "exact_snippets": "previous allergy history",
                    "criterion": "allergy history",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "known severe allergy to injectable PEG-Irinotecan",
                    "criterion": "severe allergy to injectable PEG-Irinotecan",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "known severe allergy to ... any excipient of the product",
                    "criterion": "severe allergy to any excipient of the product",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Have received HCl-Irinotecan (CPY-11) treatment in the past",
            "criterions": [
                {
                    "exact_snippets": "Have received HCl-Irinotecan (CPY-11) treatment in the past",
                    "criterion": "HCl-Irinotecan (CPY-11) treatment",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. With active brain metastasis;",
            "criterions": [
                {
                    "exact_snippets": "active brain metastasis",
                    "criterion": "brain metastasis",
                    "requirements": [
                        {
                            "requirement_type": "activity",
                            "expected_value": "active"
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Have other malignant tumors within 5 years before enrollment, except for previously treated with the purpose of radical cure such as carcinoma in situ of the cervix, squamous cell carcinoma or basal cell carcinoma",
            "criterions": [
                {
                    "exact_snippets": "Have other malignant tumors within 5 years before enrollment",
                    "criterion": "other malignant tumors",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "operator": "<=",
                                "value": 5,
                                "unit": "years"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "except for previously treated with the purpose of radical cure such as carcinoma in situ of the cervix, squamous cell carcinoma or basal cell carcinoma",
                    "criterion": "previously treated tumors",
                    "requirements": [
                        {
                            "requirement_type": "treatment purpose",
                            "expected_value": "radical cure"
                        },
                        {
                            "requirement_type": "tumor types",
                            "expected_value": [
                                "carcinoma in situ of the cervix",
                                "squamous cell carcinoma",
                                "basal cell carcinoma"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Large amount of thorax and ascites that need treatment",
            "criterions": [
                {
                    "exact_snippets": "Large amount of thorax",
                    "criterion": "thorax fluid",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": "large"
                        },
                        {
                            "requirement_type": "treatment_needed",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Large amount of ... ascites that need treatment",
                    "criterion": "ascites",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": "large"
                        },
                        {
                            "requirement_type": "treatment_needed",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Serious cardiovascular disease, including grade II and above cardiac dysfunction (NYHA standard)",
            "criterions": [
                {
                    "exact_snippets": "Serious cardiovascular disease",
                    "criterion": "cardiovascular disease",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "serious"
                        }
                    ]
                },
                {
                    "exact_snippets": "grade II and above cardiac dysfunction (NYHA standard)",
                    "criterion": "cardiac dysfunction",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "NYHA grade"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Active hepatitis b (HBsAg and/or HBCAb positive, peripheral blood HBV DNA titer test ≥1×103 IU/mL, or hepatitis c patients; or testing positive for syphilis or human immunodeficiency virus (HIV);",
            "criterions": [
                {
                    "exact_snippets": "Active hepatitis b (HBsAg and/or HBCAb positive",
                    "criterion": "hepatitis B",
                    "requirements": [
                        {
                            "requirement_type": "activity",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "peripheral blood HBV DNA titer test ≥1×103 IU/mL",
                    "criterion": "HBV DNA titer",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1000,
                                "unit": "IU/mL"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "hepatitis c patients",
                    "criterion": "hepatitis C",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "testing positive for syphilis",
                    "criterion": "syphilis",
                    "requirements": [
                        {
                            "requirement_type": "test result",
                            "expected_value": "positive"
                        }
                    ]
                },
                {
                    "exact_snippets": "testing positive for ... human immunodeficiency virus (HIV)",
                    "criterion": "HIV",
                    "requirements": [
                        {
                            "requirement_type": "test result",
                            "expected_value": "positive"
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. Subject is participating in other clinical studies or the presumed first time of drug administration is less than 4 weeks from the end of the previous clinical study (last administration or 5 half-lives of the previous study drug);",
            "criterions": [
                {
                    "exact_snippets": "Subject is participating in other clinical studies",
                    "criterion": "participation in other clinical studies",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "presumed first time of drug administration is less than 4 weeks from the end of the previous clinical study",
                    "criterion": "time since end of previous clinical study",
                    "requirements": [
                        {
                            "requirement_type": "time since end",
                            "expected_value": {
                                "operator": ">=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "5 half-lives of the previous study drug",
                    "criterion": "time since last administration of previous study drug",
                    "requirements": [
                        {
                            "requirement_type": "time since last administration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 5,
                                "unit": "half-lives"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "9. Subjects who have been treated with anti-tumor vaccines or other anti-tumor drugs (interferon, interleukin, etc.) with immune-stimulatory effects within 28 days before the assumed first medication",
            "criterions": [
                {
                    "exact_snippets": "Subjects who have been treated with anti-tumor vaccines",
                    "criterion": "treatment with anti-tumor vaccines",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": "within 28 days before the assumed first medication"
                        }
                    ]
                },
                {
                    "exact_snippets": "Subjects who have been treated with ... other anti-tumor drugs (interferon, interleukin, etc.) with immune-stimulatory effects",
                    "criterion": "treatment with other anti-tumor drugs with immune-stimulatory effects",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": "within 28 days before the assumed first medication"
                        }
                    ]
                }
            ]
        },
        {
            "line": "10. Subjects who had a severe infection within 4 weeks before the first medication， including but not limited to complications of infection, bacteremia, severe pneumonia and others requiring hospital stays;",
