Increasing Dose Study of Pramipexole in Two-way Cross-over Comparison of ER Tablet Versus IR Tablet in Japanese Healthy Male Volunteers

A Multiple Dose Study of Pramipexole With Increasing Doses (0.375 mg to 1.5 mg q.d.) of Oral Extended Release (ER) Tablet in Two-way Cross-over Comparison of 0.375 mg ER Tablet q.d. Versus 0.125 mg Immediate Release (IR) Tablet t.i.d. and 1.5 mg ER Tablet q.d. Versus 0.5 mg IR Tablet t.i.d. in Japanese Healthy Male Volunteers

The objectives of this study were to investigate relative BA at steady state and to investigate dose proportionality of pharmacokinetic parameters

Relative BA at steady state:

• Pramipexole 0.375 mg ER tablet q.d. versus pramipexole 0.125 mg IR tablet t.i.d.
• Pramipexole 1.5 mg ER tablet q.d. versus pramipexole 0.5 mg IR tablet t.i.d.

Dose proportionality of pharmacokinetic parameters:

· Pramipexole ER dosages from 0.375 to 1.5 mg q.d.

Inclusion Criteria:

• All subjects participating in the study are healthy male volunteers
• Age between 20 and 40 years
• Body mass index (BMI) between 17.6 and 26.4 kg/m2
• All volunteers must give written informed consent before screening to participate in this study and before first drug administration on Day 1 at Visit 2

Exclusion Criteria:

• Any findings of the medical examination (including blood pressure, pulse rate, ECG, and laboratory test parameters) of clinical relevance
• Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
• Diseases of the central nervous system (such as epilepsy), psychiatric disorders or neurological disorders
• History of orthostatic hypotension, fainting spells or blackouts
• Chronic or acute infections
• History of allergy/hypersensitivity (including drug allergy) which is deemed relevant to the trial as judged by the investigator
• Intake of drugs with a long half-life (>24 hours) within at least one month or less than ten half-lives of the respective drug before the administration of investigational products
• Use of any drugs which might influence the results of the trial within 7 days before the start of drug administration in the study or during the study period
• Participation in another trial with an investigational drug (within 4 months before the start of drug administration)
• Smoker (>10 cigarettes or >3 cigars or >3 pipes/day and who cannot refrain from smoking at the trial site)
• Alcohol abuse (>40 g/day)
• Drug abuse
• Blood donation (≥100 mL within 4 weeks before drug administration or during the trial)
• Excessive physical activities from 7 days before the start of drug administration to the end of this study
• Any positive results in hepatitis B surface antigen (HBsAg), anti hepatitis B core (HBc) antibodies, anti hepatitis C virus (HCV) antibodies and human immunodeficiency virus (HIV) test

The following exclusion criteria are of special interest for this study:

• Hypersensitivity to pramipexole or other dopamine agonists
• Supine blood pressure at screening of systolic <110 mmHg and diastolic <60 mmHg