Safety, Tolerability, Pharmacokinetic, Including Food Interaction, and Pharmacodynamic Profile of BIA 5-1058.
Condition: Hypertension and Chronic Heart Failure
MeSH terms: Hypertension; Heart Failure
Study type: Interventional
Phase: Phase 1

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

Detailed description: 
      This was a Phase 1, double blind, randomised, placebo-controlled combined single ascending
      dose (SAD), including food interaction (food effect, FE) analysis, and multiple ascending
      dose (MAD) study.

      SAD: This part consisted of an eligibility screening period, one study period involving
      administration of single doses of BIA 5-1058 or placebo according to a randomized design, and
      a follow-up period. Nine sequential groups of 8 healthy young male subjects were dosed.
      Within each group, 6 subjects were randomised to receive BIA 5-1058 and 2 subjects were
      randomised to receive placebo. In this first-in-human study, the subjects participating at
      the lowest dose level of 5 mg were dosed according to a sentinel dosing design to ensure
      optimal safety. Initially, 2 subjects were dosed; 1 subject with BIA 5-1058 and 1 subject
      with placebo. After the safety and tolerability results of the first 24 h following dosing
      for the initial subjects had been found to be acceptable to the MI, the other 6 subjects of
      the lowest dose level were dosed.

      MAD: This part consisted of an eligibility screening period, one study period involving
      administration of multiple doses of BIA 5-1058 or placebo once daily for 10 days, and a
      follow-up period. Five sequential groups of 8 healthy young male subjects were dosed.

      Within each group, 6 subjects were randomised to receive BIA 5-1058 and 2 subjects were
      randomised to receive placebo.

      The starting dose of 50 mg was chosen taking into consideration the dose range of the
      previous SAD sequential groups and was approved by the IEC. Escalation to the next higher
      dose and the determination of the next dose level was based on safety, tolerability and
      available PK results of the previously administered dose

      FE: This part consisted of an eligibility screening period, an open-label two-way crossover
      study period, and a follow-up period. One group of 12 subjects received single doses of 400
      mg BIA 5-1058 during 2 treatment periods, once after having fasted overnight and once after
      consumption of a high fat breakfast. Each treatment was separated by a period of at least 7
      days. The treatment sequence was determined by randomisation.
    

Intervention name(s): BIA 5-1058; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): oral administration; oral administration
Other intervention name(s): Zamicastat
Intervention MeSH terms: Zamicastat
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: BIA 5-1058; hypertension; chronic heart failure; cardiovascular disorders