The purpose of the study was to To investigate 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 entacapone 200 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 (UFHBIAL - Portela \& Cª, SA) 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 entacapone 200 mg (Comtan®) 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 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
39
1 capsule of placebo \[to be taken orally, with 240 mL of potable water\]
1 capsule of BIA 6-512 25mg or 1 capsule of BIA 6-512 50 mg or 1 capsule of BIA 6-512 75 mg or 1 capsule of BIA 6-512 100 mg \[to be taken orally, with 240 mL of potable water\]
Levodopa/benserazide immediate release tablets 200mg/50mg \[to be taken orally, with 240 mL of potable water\]
Human Pharmacology Unit (UFH) - BIAL - Portela & Cª, SA
S. Mamede Do Coronado, Portugal
Day 4 - Maximum observed plasma drug concentration (Cmax)
BIA 6-512, levodopa, 3-OMD and entacapone pharmacokinetic parameters 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)
BIA 6-512, levodopa, 3-OMD and entacapone pharmacokinetic parameters 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)
BIA 6-512, levodopa, 3-OMD and entacapone pharmacokinetic parameters 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)
BIA 6-512, levodopa, 3-OMD and entacapone pharmacokinetic parameters 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)
BIA 6-512, levodopa, 3-OMD and entacapone pharmacokinetic parameters 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-∞)
BIA 6-512, levodopa, 3-OMD and entacapone pharmacokinetic parameters 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)
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.
Entacapone 200 mg tablets \[to be taken orally, with 240 mL of potable water\]
Day 5 - Time of occurrence of Cmax (tmax)
BIA 6-512, levodopa, 3-OMD and entacapone pharmacokinetic parameters 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)
BIA 6-512, levodopa, 3-OMD and entacapone pharmacokinetic parameters 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)
BIA 6-512, levodopa, 3-OMD and entacapone pharmacokinetic parameters 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)
BIA 6-512, levodopa, 3-OMD and entacapone pharmacokinetic parameters 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-∞)
BIA 6-512, levodopa, 3-OMD and entacapone pharmacokinetic parameters on day 5
Time frame: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 16 and 24 hours post-dose