{
    "info": {
        "nct_id": "NCT02822573",
        "official_title": "A Phase 3 Randomized Placebo Controlled Clinical Trial of Donepezil in Chemotherapy Exposed Breast Cancer Survivors With Cognitive Impairment",
        "inclusion_criteria": "* Women ≥18 years old with history of invasive breast cancer\n* Must have completed at least 4 cycles of adjuvant/neo-adjuvant cytotoxic chemotherapy between 1 and 5 years prior to registration (Ongoing herceptin or other chronic human epidermal growth factor receptor 2 (HER2) directed therapies are allowed).\n* Patients receiving ongoing hormonal therapy for breast cancer must be on the same hormonal agent for at least 3 months prior to study registration and plan to continue for the duration of the study (9 months)\n* Use of psychotropic medications (anti-depressants, anxiolytics, sleeping aids, narcotics) is permitted (patient will be asked to list any that have been taken within the last 3 days on the recent medication sheet) if dose is stable over previous 12 weeks. Patients who were previously on one of these psychotropic medications and have subsequently discontinued the drug must have been off the medication for at least 4 weeks prior to enrollment. Patients who have been on a psychotropic medication for at least 12 weeks but have recently switched to a medicine in the same class (for example, switching from one selective serotonin reuptake inhibitor (SSRI) antidepressant to a different SSRI antidepressant) need to be on a stable dose of the new medication for at least 4 weeks prior to enrollment to be eligible.\n* Self-reported cognitive problem plus a measured memory deficit (score <7 on single trial of Eligibility Pre-screen Hopkins Verbal Learning Test - Revised (HVLT-R) Form 3).\n* Eastern Cooperative Oncology Group (ECOG) performance status 0-2\n* Ability to understand and the willingness to sign a written informed consent document.\n* Must be able to speak English.\n* Patients currently taking a moderate risk corrected QT interval (QTc) prolongation medication (see Appendix A) are allowed if one of the following criteria are met: 1) The moderate risk QTc prolongation medication is stopped. The patient should be off the moderate risk QTc prolongation medication for at least 5 half-lives before starting study drug. 2) Patients that continue using a moderate risk QTc prolongation medication must have a normal QTc interval (≤ 460 milliseconds) on a screening ECG following informed consent and prior to study enrollment. These patients will also be monitored at designated study follow-up visits per Section 7.5 (monitored 3-7 days after initiating study drug, at week 3, and 3-7 days after the study drug dose increase with ECG's to assess the QTc interval; the QTc level must be ≤ 500 milliseconds at these time points in order to continue on the study drug). 3) Moderate risk QTc prolongation medications that are only taken occasionally may be stopped at the discretion of the treating site physician. Patients must be off medication for at least 5 half-lives prior to starting study drug to be eligible.\n* Patients currently taking a moderate risk bradycardia-causing agent (see Appendix B) are allowed if one of the following criteria are met: 1) The moderate risk bradycardia-causing agent is stopped. The patient should be off the moderate risk bradycardia-causing agent for at least 5 half-lives before starting study drug. 2) Patients that continue using a moderate risk bradycardia-causing agent must have a resting heart rate ≥ 55 beats per minute at screening following informed consent. These patients' resting heart rate will be monitored 3-7 days after initiating study drug, at week 3, and 3-7 days after the study drug dose increase per Section 7.5. 3) Moderate risk bradycardia-causing agents that are only taken occasionally may be stopped at the discretion of the treating site physician. Patients must be off medication for at least 5 half-lives prior to starting study drug to be eligible.\nHealthy volunteers allowed\nMust be FEMALE\nMust have minimum age of 18 Years\nMust have maximum age of 75 Years",
        "exclusion_criteria": "* Evidence or suspected recurrent or metastatic disease.\n* Prior brain irradiation is not allowed.\n* Planned therapy (surgery, radiation, chemotherapy, or immunotherapy) while on the study for brain and/or extracranial primary/metastatic disease.\n* Hypersensitivity to donepezil or piperidine derivatives\n* Current use of ceritinib\n* Current use of Succinylcholine/Acetylcholinesterase Inhibitors(as listed in Appendix C). For patients who have used these medications, they must not have used them within 4 weeks prior to enrollment.\n* Current use of high-risk QTc prolonging medication(s). See Appendix D\n* Current use of quinidine or systemic ketoconazole (topical ketoconazole is acceptable to use while on study).\n* History of dementia, Alzheimer's disease, multi-infarct dementia or clinically significant Cerebrovascular Accident (history of transient ischemic attack (TIA) is allowed).\n* Current use of donepezil, galantamine, rivastigmine, tacrine, memantine, methylphenidate, dextroamphetamine, or any other specific cognition enhancing drug(s). For patients who have used these medications, they must not have used them within 4 weeks prior to pre-screening. Patients who plan to start taking a cognition enhancing drug while on this study are also excluded.\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to donepezil. Hypersensitivity to donepezil.\n* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, recent myocardial infarction, cardiac arrhythmia.\n* Major medical conditions that affect cognition, traumatic brain injury, multiple sclerosis, acute severe fatigue, chronic fatigue syndrome or fibromyalgia.\n* Psychiatric illness/social situations that would limit compliance with study requirements including but not limited to a history of schizophrenia, psychosis or substance abuse.\n* Untreated current severe depression. Currently treated depression is permitted if treatment is stable.