Pharmacokinetic-pharmacodynamic Interaction Between BIA 3-202 and Levodopa/Benserazide
Condition: Parkinson's Disease (PD)
MeSH terms: Parkinson Disease
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to determine the effect of three single oral doses of nebicapone
      (50 mg, 100 mg and 200 mg) on the levodopa pharmacokinetics when administered in combination
      with a single-dose of controlled release levodopa 100 mg/benserazide 25 mg (Madopar® HBS
      125).
    

Detailed description: 
      STUDY DESIGN AND METHODOLOGY:

      Single centre, double-blind, randomised, placebo-controlled, 4-way crossover study with 4
      single-dose treatment periods. The washout period between doses was 5 days or more.

      Screening: Subjects were screened for eligibility within 28 and 7 days before first
      admission. The screening consisted of: medical history; physical examination, vital signs;
      complete neurological examination; 12-lead ECG; haematology, coagulation, plasma biochemistry
      and urinalysis tests; HIV, hepatitis B and hepatitis C serology; drugs of abuse and alcohol
      screen; urine pregnancy test in women of childbearing potential; and review of the selection
      criteria.

      Treatment periods: In each treatment period, eligible subjects were admitted to the UFH on
      the day prior to receiving the study medication for: vital signs; medical history and
      physical examination updates; 12-lead ECG; haematology and plasma biochemistry; drugs of
      abuse and alcohol screen; and urine pregnancy test in women of childbearing potential. On
      first admission, subjects had a review of the selection criteria and were randomly assigned
      to one of the treatment sequences. On the morning of the dosing day, subjects received a dose
      of nebicapone/placebo concomitantly with a dose of Madopar® HBS 125 in fasting conditions (at
      least 8 hours) and remained in the UFH until at least 24 h post-dose; then, they left and
      returned for the next period or the follow-up visit. At given time-points between pre-dose
      and discharge, subjects were submitted to vital signs recording, brief neurological
      examination, 12-lead ECG, and blood sampling for plasma drug determination and erythrocyte
      S-COMT activity assay. At discharge, vital signs and ECG were recorded, and haematology and
      plasma biochemistry tests were performed. Blood samples (7 mL) for the determination of
      plasma concentration of levodopa, 3-O-methyldopa (3-OMD) and nebicapone, and for the assay of
      the erythrocyte S-COMT activity were taken at the following times: pre-dose, ½, 1, 1½, 2, 3,
      4, 6, 8, 12, 16 and 24 h post-dose.

      Follow-up: A follow-up visit occurred approximately 7-10 days after discharge of last
      treatment period or early discontinuation for: medical history and physical examination
      updates; vital signs; 12-lead ECG; haematology, plasma biochemistry and urinalysis tests; and
      pregnancy test in women of childbearing potential.
    

Intervention name(s): BIA 3-202; Placebo; levodopa 100 mg / benserazide 25 mg
Intervention type(s): Drug; Drug; Drug
Intervention description(s): nebicapone 50 mg tablets; oral use; Nebicapone matching placebo tablets; Madopar® HBS 125 (levodopa 100 mg / benserazide 25 mg) capsules; oral use
Other intervention name(s): Nebicapone; Madopar
Intervention MeSH terms: Levodopa; Benserazide
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment