The purpose of this study was to determine whether the administration of BIA 6-512 (25 mg, 50 mg, 75 mg and 100 mg) at steady-state affects the pharmacokinetics of levodopa when administered in combination with a single-dose of immediate release levodopa/benserazide 200/50 mg or with a single-dose of immediate release levodopa/benserazide 200/50 mg plus a single-dose of nebicapone 150 mg.
Single centre, double-blind, randomised, placebo-controlled, rising multiple dose study in four sequential groups of healthy male and female subjects. Eligible subjects were admitted to the Human Pharmacology Unit (UFH)on the day prior to receiving the first study medication. Starting in the morning of Day 1 (first dose), subjects received BIA 6-512/Placebo thrice daily until the morning of Day 5 (last dose). Concomitantly with the morning dose of BIA 6-512/Placebo on Day 4, a levodopa/benserazide 200/50 mg (Madopar® 250) single-dose was administered. On Day 5, a Madopar® 250 single-dose and a nebicapone 150 mg single-dose were administered concomitantly with the morning dose of BIA 6-512/Placebo. In the morning of Day 4 and Day 5, products were administered in fasting conditions of at least 8 hours and subjects remained fasted until 2 h post-dose. Subjects were resident in the UFH from admission (Day 0) until at least 24 h post last dose (Day 6); then, they were discharged and returned for the follow-up visit.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
38
Placebo capsules. Orally, with 240 mL of potable water.
The investigational products consisted of capsules containing BIA 6-512 25 mg, 50 mg, 75 mg, 100 mg. Orally, with 240 mL of potable water.
Levodopa/benserazide immediate release tablets 200mg/50mg. Orally, with 240 mL of potable water.
Nebicapone 150 mg tablets. Orally, with 240 mL of potable water.
Human Pharmacology Unit (UFH) - BIAL - Portela & Cª, SA
S. Mamede Do Coronado, Portugal
Day 4 - Maximum observed plasma drug concentration (Cmax)
Pharmacokinetic parameters of BIA 6-512, levodopa, and nebicapone on day 4
Time frame: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8 and 16 hours post-dose.
Day 4 - Time of occurrence of Cmax (tmax)
Pharmacokinetic parameters of BIA 6-512, levodopa, and nebicapone on day 4
Time frame: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8 and 16 hours post-dose.
Day 4 - Area under the plasma concentration-time curve (AUC) from time zero to the last sampling time at which concentrations were at or above the limit of quantification (AUC0-t)
Pharmacokinetic parameters of BIA 6-512, levodopa, and nebicapone on day 4
Time frame: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8 and 16 hours post-dose.
Day 4 - AUC from time zero to 8 h post-dose (AUC0-τ)
Pharmacokinetic parameters of BIA 6-512, levodopa, and nebicapone on day 4
Time frame: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8 and 16 hours post-dose.
Day 4 - Area under the plasma concentration versus time curve from time zero to infinity (AUC0-∞)
Pharmacokinetic parameters of BIA 6-512, levodopa, and nebicapone on day 4
Time frame: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8 and 16 hours post-dose.
Day 4 - Apparent terminal elimination half-life, calculated from ln 2/λz (t1/2)
Pharmacokinetic parameters of BIA 6-512, levodopa, and nebicapone on day 4
Time frame: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8 and 16 hours post-dose.
Day 5 - Maximum observed plasma drug concentration (Cmax)
Pharmacokinetic parameters of BIA 6-512, levodopa, and nebicapone on day 5
Time frame: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 16 and 24 hours post-dose
Day 5 - Time of occurrence of Cmax (tmax)
Pharmacokinetic parameters of BIA 6-512, levodopa, and nebicapone on day 5
Time frame: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 16 and 24 hours post-dose
Day 5 - Area under the plasma concentration-time curve (AUC) from time zero to the last sampling time at which concentrations were at or above the limit of quantification (AUC0-t)
Pharmacokinetic parameters of BIA 6-512, levodopa, and nebicapone on day 5
Time frame: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 16 and 24 hours post-dose
Day 5 - AUC from time zero to 8 h post-dose (AUC0-τ)
Pharmacokinetic parameters of BIA 6-512, levodopa, and nebicapone on day 5
Time frame: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 16 and 24 hours post-dose
Day 5 - Area under the plasma concentration versus time curve from time zero to infinity (AUC0-∞)
Pharmacokinetic parameters of BIA 6-512, levodopa, and nebicapone on day 5
Time frame: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 16 and 24 hours post-dose
Day 5 - Apparent terminal elimination half-life, calculated from ln 2/λz (t1/2)
Pharmacokinetic parameters of BIA 6-512, levodopa, and nebicapone on day 5
Time frame: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 16 and 24 hours post-dose
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.