This study is required to confirm the suitability of a candidate FDC of 16mg candesartan cilexetil/12.5mg HCTZ (GSK587323) formulation for further development and provide data to allow the design of a future pivotal bioequivalence study. This study aims to determine the relative bioavailability of a FDC tablet formulation of 16mg candesartan cilexetil/12.5mg HCTZ relative to the reference product of same fixed dose combination (16mg candesartan cilexetil/12.5mg HCTZ) in healthy adult humans. This will be an open-label, randomised, single dose, two-way crossover study. Each subject will participate in two treatment periods and will be randomized to one of two sequences and administered one of the two treatments, A or B, as per the randomization schedule. The two treatment periods will be separated by a washout period of 7 to 14 days to ensure the candesartan and HCTZ have been effectively eliminated from the subject between dosing occasions. The study will enroll 16 healthy subjects to ensure that 14 subjects complete the study as planned.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
16
Single dose of FDC tablet formulation to be taken orally.
Single dose of FDC tablet formulation to be taken orally
GSK Investigational Site
Hyderabad, India
Composite of PK parameters for candesartan and HCTZ to assess relative bioavailability.
PK parameters include: maximum observed plasma concentration (Cmax), area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC \[0-infinite\]) and area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration within a subject across all treatments (AUC \[0-t\]). Twenty four blood samples (1x 5mililiter (mL)) will be collected at the specified time points for PK analysis of candesartan and HCTZ.
Time frame: Pre dose, 0.33, 0.67, 1, 1.33, 1.67, 2.0, 2.33, 2.67, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 10, 12, 16, 24, 36, and 48hours post dose in each treatment period.
PK profile of candesartan and HCTZ.
PK parameters included: time to Cmax (tmax), Percentage of AUC (0-infinite) obtained by extrapolation, and apparent terminal phase half-life (t1/2). PK blood samples (1x 5mL)) will be collected at the specified time points for PK analysis of candesartan and HCTZ.
Time frame: Pre dose, 0.33, 0.67, 1, 1.33, 1.67, 2.0, 2.33, 2.67, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 10, 12, 16, 24, 36, and 48hours post dose in each treatment period.
Vital sign assessment as a measure of safety and tolerability.
Vital sign parameters include: systolic blood pressure, diastolic blood pressure, and pulse rate. At Baseline the average of the last two blood pressures and pulse readings will be recorded. All measurements will be measured in supine position after 5 minutes rest.
Time frame: Up to 39 days
Review of adverse events (AEs) as a measure of safety and tolerability.
An AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. All AEs and serious AEs (SAEs) will be collected from the start of dosing with Investigational Product and until the follow-up visit. However, any SAEs related to study participation or concomitant
Time frame: Up to 39 days
Clinical laboratory data assessment as measure of safety and tolerability.
All subjects for all treatments will be evaluated for any abnormal laboratory test results (haematology, clinical chemistry, or urinalysis).
Time frame: Up to 39 days
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