Pharmacokinetics of BIA 5-453 and Its Metabolites
Hypertension, Chronic Heart Failure
About this trial
This is an interventional treatment trial for Hypertension
Eligibility Criteria
Inclusion Criteria:
All subjects (young and elderly):
- A signed and dated informed consent form before any study-specific screening procedure is performed.
- Healthy as determined by the investigator on the basis of medical history, physical examination, clinical laboratory test results, vital signs and digital 12-lead electrocardiogram (ECG).
Non-smoker or smoker of <10 cigarettes per day as determined by history. Must be able to abstain from smoking during the inpatient stay.
Young subjects only:
Males aged between 18 and 45 years, inclusive.
Elderly subjects only:
- Males older than 65 years, inclusive. Specific inclusion criteria procedure: genotyping Since acetylation is an important BIA 5-453 metabolic pathway, NAT1 and NAT2 genotyping was required for inclusion for distinguishing between poor and faster acetylators (both could however be enrolled in the study).
Exclusion Criteria:
All subjects (young and elderly):
General
- Subjects who had participated in a clinical trial with an investigational drug within the 90 days prior to screening.
- Subjects who were likely to be noncompliant with the protocol, or who were felt to be unsuitable by the Investigator for any other reason.
- Positive serologic findings for human immunodeficiency virus (HIV) antibodies, hepatitis B surface antigen (HBsAg), and/or hepatitis C virus (HCV) antibodies.
Positive findings of urine drug screen (amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, methadone, opiates, MDMA [3,4-methylenedioxy-methamphetamine; ecstasy]).
Medical History
- Any significant cardiovascular, hepatic, renal, respiratory (e.g. childhood asthma), gastrointestinal, endocrine (e.g. diabetes), immunological, dermatological, haematological, neurological, or psychiatric disease and history thereof.
- Acute disease state (e.g., nausea, vomiting, fever, diarrhoea) within 7 days before study Day 1.
- Subjects proned to orthostatic hypotension: there was a measurement of supine blood pressure (BP) and heart rate (HR) after the subjects had been resting for at least 10 minutes, followed by standing BP and HR after 2 minutes of standing: orthostatic hypotension as defined by as a difference between supine systolic BP (SBP) and standing SBP ≥20 mmHg or a difference between supine diastolic BP (DBP) and standing DBP ≥10 mmHg.
- History of drug abuse within 1 year before study day 1.
- 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.
- History of any clinically important drug allergy.
- Had previously received BIA 5-453. Prohibited treatments and dietary restrictions
- 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 24 hours before study day 1.
- 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 BIA 5-453 administration.
Donation of blood (i.e. 450 mL) within 60 days before study day 1.
Young subjects only:
General
- An automatic QTc interval reading ≥450 ms at the screening assessment. Prohibited treatments and dietary restrictions
Prohibited Treatments: use of any investigational drug within 90 days (young and elderly subjects) or prescription drug within 30 days before BIA 5-453 administration.
Elderly subjects only:
General
- An automatic QTc interval reading ≥470 ms at the screening assessment.
Sites / Locations
- Biotrial
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
BIA 5-453 (Young)
BIA 5-453 (Elderly)
Each subject participated in the study for approximately 7 weeks. Participation included the screening evaluations within 28 days before the first administration, phase A (single dose, a 2-day inpatient period followed by 4 ambulatory visits), phase B (multiple-dose during 7 days, 6 ambulatory visits, followed by a 2-day inpatient period and by 5 ambulatory visits) and a follow-up visit 7 to 10 days after the last administration. Phase A: single-dose on Day 1, followed by a wash out period Phase B: repeated dose from Day 6 to Day 12 (7 days, steady-state)
Each subject participated in the study for approximately 7 weeks. Participation included the screening evaluations within 28 days before the first administration, phase A (single dose, a 2-day inpatient period followed by 4 ambulatory visits), phase B (multiple-dose during 7 days, 6 ambulatory visits, followed by a 2-day inpatient period and by 5 ambulatory visits) and a follow-up visit 7 to 10 days after the last administration. Phase A: single-dose on Day 1, followed by a wash out period Phase B: repeated dose from Day 6 to Day 12 (7 days, steady-state)