\n* Patients with a resting heart rate less than 55 beats per minute, seizure disorder or peptic ulcer disease (PUD).\n* History of congenital long QT syndrome or torsades de pointes.\n* Screening QTc of > 460 milliseconds will make the patient ineligible.\n* Pregnant women are excluded from this study. Following informed consent, women of child-bearing potential will be screened with a serum or urine pregnancy test within 10 days of enrollment. The effects of donepezil on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because donepezil is known to be teratogenic, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately.\n* It is unknown whether donepezil is excreted in breast milk, for this reason women who are currently breast-feeding are not eligible for this study.\n* On another intervention study involving medication at the time of enrollment or during participation in this study. (Exception: Patients will remain eligible for this study if they are also enrolled on the Alliance for Clinical Trials in Oncology study (NCT02927249): Aspirin in Preventing Recurrence of Cancer in Patients with HER2 Negative Stage II-III Breast Cancer After Chemotherapy, Surgery, and/or Radiation Therapy. Studies that involve only blood draws or questionnaires are also permitted.)\n* Use of investigational drugs likely to affect cognition within 30 days prior to pre-screening visit.",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "* Women ≥18 years old with history of invasive breast cancer",
            "criterions": [
                {
                    "exact_snippets": "Women",
                    "criterion": "gender",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": "female"
                        }
                    ]
                },
                {
                    "exact_snippets": "≥18 years old",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum age",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "years"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "history of invasive breast cancer",
                    "criterion": "invasive breast cancer",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Must have completed at least 4 cycles of adjuvant/neo-adjuvant cytotoxic chemotherapy between 1 and 5 years prior to registration (Ongoing herceptin or other chronic human epidermal growth factor receptor 2 (HER2) directed therapies are allowed).",
            "criterions": [
                {
                    "exact_snippets": "Must have completed at least 4 cycles of adjuvant/neo-adjuvant cytotoxic chemotherapy",
                    "criterion": "adjuvant/neo-adjuvant cytotoxic chemotherapy",
                    "requirements": [
                        {
                            "requirement_type": "completion",
                            "expected_value": {
                                "operator": ">=",
                                "value": 4,
                                "unit": "cycles"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "between 1 and 5 years prior to registration",
                    "criterion": "time since chemotherapy",
                    "requirements": [
                        {
                            "requirement_type": "time since",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 1,
                                        "unit": "years"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 5,
                                        "unit": "years"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Ongoing herceptin or other chronic human epidermal growth factor receptor 2 (HER2) directed therapies are allowed",
                    "criterion": "ongoing HER2 directed therapies",
                    "requirements": [
                        {
                            "requirement_type": "allowance",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients receiving ongoing hormonal therapy for breast cancer must be on the same hormonal agent for at least 3 months prior to study registration and plan to continue for the duration of the study (9 months)",
            "criterions": [
                {
                    "exact_snippets": "Patients receiving ongoing hormonal therapy for breast cancer",
                    "criterion": "ongoing hormonal therapy for breast cancer",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "must be on the same hormonal agent for at least 3 months prior to study registration",
                    "criterion": "same hormonal agent",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 3,
                                "unit": "months"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "plan to continue for the duration of the study (9 months)",
                    "criterion": "continuation of hormonal therapy",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": "=",
                                "value": 9,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Use of psychotropic medications (anti-depressants, anxiolytics, sleeping aids, narcotics) is permitted (patient will be asked to list any that have been taken within the last 3 days on the recent medication sheet) if dose is stable over previous 12 weeks. Patients who were previously on one of these psychotropic medications and have subsequently discontinued the drug must have been off the medication for at least 4 weeks prior to enrollment. Patients who have been on a psychotropic medication for at least 12 weeks but have recently switched to a medicine in the same class (for example, switching from one selective serotonin reuptake inhibitor (SSRI) antidepressant to a different SSRI antidepressant) need to be on a stable dose of the new medication for at least 4 weeks prior to enrollment to be eligible.",
            "criterions": [
                {
                    "exact_snippets": "Use of psychotropic medications (anti-depressants, anxiolytics, sleeping aids, narcotics) is permitted",
                    "criterion": "use of psychotropic medications",
                    "requirements": [
                        {
