Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized, Double-Blind, Clinical Trial to Compare the Safety and Efficacy of Cerebrolysin and Aricept (Donepezil) and a Combination Therapy in Patients With Probable Alzheimer's Disease (AD)
Brief Summary: The study was performed to compare the safety and efficacy of Cerebrolysin (10 mililiters \[ml\]), Aricept (10 miligrams \[mg\]), and a combination of both treatments on cognitive performance and global function in patients with probable Alzheimer's Disease (AD). It should also be assessed if the treatments have a positive effect on activities of daily living and neuropsychiatric symptoms.

Oral treatment with Aricept or Placebo was given once daily throughout the study. Intravenous treatment with Cerebrolysin or Placebo was given once daily for 5 days per week during week 1 to 4 and during week 13 to 16 of the study. During the study patients had six visits at the hospital for evaluation.


Options:
A: Inclusion Criteria:

* Age between 18 and 85 years
* Focal neurological deficit
* Clinical diagnosis of acute hemispheric ischemic stroke
* CT or MRI results compatible with clinical diagnosis of acute hemispheric stroke
* NIH Stroke Scale Score between 6 and 22, both inclusive
* Functionally independent prior to stroke with a pre-stroke Rankin Score of 0 or 1
* Randomization and first treatment with the trial medication within 12h after stroke onset
* Informed consent given by the patient and/or the patient's legally acceptable representative

Exclusion Criteria:

* Evidence on CT/MRI of acute or chronic intracerebral hemorrhage, SAH, AVM, cerebral aneurysm, or neoplasm
* Signs of herniation, increased intracranial pressure or likely etiology other than brain ischemia at baseline CT scan
* Patients with a substantial decrease of consciousness or alertness at the time of randomization, defined as score of 2 or more one of the NIH Stroke Scale questions 1a.
* Neurological signs and symptoms that improve rapidly during screening and are likely to resolve completely within 24h
* Severe coexisting systemic disease that significantly limits life expectancy
* Systolic blood pressure over 220 mmHg or diastolic blood pressure over 120 mmHg on repeated measurement (interval of 30 min) prior to study entry
* Severe congestive heart failure or presentation with acute myocardial infarction at study entry
* Epilepsy or epileptic seizures at onset of stroke
* Pre-existing disorders or conditions that would impair interpretation of neurological assessment (eg. severe dementia, severe psychiatric illnesses, etc).
* Concomitant treatment with other neuroprotective or nootropic drugs (e.g. piracetam, citicoline, investigational neuroprotective substances)
* Patients which cannot tolerate or have contraindication to aspirin or Cerebrolysin treatment
* Concomitant treatment with substances that have a dilative effect on blood vessels like naftidrofuryl, cinnarizine, flunarizine or nimodipine
* Pregnancy and lactation period; for women with child-bearing potential a negative pregnancy test is required
* Participation in a clinical trial with an investigational drug in the past 4 weeks
B: Inclusion criteria

* Diagnosis of probable AD (Diagnostic and Statistical Manual of Mental Disorders, 4th revision \[DSM-IV\], National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association \[NINCDS-ADRDA\])
* Mini-Mental-State-Examination (MMSE) of 12-25, inclusive
* Modified Hachinski score ≤4
* Computed tomography (CT) or magnetic resonance imaging (MRI) scan within 12 months prior to screening without evidence of infection, infarction, or other focal lesions and without clinical symptoms suggestive of intervening neurological disease. Patients who have had a single, clinically silent lacunar infarct are eligible provided the lacunar infarct is not felt to be responsible for the patient's symptoms, is \<1 centimeter (cm) maximal diameter in any dimension, is not present in hippocampus of either hemisphere, head of the left caudate, or the dorsomedial region of the left thalamus. Subjects with scans showing atrophy, ventricular enlargement or mild to moderate white matter changes (involving up to approximately 25% of hemispheric white matter) are eligible if the study is otherwise normal.
* Hamilton Depression Scale score of ≤15
* Adequate visual and auditory acuity to allow neuropsychological testing
* Ability to attempt all sections of the Alzheimer's Disease Assessment Scale Cognitive Subpart (extended version)(ADAS-cog+)
* Good general health without additional diseases expected to interfere with the study
* Normal B12, folic acid, venereal disease research laboratory (VDRL), and thyroid-stimulating hormone (TSH) or without any clinically significant laboratory abnormalities that would be expected to interfere with the study
* Electrocardiogram (ECG) and chest x-ray (if clinically necessary per Investigator) without clinically significant laboratory abnormalities that would be expected to interfere with the study
* Patient is not institutionalized
* Patient is not pregnant, lactating, or of childbearing potential
* Sufficient language skills to complete all testing without assistance of a language interpreter
* Responsible caregiver being present during administration of study drug, monitor the patient's compliance with study procedures and adverse events, and accompany the patient to all clinic visits
* Written informed consent obtained from the patient and caregiver prior to entry into the study

