Safety, Tolerability, Pharmacokinetic, Including Food Interaction, and Pharmacodynamic Profile of BIA 5-1058.
Condition: Hypertension and Chronic Heart Failure
MeSH terms: Hypertension; Heart Failure
Intervention: BIA 5-1058; Placebo
Intervention description: oral administration; oral administration
Intervention MeSH terms: Zamicastat
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 124.0
Sex: Male
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: BIA 5-1058; hypertension; chronic heart failure; cardiovascular disorders

Summary:

      The purpose of this study is to to assess the safety and tolerability of BIA 5 1058 after
      single and multiple oral doses
    

Eligibility criteria:

        Inclusion Criteria:

        Subjects were eligible for the study if they met all the following inclusion criteria:

          -  Gender - male

          -  Age - 18 - 55 years, inclusive

          -  Body Mass Index (BMI) - 18.0 - 30.0 kg m2 (BMI (kg m2) = Body weight (kg) - Heigh t2
             (m 2))

          -  Ability and willingness to abstain from alcohol, methylxanthine-containing beverages
             or food (coffee, tea, cola, chocolate, power drinks), grapefruit (juice) and tobacco
             products from 48 h prior to entry in the clinical research centre until discharge

          -  Medical history without major pathology

          -  Normal resting supine blood pressure and pulse rate showing no clinically relevant
             deviations as judged by the MI

          -  Computerised (12-lead) ECG recording without signs of clinically relevant pathology or
             showing no clinically relevant deviations as judged by the MI

          -  All values for haematology and for clinical chemistry tests of blood and urine within
             the normal range or showing no clinically relevant deviations as judged by the MI

          -  Willingness to sign the written ICF

        Exclusion Criteria:

        Subjects were excluded from participation if any of the following exclusion criteria
        applied

          -  Any significant cardiovascular (e.g. hypertension), hepatic, renal, respiratory (e.g.
             childhood asthma), gastrointestinal, endocrine (e.g. diabetes, dyslipidemia),
             immunologic, haematological, neurologic, or psychiatric disease

          -  An automatic ECG QTc interval reading at screening or enrolment of + 440 ms.

          -  Evidence of clinically relevant pathology

          -  Mental handicap

          -  History of relevant drug and or food allergies

          -  Smoking more than 10 cigarettes and or cigars and or pipes daily

          -  History of alcohol abuse or drug addiction (including soft drugs like cannabis
             products)

          -  Use of any prescription drug within 30 days before study drug administration with the
             exception of influenza vaccination

          -  Use of any over-the-counter drugs including health supplements, herbal supplements
             such as St. John's Wort extract (except for the occasional use of acetaminophen
             (paracetamol), aspirin and vitamins - 100 recommended daily allowance) within 7 days
             before study drug administration. The use of paracetamol and or topical medication was
             allowed up to 3 days before entrance into the clinical research facility

          -  Participation in a drug study within 90 days prior to drug administration

          -  Participation in more than 3 other drug studies in the 10 months preceding the start
             of this study (this was the first administration of study drug)

          -  Donation of more than 50 mL of blood within 90 days prior to first drug administration

          -  Donation of more than 1.5 litres of blood in the 10 months preceding the start of this
             study (this was the first administration of study drug)

          -  Positive screen on drugs of abuse (opiates, methadone, cocaine, amphetamines,
             cannabinoids), barbiturates, benzodiazepines, tricyclic antidepressants and alcohol

          -  Intake of more than 24 units of alcohol per week (1 unit of alcohol equals
             approximately 250 mL of beer, 100 mL of wine or 35 mL of spirits)

          -  Positive screen on hepatitis B surface antigen (HBsAg)

          -  Positive screen on anti hepatitis C virus (HCV)

          -  Positive screen on anti human immunodeficiency virus (HIV) 1 - 2

          -  Acute disease state indicated as clinically relevant by the MI (e.g. nausea, vomiting,
             fever, diarrhoea) within 7 days before the first drug administration

          -  Non-willingness to consume the Food and Drug Administration (FDA) breakfast (FE part
             only)