Safety, Tolerability, Pharmacokinetics (Including Food Interaction), and Pharmacodynamics of BIA 3-202
Condition: Parkinson's Disease
MeSH terms: Parkinson Disease
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to investigate the safety and tolerability of single oral rising
      doses of BIA 3-202 up to 800 mg (proposed doses 10 mg, 30 mg, 50 mg, 100 mg, 200 mg, 400 mg
      and 800 mg) in groups of 9 healthy male adult subjects, to characterise the preliminary
      pharmacokinetics of single rising oral doses of BIA 3-202 in healthy male adult subjects, to
      investigate the effects of single doses of BIA 3-202 on COMT activity in human erythrocytes
      and to investigate the effect of food on the pharmacokinetics of a single dose of BIA 3-202.
    

Detailed description: 
      The study was conducted in two parts, with separate groups of subjects participating in each
      part.

      Part 1 was designed as follows:

        -  Single centre, Phase I, double-blind, randomised, placebo-controlled study to
           investigate single rising oral doses of BIA 3-202 of up to 800 mg in sequential groups
           of nine healthy male adult subjects.

        -  Within each group of nine subjects, two were to be randomised to receive placebo and the
           remaining seven were to be randomised to receive BIA 3-202.

        -  No subject was to be a member of more than one treatment group.

        -  Doses of BIA 3-202 were to be investigated in ascending order.

        -  The lowest proposed dose of BIA 3-202 (10 mg) was to be investigated in the first
           instance.

        -  Progression to the next higher dose was only to occur if the previous dose level was
           deemed to be safe and well tolerated by the investigator and the sponsor.

        -  Following discussion between the investigator and the sponsor an intermediate or repeat
           dose level could be administered if it was deemed appropriate to increase the safety or
           scientific value of this first in man exploratory study.

        -  An appropriate interval of at least 7 days was to separate the investigation of dose
           levels to permit a timely review and evaluation of safety data prior to proceeding to a
           higher dose level.

      The proposed doses to be used in Part 1 of the study were 10 mg, 30 mg, 50 mg, 100 mg, 200
      mg, 400 mg and 800 mg.

      In Part 2 of the study, an additional group of eight subjects was to receive a single dose of
      BIA 3-202, either having fasted overnight or with a high fat meal, in an open label two-way
      crossover design. Each treatment was to be separated by a period of at least 7 days.

      The dose administered in Part 2 was to be determined from the safety and pharmacokinetic data
      from Part 1 of the study.

      Following the review of Part 1 data, protocol amendment 1 was issued, in which it was stated
      that the dose of BIA 3-202 to be used was 400 mg.

      Screening Potential subjects were screened for eligibility within 28 days of admission.
      Screening consisted of review of medical history, physical examination, neurological
      examination, vital signs, 12 lead ECG, clinical laboratory safety tests (haematology,
      coagulation plasma biochemistry, urinalysis, urinary microproteins, HbsAg, anti-HCV and HIV I
      & II, drugs of abuse and alcohol screen).

      Treatment Periods The results of screening were known to the Investigator prior to the
      subject's admission. On admission the inclusion/exclusion criteria were reviewed and subject
      written informed consent was obtained.

      Eligible subjects were to be admitted to the unit for one treatment period (groups 1-7, in
      Part 1 of the study) or two treatment periods (group 8, Part 2), on the day prior to
      receiving trial medication and were to remain in the unit under clinical supervision until at
      least 24 hours post dose.

      BIA 3-202 /placebo was to be administered orally in the morning of day 1.

      Safety was to be evaluated by monitoring of adverse events, clinical laboratory safety tests
      (haematology, biochemistry, coagulation, urinalysis, and urinary microproteins), vital signs,
      12-lead ECG, and physical examination, including brief neurological examinations.

      Blood samples and urine collections were to be taken at pre-determined time-points for the
      assay of BIA 3-202 and its metabolite BIA 3-270. Blood samples were also to be taken for the
      assessment of COMT activity in erythrocytes.

      Follow Up Subjects were to attend for a follow up visit 5-7 days following their last
      discharge. At follow-up, medical history and adverse events were to be reviewed, and clinical
      laboratory safety tests were to be performed.
    

Intervention name(s): BIA 3-202; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): single rising oral doses (10 mg, 30 mg, 50 mg, 100 mg, 200 mg, 400 mg, 800 mg); Identical placebo
Other intervention name(s): Nebicapone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment