Single-site, open-label, randomized, crossover study in healthy subjects to evaluate bioequivalence of rotigotine transdermal patches (2mg/24H) from 2 different manufacturing sites

The rotigotine transdermal patch is an approved drug in the European Union
(called Neupro®) and in the USA for the treatment of the symptoms of
Parkinson*s disease and Restless Legs Syndrome (RLS).

Parkinson's disease is a result of there being less of a chemical called
dopamine in the brain. This lack of dopamine causes symptoms such as shaking,
muscle stiffness, and slow movement. Rotigotine is a dopamine-receptor agonist
which means that it acts on the same receptors in the brain as dopamine. In
effect, it acts like a partial substitute for dopamine and this helps to ease
Parkinson's disease symptoms. It may be used alone, or in combination with
other medicines to treat Parkinson's disease.

Restless Legs Syndrome is characterized by an uncomfortable feeling in the
legs, which gives the urge to move the legs to get relief. Administration of
rotigotine can help when these feelings are severe enough to cause distress.

Currently, all rotigotine transdermal patches are manufactured at 1
manufacturing site. A second site has been built to manufacture the same
patches. Before these patches may be used, it needs to be investigated if they
are exactly the same as those manufactured at the current site. Therefore, this
study will compare the patches from both manufacturing sites with regard to how
quickly and to what extent rotigotine is absorbed and eliminated from the body
(this is called pharmacokinetics). This pharmacokinetic comparison is called a
bioequivalence study. Further, the safety, tolerability and adhesiveness of the
2 different patches will be compared.

The actual study will consist of 2 periods. In both periods the volunteer will
stay in the clinical research center in Zuidlaren from Day -1 to Day 3 (being 4
days and 3 nights). The time interval between Day -1 of each period is at least
5 days.

In this study you will receive 2 different treatments:

Treatment A:
1 rotigotine transdermal patch from the *new* manufacturing site containing 2
milligrams of rotigotine applied for 24 hours on the skin

Treatment B:
1 rotigotine transdermal patch from the *old* manufacturing site containing 2
milligrams of rotigotine applied for 24 hours on the skin

As the rotigotine patch is already prescribed and used, adverse effects have
been reported following its use. The very commonly reported adverse effects are
feeling sick, vomiting, tiredness, localized skin irritations under the patch
(such as redness and itching), sleepiness, dizziness and headache. Another
adverse effect can be an allergic reaction that may include swelling of the
face, lip and tongue.

Procedures: pain, minor bleeding, bruising, possible infection