                            "requirement_type": "permitted",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "dose is stable over previous 12 weeks",
                    "criterion": "dose stability",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 12,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients who were previously on one of these psychotropic medications and have subsequently discontinued the drug must have been off the medication for at least 4 weeks prior to enrollment",
                    "criterion": "discontinuation of psychotropic medications",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients who have been on a psychotropic medication for at least 12 weeks but have recently switched to a medicine in the same class ... need to be on a stable dose of the new medication for at least 4 weeks prior to enrollment",
                    "criterion": "switching psychotropic medications",
                    "requirements": [
                        {
                            "requirement_type": "duration on previous medication",
                            "expected_value": {
                                "operator": ">=",
                                "value": 12,
                                "unit": "weeks"
                            }
                        },
                        {
                            "requirement_type": "duration on stable dose of new medication",
                            "expected_value": {
                                "operator": ">=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Self-reported cognitive problem plus a measured memory deficit (score <7 on single trial of Eligibility Pre-screen Hopkins Verbal Learning Test - Revised (HVLT-R) Form 3).",
            "criterions": [
                {
                    "exact_snippets": "Self-reported cognitive problem",
                    "criterion": "cognitive problem",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "measured memory deficit ... score <7 on single trial of Eligibility Pre-screen Hopkins Verbal Learning Test - Revised (HVLT-R) Form 3",
                    "criterion": "memory deficit",
                    "requirements": [
                        {
                            "requirement_type": "score",
                            "expected_value": {
                                "operator": "<",
                                "value": 7,
                                "unit": "N/A"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Eastern Cooperative Oncology Group (ECOG) performance status 0-2",
            "criterions": [
                {
                    "exact_snippets": "Eastern Cooperative Oncology Group (ECOG) performance status 0-2",
                    "criterion": "ECOG performance status",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 0,
                                        "unit": "N/A"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 2,
                                        "unit": "N/A"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Ability to understand and the willingness to sign a written informed consent document.",
            "criterions": [
                {
                    "exact_snippets": "Ability to understand",
                    "criterion": "cognitive ability",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "willingness to sign a written informed consent document",
                    "criterion": "willingness to consent",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Must be able to speak English.",
            "criterions": [
                {
                    "exact_snippets": "Must be able to speak English.",
                    "criterion": "English language proficiency",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients currently taking a moderate risk corrected QT interval (QTc) prolongation medication (see Appendix A) are allowed if one of the following criteria are met: 1) The moderate risk QTc prolongation medication is stopped. The patient should be off the moderate risk QTc prolongation medication for at least 5 half-lives before starting study drug. 2) Patients that continue using a moderate risk QTc prolongation medication must have a normal QTc interval (≤ 460 milliseconds) on a screening ECG following informed consent and prior to study enrollment. These patients will also be monitored at designated study follow-up visits per Section 7.5 (monitored 3-7 days after initiating study drug, at week 3, and 3-7 days after the study drug dose increase with ECG's to assess the QTc interval; the QTc level must be ≤ 500 milliseconds at these time points in order to continue on the study drug). 3) Moderate risk QTc prolongation medications that are only taken occasionally may be stopped at the discretion of the treating site physician. Patients must be off medication for at least 5 half-lives prior to starting study drug to be eligible.",
            "criterions": [
                {
                    "exact_snippets": "Patients currently taking a moderate risk corrected QT interval (QTc) prolongation medication",
                    "criterion": "moderate risk QTc prolongation medication",
                    "requirements": [
                        {
                            "requirement_type": "usage",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "The moderate risk QTc prolongation medication is stopped",
                    "criterion": "moderate risk QTc prolongation medication",
                    "requirements": [
                        {
                            "requirement_type": "usage",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "The patient should be off the moderate risk QTc prolongation medication for at least 5 half-lives before starting study drug",
                    "criterion": "moderate risk QTc prolongation medication",
                    "requirements": [
                        {
                            "requirement_type": "off medication duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 5,
