{
    "info": {
        "nct_id": "NCT02867020",
        "official_title": "Phase II Randomized Study of Abiraterone Acetate Plus ADT Versus APALUTAMIDE Versus Abiraterone and APALUTAMIDE in Patients With Advanced Prostate Cancer With Non-castrate Testosterone Levels",
        "inclusion_criteria": "1. Histologically confirmed prostate adenocarcinoma;\n2. Hormone naïve patients with indication to ADT in the following settings:\n\n   * Advanced loco-regional disease not amenable to curative local therapy (surgery or radiotherapy): T category T3/4 or node positive\n   * Biochemical relapse after primary treatment (surgery or radiotherapy): patients in whom primary therapy is not appropriate or feasible with Previously treated with radical surgery and/or radiotherapy, now relapsing with at least one of the criteria: PSA >= 4 ng/ml and rising with doubling time less than 10 months. or PSA >= 20 ng/ml or N+ or M+\n   * Newly diagnosed metastatic disease: Tany Nany M+\n3. Patient is asymptomatic or moderately symptomatic regarding bone symptoms, i.e., no need for palliative radiation or radionuclide therapy;\n4. Non-castration level of testosterone > 230ng/dL (> 8 nmol/L);\n5. Baseline level of prostatespecific antigen (PSA) > 2ng/dL;\n6. ECOG performance status of 0 to 2;\n7. Adequate hematologic, hepatic and renal function:\n\n   1. hemoglobin > 10 g/dL, neutrophils > 1.5×109 / L, platelets> 100×109 / L;\n   2. total bilirubin < 1.5x upper limit of normal (ULN); alanine (ALT) and aspartate (AST) aminotransferase < 2.5 x ULN;\n   3. serum creatinine < 1.5x ULN; potassium > 3.5 mM;\n8. No previous cancer (except treated basal-cell skin cancer);\n9. Written informed consent obtained prior to any study procedure;\n10. Men age 18 years and older;\n11. Agrees to use a condom and another effective method of birth control if he is having sex with a woman of childbearing potential or agrees to use a condom if he is having sex with a woman who is pregnant.\nHealthy volunteers allowed\nMust be MALE\nMust have minimum age of 18 Years",
        "exclusion_criteria": "1. Prostate adenocarcinoma with neuroendocrine differentiation or small cell histology;\n2. Biochemical recurrence without evidence of clinical or radiological disease;\n3. Use of hormonal therapy or chemotherapy prior to randomization. Exception is courses of hormone therapy for localised disease must have been completed at least 12 months previously. It can have been given as adjuvant or neoadjuvant therapy.\n4. Prior radiation therapy for a primary tumour within the 3 months before enrollment or for the treatment of metastases;\n5. Known or suspected brain or skull metastases or leptomeningeal metastatic disease;\n6. Any concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study;\n7. Administration of an investigational therapeutic or invasive surgical procedure (not including surgical castration) within 28 days of Cycle 1 Day 1 or currently enrolled in an investigational study;\n8. Active or symptomatic viral hepatitis or chronic liver disease; ascites or bleeding disorders secondary to hepatic dysfunction;\n9. Current or prior treatment with anti-epileptic medications for the treatment of seizures;\n10. Impaired cardiac function, including any of the following:\n\n    1. Uncontrolled hypertension (systolic blood pressure ≥160 mmHg or diastolic BP ≥95 mmHg);\n    2. Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events or history of cardiac failure in the past 6 months, severe or unstable angina, or New York Heart Association (NYHA) Class II-IV heart disease;\n    3. Existing atrial fibrillation with or without pharmacotherapy. Other cardiac arrhythmia requiring pharmacotherapy;\n    4. History of seizure or condition that may predispose to seizure (including, but not limited to prior stroke, transient ischemic attack or loss of consciousness ≤1 year prior to randomization; brain arteriovenous malformation; or intracranial masses such as schwannomas and meningiomas that are causing edema or mass effect);\n11. Specific underlying conditions for oral agents. For example: impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of abiraterone or APALUTAMIDE (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)\n12. General excluded medications (e.g., relevant to cytochrome P450 interactions)\n\n    1. Use of prescription drugs within 14 days prior to dosing or over-the-counter (OTC) medication within 7 days prior to dosing;\n    2. Consumption of grapefruit product or St John's wort within 7 days prior to dosing;\n    3. G-CSF, GM-CSF, erythropoietin, etc;\n    4. Coumadin;\n    5. Drugs which may cause QT prolongation;\n    6. Known sensitivity to drugs or metabolites from similar classes;\n    7. Known or suspected contraindications or hypersensitivity to APALUTAMIDE, bicalutamide or GnRH agonists or any of the components of the formulations;\n13. Any condition or situation which, in the opinion of the investigator, would put the subject at risk, may confound study results, or interfere with the subject's participation in this study.",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "1. Histologically confirmed prostate adenocarcinoma;",
            "criterions": [
                {
                    "exact_snippets": "Histologically confirmed prostate adenocarcinoma",
                    "criterion": "prostate adenocarcinoma",
                    "requirements": [
                        {
                            "requirement_type": "confirmation method",
                            "expected_value": "histologically confirmed"
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Hormone naïve patients with indication to ADT in the following settings:",
            "criterions": [
                {
                    "exact_snippets": "Hormone naïve patients",
                    "criterion": "hormone naïve status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "naïve"
                        }
                    ]
                },
                {
                    "exact_snippets": "indication to ADT",
                    "criterion": "indication for ADT",
                    "requirements": [
                        {
                            "requirement_type": "indication",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Advanced loco-regional disease not amenable to curative local therapy (surgery or radiotherapy): T category T3/4 or node positive",
            "criterions": [
                {
                    "exact_snippets": "Advanced loco-regional disease not amenable to curative local therapy (surgery or radiotherapy)",
                    "criterion": "loco-regional disease",
                    "requirements": [
                        {
                            "requirement_type": "amenability to curative local therapy",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "T category T3/4",
