{
    "info": {
        "nct_id": "NCT03117101",
        "official_title": "An Open-label, Dose-finding Phase I Study to Determine the Maximum Tolerated Dose, Recommended Dose, Pharmacokinetics, Pharmacodynamics of the Dual -VEGFR-FGFR Tyrosine Kinase Inhibitor, AL3810, Givenorally as Single Agent to Patients With Advanced Solid Tumours",
        "inclusion_criteria": "1. Chinese male or female patient aged ≥ 18 years old and ≤ 70 years old.\n2. Estimated life expectancy ≥ 12 weeks.\n3. Histologically or cytologically confirmed, locally advanced or metastatic solid tumor, refractory to standard therapy or no standard therapy available.\n4. Full recovery (to grade ≤ 1) from any prior surgical procedure(s) and from reversible side effects of prior therapy for cancer including radiation therapy, chemotherapy, small molecule therapeutics and immunotherapy.\n5. Patients should be evaluable according to RECIST criteria, version 1.1.\n6. Adequate haematological, hepatic and renal functions:\n\n   Absolute neutrophil count (ANC) ≥ 1.5x 10^9/L Platelet counts ≥ 100 x 10^9/L. Haemoglobin ≥ 9 g/dL. Creatinine clearance > 50 mL/min (assessed with MDRD formula). Proteinuria qualitative test < 1+. If proteinuria qualitative test ≥ 1+, proteinuria over 24 hours should be < 1.0 g/24hrs.\n\n   INR ≤ 1.5. AST, ALT ≤ 1.5 x Upper Limit of Normal Value (ULN) (≤ 3 x ULN in case of liver metastasis).\n\n   Bilirubin < 1.5 x ULN.\n7. Eastern Co-operative Group (ECOG) performance status ≤ 1.\n8. Ability to swallow oral capsules.\n9. Negative serum pregnancy test at screening in women of childbearing potential within 7 days prior the study drug intake.\n10. Willingness and ability to comply with study procedures.\n11. Signed written Informed Consent Form.\nHealthy volunteers allowed\nMust have minimum age of 18 Years\nMust have maximum age of 70 Years",
        "exclusion_criteria": "12. Participation in another therapeutic clinical trial at the same time or within 4 weeks prior to first AL3810 intake. In case of involvement in a non-interventional clinical trial (e.g. epidemiological study), inclusion in the present study is possible.\n13. Foreseeable poor compliance to the study procedures.\n14. Known active central nervous system (CNS) metastases not controlled by prior surgery or radiotherapy and/or low dose steroids.\n15. Active second malignancy or history of other malignancy within 2 years, with the exception of non-melanoma skin cancers or carcinoma in situ (CIS) of the breast or cervix or controlled, superficial carcinoma of the bladder.\n16. Chemotherapy including biologic/targeted therapy or immunological agents within 4 weeks or 5 half-lives of the agent, whichever the longest, before inclusion.\n17. Previous treatment with bevacizumab within 3 months before the first day of AL3810 administration.\n18. Patients who received radiotherapy within 4 weeks of starting study treatment.\n19. Major surgery within 4 weeks before first day of study drug administration.\n20. History of clinically significant or uncontrolled cardiac disease, including congestive heart failure (New York Heart Association functional classification ≥ 3), angina, myocardial infarction or ventricular arrhythmia.\n21. Significant cardiovascular disease or condition, including:\n\n    Congestive heart failure requiring therapy. Ventricular and/or supra-ventricular arrhythmia requiring therapy. Severe conduction disturbance (including QTc interval prolongation > 450 msec [corrected], history of severe arrhythmia, or history of familial arrhythmia [e.g., Wolff-Parkinson-White syndrome]).\n\n    Angina pectoris requiring therapy. Left ventricular ejection fraction (LVEF) < 50% evaluated by cardiac ultrasound (ECHO) or Multi Gated Acquisition Scan (MUGA).\n\n    Myocardial infarction (MI) within 6 months prior to administration of the first dose.\n\n    Cardiovascular disease > Class I, according to the New York Heart Association's (NYHA) Functional Criteria.\n\n    Uncontrolled arterial hypertension (defined as systolic blood pressure ≥ 140mmHg and/or diastolic blood pressure ≥ 90mmHg with optimized antihypertensive therapy or patients treated with ≥2 antihypertensive agents) or systolic blood pressure ≥ 160mmHg and/or diastolic blood pressure ≥ 100mmHg with or without antihypertensive therapy.\n22. Patients with thromboembolic events < 12 months prior to treatment start or at high risk of such events.\n23. Ongoing treatment with warfarin or other oral anticoagulant.\n24. Unavoidable concomitant treatment with any drug known for potential risk of causing Torsades de Pointes.\n25. Serum potassium (K+) levels below LLN or 3.0 mmol/L at screening.\n26. Patients who received administration of strong inhibitors of CYP2C8 and/or CYP3A4 or strong inducers of CYP3A4 within 7 days before the first dose of AL3810 or have on-going requirements for these medications (appendix 15).\n27. Significant gastrointestinal abnormalities, including ulcerative colitis, chronic diarrhoea associated with intestinal malabsorption, Crohn's disease, or decided by investigator.\n28. Known pre-existing clinically significant disorder of the hypothalamic-pituitary axis, thyroid and adrenal gland.\n29. Serious/active bacterial, viral or fungal infection (including known active human immunodeficiency virus [HIV] infection) requiring systemic treatment.\n30. Concomitant uncontrolled severe systemic disease (e.g., uncontrolled diabetes mellitus, etc.).\n31. Psychiatric disorder or altered mental status that would preclude understanding of the informed consent process and/or completion of the necessary study procedures.\n32. Known organ dysfunction which would either compromise the patient's safety or interfere with the evaluation of AL3810.\n33. Men and women of child bearing potential unable or unwilling to employ effective contraception (abstinence, barrier method with spermicide, intrauterine device, or steroidal contraceptive for women and barrier method) during the study and for 6 months thereafter.",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "1. Chinese male or female patient aged ≥ 18 years old and ≤ 70 years old.",
            "criterions": [
                {
                    "exact_snippets": "Chinese male or female patient",
                    "criterion": "ethnicity",
                    "requirements": [