Exclusion criteria

* Any clinically significant laboratory abnormalities on the battery of screening tests
* Patients who in the past have not tolerated treatment with 10 mg Aricept or treatment with a corresponding dose of another cholinesterase inhibitor
* Severe psychotic features, depression, agitation or behavioral problems within the last three months that could lead to difficulty complying with the protocol
* Any significant systemic illness or unstable medical condition that could lead to difficulty complying with the protocol
* Patients who in the Investigator's opinion would not comply with study procedures
* Any significant neurological disease other than Alzheimer's Disease, within the past five years, or with residual effects
* Delusional symptoms are often characteristic of Alzheimer's Disease, but patients with symptoms so pronounced that they warrant an alternative diagnosis are excluded
* History of alcohol or substance abuse or dependence within the past two years (DSM-IV)
* History of schizophrenia (DSM-IV)
* Patients with a history of systemic cancer within the past two years are excluded
* History of myocardial infarction in the past year or unstable or severe cardiovascular disease, including uncontrolled hypertension
* Uncontrolled insulin-requiring diabetes or non-insulin dependent diabetes mellitus (Haemoglobin A1c \[HBA1c\] \> 10.0)
* Use of:

  * systemic corticosteroids for more than one week within three months prior to Baseline (BL)
  * Anti-Parkinsonian agents within two months prior to baseline (BL)
  * Approved or investigational Cholinesterase Inhibitors within 30 days or five half-lives, whichever is longer, prior to BL
  * Memantine or other N-methyl-D-aspartic acid (NMDA) antagonists within 30 days or five half-lives, whichever is longer, prior to BL
  * Treatment with high potency neuroleptics or narcotic analgesics within four weeks prior to BL
  * Cimetidine within four weeks prior to BL
  * Sedatives more frequently than two times per week for sleep within four weeks prior to BL
C: Inclusion Criteria:

1. 1st cortical or subcortical unilateral infarction (supratentorial lesion)
2. Confirmed by CT or MRI
3. Subacute stage: less than 1 week
4. Moderate to severe motor function involvement-total of FMA: 0-84
5. Age: between 18 and 80 years
6. Inpatients

Exclusion Criteria:

1. Progressive or unstable stroke
2. Pre-existing and active major neurological disease
3. Pre-existing and active (e.g., on chronic medication) major psychiatric disease, such as major depression, schizophrenia, bipolar disease, or dementia
4. A history of significant alcohol or drug abuse in the prior 3 years
5. Advanced liver, kidney, cardiac, or pulmonary disease
6. A terminal medical diagnosis consistent with survival \< 1 year
7. Substantial decrease in alertness at the time of randomization, defined as score of 2 on NIH Stroke Scale
8. Pregnancy or lactating; note that a negative pregnancy test will be required if the patient is a female in reproductive years
9. Any condition that would represent a contraindication to Cerebrolysin, including allergy to Cerebrolysin
10. Current enrolment in another therapeutic study of stroke or stroke recovery
11. Total serum bilirubin \> 4 mg/dL, alkaline phosphatase \> 250 U/L, SGOT/AST \> 150 U/L, SGPT/ALT \> 150 U/L, or creatinine \> 3.5 mg/dL; or cardiopulmonary deficits large enough to interfere with reasonable participation in physiotherapy during the trial.
12. Previous porcine brain peptide administration history
D: Inclusion Criteria:

