Validation of Dyskinesia Rating Scales

Objective/Rationale:

Dyskinesias, or involuntary jerking movements, are troublesome problems for many Parkinson's
disease patients. Chemical studies have led to the development of several new treatment
strategies. However, because dyskinesias are cause various degrees of difficulty for
patients and are often perceived by patients and caregivers differently than by doctors, the
rating of dyskinesias remains a scientific challenge. This program will examine a wide
gamut of available rating scales to determine which one(s) detect change during dyskinesia
treatment. Establishing excellent measurement tools of dyskinesias will allow future
treatments to be evaluated in a uniform and maximally effective manner.

Project Description:

An team of experts will test several dyskinesia scales in a group of Parkinson's disease
patients with dyskinesia. Patients will be treated with either amantadine or placebo (an
inactive product). The study will be "blinded" so that the raters and the patients do not
know if a given patient is receiving amantadine or placebo. Amantadine is selected for this
trial, because it is the only drug that has received the designation of Efficacious for
dyskinesia by the Movement Disorder Society. This conclusion was based however, on small
studies and no large clinical trial of this drug has been conducted in dyskinetic patients.
The scales will assess dyskinesia before and after several weeks of treatment.

Relevance to Diagnosis/Treatment of Parkinson's Disease:

This study will establish a "gold standard" for rating dyskinesia in future trials of
treatments in Parkinson's disease patients. It will allow physicians to know the level of
change that occurs with a standard and available treatment (amantadine) and to compare that
level with changes that occur with newer treatments. Patients will benefit from this new
international standard, because they can compare the likelihood and magnitude of anticipated
improvement from different dyskinesia treatments, whether medical or surgical.

Anticipated Outcome:

The anticipated outcomes of this study are:

- The impact of amantadine treatment on dyskinesia will be clearly defined.

- The effect that participation in a clinical program, even if no amantadine is given
("placebo improvements") will be delineated.

- A hierarchy of numerous scales will be determined based on their absolute and relative
capability to detect change during treatment.

- The best scale(s) to evaluate dyskinesia in clinical practice and research efforts will
be identified.

Inclusion Criteria:

1. Parkinson's disease patient, defined by UK Brain Bank criteria

2. Current age between 30-90

3. Clinically pertinent dyskinesias defined by CGI-s score (see attachment) > 3 (mild)
established by clinician's total assessment of patient including objective
observation during the screening process. *

4. Documentation of creatinine level at screening evaluation that is within the normal
range for the local university laboratory.

5. Stable doses of all antiparkinsonian medications for at least 4 weeks

6. No treatment with amantadine for at least 3 months.

7. Presence of a caregiver willing to participate in the study

8. Subjects/caregivers must demonstrate the capacity to complete an accurate home diary
based on training and evaluation during the screening period (see attached training
rules).

9. Subjects must be able to provide written informed consent.

10. If the subject received amantadine in the past, the drug was stopped for reason other
than adverse events.

11. In the opinion of the enrolling investigator, the subject will be able to maintain
current dosing schedule of antiparkinsonian drugs for the duration of the trial.

12. The subject must be willing to participate in all study related activities and
visits.

Exclusion Criteria:

1. Subjects who have had prior brain surgery.

2. Subjects with other major illnesses that could be complicated by amantadine exposure,
including glaucoma, current hallucinations, urinary retention.

3. Subjects with dementia, depression and psychosis as determined by clinical
examination.