                        {
                            "requirement_type": "ethnicity",
                            "expected_value": "Chinese"
                        }
                    ]
                },
                {
                    "exact_snippets": "male or female patient",
                    "criterion": "gender",
                    "requirements": [
                        {
                            "requirement_type": "gender",
                            "expected_value": [
                                "male",
                                "female"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "aged ≥ 18 years old and ≤ 70 years old",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "age",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 18,
                                        "unit": "years"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 70,
                                        "unit": "years"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Estimated life expectancy ≥ 12 weeks.",
            "criterions": [
                {
                    "exact_snippets": "Estimated life expectancy ≥ 12 weeks.",
                    "criterion": "life expectancy",
                    "requirements": [
                        {
                            "requirement_type": "N/A",
                            "expected_value": {
                                "operator": ">=",
                                "value": 12,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Histologically or cytologically confirmed, locally advanced or metastatic solid tumor, refractory to standard therapy or no standard therapy available.",
            "criterions": [
                {
                    "exact_snippets": "Histologically or cytologically confirmed",
                    "criterion": "tumor confirmation method",
                    "requirements": [
                        {
                            "requirement_type": "method",
                            "expected_value": [
                                "histologically",
                                "cytologically"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "locally advanced or metastatic solid tumor",
                    "criterion": "tumor stage",
                    "requirements": [
                        {
                            "requirement_type": "stage",
                            "expected_value": [
                                "locally advanced",
                                "metastatic"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "refractory to standard therapy",
                    "criterion": "response to standard therapy",
                    "requirements": [
                        {
                            "requirement_type": "response",
                            "expected_value": "refractory"
                        }
                    ]
                },
                {
                    "exact_snippets": "no standard therapy available",
                    "criterion": "availability of standard therapy",
                    "requirements": [
                        {
                            "requirement_type": "availability",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Full recovery (to grade ≤ 1) from any prior surgical procedure(s) and from reversible side effects of prior therapy for cancer including radiation therapy, chemotherapy, small molecule therapeutics and immunotherapy.",
            "criterions": [
                {
                    "exact_snippets": "Full recovery (to grade ≤ 1) from any prior surgical procedure(s)",
                    "criterion": "recovery from prior surgical procedures",
                    "requirements": [
                        {
                            "requirement_type": "recovery grade",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1,
                                "unit": "grade"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Full recovery (to grade ≤ 1) ... from reversible side effects of prior therapy for cancer including radiation therapy, chemotherapy, small molecule therapeutics and immunotherapy",
                    "criterion": "recovery from reversible side effects of prior cancer therapy",
                    "requirements": [
                        {
                            "requirement_type": "recovery grade",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1,
                                "unit": "grade"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Patients should be evaluable according to RECIST criteria, version 1.1.",
            "criterions": [
                {
                    "exact_snippets": "evaluable according to RECIST criteria, version 1.1.",
                    "criterion": "RECIST criteria evaluation",
                    "requirements": [
                        {
                            "requirement_type": "version",
                            "expected_value": "1.1"
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Adequate haematological, hepatic and renal functions:",
            "criterions": [
                {
                    "exact_snippets": "Adequate haematological ... functions",
                    "criterion": "haematological functions",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Adequate ... hepatic ... functions",
                    "criterion": "hepatic functions",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Adequate ... renal functions",
                    "criterion": "renal functions",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "Absolute neutrophil count (ANC) ≥ 1.5x 10^9/L Platelet counts ≥ 100 x 10^9/L. Haemoglobin ≥ 9 g/dL. Creatinine clearance > 50 mL/min (assessed with MDRD formula). Proteinuria qualitative test < 1+. If proteinuria qualitative test ≥ 1+, proteinuria over 24 hours should be < 1.0 g/24hrs.",
            "criterions": [
                {
                    "exact_snippets": "Absolute neutrophil count (ANC) ≥ 1.5x 10^9/L",
                    "criterion": "absolute neutrophil count (ANC)",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1.5,
                                "unit": "x 10^9/L"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Platelet counts ≥ 100 x 10^9/L",