                    "criterion": "T category",
                    "requirements": [
                        {
                            "requirement_type": "category",
                            "expected_value": [
                                "T3",
                                "T4"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "node positive",
                    "criterion": "node status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "positive"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Biochemical relapse after primary treatment (surgery or radiotherapy): patients in whom primary therapy is not appropriate or feasible with Previously treated with radical surgery and/or radiotherapy, now relapsing with at least one of the criteria: PSA >= 4 ng/ml and rising with doubling time less than 10 months. or PSA >= 20 ng/ml or N+ or M+",
            "criterions": [
                {
                    "exact_snippets": "Biochemical relapse after primary treatment (surgery or radiotherapy)",
                    "criterion": "biochemical relapse",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "primary therapy is not appropriate or feasible",
                    "criterion": "primary therapy appropriateness",
                    "requirements": [
                        {
                            "requirement_type": "appropriateness",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Previously treated with radical surgery and/or radiotherapy",
                    "criterion": "previous treatment",
                    "requirements": [
                        {
                            "requirement_type": "treatment type",
                            "expected_value": [
                                "radical surgery",
                                "radiotherapy"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "PSA >= 4 ng/ml and rising with doubling time less than 10 months",
                    "criterion": "PSA level",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">=",
                                "value": 4,
                                "unit": "ng/ml"
                            }
                        },
                        {
                            "requirement_type": "trend",
                            "expected_value": "rising"
                        },
                        {
                            "requirement_type": "doubling time",
                            "expected_value": {
                                "operator": "<",
                                "value": 10,
                                "unit": "months"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "PSA >= 20 ng/ml",
                    "criterion": "PSA level",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">=",
                                "value": 20,
                                "unit": "ng/ml"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "N+",
                    "criterion": "nodal involvement",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "M+",
                    "criterion": "metastatic involvement",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Newly diagnosed metastatic disease: Tany Nany M+",
            "criterions": [
                {
                    "exact_snippets": "Newly diagnosed metastatic disease",
                    "criterion": "metastatic disease",
                    "requirements": [
                        {
                            "requirement_type": "diagnosis status",
                            "expected_value": "newly diagnosed"
                        }
                    ]
                },
                {
                    "exact_snippets": "Tany",
                    "criterion": "tumor size",
                    "requirements": [
                        {
                            "requirement_type": "stage",
                            "expected_value": "any"
                        }
                    ]
                },
                {
                    "exact_snippets": "Nany",
                    "criterion": "lymph node involvement",
                    "requirements": [
                        {
                            "requirement_type": "stage",
                            "expected_value": "any"
                        }
                    ]
                },
                {
                    "exact_snippets": "M+",
                    "criterion": "distant metastasis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Patient is asymptomatic or moderately symptomatic regarding bone symptoms, i.e., no need for palliative radiation or radionuclide therapy;",
            "criterions": [
                {
                    "exact_snippets": "Patient is asymptomatic or moderately symptomatic regarding bone symptoms",
                    "criterion": "bone symptoms",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": [
                                "asymptomatic",
                                "moderately symptomatic"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "no need for palliative radiation or radionuclide therapy",
                    "criterion": "need for palliative radiation or radionuclide therapy",
                    "requirements": [
                        {
                            "requirement_type": "necessity",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Non-castration level of testosterone > 230ng/dL (> 8 nmol/L);",
            "criterions": [
                {
                    "exact_snippets": "Non-castration level of testosterone > 230ng/dL (> 8 nmol/L);",
                    "criterion": "testosterone level",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">",
                                        "value": 230,
                                        "unit": "ng/dL"
                                    },
                                    {
                                        "operator": ">",
                                        "value": 8,
                                        "unit": "nmol/L"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Baseline level of prostatespecific antigen (PSA) > 2ng/dL;",
            "criterions": [
                {
                    "exact_snippets": "Baseline level of prostatespecific antigen (PSA) > 2ng/dL",
                    "criterion": "prostatespecific antigen (PSA) level",
                    "requirements": [
                        {
                            "requirement_type": "baseline level",
                            "expected_value": {
                                "operator": ">",
                                "value": 2,
                                "unit": "ng/dL"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. ECOG performance status of 0 to 2;",
            "criterions": [