            "criterions": [
                {
                    "exact_snippets": "severe infection within 4 weeks before the first medication",
                    "criterion": "severe infection",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": "within 4 weeks before the first medication"
                        }
                    ]
                },
                {
                    "exact_snippets": "complications of infection",
                    "criterion": "complications of infection",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "bacteremia",
                    "criterion": "bacteremia",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "severe pneumonia",
                    "criterion": "severe pneumonia",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "requiring hospital stays",
                    "criterion": "hospital stays",
                    "requirements": [
                        {
                            "requirement_type": "necessity",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "11. Patient has electrolyte disorder with clinically significance",
            "criterions": [
                {
                    "exact_snippets": "electrolyte disorder with clinically significance",
                    "criterion": "electrolyte disorder",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "clinically significant"
                        }
                    ]
                }
            ]
        },
        {
            "line": "12. Subject has clinically severe gastrointestinal disorders, (positive fecal occult blood with severe gastrointestinal bleeding, gastrointestinal infection, obstruction or diarrhea of grade 1 or above on endoscopic examination (the number of stool increases ≥4 times per day))",
            "criterions": [
                {
                    "exact_snippets": "clinically severe gastrointestinal disorders",
                    "criterion": "gastrointestinal disorders",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "clinically severe"
                        }
                    ]
                },
                {
                    "exact_snippets": "positive fecal occult blood",
                    "criterion": "fecal occult blood",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "severe gastrointestinal bleeding",
                    "criterion": "gastrointestinal bleeding",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "severe"
                        }
                    ]
                },
                {
                    "exact_snippets": "gastrointestinal infection",
                    "criterion": "gastrointestinal infection",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "obstruction",
                    "criterion": "gastrointestinal obstruction",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "diarrhea of grade 1 or above",
                    "criterion": "diarrhea",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1,
                                "unit": "grade"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "the number of stool increases ≥4 times per day",
                    "criterion": "stool frequency",
                    "requirements": [
                        {
                            "requirement_type": "frequency",
                            "expected_value": {
                                "operator": ">=",
                                "value": 4,
                                "unit": "times per day"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "13. Patients with bleeding tendency or receiving thrombolytic or anticoagulant therapy",
            "criterions": [
                {
                    "exact_snippets": "Patients with bleeding tendency",
                    "criterion": "bleeding tendency",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "receiving thrombolytic or anticoagulant therapy",
                    "criterion": "thrombolytic or anticoagulant therapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "14. Within 14 days before receiving the study drug treatment subject have used a strong CYP3A4 inducer (Phenytoin or Carbamazepine, Barbiturates, Rifampicin or Rifabutin, Hypericum perforatum, etc.);",
            "criterions": [
                {
                    "exact_snippets": "Within 14 days before receiving the study drug treatment subject have used a strong CYP3A4 inducer",
                    "criterion": "use of strong CYP3A4 inducer",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": "within 14 days before receiving the study drug treatment"
                        },
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "15. Within 7 days prior drug treatment, patients have used strong CYP3A4 inhibitors (Clarithromycin, Ketoconazole or Itraconazole, Indinavir, Lopinavir, Nafazodone, Nelfinavir, Ritonavir, Saquinavir, Trapavir, Voriconazole, etc.)",
            "criterions": [
                {
                    "exact_snippets": "Within 7 days prior drug treatment, patients have used strong CYP3A4 inhibitors (Clarithromycin, Ketoconazole or Itraconazole, Indinavir, Lopinavir, Nafazodone, Nelfinavir, Ritonavir, Saquinavir, Trapavir, Voriconazole, etc.)",
                    "criterion": "use of strong CYP3A4 inhibitors",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": "within 7 days prior to drug treatment"
                        },
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "16. Within 7 days before receiving study drug treatment, subject has used strong UGT1A1 inhibitors (Atazanavir, Gemfibrozil, etc.)",
            "criterions": [
                {
                    "exact_snippets": "Within 7 days before receiving study drug treatment, subject has used strong UGT1A1 inhibitors",
                    "criterion": "use of strong UGT1A1 inhibitors",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": "within 7 days before receiving study drug treatment"
                        }
                    ]
                }
            ]
        },
        {
            "line": "17. Clear history of neuropathy or mental disorders (including epilepsy or dementia)",
            "criterions": [
                {
                    "exact_snippets": "Clear history of neuropathy",
                    "criterion": "neuropathy",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": "clear"
                        }
                    ]
                },
                {
                    "exact_snippets": "Clear history of ... mental disorders",
                    "criterion": "mental disorders",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": "clear"
                        }
                    ]
                },
                {
                    "exact_snippets": "mental disorders (including epilepsy or dementia)",
                    "criterion": "mental disorders",
                    "requirements": [
                        {
                            "requirement_type": "types",
                            "expected_value": [
                                "epilepsy",
                                "dementia"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "18. Persons with a history of alcohol or drug abuse",
            "criterions": [
                {
                    "exact_snippets": "history of alcohol",
                    "criterion": "alcohol abuse",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "history of ... drug abuse",
                    "criterion": "drug abuse",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "19. Pregnant or lactating women",
            "criterions": [
                {
                    "exact_snippets": "Pregnant",
                    "criterion": "pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "lactating women",
                    "criterion": "lactation",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "20. Investigator considered the subject who are not suitable to participate in this study",
            "criterions": [
                {
                    "exact_snippets": "Investigator considered the subject who are not suitable to participate",
                    "criterion": "suitability for participation",
                    "requirements": [
                        {
                            "requirement_type": "determination",
                            "expected_value": "investigator considered not suitable"
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}