                    "criterion": "platelet counts",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 100,
                                "unit": "x 10^9/L"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Haemoglobin ≥ 9 g/dL",
                    "criterion": "haemoglobin",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 9,
                                "unit": "g/dL"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Creatinine clearance > 50 mL/min (assessed with MDRD formula)",
                    "criterion": "creatinine clearance",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">",
                                "value": 50,
                                "unit": "mL/min"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Proteinuria qualitative test < 1+",
                    "criterion": "proteinuria qualitative test",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": "<",
                                "value": 1,
                                "unit": "+"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "If proteinuria qualitative test ≥ 1+, proteinuria over 24 hours should be < 1.0 g/24hrs",
                    "criterion": "proteinuria over 24 hours",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "<",
                                "value": 1.0,
                                "unit": "g/24hrs"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "INR ≤ 1.5. AST, ALT ≤ 1.5 x Upper Limit of Normal Value (ULN) (≤ 3 x ULN in case of liver metastasis).",
            "criterions": [
                {
                    "exact_snippets": "INR ≤ 1.5",
                    "criterion": "INR",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "N/A"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "AST, ALT ≤ 1.5 x Upper Limit of Normal Value (ULN)",
                    "criterion": "AST, ALT",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "x ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "AST, ALT ... ≤ 3 x ULN in case of liver metastasis",
                    "criterion": "AST, ALT in case of liver metastasis",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": "<=",
                                "value": 3,
                                "unit": "x ULN"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "Bilirubin < 1.5 x ULN.",
            "criterions": [
                {
                    "exact_snippets": "Bilirubin < 1.5 x ULN",
                    "criterion": "bilirubin level",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<",
                                "value": 1.5,
                                "unit": "x ULN"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Eastern Co-operative Group (ECOG) performance status ≤ 1.",
            "criterions": [
                {
                    "exact_snippets": "Eastern Co-operative Group (ECOG) performance status ≤ 1",
                    "criterion": "ECOG performance status",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1,
                                "unit": "N/A"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. Ability to swallow oral capsules.",
            "criterions": [
                {
                    "exact_snippets": "Ability to swallow oral capsules",
                    "criterion": "ability to swallow oral capsules",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "9. Negative serum pregnancy test at screening in women of childbearing potential within 7 days prior the study drug intake.",
            "criterions": [
                {
                    "exact_snippets": "Negative serum pregnancy test",
                    "criterion": "serum pregnancy test",
                    "requirements": [
                        {
                            "requirement_type": "result",
                            "expected_value": "negative"
                        }
                    ]
                },
                {
                    "exact_snippets": "women of childbearing potential",
                    "criterion": "childbearing potential",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "women of childbearing potential"
                        }
                    ]
                },
                {
                    "exact_snippets": "within 7 days prior the study drug intake",
                    "criterion": "timing of test",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": "within 7 days prior to study drug intake"
                        }
                    ]
                }
            ]
        },
        {
            "line": "10. Willingness and ability to comply with study procedures.",
            "criterions": [
                {
                    "exact_snippets": "Willingness and ability to comply with study procedures.",
                    "criterion": "compliance with study procedures",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "11. Signed written Informed Consent Form.",
            "criterions": [
                {
                    "exact_snippets": "Signed written Informed Consent Form",
                    "criterion": "informed consent form",
                    "requirements": [
                        {
                            "requirement_type": "signed",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "written",
                            "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": "12. Participation in another therapeutic clinical trial at the same time or within 4 weeks prior to first AL3810 intake. In case of involvement in a non-interventional clinical trial (e.g. epidemiological study), inclusion in the present study is possible.",
            "criterions": [
                {
                    "exact_snippets": "Participation in another therapeutic clinical trial at the same time or within 4 weeks prior to first AL3810 intake.",
                    "criterion": "participation in another therapeutic clinical trial",
                    "requirements": [
                        {
                            "requirement_type": "timeframe",
                            "expected_value": "at the same time or within 4 weeks prior to first AL3810 intake"
                        }
                    ]
                },
                {