                                "unit": "half-lives"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients that continue using a moderate risk QTc prolongation medication must have a normal QTc interval (≤ 460 milliseconds) on a screening ECG",
                    "criterion": "QTc interval on screening ECG",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": "<=",
                                "value": 460,
                                "unit": "milliseconds"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "the QTc level must be ≤ 500 milliseconds at these time points in order to continue on the study drug",
                    "criterion": "QTc interval during follow-up",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": "<=",
                                "value": 500,
                                "unit": "milliseconds"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Moderate risk QTc prolongation medications that are only taken occasionally may be stopped at the discretion of the treating site physician",
                    "criterion": "occasional moderate risk QTc prolongation medication",
                    "requirements": [
                        {
                            "requirement_type": "discretionary stopping",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients must be off medication for at least 5 half-lives prior to starting study drug to be eligible",
                    "criterion": "off medication duration for occasional use",
                    "requirements": [
                        {
                            "requirement_type": "off medication duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 5,
                                "unit": "half-lives"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients currently taking a moderate risk bradycardia-causing agent (see Appendix B) are allowed if one of the following criteria are met: 1) The moderate risk bradycardia-causing agent is stopped. The patient should be off the moderate risk bradycardia-causing agent for at least 5 half-lives before starting study drug. 2) Patients that continue using a moderate risk bradycardia-causing agent must have a resting heart rate ≥ 55 beats per minute at screening following informed consent. These patients' resting heart rate will be monitored 3-7 days after initiating study drug, at week 3, and 3-7 days after the study drug dose increase per Section 7.5. 3) Moderate risk bradycardia-causing agents that are only taken occasionally may be stopped at the discretion of the treating site physician. Patients must be off medication for at least 5 half-lives prior to starting study drug to be eligible.",
            "criterions": [
                {
                    "exact_snippets": "Patients currently taking a moderate risk bradycardia-causing agent",
                    "criterion": "use of moderate risk bradycardia-causing agent",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "The moderate risk bradycardia-causing agent is stopped",
                    "criterion": "cessation of moderate risk bradycardia-causing agent",
                    "requirements": [
                        {
                            "requirement_type": "action",
                            "expected_value": "stopped"
                        }
                    ]
                },
                {
                    "exact_snippets": "The patient should be off the moderate risk bradycardia-causing agent for at least 5 half-lives",
                    "criterion": "time off moderate risk bradycardia-causing agent",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 5,
                                "unit": "half-lives"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "resting heart rate ≥ 55 beats per minute",
                    "criterion": "resting heart rate",
                    "requirements": [
                        {
                            "requirement_type": "measurement",
                            "expected_value": {
                                "operator": ">=",
                                "value": 55,
                                "unit": "beats per minute"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Moderate risk bradycardia-causing agents that are only taken occasionally may be stopped",
                    "criterion": "occasional use of moderate risk bradycardia-causing agent",
                    "requirements": [
                        {
                            "requirement_type": "action",
                            "expected_value": "may be stopped"
                        }
                    ]
                }
            ]
        },
        {
            "line": "Healthy volunteers allowed",
            "criterions": [
                {
                    "exact_snippets": "Healthy volunteers allowed",
                    "criterion": "volunteer health status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "healthy"
                        }
                    ]
                }
            ]
        },
        {
            "line": "Must be FEMALE",
            "criterions": [
                {
                    "exact_snippets": "Must be FEMALE",
                    "criterion": "gender",
                    "requirements": [
                        {
                            "requirement_type": "expected_value",
                            "expected_value": "female"
                        }
                    ]
                }
            ]
        },
        {
            "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 75 Years",
            "criterions": [
                {
                    "exact_snippets": "maximum age of 75 Years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "maximum",
                            "expected_value": {
                                "operator": "<=",
                                "value": 75,
                                "unit": "Years"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "exclusion_lines": [