                {
                    "exact_snippets": "ECOG performance status of 0 to 2",
                    "criterion": "ECOG performance status",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 0,
                                        "unit": "N/A"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 2,
                                        "unit": "N/A"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Adequate hematologic, hepatic and renal function:",
            "criterions": [
                {
                    "exact_snippets": "Adequate hematologic ... function",
                    "criterion": "hematologic function",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Adequate ... hepatic ... function",
                    "criterion": "hepatic function",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Adequate ... renal function",
                    "criterion": "renal function",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "1. hemoglobin > 10 g/dL, neutrophils > 1.5×109 / L, platelets> 100×109 / L;",
            "criterions": [
                {
                    "exact_snippets": "hemoglobin > 10 g/dL",
                    "criterion": "hemoglobin level",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">",
                                "value": 10,
                                "unit": "g/dL"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "neutrophils > 1.5×109 / L",
                    "criterion": "neutrophil count",
                    "requirements": [
                        {
                            "requirement_type": "count",
                            "expected_value": {
                                "operator": ">",
                                "value": 1.5,
                                "unit": "×10^9/L"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "platelets> 100×109 / L",
                    "criterion": "platelet count",
                    "requirements": [
                        {
                            "requirement_type": "count",
                            "expected_value": {
                                "operator": ">",
                                "value": 100,
                                "unit": "×10^9/L"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. total bilirubin < 1.5x upper limit of normal (ULN); alanine (ALT) and aspartate (AST) aminotransferase < 2.5 x ULN;",
            "criterions": [
                {
                    "exact_snippets": "total bilirubin < 1.5x upper limit of normal (ULN)",
                    "criterion": "total bilirubin",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<",
                                "value": 1.5,
                                "unit": "x ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "alanine (ALT) and aspartate (AST) aminotransferase < 2.5 x ULN",
                    "criterion": "alanine (ALT) aminotransferase",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<",
                                "value": 2.5,
                                "unit": "x ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "alanine (ALT) and aspartate (AST) aminotransferase < 2.5 x ULN",
                    "criterion": "aspartate (AST) aminotransferase",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<",
                                "value": 2.5,
                                "unit": "x ULN"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. serum creatinine < 1.5x ULN; potassium > 3.5 mM;",
            "criterions": [
                {
                    "exact_snippets": "serum creatinine < 1.5x ULN",
                    "criterion": "serum creatinine",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<",
                                "value": 1.5,
                                "unit": "x ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "potassium > 3.5 mM",
                    "criterion": "potassium",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">",
                                "value": 3.5,
                                "unit": "mM"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. No previous cancer (except treated basal-cell skin cancer);",
            "criterions": [
                {
                    "exact_snippets": "No previous cancer (except treated basal-cell skin cancer)",
                    "criterion": "previous cancer",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "except treated basal-cell skin cancer",
                    "criterion": "treated basal-cell skin cancer",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "9. Written informed consent obtained prior to any study procedure;",
            "criterions": [
                {
                    "exact_snippets": "Written informed consent obtained",
                    "criterion": "informed consent",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "10. Men age 18 years and older;",
            "criterions": [
                {
                    "exact_snippets": "Men",
                    "criterion": "gender",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": "male"
                        }
                    ]
                },
                {
                    "exact_snippets": "age 18 years and older",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum age",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "11. Agrees to use a condom and another effective method of birth control if he is having sex with a woman of childbearing potential or agrees to use a condom if he is having sex with a woman who is pregnant.",
            "criterions": [
                {
                    "exact_snippets": "Agrees to use a condom and another effective method of birth control if he is having sex with a woman of childbearing potential",
                    "criterion": "birth control method for sex with a woman of childbearing potential",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "agrees to use a condom if he is having sex with a woman who is pregnant",
                    "criterion": "birth control method for sex with a pregnant woman",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "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 be MALE",
            "criterions": [
                {
                    "exact_snippets": "Must be MALE",
                    "criterion": "gender",
                    "requirements": [
                        {
                            "requirement_type": "expected_value",
                            "expected_value": "male"
                        }
                    ]
                }
            ]
        },
        {
            "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"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "exclusion_lines": [
        {
