A single-center, open-label, randomized, 3-way crossover study to compare the rate and extent of Rivastigmine absorption from two different formulations of 7 day Rivastigmine transdermal systems (7-day RTS) with 24-hour Exelon® patches applied daily for 7 days in healthy male and female subjects.

The 7-day rivastigmine transdermal system (RTS) is a new, investigational
transdermal application form (transdermal means: patch for administration via
the skin) of the known drug rivastigmine that may eventually be used for the
treatment of mild to moderate Alzheimer*s disease related dementia and
Parkinson*s disease related dementia.
Rivastigmine blocks the degradation of acetylcholine, a compound involved in
signal transduction between nervous cells decreasing the symptoms of dementia.
The 7-day RTS being studied will be worn for 7 continuous days and has not been
registered as an administration form. Rivastigmine has been given to humans
using a transdermal patch before. The Exelon® transdermal patch contains
rivastigmine is worn for 24 hours, and is a registered drug.

To compare the rate and extent of rivastigmine absorption from two different
formulations of 7-day rivastigmine transdermal systems (7-day RTS) with 24-hour
Exelon® patch applied daily for 7 days in healthy adult male and female
subjects.

To assess skin irritation, discomfort, patch adhesion and adhesive residue of
7-day RTS and Exelon® transdermal patch in healthy adult male and female
subjects.

To assess the safety and tolerability of 7-day RTS and Exelon® transdermal
patch in healthy adult male and female subjects.

The study will consist of 3 periods during which the volunteer will stay in the
clinical research center in Zuidlaren for 10 days (9 nights). The time interval
between the different periods is at least 5 days between leaving the clinical
research center and entering the clinical research center for the next period.

The volunteers are expected at the clinical research center at 14:00 h in the
afternoon prior to the day of administration of study medication.

They willl leave the clinical research center on Day 9 of each period (Day 1 is
the day of administration of study medication).

The participation to the entire study, from pre-study screening until the post
study screening, will be maximally 75 days.

On Day 1 of each period RTS or Exelon® will be applied after a fasting period
(no food or drinks) of at least 10 hours. The transdermal patches will be
applied to the upper back. Per period the volunteer will receive 1 of the
treatments. During the study they will receive all 3 treatments once. The
sequence of the treatments will be determined by chance.

The Exelon® patch will be removed every morning and a new patch will be applied
to a different site on the back. In the morning of Day 8 the (last) patch will
be removed.

On Day 7 of each period the volunteer will also have to remain fasted for 10
hours before the time of patch application.

For all groups the fasting period on Days 1 and 7 will continue until 4 hours
after the time of patch application. Then they will receive a lunch. During
fasting and after patch application, the volunteer is allowed to drink water.

Procedures: pain, light bleeding, heamatoma, possibly an infection.

Rivastigmine has been on the market since 1998. Transdermal patches containing
rivastigmine have been on the market from 2006 onwards. The 7-day RTS was
tested in 1 earlier study with 18 subjects. The most important adverse events
were headache, itch at the application site, hematoma at the site of the
cannula and application site irritation.

Common side effects associated with the use of a transdermal system may
include, but are not limited to, local skin irritation of the patch site
(including redness, itching, or rash). The most common side effects of
rivastigmine are nausea, vomiting, and diarrhea. Other side effects that are
not as common are tremors, anorexia and dizziness.