        {
            "line": "* Evidence or suspected recurrent or metastatic disease.",
            "criterions": [
                {
                    "exact_snippets": "Evidence or suspected recurrent ... disease.",
                    "criterion": "recurrent disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Evidence or suspected ... metastatic disease.",
                    "criterion": "metastatic disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Prior brain irradiation is not allowed.",
            "criterions": [
                {
                    "exact_snippets": "Prior brain irradiation is not allowed.",
                    "criterion": "prior brain irradiation",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Planned therapy (surgery, radiation, chemotherapy, or immunotherapy) while on the study for brain and/or extracranial primary/metastatic disease.",
            "criterions": [
                {
                    "exact_snippets": "Planned therapy (surgery, radiation, chemotherapy, or immunotherapy)",
                    "criterion": "planned therapy",
                    "requirements": [
                        {
                            "requirement_type": "types",
                            "expected_value": [
                                "surgery",
                                "radiation",
                                "chemotherapy",
                                "immunotherapy"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "brain and/or extracranial primary/metastatic disease",
                    "criterion": "disease location",
                    "requirements": [
                        {
                            "requirement_type": "location",
                            "expected_value": [
                                "brain",
                                "extracranial"
                            ]
                        },
                        {
                            "requirement_type": "disease type",
                            "expected_value": [
                                "primary",
                                "metastatic"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Hypersensitivity to donepezil or piperidine derivatives",
            "criterions": [
                {
                    "exact_snippets": "Hypersensitivity to donepezil",
                    "criterion": "hypersensitivity to donepezil",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Hypersensitivity to ... piperidine derivatives",
                    "criterion": "hypersensitivity to piperidine derivatives",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Current use of ceritinib",
            "criterions": [
                {
                    "exact_snippets": "Current use of ceritinib",
                    "criterion": "ceritinib use",
                    "requirements": [
                        {
                            "requirement_type": "current use",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Current use of Succinylcholine/Acetylcholinesterase Inhibitors(as listed in Appendix C). For patients who have used these medications, they must not have used them within 4 weeks prior to enrollment.",
            "criterions": [
                {
                    "exact_snippets": "Current use of Succinylcholine/Acetylcholinesterase Inhibitors",
                    "criterion": "use of Succinylcholine/Acetylcholinesterase Inhibitors",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "patients who have used these medications ... must not have used them within 4 weeks prior to enrollment",
                    "criterion": "use of Succinylcholine/Acetylcholinesterase Inhibitors within 4 weeks prior to enrollment",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Current use of high-risk QTc prolonging medication(s). See Appendix D",
            "criterions": [
                {
                    "exact_snippets": "Current use of high-risk QTc prolonging medication(s)",
                    "criterion": "QTc prolonging medication use",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "risk level",
                            "expected_value": "high-risk"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Current use of quinidine or systemic ketoconazole (topical ketoconazole is acceptable to use while on study).",
            "criterions": [
                {
                    "exact_snippets": "Current use of quinidine",
                    "criterion": "quinidine use",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Current use of ... systemic ketoconazole",
                    "criterion": "systemic ketoconazole use",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* History of dementia, Alzheimer's disease, multi-infarct dementia or clinically significant Cerebrovascular Accident (history of transient ischemic attack (TIA) is allowed).",
            "criterions": [
                {
                    "exact_snippets": "History of dementia",
                    "criterion": "dementia",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Alzheimer's disease",
                    "criterion": "Alzheimer's disease",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "multi-infarct dementia",
                    "criterion": "multi-infarct dementia",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "clinically significant Cerebrovascular Accident",
                    "criterion": "Cerebrovascular Accident",
                    "requirements": [
                        {
                            "requirement_type": "clinical significance",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "history",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "history of transient ischemic attack (TIA) is allowed",