                    "exact_snippets": "involvement in a non-interventional clinical trial (e.g. epidemiological study)",
                    "criterion": "involvement in a non-interventional clinical trial",
                    "requirements": [
                        {
                            "requirement_type": "allowance",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "13. Foreseeable poor compliance to the study procedures.",
            "criterions": [
                {
                    "exact_snippets": "Foreseeable poor compliance to the study procedures.",
                    "criterion": "compliance to the study procedures",
                    "requirements": [
                        {
                            "requirement_type": "compliance",
                            "expected_value": "not poor"
                        }
                    ]
                }
            ]
        },
        {
            "line": "14. Known active central nervous system (CNS) metastases not controlled by prior surgery or radiotherapy and/or low dose steroids.",
            "criterions": [
                {
                    "exact_snippets": "Known active central nervous system (CNS) metastases",
                    "criterion": "central nervous system (CNS) metastases",
                    "requirements": [
                        {
                            "requirement_type": "activity",
                            "expected_value": "active"
                        }
                    ]
                },
                {
                    "exact_snippets": "not controlled by prior surgery or radiotherapy and/or low dose steroids",
                    "criterion": "control of CNS metastases",
                    "requirements": [
                        {
                            "requirement_type": "control method",
                            "expected_value": [
                                "prior surgery",
                                "radiotherapy",
                                "low dose steroids"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "15. Active second malignancy or history of other malignancy within 2 years, with the exception of non-melanoma skin cancers or carcinoma in situ (CIS) of the breast or cervix or controlled, superficial carcinoma of the bladder.",
            "criterions": [
                {
                    "exact_snippets": "Active second malignancy",
                    "criterion": "second malignancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "history of other malignancy within 2 years",
                    "criterion": "history of other malignancy",
                    "requirements": [
                        {
                            "requirement_type": "time since diagnosis",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 2,
                                        "unit": "years"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "with the exception of non-melanoma skin cancers",
                    "criterion": "non-melanoma skin cancers",
                    "requirements": [
                        {
                            "requirement_type": "exception",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "with the exception of ... carcinoma in situ (CIS) of the breast or cervix",
                    "criterion": "carcinoma in situ (CIS) of the breast or cervix",
                    "requirements": [
                        {
                            "requirement_type": "exception",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "with the exception of ... controlled, superficial carcinoma of the bladder",
                    "criterion": "controlled, superficial carcinoma of the bladder",
                    "requirements": [
                        {
                            "requirement_type": "exception",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "16. Chemotherapy including biologic/targeted therapy or immunological agents within 4 weeks or 5 half-lives of the agent, whichever the longest, before inclusion.",
            "criterions": [
                {
                    "exact_snippets": "Chemotherapy including biologic/targeted therapy or immunological agents within 4 weeks or 5 half-lives of the agent, whichever the longest, before inclusion.",
                    "criterion": "chemotherapy",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 4,
                                        "unit": "weeks"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "biologic/targeted therapy or immunological agents within 4 weeks or 5 half-lives of the agent, whichever the longest, before inclusion.",
                    "criterion": "biologic/targeted therapy or immunological agents",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": "4 weeks or 5 half-lives of the agent, whichever the longest"
                        }
                    ]
                }
            ]
        },
        {
            "line": "17. Previous treatment with bevacizumab within 3 months before the first day of AL3810 administration.",
            "criterions": [
                {
                    "exact_snippets": "Previous treatment with bevacizumab within 3 months before the first day of AL3810 administration.",
                    "criterion": "previous treatment with bevacizumab",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "operator": "<=",
                                "value": 3,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "18. Patients who received radiotherapy within 4 weeks of starting study treatment.",
            "criterions": [
                {
                    "exact_snippets": "received radiotherapy within 4 weeks of starting study treatment",
                    "criterion": "radiotherapy",
                    "requirements": [
                        {
                            "requirement_type": "time since treatment",
                            "expected_value": {
                                "operator": "<=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "19. Major surgery within 4 weeks before first day of study drug administration.",
            "criterions": [
                {
                    "exact_snippets": "Major surgery within 4 weeks before first day of study drug administration.",
                    "criterion": "major surgery",
