A Trial of 18F-AV-133 Positron Emission Tomography (PET) Imaging to Differentiate Subjects With Parkinson's Disease (PD) From Other Movement Disorders

The early detection and monitoring of neurodegenerative diseases including Parkinson's
disease (PD), Alzheimer's disease (AD), Dementia with Lewy Bodies (DLB), and other dementias
and movement disorders represent a very significant unmet medical need. Disease mechanisms
are gradually becoming understood, and disease-modifying drugs are emerging that target the
specific molecular pathology underlying each of these diseases. Tools for accurate and early
differential diagnosis are thus necessary to determine the appropriate treatment for
patients and to minimize inappropriate use of potentially harmful treatments. In addition,
such diagnostic imaging tools are expected to permit monitoring of disease progression and
will thus accelerate testing and development of disease-modifying drugs. Furthermore, the
new imaging test may be useful as a prognostic tool by identifying humans suffering from
neurodegenerative diseases before the clinical manifestations become evident.

Inclusion Criteria:

- Males or females ≥ 40 years of age;

- Presenting (within the last 3 months) for an initial evaluation to a movement
disorders specialist with signs or symptoms suggestive of a movement disorder;

- The subject's signs or symptoms were previously evaluated by a physician who was not
a movement disorders specialist during the previous six months;

- Absence of an established clinical movement disorder diagnosis;

- Symptoms mild in intensity, this includes Hoehn & Yahr ≤ 2 (Exceptions are allowed
for subjects who meet criteria for Hoehn & Yahr stage 3 due to early onset of
postural instability and/or gait impairment out of proportion to his/her other
Parkinson signs and symptoms);

- Montreal Cognitive Assessment (MoCA) score ≥ 22;

- Can tolerate imaging visit procedures; and

- Provide written informed consent prior to study entry.

Exclusion Criteria:

- Have been referred to the movement disorders clinic primarily for the purpose of
disease management (no diagnostic uncertainty exists on the part of the
non-specialist or referring physician);

- Have a previous movement disorder diagnosis given by a movement disorders specialist
prior to the time of enrollment;

- Have received a total of more than 90 days treatment with dopaminergic medications,
including direct dopamine agonists or precursors (levodopa) or have received a total
of more than 180 days treatment with MAO-B inhibitors, amantadine, anticholinergics
or primidone or beta-blockers prescribed for treatment of tremor or signs of
parkinsonism;

- Have had a sustained and clinically meaningful response to anti-parkinsonian
medications;

- Are currently taking or have taken MAO-B inhibitors in the past 4 weeks;

- Have a known CNS structural lesion such as stroke or tumor that likely accounts for
their symptoms;

- Have clinically meaningful cognitive impairment or dementia (mild cognitive problems
as might be expected in the earliest stages of PD are not exclusionary);

- Have current clinically significant cardiovascular disease or clinically important
abnormalities on screening ECG (including but not limited to QTc > 450 msec);

- Are currently taking medications that are known to cause QT-prolongation;

- Are currently taking medications with narrow therapeutic windows (e.g. warfarin or
other anticoagulant therapies);

- Are currently taking tetrabenazine (TBZ), amphetamine type drugs;

- Have a current clinically significant endocrine or metabolic disease, pulmonary,
renal or hepatic impairment, or cancer (excluding localized basal cell carcinoma and
in situ prostate cancer) that would interfere with completion of the study;

- Have a recent history (within the past year) of alcohol or substance abuse or
dependence;

- Are females of childbearing potential who are not surgically sterile, not refraining
from sexual activity or not using reliable contraception. Females must not be
pregnant (negative serum beta-hCG at the time of screening and negative urine
beta-hCG on the day of imaging), must not be breastfeeding at screening, must avoid
becoming pregnant and use adequate contraceptive methods for 14 days prior to and 24
hours after administration of 18F-AV-133 for injection;

- Have had prior intracranial surgery; and

- Are receiving any investigational medications, or have participated in a trial with
investigational medications within the last 30 days.