                    "criterion": "transient ischemic attack (TIA)",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Current use of donepezil, galantamine, rivastigmine, tacrine, memantine, methylphenidate, dextroamphetamine, or any other specific cognition enhancing drug(s). For patients who have used these medications, they must not have used them within 4 weeks prior to pre-screening. Patients who plan to start taking a cognition enhancing drug while on this study are also excluded.",
            "criterions": [
                {
                    "exact_snippets": "Current use of donepezil, galantamine, rivastigmine, tacrine, memantine, methylphenidate, dextroamphetamine, or any other specific cognition enhancing drug(s).",
                    "criterion": "current use of cognition enhancing drugs",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "For patients who have used these medications, they must not have used them within 4 weeks prior to pre-screening.",
                    "criterion": "use of cognition enhancing drugs within 4 weeks prior to pre-screening",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients who plan to start taking a cognition enhancing drug while on this study are also excluded.",
                    "criterion": "plan to start taking cognition enhancing drugs while on study",
                    "requirements": [
                        {
                            "requirement_type": "intention",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* History of allergic reactions attributed to compounds of similar chemical or biologic composition to donepezil. Hypersensitivity to donepezil.",
            "criterions": [
                {
                    "exact_snippets": "History of allergic reactions attributed to compounds of similar chemical or biologic composition to donepezil.",
                    "criterion": "allergic reactions to compounds similar to donepezil",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Hypersensitivity to donepezil.",
                    "criterion": "hypersensitivity to donepezil",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, recent myocardial infarction, cardiac arrhythmia.",
            "criterions": [
                {
                    "exact_snippets": "Uncontrolled intercurrent illness ... ongoing or active infection",
                    "criterion": "ongoing or active infection",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Uncontrolled intercurrent illness ... symptomatic congestive heart failure",
                    "criterion": "symptomatic congestive heart failure",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Uncontrolled intercurrent illness ... unstable angina pectoris",
                    "criterion": "unstable angina pectoris",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Uncontrolled intercurrent illness ... recent myocardial infarction",
                    "criterion": "recent myocardial infarction",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Uncontrolled intercurrent illness ... cardiac arrhythmia",
                    "criterion": "cardiac arrhythmia",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Major medical conditions that affect cognition, traumatic brain injury, multiple sclerosis, acute severe fatigue, chronic fatigue syndrome or fibromyalgia.",
            "criterions": [
                {
                    "exact_snippets": "Major medical conditions that affect cognition",
                    "criterion": "major medical conditions affecting cognition",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "traumatic brain injury",
                    "criterion": "traumatic brain injury",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "multiple sclerosis",
                    "criterion": "multiple sclerosis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "acute severe fatigue",
                    "criterion": "acute severe fatigue",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "chronic fatigue syndrome",
                    "criterion": "chronic fatigue syndrome",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "fibromyalgia",
                    "criterion": "fibromyalgia",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Psychiatric illness/social situations that would limit compliance with study requirements including but not limited to a history of schizophrenia, psychosis or substance abuse.",
            "criterions": [
                {
                    "exact_snippets": "Psychiatric illness/social situations that would limit compliance with study requirements",
                    "criterion": "psychiatric illness/social situations",
                    "requirements": [
                        {
                            "requirement_type": "impact on compliance",
                            "expected_value": "limit compliance with study requirements"
                        }
                    ]
                },
                {
                    "exact_snippets": "history of schizophrenia",
                    "criterion": "schizophrenia",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "history of ... psychosis",
                    "criterion": "psychosis",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "history of ... substance abuse",
                    "criterion": "substance abuse",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Untreated current severe depression. Currently treated depression is permitted if treatment is stable.",
            "criterions": [
                {
                    "exact_snippets": "Untreated current severe depression",
                    "criterion": "current severe depression",
                    "requirements": [
                        {
                            "requirement_type": "treatment status",
                            "expected_value": "untreated"
                        }
                    ]
                },
                {
                    "exact_snippets": "Currently treated depression is permitted if treatment is stable",
                    "criterion": "currently treated depression",
                    "requirements": [
                        {
                            "requirement_type": "treatment stability",
