To investigate the tolerability and safety of four multiple-dose regimens of BIA 6-512 (25 mg, 50 mg, 100 mg, and 150 mg 6 times daily) in healthy volunteers and to characterise the steady-state pharmacokinetic profiles of BIA 6-512 (25 mg, 50 mg, 100 mg, and 150 mg 6 times daily) in healthy volunteers.
Single-centre, double-blind, randomised, placebo-controlled study of four multiple-rising doses in four sequential groups of 10 healthy volunteers each. Eligible subjects were admitted to the UFH on the day (Day 0) prior to receiving the first dose of study medication. On the morning of the next day (Day 1), subjects started receiving BIA 6-512/Placebo at 4 h intervals (6 times/day) for 48 h (13 investigational product administrations, in total). Subjects remained confined in the UFH from admission (Day 0) until at least 24 h post last dose (Day 4); then, they were discharged and were requested to return for the follow-up visit. At given time-points, subjects were submitted to vital signs recording, brief neurological examination, and 12-lead ECG. Blood samples for plasma drug assays were taken at the following times: Dose 1: pre-dose and ¼, ½, ¾, 1, 1½, 2, and 3 hours post-dose; Doses 2, 3, 4, 5, 7, 8, 9, 10, 11: pre-dose; Dose 13: pre-dose and ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
40
The investigational products consisted of capsules containing BIA 6-512 25 mg, 50 mg, 100 mg and 150 mg. Products were administered orally, with approximately 240 mL of water in case of Doses 1 and 13, and at least 150 mL of water in case of Doses 2 to 12. First dose (Dose 1) and last dose (Dose 13) were administered in fasting of at least 8 hours and subject remained fasted until to 2.5 h post-dose. Meals were not served within 1 hour prior and 1 hour after investigational product administration in Doses 2 to 12
Matching placebo capsules
Human Pharmacology Unit (UFH) - BIAL - Portela & Cª, SA
S. Mamede Do Coronado, Portugal
Cmax - the maximum plasma concentration - first dose (dose 1)
BIA 6-512 pharmacokinetic parameters following the first dose (Dose 1)
Time frame: Dose 1: pre-dose and ¼, ½, ¾, 1, 1½, 2, and 3 hours post-dose
tmax - the time of occurrence of Cmax - first dose (dose 1)
BIA 6-512 pharmacokinetic parameters following the first dose (Dose 1)
Time frame: Dose 1: pre-dose and ¼, ½, ¾, 1, 1½, 2, and 3 hours post-dose
AUC0-t - the area under the plasma concentration-time curve from time zero to the last sampling time at which concentrations are at or above the limit of quantification, calculated by the linear trapezoidal rule - first dose (dose 1)
BIA 6-512 pharmacokinetic parameters following the first dose (Dose 1)
Time frame: Dose 1: pre-dose and ¼, ½, ¾, 1, 1½, 2, and 3 hours post-dose
AUC0-τ - the area under the plasma concentration versus time curve over the dosing interval (4 h), calculated by the linear trapezoidal rule - first dose (dose 1)
BIA 6-512 pharmacokinetic parameters following the first dose (Dose 1)
Time frame: Dose 1: pre-dose and ¼, ½, ¾, 1, 1½, 2, and 3 hours post-dose
AUC0-¥ - the area under the plasma concentration versus time curve from time zero to infinity, calculated from AUC0-t + (Clast/lz), where Clast is the last quantifiable concentration and lz the apparent terminal rate constant - first dose (dose 1)
BIA 6-512 pharmacokinetic parameters following the first dose (Dose 1)
Time frame: Dose 1: pre-dose and ¼, ½, ¾, 1, 1½, 2, and 3 hours post-dose
t½ - the apparent elimination half-life, calculated from ln 2/lz - first dose (dose 1)
BIA 6-512 pharmacokinetic parameters following the first dose (Dose 1)
Time frame: Dose 1: pre-dose and ¼, ½, ¾, 1, 1½, 2, and 3 hours post-dose
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Cmax - the maximum plasma concentration - last dose (dose 13)
BIA 6-512 pharmacokinetic parameters following the last dose (Dose 13)
Time frame: Dose 13: pre-dose and ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose
tmax - the time of occurrence of Cmax - last dose (dose 13)
BIA 6-512 pharmacokinetic parameters following the last dose (Dose 13)
Time frame: Dose 13: pre-dose and ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose
AUC0-t - the area under the plasma concentration-time curve from time zero to the last sampling time at which concentrations are at or above the limit of quantification, calculated by the linear trapezoidal rule - last dose (dose 13)
BIA 6-512 pharmacokinetic parameters following the last dose (Dose 13)
Time frame: Dose 13: pre-dose and ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose
AUC0-τ - the area under the plasma concentration versus time curve over the dosing interval (4 h), calculated by the linear trapezoidal rule - last dose (dose 13)
BIA 6-512 pharmacokinetic parameters following the last dose (Dose 13)
Time frame: Dose 13: pre-dose and ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose
AUC0-¥ - the area under the plasma concentration versus time curve from time zero to infinity, calculated from AUC0-t + (Clast/lz), where Clast is the last quantifiable concentration and lz the apparent terminal rate constant - last dose (dose 13)
BIA 6-512 pharmacokinetic parameters following the last dose (Dose 13)
Time frame: Dose 13: pre-dose and ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose
t½ - the apparent elimination half-life, calculated from ln 2/lz - last dose (dose 13)
BIA 6-512 pharmacokinetic parameters following the last dose (Dose 13)
Time frame: Dose 13: pre-dose and ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose