The study is designed to estimate the bioavailability of amlodipine and enalapril maleate fixed dose combination (FDC) relative to co-administration of amlodipine and enalapril maleate tablets. The rational for this study is to provide a more convenient dosing regimen for patients. This is an open-label, randomized, single dose, two-way crossover study, in which 16 healthy adult male and female subjects will be enrolled and dosed under fasting conditions. Each subject will participate in two treatment periods of 7 days each. There will be at least 14 days of wash out period between the two dosing periods and a follow-up period of up to 21 days after treatment period 2. The total duration of study will be approximately 35 days from the start of the first treatment.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
15
Uncoated, round, yellow white bilayer fixed dose combination tablet containing 5 mg amlodipine and 20 mg enalapril for single dose oral administration in each period.
Emerald-shaped white 5 mg amlodipine table for single dose oral co-administration with enalapril maleate tablet in each period.
Peach triangle shaped 20 mg enalapril maleate tablet for single dose oral co-administration with amlodipine in each period.
GSK Investigational Site
Randwick, New South Wales, Australia
Relative oral bioavailability of GSK2944404 FDC to amlodipine and enalapril maleate tablets co-administered as assessed by composite of pharmacokinetic (PK) parameters.
PK parameters include: maximum observed concentration (Cmax) of amlodipine and enalapril in all treatments, area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration within a subject across all treatments (AUC\[0-t\]), and area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC \[0-infinity\]. Bioavailability is defined as the amount of drug available at the site of action after administration.
Time frame: PK samples will be collected at Pre-dose, 0.25, 0.5, 0.75, 1, 1.33, 1.66, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 36, 48, 72, 96, 120, and 144 hours post dose at each dosing session.
Composite of PK parameters for enalaprilat following administration of GSK2944404 and co-administration of amlodipine and enalapril maleate as data permit.
PK parameters include: AUC (0-infinity), AUC (0-t), Cmax, time of occurrence of Cmax (tmax), percentage of AUC (0-infinity) obtained by extrapolation (percentage AUCex), last observed quantifiable concentration (Clast), and terminal phase half-life (t1/2).
Time frame: PK samples will be collected at Pre-dose, 0.25, 0.5, 0.75, 1, 1.33, 1.66, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post dose at each dosing session.
Composite of PK parameters for amlodipine and enalapril maleate following administration of GSK2944404 and co-administration of amlodipine and enalapril maleate as data permit.
PK parameters include: tmax, Clast, percentage AUCex, and t1/2.
Time frame: PK samples will be collected at Pre-dose, 0.25, 0.5, 0.75, 1, 1.33, 1.66, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 36, 48, 72, 96, 120, and 144 hours post dose at each dosing session.
Number of participants with adverse events (AEs) as a measure of safety and tolerability.
AEs will be collected from the start of Study Treatment and until the follow-up contact visit.
Time frame: Up to 35 days.
Vital signs measurements to assess safety and tolerability.
Vital signs include blood pressure and pulse rate measurement. Orthostatic (sitting in upright position) as well as supine vitals will be measured.
Time frame: Up to 35 days.
Absolute values and change over time of Clinical laboratory parameters to assess safety and tolerability.
Clinical laboratory parameters include: hematology, clinical chemistry, urinalysis and additional parameters.
Time frame: Up to 35 days.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.