* Female or male inpatients.
* Age: 18-80 years.
* If female, patient must not be pregnant
* Clinical diagnosis of ischemic stroke causing a measurable neurological deficit defined as impairment of language, motor function, cognition and/or gaze,vision or neglect. Ischemic stroke is defined as an event characterized by the sudden onset of an acute focal neurologic deficit presumed to be due to cerebral ischemia after CT scan excludes haemorrhage.
* Onset of symptoms within 3 hours prior to initiation of rt-PA administration.
* Stroke symptoms are to be present for at least 30 minutes and have not significantly improved before treatment. Symptoms must be distinguishable from an episode of generalized ischemia (i.e. syncope), seizure or migraine disorder.
* Patient is willing to participate voluntarily and to sign a written patient informed consent. Informed consent will be obtained from each patient or the subject's legally authorized representative or relatives, or deferred where applicable, according to the regulatory and legal requirements of the participating country.
* Patients who are unable to sign but who are able to understand the meaning of participation in the study may give an oral witnessed informed consent. These patients have to make clear undoubtful that they are willing to participate voluntarily and must be able to understand an explanation of the contents of the information sheet. A written consent has to be obtained as soon as possible.
* Willingness and ability to comply with the protocol.

Exclusion Criteria:

* Evidence of intracranial haemorrhage (ICH) on the CT-scan
* Violation of inclusion criteria not approved by clinical study director or study safety officer
* Failure to perform or to evaluate screening or baseline examinations
* Hospitalisation (except for study purposes) or change of concomitant medication 4 weeks prior to screening or during screening period
* Participation in another therapeutic clinical trial 3 months before baseline
* Patients with any history of prior stroke and concomitant diabetes
* Prior stroke within the last 3 months
* Platelet count of below 100x103/mm3
* Blood glucose \<50 or \>400 mg/dl (\<2.77 or \>22.15 mmol/L)
* Known haemorrhagic diathesis
* Manifest or recent severe or dangerous bleeding
* Known bacterial endocarditis, pericarditis
* Acute pancreatitis
* Documented ulcerative gastrointestinal disease during the last 3 months, oesophageal varices, arterial-aneurysm, arterial/venous malformation
* Neoplasm with increased bleeding risk
* Severe liver disease, including hepatic failure, cirrhosis, portal hypertension, oesaphageal varices) and active hepatitis
* Major surgery or significant trauma in past 3 months
* Lab values seriously abnormal, and/or more than 2 lab values abnormal not approved by clinical study director or study safety officer
* Serious drug allergies
* Hypersensitivity to one of the components of the drug
* Severe renal impairment
* Systolic blood pressure \>185 mmHg or diastolic blood pressure \>110 mmHg, or aggressive management (IV medication) necessary to reduce BP to these limits
* Recent (less than 10 days) traumatic external heart massage, obstetrical delivery, recent puncture of a non-compressible blood-vessel (e.g. subclavian or jugular vein puncture)
* Chronic intoxication or chronic substance use disorder with pharmaceuticals, drugs, alcohol or industrial poisons
* Symptoms of ischemic attack began more than 3 hours prior to start of thrombolytic therapy or if time of symptom onset is unknown
* Minor neurological deficit or symptoms rapidly improving before start of infusion
* Severe stroke as assessed clinically (e.g. NIHSS \>25) and/or by appropriate imaging techniques
* Epilepsy or epileptic seizure at onset of stroke
* Symptoms suggestive of subarachnoid haemorrhage, even if the CT-scan is normal
* Known history of or suspected intracranial haemorrhage
* Suspected subarachnoid haemorrhage or condition after subarachnoid hemorrhage from aneurysm
* Any history of central nervous system damage (i.e. neoplasm, aneurysm, intracranial or spinal surgery)
* Haemorrhagic retinopathy, e.g. in diabetes (vision disturbances may indicate haemorrhagic retinopathy)
* Administration of heparin within the previous 48 hours and a thromboplastin time exceeding the upper limit of normal for laboratory
* Patients receiving oral anticoagulants, e.g. warfarin sodium
* Special attention should be given to possible additive effects when used in conjunction with anti-depressants or MAO-inhibitors
* Cerebrolysin should not be mixed with balanced amino acid solutions in an infusion

Answer: B