the purpose of this study is to determine the effect of age on the Pharmacokinetics (PK) profile of BIA 5-1058 at steady state after multiple oral doses
This was a single-centre, open-label, parallel group, non-randomised, two-part multiple dose 10-day study in healthy young and elderly male and female subjects. The study comprised a screening evaluation between 2 and 28 days before the first Investigational Medicinal Product (IMP) administration, a hospitalisation period of 15 days comprising a treatment period of 10 days, and a follow-up visit approximately 7 days after discharge. Part 1: Subjects received 1200 mg of BIA 5-1058 once a day (od), in fasting conditions, for 10 days Part 2 : Subjects received 400 mg of BIA 5-1058 od, in fasting conditions, for 10 days.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
61
Each subject was administered either 1200 mg (Part 1) or 400 mg (Part 2) BIA 5-1058 od for 10 days, in fasting conditions for 8 hours \[Day (D)2 to D9\] or 10 hours (D1 and D13), and remained fasted for 2 hours (D2 to D9) or 4 hours (D1 and D13) post-dose. The formulation was tablets 100 mg and the mode of administration was oral.
Maximum observed plasma concentration (Cmax)
Pharmacokinetic analysis Blood samples for PK analysis were taken at the following times: On D1: before BIA 5-1058 dosing (pre-dose), and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16 and 24 h post-dose (before the second administration on D2). On D3, D7, D8 and D9: before BIA 5-1058 dosing. From D10 to D13: before BIA 5-1058 dosing, and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24 (D11), 36 (D11), 48 (D12), 60 (D12) and 72h post-dose (D13).
Time frame: Up to 4 weeks
Time of occurrence of Cmax (tmax)
Pharmacokinetic analysis Blood samples for PK analysis were taken at the following times: On D1: before BIA 5-1058 dosing (pre-dose), and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16 and 24 h post-dose (before the second administration on D2). On D3, D7, D8 and D9: before BIA 5-1058 dosing. From D10 to D13: before BIA 5-1058 dosing, and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24 (D11), 36 (D11), 48 (D12), 60 (D12) and 72h post-dose (D13).
Time frame: Up to 4 weeks
Area under the plasma concentration-time curve (AUC) from time zero to the last sampling time at which the drug concentration was at or above the lower limit of quantification (AUC0-t)
Pharmacokinetic analysis Blood samples for PK analysis were taken at the following times: On D1: before BIA 5-1058 dosing (pre-dose), and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16 and 24 h post-dose (before the second administration on D2). On D3, D7, D8 and D9: before BIA 5-1058 dosing. From D10 to D13: before BIA 5-1058 dosing, and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24 (D11), 36 (D11), 48 (D12), 60 (D12) and 72h post-dose (D13).
Time frame: Up to 4 weeks
Area under the plasma concentration-time curve from time zero to 24 hours after last dosing (AUC0-24)
Pharmacokinetic analysis Blood samples for PK analysis were taken at the following times: On D1: before BIA 5-1058 dosing (pre-dose), and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16 and 24 h post-dose (before the second administration on D2). On D3, D7, D8 and D9: before BIA 5-1058 dosing. From D10 to D13: before BIA 5-1058 dosing, and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24 (D11), 36 (D11), 48 (D12), 60 (D12) and 72h post-dose (D13).
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Time frame: Up to 4 weeks
Apparent terminal half-life (t½)
Pharmacokinetic analysis Blood samples for PK analysis were taken at the following times: On D1: before BIA 5-1058 dosing (pre-dose), and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16 and 24 h post-dose (before the second administration on D2). On D3, D7, D8 and D9: before BIA 5-1058 dosing. From D10 to D13: before BIA 5-1058 dosing, and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24 (D11), 36 (D11), 48 (D12), 60 (D12) and 72h post-dose (D13).
Time frame: Up to 4 weeks
Apparent total body clearance (CL/F)
Pharmacokinetic analysis Blood samples for PK analysis were taken at the following times: On D1: before BIA 5-1058 dosing (pre-dose), and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16 and 24 h post-dose (before the second administration on D2). On D3, D7, D8 and D9: before BIA 5-1058 dosing. From D10 to D13: before BIA 5-1058 dosing, and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24 (D11), 36 (D11), 48 (D12), 60 (D12) and 72h post-dose (D13).
Time frame: Up to 4 weeks