            "line": "1. Prostate adenocarcinoma with neuroendocrine differentiation or small cell histology;",
            "criterions": [
                {
                    "exact_snippets": "Prostate adenocarcinoma",
                    "criterion": "prostate adenocarcinoma",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "neuroendocrine differentiation",
                    "criterion": "neuroendocrine differentiation",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "small cell histology",
                    "criterion": "small cell histology",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Biochemical recurrence without evidence of clinical or radiological disease;",
            "criterions": [
                {
                    "exact_snippets": "Biochemical recurrence",
                    "criterion": "biochemical recurrence",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "without evidence of clinical or radiological disease",
                    "criterion": "clinical or radiological disease",
                    "requirements": [
                        {
                            "requirement_type": "evidence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Use of hormonal therapy or chemotherapy prior to randomization. Exception is courses of hormone therapy for localised disease must have been completed at least 12 months previously. It can have been given as adjuvant or neoadjuvant therapy.",
            "criterions": [
                {
                    "exact_snippets": "Use of hormonal therapy or chemotherapy prior to randomization.",
                    "criterion": "prior hormonal therapy or chemotherapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "courses of hormone therapy for localised disease must have been completed at least 12 months previously.",
                    "criterion": "hormone therapy for localised disease",
                    "requirements": [
                        {
                            "requirement_type": "completion time",
                            "expected_value": {
                                "operator": ">=",
                                "value": 12,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Prior radiation therapy for a primary tumour within the 3 months before enrollment or for the treatment of metastases;",
            "criterions": [
                {
                    "exact_snippets": "Prior radiation therapy for a primary tumour within the 3 months before enrollment",
                    "criterion": "prior radiation therapy for a primary tumour",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "operator": "<=",
                                "value": 3,
                                "unit": "months"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Prior radiation therapy ... for the treatment of metastases",
                    "criterion": "prior radiation therapy for metastases",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Known or suspected brain or skull metastases or leptomeningeal metastatic disease;",
            "criterions": [
                {
                    "exact_snippets": "Known or suspected brain or skull metastases",
                    "criterion": "brain or skull metastases",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "leptomeningeal metastatic disease",
                    "criterion": "leptomeningeal metastatic disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Any concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study;",
            "criterions": [
                {
                    "exact_snippets": "concurrent severe and/or uncontrolled medical conditions",
                    "criterion": "medical conditions",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "severe"
                        },
                        {
                            "requirement_type": "control",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Administration of an investigational therapeutic or invasive surgical procedure (not including surgical castration) within 28 days of Cycle 1 Day 1 or currently enrolled in an investigational study;",
            "criterions": [
                {
                    "exact_snippets": "Administration of an investigational therapeutic ... within 28 days of Cycle 1 Day 1",
                    "criterion": "investigational therapeutic administration",
                    "requirements": [
                        {
                            "requirement_type": "time since last administration",
                            "expected_value": {
                                "operator": "<=",
                                "value": 28,
                                "unit": "days"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "invasive surgical procedure (not including surgical castration) within 28 days of Cycle 1 Day 1",
                    "criterion": "invasive surgical procedure",
                    "requirements": [
                        {
                            "requirement_type": "time since last procedure",
                            "expected_value": {
                                "operator": "<=",
                                "value": 28,
                                "unit": "days"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "currently enrolled in an investigational study",
                    "criterion": "enrollment in investigational study",
                    "requirements": [
                        {
                            "requirement_type": "enrollment status",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. Active or symptomatic viral hepatitis or chronic liver disease; ascites or bleeding disorders secondary to hepatic dysfunction;",
            "criterions": [
                {
                    "exact_snippets": "Active or symptomatic viral hepatitis",
                    "criterion": "viral hepatitis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "chronic liver disease",
                    "criterion": "chronic liver disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "ascites",
                    "criterion": "ascites",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "bleeding disorders secondary to hepatic dysfunction",
                    "criterion": "bleeding disorders secondary to hepatic dysfunction",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "9. Current or prior treatment with anti-epileptic medications for the treatment of seizures;",
            "criterions": [
                {
                    "exact_snippets": "Current or prior treatment with anti-epileptic medications for the treatment of seizures",
                    "criterion": "treatment with anti-epileptic medications",
                    "requirements": [
                        {
                            "requirement_type": "temporal",
