Switching From Oral Dopamine Agonists to Rotigotine

The study will consist of 3 in-person visits and 4 scheduled telephone appointments over the
course of approximately 6 weeks. The first visit will be the screening visit during which
eligibility will be confirmed and informed consent obtained. After the first visit,
subjects will continue their current oral dopamine agonist for a one-week baseline period
during which they will record RLS symptoms daily.

The second visit will be the baseline visit. The IRLS scale, a commonly used measure of RLS
symptoms, will be obtained. An individualized schedule for down-titration of oral dopamine
agonist and concomitant up-titration of rotigotine will be provided. After the second visit,
subjects will begin this cross-titration. This will entail a pre-determined incremental
taper of the oral medication and flexible up-titration of rotigotine according to symptoms.
During this time, subjects will keep diaries of RLS symptoms and will speak with the
investigator over the phone a total of 3 times (visits 2a-2c) to discuss dosing of
rotigotine.

After the titration is complete, subjects will enter the maintenance period, which will last
28 days. There will be another phone contact (2d) one week after the titration is complete
to adjust the dose of rotigotine as needed. The subject will then continue the chosen dose
for the next 3 weeks of the maintenance period. There will be one final phone contact (2e)
1 week prior to the end of the maintenance period to remind subjects to resume RLS symptom
diaries during the final week of the maintenance period.

The third and final visit will take place at the end of the maintenance period. RLS symptoms
will be discussed and the IRLS scale, Clinician Global Impression of Change (CGIC), Patient
Global Impression of Change (PGIC), and Preference of Medication Scale (POMS) will be
administered.

Inclusion Criteria:

- A diagnosis of RLS, defined by International Restless Legs Study Group (IRLS)
essential criteria:

1. An urge to move the legs, usually accompanied or caused by uncomfortable and
unpleasant sensations in the legs.

2. The urge to move or unpleasant sensations begin or worsen during periods of rest
or inactivity such as lying down or sitting.

3. The urge to move or unpleasant sensations are partially or totally relieved by
movement, such as walking or stretching, at least as long as the activity
continues.

4. The urge to move or unpleasant sensations are worse in the evening or night than
during the day or only occur in the evening or night.

(Although some subjects may not meet these criteria on their current oral regimen, these
symptoms must have been present prior to treatment.)

- Current treatment with either pramipexole (≤1 mg total daily dose) or ropinirole (≤4
mg total daily dose) with unchanged dose for the past 30 days. Patients also on
other RLS medications will be allowed to participate if the dosing has been stable
for the past 30 days and the subject agrees to maintain a stable dose for the
duration of the trial.

- Inadequate symptom control or patient dissatisfaction with current oral regimen.

- Able to speak and read English.

- Able to provide informed consent.

- Able to learn and demonstrate appropriate patch application.

- Returns appropriately completed RLS symptom log at Visit 2.

- Confirms understanding of cross-titration schedule and is able to restate or
summarize these instructions at Visit 2.

- Age ≥18 and ≤75.

- BMI ≥18 and ≤35

- History and/or clinical records document no change in medications active in the
central nervous system (antidepressants, analgesics, antipsychotics, antiepileptics,
hypnotics, etc.) for at least 30 days prior to visit 1.

- Able to understand study procedures and agrees to remain on stable medications during
the period of the study.

- Women of childbearing potential must agree to use a medically accepted method of
birth control. Acceptable forms of birth control include:

1. Condom + spermicide

- b. Diaphragm + spermicide

- c. Oral contraceptive pills, hormone implants (like Norplant),or injections
(like Depo-Provera)

- Intrauterine Device

Exclusion Criteria:

- Known secondary cause of RLS, including end-stage renal disease, severe iron
deficiency (ferritin <18), pregnancy.

- History of frequent symptomatic orthostatic hypotension.

- Current treatment with a dopamine antagonist medication.

- Another chronic pain syndrome that would, in the opinion of the investigator,
interfere with evaluation of RLS symptoms or the response to the study medication.

- Plan to undergo a procedure that may require short or long-term opiates for pain
control during the course of the trial.

- Women who are pregnant, lactating, or planning to become pregnant.

- Shift work or other commitments that do not allow for regular sleep at night.

- Known hypersensitivity or intolerance to rotigotine.

- Known allergy to sulfite-containing drugs.

- History of problematic skin hypersensitivity to adhesives.

- Previous or current clinically significant impulse control disorder, as determined by
clinical interview.

- Anticipated change in psychiatric or neurologic status likely to require adjustment
of CNS-active medications during the study period.

- Unwillingness of subject to remain on stable doses of CNS-active medications.

- Unwillingness of subject to refrain from as-needed use of RLS medications.

- Significant risk for suicide by clinical interview.

- History of severe mental illness or psychosis

- Current unstable medical illness.

- Any medical or psychiatric condition that, in the opinion of the investigator, would
interfere with participation in the study.