Tolerability, Pharmacokinetics and Dopamine ß-hydroxylase (DßH) Inhibition Profile of BIA 5-453

Exclusion Criteria

• •Medical History
• •1. Any significant cardiovascular (e.g. hypertension), hepatic, renal, respiratory (e.g. childhood asthma), gastrointestinal, endocrine (e.g. diabetes, dyslipidemia), immunologic, dermatological, haematological, neurologic, or psychiatric disease.
• •2. Acute disease state (e.g., nausea, vomiting, fever, diarrhoea) within 7 days before study day 1.
• •3. History of drug abuse within 1 year before study day 1.
• •4. History of alcoholism within 1 year before day 1. Consumption of more than 50 g of ethanol per day (12.5 cL glass of 10° \[10%\] wine = 12 g; 4 cL of aperitif, 42° \[42%\] whiskey = 17 g; 25 cL glass of 3° \[3%\] beer = 7.5 g; 25 cL glass of 6° \[6%\] beer = 15 g
• •5. History of any clinically important drug allergy.
• •Physical and Laboratory Findings
• •6. An automatic ECG QTc interval reading at screening or enrolment \>450 ms.
• •7. Positive serologic findings for human immunodeficiency virus (HIV) antibodies, hepatitis B surface antigen (HBsAg), and/or hepatitis C virus (HCV) antibodies.
• •8. Positive findings of urine drug screen (eg, amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, methadone, opiates, MDMA \[3,4-methylenedioxy-methamphetamine; ecstasy\]).
• •Prohibited treatments
• •9. Prohibited Treatments: use of any investigational drug within 90 days or prescription drug within 30 days before investigational medical product (IMP) administration.
• •10. Consumption of any caffeine-containing products (e.g., coffee, tea, chocolate, or soda) in excess of 6 cups per day (or equivalent), of grapefruit, grapefruit-containing products, or alcoholic beverages within 72 before study day -1.
• •11. Use of any over-the-counter drugs including herbal supplements (except for the occasional use of acetaminophen \[paracetamol\], aspirin and vitamins ≤100% recommended daily allowance) within 7 days before IMP administration.
• •12. Donation of blood (ie 450 ml) within 90 days before study day 1.