                            "expected_value": [
                                "current",
                                "prior"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "treatment of seizures",
                    "criterion": "seizures",
                    "requirements": [
                        {
                            "requirement_type": "treatment",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "10. Impaired cardiac function, including any of the following:",
            "criterions": [
                {
                    "exact_snippets": "Impaired cardiac function",
                    "criterion": "cardiac function",
                    "requirements": [
                        {
                            "requirement_type": "impairment",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "1. Uncontrolled hypertension (systolic blood pressure ≥160 mmHg or diastolic BP ≥95 mmHg);",
            "criterions": [
                {
                    "exact_snippets": "Uncontrolled hypertension",
                    "criterion": "hypertension",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "systolic blood pressure ≥160 mmHg",
                    "criterion": "systolic blood pressure",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">=",
                                "value": 160,
                                "unit": "mmHg"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "diastolic BP ≥95 mmHg",
                    "criterion": "diastolic blood pressure",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">=",
                                "value": 95,
                                "unit": "mmHg"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events or history of cardiac failure in the past 6 months, severe or unstable angina, or New York Heart Association (NYHA) Class II-IV heart disease;",
            "criterions": [
                {
                    "exact_snippets": "Clinically significant heart disease as evidenced by myocardial infarction",
                    "criterion": "myocardial infarction",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Clinically significant heart disease as evidenced by ... arterial thrombotic events",
                    "criterion": "arterial thrombotic events",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Clinically significant heart disease as evidenced by ... history of cardiac failure in the past 6 months",
                    "criterion": "history of cardiac failure",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": "past 6 months"
                        }
                    ]
                },
                {
                    "exact_snippets": "Clinically significant heart disease as evidenced by ... severe or unstable angina",
                    "criterion": "severe or unstable angina",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Clinically significant heart disease as evidenced by ... New York Heart Association (NYHA) Class II-IV heart disease",
                    "criterion": "New York Heart Association (NYHA) Class II-IV heart disease",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": [
                                "Class II",
                                "Class III",
                                "Class IV"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Existing atrial fibrillation with or without pharmacotherapy. Other cardiac arrhythmia requiring pharmacotherapy;",
            "criterions": [
                {
                    "exact_snippets": "Existing atrial fibrillation",
                    "criterion": "atrial fibrillation",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Other cardiac arrhythmia requiring pharmacotherapy",
                    "criterion": "cardiac arrhythmia",
                    "requirements": [
                        {
                            "requirement_type": "pharmacotherapy requirement",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. History of seizure or condition that may predispose to seizure (including, but not limited to prior stroke, transient ischemic attack or loss of consciousness ≤1 year prior to randomization; brain arteriovenous malformation; or intracranial masses such as schwannomas and meningiomas that are causing edema or mass effect);",
            "criterions": [
                {
                    "exact_snippets": "History of seizure",
                    "criterion": "seizure history",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "condition that may predispose to seizure",
                    "criterion": "condition predisposing to seizure",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "prior stroke",
                    "criterion": "prior stroke",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "transient ischemic attack",
                    "criterion": "transient ischemic attack",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "loss of consciousness ≤1 year prior to randomization",
                    "criterion": "loss of consciousness",
                    "requirements": [
                        {
                            "requirement_type": "time since event",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1,
                                "unit": "year"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "brain arteriovenous malformation",
                    "criterion": "brain arteriovenous malformation",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "intracranial masses such as schwannomas and meningiomas",
                    "criterion": "intracranial masses",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "causing edema or mass effect",
                    "criterion": "edema or mass effect",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "11. Specific underlying conditions for oral agents. For example: impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of abiraterone or APALUTAMIDE (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)",
            "criterions": [
                {
                    "exact_snippets": "impairment of gastrointestinal (GI) function or GI disease",
                    "criterion": "gastrointestinal (GI) function or GI disease",
                    "requirements": [
                        {
                            "requirement_type": "impairment",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "ulcerative diseases",
                    "criterion": "ulcerative diseases",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "uncontrolled nausea",
                    "criterion": "nausea",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": "uncontrolled"
                        }
                    ]
                },
                {
                    "exact_snippets": "vomiting",
                    "criterion": "vomiting",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "diarrhea",