                            "expected_value": "stable"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients with a resting heart rate less than 55 beats per minute, seizure disorder or peptic ulcer disease (PUD).",
            "criterions": [
                {
                    "exact_snippets": "resting heart rate less than 55 beats per minute",
                    "criterion": "resting heart rate",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "<",
                                "value": 55,
                                "unit": "beats per minute"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "seizure disorder",
                    "criterion": "seizure disorder",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "peptic ulcer disease (PUD)",
                    "criterion": "peptic ulcer disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* History of congenital long QT syndrome or torsades de pointes.",
            "criterions": [
                {
                    "exact_snippets": "History of congenital long QT syndrome",
                    "criterion": "congenital long QT syndrome",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "History of ... torsades de pointes",
                    "criterion": "torsades de pointes",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Screening QTc of > 460 milliseconds will make the patient ineligible.",
            "criterions": [
                {
                    "exact_snippets": "Screening QTc of > 460 milliseconds",
                    "criterion": "QTc interval",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">",
                                "value": 460,
                                "unit": "milliseconds"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Pregnant women are excluded from this study. Following informed consent, women of child-bearing potential will be screened with a serum or urine pregnancy test within 10 days of enrollment. The effects of donepezil on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because donepezil is known to be teratogenic, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately.",
            "criterions": [
                {
                    "exact_snippets": "Pregnant women are excluded",
                    "criterion": "pregnancy status",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "women of child-bearing potential will be screened with a serum or urine pregnancy test",
                    "criterion": "pregnancy test",
                    "requirements": [
                        {
                            "requirement_type": "type",
                            "expected_value": [
                                "serum",
                                "urine"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence)",
                    "criterion": "contraception use",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "methods",
                            "expected_value": [
                                "hormonal",
                                "barrier method of birth control",
                                "abstinence"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* It is unknown whether donepezil is excreted in breast milk, for this reason women who are currently breast-feeding are not eligible for this study.",
            "criterions": [
                {
                    "exact_snippets": "women who are currently breast-feeding are not eligible",
                    "criterion": "breast-feeding status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "not breast-feeding"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* On another intervention study involving medication at the time of enrollment or during participation in this study. (Exception: Patients will remain eligible for this study if they are also enrolled on the Alliance for Clinical Trials in Oncology study (NCT02927249): Aspirin in Preventing Recurrence of Cancer in Patients with HER2 Negative Stage II-III Breast Cancer After Chemotherapy, Surgery, and/or Radiation Therapy. Studies that involve only blood draws or questionnaires are also permitted.)",
            "criterions": [
                {
                    "exact_snippets": "On another intervention study involving medication at the time of enrollment or during participation in this study.",
                    "criterion": "participation in another intervention study involving medication",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Exception: Patients will remain eligible for this study if they are also enrolled on the Alliance for Clinical Trials in Oncology study (NCT02927249)",
                    "criterion": "enrollment in Alliance for Clinical Trials in Oncology study (NCT02927249)",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Studies that involve only blood draws or questionnaires are also permitted.",
                    "criterion": "participation in studies involving only blood draws or questionnaires",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Use of investigational drugs likely to affect cognition within 30 days prior to pre-screening visit.",
            "criterions": [
                {
                    "exact_snippets": "Use of investigational drugs likely to affect cognition",
                    "criterion": "use of investigational drugs",
                    "requirements": [
                        {
                            "requirement_type": "effect on cognition",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "within 30 days prior to pre-screening visit",
                    "criterion": "time since last use of investigational drugs",
                    "requirements": [
                        {
                            "requirement_type": "time since last use",
                            "expected_value": {
                                "operator": "<=",
                                "value": 30,
                                "unit": "days"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}