Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Rising Dose Regimens of BIA 5-453

Inclusion Criteria: 1. A signed and dated informed consent form before any study-specific screening procedure is performed. 2. Male patients aged between 18 and 65 years (inclusive) 3. Body mass index (BMI) between 18 and 35 kg/m2 (inclusive) 4. Patients with essential hypertension, without previous treatment (but in which treatment was justified), defined at the selection visit as blood pressure (BP) after 10 minutes of rest in supine position of * diastolic blood pressure (DBP) ≥ 90 mmHg and/or, * systolic blood pressure (SBP) ≥ 140 mmHg 5. Patients with essential hypertension, with previous treatment, defined at the end of the screening period (i.e. after 3 weeks wash-out of antihypertensive treatment(s) and before D-1) as blood pressure (BP) after 10 minutes of rest in supine position of * diastolic blood pressure (DBP) ≥ 90 mmHg and/or, * systolic blood pressure (SBP) ≥ 140 mmHg 6. Naive or patients taking any class of antihypertensive treatment including (but not limited to) one of the following authorised treatments: B-blockers, diuretics, angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB), calcium channel blockers. Patients observed a wash-out for their antihypertensive treatments of approximately 3 weeks. 7. Laboratory tests within the normal range of the laboratory (haematology, biochemistry and urinalysis) or considered as not clinically significant by the investigator. 8. Electrocardiogram recording on a 12-lead ECG without any clinically significant abnormality 9. Covered by National Health Insurance 10. Once clinical eligibility had been established, patients conducted 24 h ambulatory blood pressure monitoring (ABPM) at the end of the screening period, and after treatment wash-out for patients already treated. They had to meet the following off-treatment criteria for mean 24 h ambulatory blood pressure measurements to be included in the study: * Average daytime ambulatory systolic/diastolic BP ≥ 135 / 85 mm Hg and/or * Ambulatory night-time systolic/diastolic BP ≥ 120 / 70 mm Hg. Exclusion Criteria: Criteria associated with hypertension, associated risk factors, and target organ damage: 1. Severe hypertension (SBP≥180 mm Hg and/or DBP≥110 mm Hg) at any time during the study from screening period to end of study visit or in the medical history, malignant hypertension 2. Secondary hypertension (including known renovascular hypertension, pheochromocytoma) 3. Any recent history of coronary artery disease (in the previous 6 months) and including myocardial infarction, or precordial pain suggesting angina pectoris and coronary revascularisation 4. Any recent history of cardiac failure (in the previous 6 months) 5. Any recent history of cerebrovascular stroke or transient ischemia (in the previous 6 months) 6. Any known aortic or mitral valve stenosis or hypertrophic obstructive myocardiopathy 7. Any known severe ocular complication of hypertension (stage III or IV retinopathy), 8. Any history of ventricular rhythm disorders (torsades de pointes, ventricular tachycardia, polymorphic ventricular extra-systoles except isolated extra-systoles), auricular disorders (fibrillation or flutter). 9. Any surgical or medical condition that might significantly alter the absorption, distribution, metabolism, or excretion of Etamicastat (BIA 5-453) 10. Presence or history of clinically relevant cardiovascular, pulmonary, gastrointestinal, hepatic, renal, metabolic, haematological, neurological or psychiatric disease. 11. Frequent headaches and/or migraine, recurrent nausea and/or vomiting (more than twice a month). Criteria associated with patient characteristic: 12. History or presence of drug dependence. 13. Patients smoking more than 10 cigarettes per day 14. 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 15. Participation in a drug trial within 3 months preceding the selection visit. 16. Positive result from the hepatitis serology for hepatitis B (HBs Ag) and/or hepatitis C (HCV Ab). 17. Positive result for HIV1+2 serology. 18. Positive Urine Drug Screen (UDS) (amphetamines, benzodiazepines, ecstasy, cocaine, opiates). 19. Loss of greater than 400 mL or blood donation within the last 3 months. Criteria associated with concomitant diseases: 20. Patients taking one of the following treatments: aldosterone antagonists, nitrite derivatives. 21. Presence or history of any allergic or unusual reaction to drugs. 22. Excessive consumption of beverages containing xanthine bases (more than six cups or glasses per day) or inability to stop consumption during the hospitalization.