                    "requirements": [
                        {
                            "requirement_type": "time since surgery",
                            "expected_value": {
                                "operator": "<",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "20. History of clinically significant or uncontrolled cardiac disease, including congestive heart failure (New York Heart Association functional classification ≥ 3), angina, myocardial infarction or ventricular arrhythmia.",
            "criterions": [
                {
                    "exact_snippets": "clinically significant or uncontrolled cardiac disease",
                    "criterion": "cardiac disease",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "clinically significant or uncontrolled"
                        }
                    ]
                },
                {
                    "exact_snippets": "congestive heart failure (New York Heart Association functional classification ≥ 3)",
                    "criterion": "congestive heart failure",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 3,
                                "unit": "New York Heart Association functional classification"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "angina",
                    "criterion": "angina",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "myocardial infarction",
                    "criterion": "myocardial infarction",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "ventricular arrhythmia",
                    "criterion": "ventricular arrhythmia",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "21. Significant cardiovascular disease or condition, including:",
            "criterions": [
                {
                    "exact_snippets": "Significant cardiovascular disease or condition",
                    "criterion": "cardiovascular disease or condition",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "significant"
                        }
                    ]
                }
            ]
        },
        {
            "line": "Congestive heart failure requiring therapy. Ventricular and/or supra-ventricular arrhythmia requiring therapy. Severe conduction disturbance (including QTc interval prolongation > 450 msec [corrected], history of severe arrhythmia, or history of familial arrhythmia [e.g., Wolff-Parkinson-White syndrome]).",
            "criterions": [
                {
                    "exact_snippets": "Congestive heart failure requiring therapy.",
                    "criterion": "congestive heart failure",
                    "requirements": [
                        {
                            "requirement_type": "therapy requirement",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Ventricular and/or supra-ventricular arrhythmia requiring therapy.",
                    "criterion": "ventricular and/or supra-ventricular arrhythmia",
                    "requirements": [
                        {
                            "requirement_type": "therapy requirement",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Severe conduction disturbance (including QTc interval prolongation > 450 msec [corrected]",
                    "criterion": "QTc interval",
                    "requirements": [
                        {
                            "requirement_type": "prolongation",
                            "expected_value": {
                                "operator": ">",
                                "value": 450,
                                "unit": "msec"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "history of severe arrhythmia",
                    "criterion": "history of severe arrhythmia",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "history of familial arrhythmia [e.g., Wolff-Parkinson-White syndrome]",
                    "criterion": "history of familial arrhythmia",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "Angina pectoris requiring therapy. Left ventricular ejection fraction (LVEF) < 50% evaluated by cardiac ultrasound (ECHO) or Multi Gated Acquisition Scan (MUGA).",
            "criterions": [
                {
                    "exact_snippets": "Angina pectoris requiring therapy.",
                    "criterion": "angina pectoris",
                    "requirements": [
                        {
                            "requirement_type": "therapy requirement",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Left ventricular ejection fraction (LVEF) < 50%",
                    "criterion": "left ventricular ejection fraction (LVEF)",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": "<",
                                "value": 50,
                                "unit": "%"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "Myocardial infarction (MI) within 6 months prior to administration of the first dose.",
            "criterions": [
                {
                    "exact_snippets": "Myocardial infarction (MI) within 6 months prior to administration of the first dose.",
                    "criterion": "myocardial infarction",
                    "requirements": [
                        {
                            "requirement_type": "time since occurrence",
                            "expected_value": {
                                "operator": "<=",
                                "value": 6,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "Cardiovascular disease > Class I, according to the New York Heart Association's (NYHA) Functional Criteria.",
            "criterions": [
                {
                    "exact_snippets": "Cardiovascular disease > Class I, according to the New York Heart Association's (NYHA) Functional Criteria.",
                    "criterion": "cardiovascular disease",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">",
                                "value": 1,
                                "unit": "NYHA Class"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "Uncontrolled arterial hypertension (defined as systolic blood pressure ≥ 140mmHg and/or diastolic blood pressure ≥ 90mmHg with optimized antihypertensive therapy or patients treated with ≥2 antihypertensive agents) or systolic blood pressure ≥ 160mmHg and/or diastolic blood pressure ≥ 100mmHg with or without antihypertensive therapy.",
