Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of BIA 5-1058
Condition: Cardiovascular Disease+Pulmonary Disease; Pulmonary Arterial Hypertension
MeSH terms: Pulmonary Arterial Hypertension; Cardiovascular Diseases
Study type: Interventional
Phase: Phase 1

Summary: 
      This is a single centre, double-blind, randomised, placebo-controlled, parallel staggered
      group study of BIA 5-1058 in 11 different cohorts of 15 healthy subjects. Subjects will be
      randomly assigned to receive once-daily oral doses of BIA 5-1058 or matching placebo for 10
      days.

      The primary objectives of the study are to assess the safety and tolerability of BIA 5-1058
      after repeated ascending doses under fed and fasted conditions and to assess the
      pharmacokinetics (PK) of BIA 5-1058 after repeated ascending doses under fed conditions
      having matching fasting cohorts for comparison of bioavailability.

      It is planned that comparison cohorts will be dosed in parallel, i.e. Cohorts 1 and 2, 3 and
      4, 5 and 6, 7 and 8 and 9 and 10. Cohorts may be split or dosed sequentially for logistical
      purposes; however, data from both comparison cohorts (e.g. Cohorts 1 and 2) must be available
      before dose escalation to the next dose levels.
    

Detailed description: 
      Each cohort will follow the same study design. Subjects will be screened for inclusion in the
      study between 28 and 3 days before the first dose. Eligible subjects will be admitted 2 days
      before dosing (Day -2) for all regimens, and will remain resident in the clinic until 72 h
      after the last dose (Day 13). On Day -1, blood samples will be taken in all cohorts for PD
      assessments at pre-defined time points. These time points will be time matched to Day 1 PK
      and PD time points. Subjects in Cohorts 2, 4, 6, 8, 10 and 11 (fed cohorts) will also undergo
      continuous cardiac monitoring via 24 h Holter recordings on Day -1.

      Subjects in Cohorts 1, 3, 5, 7 and 9 will receive oral doses of BIA 5-1058 or matching
      placebo once daily from Day 1 to Day 10, administered in the morning of each day after a
      minimum of 8 h fast and will remain fasted until 4 h post-dose. Subjects in Cohorts 2, 4, 6,
      8, 10 and 11 will receive oral doses of BIA 5-1058 or matching placebo once daily from Day 1
      to Day 10, administered in the morning of each day, 30 minutes after the start of a moderate
      breakfast containing approximately 550 kcal with fat contributing approximately 150 kcal.
    

Intervention name(s): BIA 5-1058; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): 25 mg and 100 mg tablets; Oral, once-daily, from Day 1 to Day 10. In Cohorts 1, 3, 5, 7 and 9 (fasted), BIA 5-1058 will be orally administered in the morning after a minimum of 8 h fast. Subjects will remain fasted until 4 h post-dose and will receive lunch approximately 4 h after dosing.
In Cohorts 2, 4, 6, 8 and 10 (fed), BIA 5-1058 will be orally administered in the morning after a moderate breakfast (containing approximately 550 kcal with fat contributing approximately 150 kcal). The meal should be consumed over a maximum period of 25 min, with dosing occurring 30 min after the start of the meal.
Each dose will be administered with 240 mL water.; matching placebo tablet; Oral, once-daily, from Day 1 to Day 10. In Cohorts 1, 3, 5, 7 and 9 (fasted), placebo will be orally administered in the morning after a minimum of 8 h fast. Subjects will remain fasted until 4 h post-dose and will receive lunch approximately 4 h after dosing.
In Cohorts 2, 4, 6, 8 and 10 (fed), placebo will be orally administered in the morning after a moderate breakfast (containing approximately 550 kcal with fat contributing approximately 150 kcal). The meal should be consumed over a maximum period of 25 min, with dosing occurring 30 min after the start of the meal.
Each dose will be administered with 240 mL water.
Other intervention name(s): Zamicastat
Intervention MeSH terms: Zamicastat
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment