An open label, crossover study to investigate the safety and tolerability of Sifrol® (pramipexole) (Boehringer Ingelheim) prolonged release tablets in order to establish the maximum tolerable dose and to assess bioequivalence of Pramipexole prolonged release tablets (Synthon B.V.) compared to Sifrol® prolonged release tablets (Boehringer Ingelheim) in healthy subjects in steady-state conditions

The research medication is a medication under development for treatment of the
signs and symptoms of idiopathic Parkinson*s disease.

To determine the relative bioavailability of pramipexole 4.5 mg tablets vs.
4.5 mg Sifrol in healthy subjects after up-titration.

This is an open-label, 2-period crossover study.

The study will start with a screening At the screening a physical examination
will take place and a few other standard medical assessments will be performed
( Vital Signs). Furthermore a blood and urine sample will be taken for
laboratory tests and a pregnancy test and drug screen will be done.
During the stay in the clinic the subject will receive the study medication and
on several time points blood and urine will be taken. The subjects will be
asked for possible side effects on a regular basis. Furthermore several safety
assessments will be done frequently.

Finally a follow up visit will take place.

Pramipexole is a registered drug (trade name: Sifrol®) that is well tolerated.
However, as with any medicine, it is possible that pramipexole can cause side
effects. Several clinical studies were conducted with patients with Parkinson's
Disease and patients with Restless Legg Syndrome. The following adverse
reactions are expected under the use of SIFROL: abnormal dreams, loss of
memory, behavioural symptoms of impulse control disorders and compulsions such
as binge eating (frequently eating abnormal quantities of food), compulsive
shopping, hypersexuality and pathological gambling; cardiac failure, confusion,
constipation, delusion, dizziness, presence of involuntary movements
(dyskinesia), difficult or laborated breathing (dyspnea), fatigue,
hallucinations, headache, hiccups, increased muscular movements (hyperkinesia),
hyperphagia, hypotension, insomnia, libido disorders, nausea, paranoia,
peripheral oedema, lung infection (pneumonia), pruritus, rash and other
hypersensitivity; restlessness, somnolence, sudden onset of sleep, fainting
(syncope), visual impairment including double vision (diplopia), vision blurred
and visual acuity reduced, vomiting, weight decrease including decreased
appetite, weight increase.

The research medication Premixole (Synthon B.V.) is not a registered drug.
Nevertheless, Premixole (Synthon B.V.) is expected to be similar to Sifrol,
since the active substance of both drugs is pramixole.

Furthermore, to reduce risk only subjects that are caucasian will be included
in the study and each subject will receive the concomitant medication
domperidone (10 mg Motilium®) three times a day against orthostatic hypotension
and nausea.

The blood collection may cause discomfort and bruising. Occasionally, fainting,
an infection at the blood sampling site, bleeding and blood clot formation can
occur.