            "criterions": [
                {
                    "exact_snippets": "Uncontrolled arterial hypertension",
                    "criterion": "arterial hypertension",
                    "requirements": [
                        {
                            "requirement_type": "control status",
                            "expected_value": "uncontrolled"
                        }
                    ]
                },
                {
                    "exact_snippets": "systolic blood pressure ≥ 140mmHg",
                    "criterion": "systolic blood pressure",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">=",
                                "value": 140,
                                "unit": "mmHg"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "diastolic blood pressure ≥ 90mmHg",
                    "criterion": "diastolic blood pressure",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">=",
                                "value": 90,
                                "unit": "mmHg"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "optimized antihypertensive therapy",
                    "criterion": "antihypertensive therapy",
                    "requirements": [
                        {
                            "requirement_type": "optimization",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "patients treated with ≥2 antihypertensive agents",
                    "criterion": "antihypertensive agents",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "agents"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "systolic blood pressure ≥ 160mmHg",
                    "criterion": "systolic blood pressure",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">=",
                                "value": 160,
                                "unit": "mmHg"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "diastolic blood pressure ≥ 100mmHg",
                    "criterion": "diastolic blood pressure",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">=",
                                "value": 100,
                                "unit": "mmHg"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "with or without antihypertensive therapy",
                    "criterion": "antihypertensive therapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": "with or without"
                        }
                    ]
                }
            ]
        },
        {
            "line": "22. Patients with thromboembolic events < 12 months prior to treatment start or at high risk of such events.",
            "criterions": [
                {
                    "exact_snippets": "thromboembolic events < 12 months prior to treatment start",
                    "criterion": "thromboembolic events",
                    "requirements": [
                        {
                            "requirement_type": "time since event",
                            "expected_value": {
                                "operator": "<",
                                "value": 12,
                                "unit": "months"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "high risk of such events",
                    "criterion": "risk of thromboembolic events",
                    "requirements": [
                        {
                            "requirement_type": "risk level",
                            "expected_value": "high"
                        }
                    ]
                }
            ]
        },
        {
            "line": "23. Ongoing treatment with warfarin or other oral anticoagulant.",
            "criterions": [
                {
                    "exact_snippets": "Ongoing treatment with warfarin",
                    "criterion": "warfarin treatment",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Ongoing treatment with ... other oral anticoagulant",
                    "criterion": "oral anticoagulant treatment",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "24. Unavoidable concomitant treatment with any drug known for potential risk of causing Torsades de Pointes.",
            "criterions": [
                {
                    "exact_snippets": "Unavoidable concomitant treatment with any drug known for potential risk of causing Torsades de Pointes",
                    "criterion": "concomitant treatment with drug causing Torsades de Pointes",
                    "requirements": [
                        {
                            "requirement_type": "unavoidability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "25. Serum potassium (K+) levels below LLN or 3.0 mmol/L at screening.",
            "criterions": [
                {
                    "exact_snippets": "Serum potassium (K+) levels below LLN or 3.0 mmol/L",
                    "criterion": "serum potassium levels",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<",
                                        "value": 3.0,
                                        "unit": "mmol/L"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "26. Patients who received administration of strong inhibitors of CYP2C8 and/or CYP3A4 or strong inducers of CYP3A4 within 7 days before the first dose of AL3810 or have on-going requirements for these medications (appendix 15).",
            "criterions": [
                {
                    "exact_snippets": "Patients who received administration of strong inhibitors of CYP2C8",
                    "criterion": "administration of strong inhibitors of CYP2C8",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": "within 7 days before the first dose of AL3810"
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients who received administration of ... strong inducers of CYP3A4",
                    "criterion": "administration of strong inducers of CYP3A4",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": "within 7 days before the first dose of AL3810"
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients who ... have on-going requirements for these medications",
                    "criterion": "on-going requirements for strong inhibitors of CYP2C8 and/or CYP3A4 or strong inducers of CYP3A4",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "27. Significant gastrointestinal abnormalities, including ulcerative colitis, chronic diarrhoea associated with intestinal malabsorption, Crohn's disease, or decided by investigator.",