                    "criterion": "diarrhea",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "malabsorption syndrome",
                    "criterion": "malabsorption syndrome",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "small bowel resection",
                    "criterion": "small bowel resection",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "12. General excluded medications (e.g., relevant to cytochrome P450 interactions)",
            "criterions": [
                {
                    "exact_snippets": "General excluded medications (e.g., relevant to cytochrome P450 interactions)",
                    "criterion": "medications",
                    "requirements": [
                        {
                            "requirement_type": "exclusion",
                            "expected_value": "relevant to cytochrome P450 interactions"
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Consumption of grapefruit product or St John's wort within 7 days prior to dosing;",
            "criterions": [
                {
                    "exact_snippets": "Consumption of grapefruit product",
                    "criterion": "grapefruit product consumption",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Consumption of ... St John's wort",
                    "criterion": "St John's wort consumption",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "within 7 days prior to dosing",
                    "criterion": "time since last consumption",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 7,
                                        "unit": "days"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. G-CSF, GM-CSF, erythropoietin, etc;",
            "criterions": [
                {
                    "exact_snippets": "G-CSF",
                    "criterion": "G-CSF",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "GM-CSF",
                    "criterion": "GM-CSF",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "erythropoietin",
                    "criterion": "erythropoietin",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Coumadin;",
            "criterions": [
                {
                    "exact_snippets": "Coumadin",
                    "criterion": "Coumadin use",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Drugs which may cause QT prolongation;",
            "criterions": [
                {
                    "exact_snippets": "Drugs which may cause QT prolongation",
                    "criterion": "drugs causing QT prolongation",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Known sensitivity to drugs or metabolites from similar classes;",
            "criterions": [
                {
                    "exact_snippets": "Known sensitivity to drugs or metabolites from similar classes",
                    "criterion": "sensitivity to drugs or metabolites",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Known or suspected contraindications or hypersensitivity to APALUTAMIDE, bicalutamide or GnRH agonists or any of the components of the formulations;",
            "criterions": [
                {
                    "exact_snippets": "Known or suspected contraindications ... to APALUTAMIDE",
                    "criterion": "contraindications to APALUTAMIDE",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "hypersensitivity to APALUTAMIDE",
                    "criterion": "hypersensitivity to APALUTAMIDE",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "contraindications ... to ... bicalutamide",
                    "criterion": "contraindications to bicalutamide",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "hypersensitivity to ... bicalutamide",
                    "criterion": "hypersensitivity to bicalutamide",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "contraindications ... to ... GnRH agonists",
                    "criterion": "contraindications to GnRH agonists",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "hypersensitivity to ... GnRH agonists",
                    "criterion": "hypersensitivity to GnRH agonists",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "contraindications ... to ... any of the components of the formulations",
                    "criterion": "contraindications to any of the components of the formulations",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "hypersensitivity to ... any of the components of the formulations",
                    "criterion": "hypersensitivity to any of the components of the formulations",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "13. Any condition or situation which, in the opinion of the investigator, would put the subject at risk, may confound study results, or interfere with the subject's participation in this study.",
            "criterions": [
                {
                    "exact_snippets": "Any condition or situation ... would put the subject at risk",
                    "criterion": "condition or situation",
                    "requirements": [
                        {
                            "requirement_type": "risk to subject",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Any condition or situation ... may confound study results",
                    "criterion": "condition or situation",
                    "requirements": [
                        {
                            "requirement_type": "confounding study results",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Any condition or situation ... interfere with the subject's participation",
                    "criterion": "condition or situation",
                    "requirements": [
                        {
                            "requirement_type": "interference with participation",
                            "expected_value": true
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [
        {
            "line": "1. Use of prescription drugs within 14 days prior to dosing or over-the-counter (OTC) medication within 7 days prior to dosing;",
            "criterions": [
                {
                    "exact_snippets": "Use of prescription drugs within 14 days prior to dosing",
                    "criterion": "prescription drug use",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "operator": "<=",
                                "value": 14,
                                "unit": "days"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "use of ... over-the-counter (OTC) medication within 7 days prior to dosing",
                    "criterion": "over-the-counter medication use",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "operator": "<=",
                                "value": 7,
                                "unit": "days"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "failed_miscellaneous": []
}