| Eligibility |
Inclusion Criteria;
- General Subject Inclusion Criteria
In order to be eligible for participation in this trial, the subject must:
1. Be able to read at a 6th grade level or equivalent, (as determined by the
investigator, and must have a history of academic achievement and/or employment
sufficient to exclude mental retardation.)
2. Be able to speak, read, hear, and understand the language of the trial staff, and the
informed consent form, and possess the ability to respond verbally to questions,
follow instructions, and complete questionnaires and detailed neuropsychological test.
3. Have results of clinical laboratory tests/physical examination, vital signs, and
Electrocardiogram within normal limits (at 45 days prior to [18F]THK-5351 Positron
Emission Tomography scan ) or clinically acceptable to the investigator at screening.
4. Be able to possess the ability to respond verbally to questions, follow instructions,
and underwent research assessment, including brain images based on the investigator's
judgment. Each subject is also able and willing to adhere visit schedules.
5. If female, not be of childbearing potential as indicated by one of the following
1. has reached natural menopause, defined as = 24 months of spontaneous amenorrhea
or
2. has had a hysterectomy; or
3. has had a bilateral oophorectomy (with or without a hysterectomy) and more than 6
weeks have passed since the surgery.
6. Each subject (or legal representative) must sign the informed consent form in
accordance with local requirements after the scope and nature of the investigation
have been explained to them, and before screening assessments.
- Normal Subject Inclusion Criteria
1. . Be = 20 years of age at the screening visit
2. Each subject must not report a history of memory decline with gradual onset and slow
progression, that is either corroborated by an informant who knows the subject well or
is documented in medical records. Each subject must have general cognitive function
and activities of daily living sufficiently intact, based on clinical assessment, so
as not to meet criteria for mild AD dementia (based on DSM-IV-TR(Diagnostic and
Statistical Manual of Mental Disorders, 4th Edition) and NINCDS-ADRDA(National
Institute of Neurological and Communicative Disorders and Stroke; Alzheimer's Disease
and Related Disorders Association) criteria).
3. Each subject must have results of Korean-Mini Mental State Exam (K-MMSE) at screening
that is =1.5 SD above the appropriate population mean, corrected age and education.
4. Each subject must not have objective impairment in memory at screening that is =1.5 SD
above the appropriate population mean, corrected age and education, as measured by the
Seoul Verbal Learning Test (SVLT) delayed recall score of the Seoul Neuropsychological
Screening Battery (SNSB)-?.
5. Each subject must have normal level of general cognitive function and activities of
daily living sufficiently intact, that is 0 score as measured by the Clinical Dementia
Rating (CDR).
6. Each subject must have an MRI scan obtained at screening that supports diagnosing the
current status of normal cognition. The MRI for research must be consistent and
sufficient in quality enough to analyze volume of interest (VOI) with partial volume
correction (Detailed protocol is described in the MRI scanning manual).
7. Each subject must be willing to provided blood samples for genotyping apolipoprotein
E.
- Alzheimer's Disease Inclusion Criteria
1. Be = 50 and < 80 years of age at the Screening Visit.
2. Each subject must have general cognitive function and activities of daily living
impairment, based on clinical assessment, so as to meet criteria for AD dementia
(based on DSM-IV-TR and NINCDS-ADRDA criteria).
3. Each subject's K-MMSE score ranges 15-26 and CDR 0.5, 1 or 2.
4. Each subject must have a Rosen-modified Hachinski Ischemia Score = 4 at Screening.
5. Each subject must have a reliable and competent trial partner/informant who must have
a close relationship with the subject, and can be accompanied at all visits in this
study.
6. Each subject must have an MRI scan obtained at screening that supports diagnosing
Alzheimer's disease. The MRI for research must be consistent and sufficient in quality
enough to analyze volume of interest (VOI) with partial volume correction (Detailed
protocol is described in the MRI scanning manual).
7. If receiving some medications, be on a stable dose for at least the 4 weeks before
performing THK5351 PET scan, and the subject must be willing to remain on the same
dose for the duration of the trial.
8. Each subject must be willing to provided blood samples for genotyping ApoE.
9. Each subject must shows positive in amyloid PET scan.
Exclusion Criteria:
The subject must be excluded from participating in the trial if the subject fulfil any
single criteria described below:
- General Exclusion Criteria 1. Based on the investigators' judgement, if the patient is
not capable of communicating with the site personnel, if the patient is not proficient
in the language in which the psychometric tests will be completed, or if the patient
is not sufficient for compliance with the study procedures.
2. The patient has an abnormal physical examination, abnormal laboratory test or
electrocardiography results at the screening that are clinically significant to affect
results of the research, as judged by the investigator.
3. If the patient has or is suspicious of having a hypersensitivity or allergy to
[18F] THK-5351 or its derivatives.
4. The patient is pregnant, is attempting to become pregnant, or is nursing
(breast-feeding) children.
5. The patient has a history of alcoholism or drug dependency/abuse within the last 2
years before screening.
6. The patient has contraindications to undergo PET or MRI, which include but are not
restricted to the examples below: claustrophobia, cardiac pacemaker, metal devices
around the eye or spinal cord, cochlear implant, etc.) at the screening visit.
7. The patient has been treated with any investigational medicinal product (IMP)
within 30 days prior to the screening visit.
8. The patient has been tested positive for hepatitis B surface antigen (HBsAg),
hepatitis C virus antibodies (anti-HCV), HIV Antibody, or syphilis serum test at the
screening visit.
9. The patient has been receiving an anti-cholinergic drug in a regular basis within 3
months prior to the screening visit.
10. The patient has evidence of a clinically relevant neurological disorders other
than the disease being studied (i.e., prodromal AD) at screening, including but not
limited to: territorial cerebral infarction, intracranial hemorrhage, multiple
sclerosis, neurosyphilis, mental retardation, hypoxic encephalopathy, major head
trauma with loss of consciousness that led to persistent cognitive deficits.
11. The patients has disorders related to blood coagulation which could be
inappropriate for arterial or venous sampling.
- Normal Subject Exclusion Criteria 1. The patient has evidence of a clinically
significant medical disorder, neurological disorder, has an abnormal physical
examination or abnormal laboratory evaluations from the screening visit, or has other
abnormal findings that are clinically significant, as judged by the investigator.
2. The patient has more than one direct family members who were diagnosed with
Alzheimer's disease.
- Alzheimer's Disease Exclusion Criteria
1. The patient has evidence of any clinically significant neurodegenerative disease,
or other serious neurological disorders other than AD including but not limited
to stroke, traumatic brain injury, non-Alzheimer tauopathy, Parkinson's disease,
or has evidence of a clinically relevant or unstable psychiatric disorders,
including but not limited to major depression, schizophrenia, or bipolar
disorder.
2. The patient has more than two direct family members who were diagnosed with
Alzheimer's disease.
3. The patient has a stroke or an evidence of significant cerebrovascular disease
from screening imaging scan that is clinically important in the investigator's
opinion.
4. The patient has received any of the treatments targeting tau protein prior to
[18F]THK-5351 PET scan.
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