            "criterions": [
                {
                    "exact_snippets": "Significant gastrointestinal abnormalities, including ulcerative colitis",
                    "criterion": "ulcerative colitis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Significant gastrointestinal abnormalities, including ... chronic diarrhoea associated with intestinal malabsorption",
                    "criterion": "chronic diarrhoea associated with intestinal malabsorption",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Significant gastrointestinal abnormalities, including ... Crohn's disease",
                    "criterion": "Crohn's disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Significant gastrointestinal abnormalities, including ... decided by investigator",
                    "criterion": "gastrointestinal abnormalities",
                    "requirements": [
                        {
                            "requirement_type": "significance",
                            "expected_value": "decided by investigator"
                        }
                    ]
                }
            ]
        },
        {
            "line": "28. Known pre-existing clinically significant disorder of the hypothalamic-pituitary axis, thyroid and adrenal gland.",
            "criterions": [
                {
                    "exact_snippets": "Known pre-existing clinically significant disorder of the hypothalamic-pituitary axis",
                    "criterion": "hypothalamic-pituitary axis disorder",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Known pre-existing clinically significant disorder of the ... thyroid",
                    "criterion": "thyroid disorder",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Known pre-existing clinically significant disorder of the ... adrenal gland",
                    "criterion": "adrenal gland disorder",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "29. Serious/active bacterial, viral or fungal infection (including known active human immunodeficiency virus [HIV] infection) requiring systemic treatment.",
            "criterions": [
                {
                    "exact_snippets": "Serious/active bacterial, viral or fungal infection",
                    "criterion": "bacterial, viral or fungal infection",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "serious/active"
                        }
                    ]
                },
                {
                    "exact_snippets": "known active human immunodeficiency virus [HIV] infection",
                    "criterion": "human immunodeficiency virus [HIV] infection",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "known active"
                        }
                    ]
                },
                {
                    "exact_snippets": "requiring systemic treatment",
                    "criterion": "systemic treatment",
                    "requirements": [
                        {
                            "requirement_type": "necessity",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "30. Concomitant uncontrolled severe systemic disease (e.g., uncontrolled diabetes mellitus, etc.).",
            "criterions": [
                {
                    "exact_snippets": "Concomitant uncontrolled severe systemic disease",
                    "criterion": "systemic disease",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": "uncontrolled"
                        },
                        {
                            "requirement_type": "severity",
                            "expected_value": "severe"
                        }
                    ]
                },
                {
                    "exact_snippets": "uncontrolled diabetes mellitus",
                    "criterion": "diabetes mellitus",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": "uncontrolled"
                        }
                    ]
                }
            ]
        },
        {
            "line": "31. Psychiatric disorder or altered mental status that would preclude understanding of the informed consent process and/or completion of the necessary study procedures.",
            "criterions": [
                {
                    "exact_snippets": "Psychiatric disorder",
                    "criterion": "psychiatric disorder",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "altered mental status",
                    "criterion": "altered mental status",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "32. Known organ dysfunction which would either compromise the patient's safety or interfere with the evaluation of AL3810.",
            "criterions": [
                {
                    "exact_snippets": "Known organ dysfunction",
                    "criterion": "organ dysfunction",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "33. Men and women of child bearing potential unable or unwilling to employ effective contraception (abstinence, barrier method with spermicide, intrauterine device, or steroidal contraceptive for women and barrier method) during the study and for 6 months thereafter.",
            "criterions": [
                {
                    "exact_snippets": "Men and women of child bearing potential",
                    "criterion": "child bearing potential",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "unable or unwilling to employ effective contraception (abstinence, barrier method with spermicide, intrauterine device, or steroidal contraceptive for women and barrier method) during the study and for 6 months thereafter",
                    "criterion": "use of effective contraception",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "methods",
                            "expected_value": [
                                "abstinence",
                                "barrier method with spermicide",
                                "intrauterine device",
                                "steroidal contraceptive for women",
                                "barrier method"
                            ]
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}