This is a three-period, three sequence, reference replicated, cross-over study to determine the bioequivalence of two amlodipine and losartan FDC tablet formulations FDC5/50 and FDC5/100 (GSK2944406; 5 mg amlodipine and 50 mg and 100 mg losartan) to reference amlodipine and losartan tablets co-administered in two groups enrolling 102 healthy adult male and female subjects under fasting conditions. A description of each treatment is provided below: A (Reference) = 1 x 5 mg amlodipine tablet and 1 x 50 mg losartan tablet. B (FDC5/50) = 1 x 5 mg amlodipine and 50 mg losartan tablet C (Reference) = 1 x 5 mg amlodipine tablet and 1 x 100 mg losartan tablet D (FDC5/100) = 1 x 5 mg amlodipine and100 mg losartan tablet The treatments will be administered in accordance with the randomisation schedule as. Group 1: A → A → B or A → B → A or B → A → A Group 2: C → C → D or C → D → C or D → C → C All subjects will attend a screening visit within 28 days of their first dosing period (Day 1). The baseline assessments will be conducted the day before the first dosing. In each treatment period, subjects will be admitted to the clinic in the evening before Day 1. All subjects will receive a single oral dose of amlodipine and losartan in the morning on Day 1. All the subjects will remain in the clinical unit until completion of all assessments at 24 hours post-dose on Day 2 including collection of the 24 hour post-dose PK sample. Subjects will return to the clinic for pharmacokinetic samples at 36, 48, 72 and 96 hours post-dose. The three treatment periods will be separated by a washout period of 10-17 days. Upon completion of the last dosing period, or early withdrawal, subjects will return to the clinical unit within 14-21 days for a follow up visit.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
102
Subjects will receive 1 x 5 mg amlodipine tablet with 1 x 50 mg losartan tablet administered orally in fasted state as a single dose
Subjects will receive 1 x 5 mg amlodipine tablet with 1 x 100 mg losartan tablet administered orally in fasted state as a single dose
Subjects will receive single oral dose of 1 tablet containing 5 mg amlodipine and 50 mg losartan in fasted state
Subjects will receive single oral dose of 1 tablet containing 5 mg amlodipine and 100 mg losartan in fasted state
GSK Investigational Site
Bloemfontein, South Africa
Plasma pharmacokinetic parameters for amlodipine and losartan in relevant treatments
Pharmacokinetic (PK) parameters for amlodipine and losartan will include the 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), area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time exposure over the dosing and interval area under the plasma concentration time curve (AUC (0- infinity)), and maximum plasma concentration (Cmax)
Time frame: Up to 25 days at regular time points
Plasma pharmacokinetic (PK) parameters tmax, Clast, percentage AUCex and t½ for amlodipine and losartan
The PK parameters: time of occurrence of Cmax (tmax), last observed quantifiable concentration (Clast), percentage AUCex and terminal phase half-life (t½) will be determined from the plasma concentration-time data
Time frame: Up to 25 Days at regular time points
Plasma Pharmacokinetic parameters for carboxylic acid (active losartan metabolite)
The PK paramenters for carboxylic acid: AUC (0-t), AUC (0-infinity), Cmax, tmax, %AUCex, Clast and t½will be determined from the plasma concentration-time data
Time frame: Up to 25 Days at regular time points
Measure of clinical laboratory test values to access safety and tolerability
Clinical laboratory tests will include hematology, clinical chemistry and urinalysis
Time frame: Up to 45 Days
Safety assessed by vital sign measurements
Vital sign measurements will include pulse rate and blood pressure
Time frame: Up to 45 Days
Number of subjects with adverse events (AE)s
Safety and tolerability parameters will include recording of AEs
Time frame: Up to 45 Days
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