The current study will examine the safety, tolerability, plasma pharmacokinetics (PK), and plasma pharmacodynamics (PD) of single-doses of GSK2647544.The study will be conducted as a randomized, single-blind, placebo controlled, 4-way crossover single oral ascending dose design in 2 independent cohorts, eight healthy male subjects in each of the cohorts. Each potential subject will undergo Screening visit, Treatment Phase and Follow-up visit.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
27
Capsules containing 0.5mg to 50mg of GSK2647544.
Matching placebo capsules.
GSK Investigational Site
Randwick, New South Wales, Australia
Safety and tolerability of GSK2647544 as assessed by number of subjects with adverse events (AE)s
Safety and tolerability parameters will include recording of AEs
Time frame: 5 days in each of the 4 dosing session
Safety and tolerability of GSK2647544 as assessed by change from Baseline in laboratory values
Safety and tolerability parameters will include laboratory (haematology, clinical chemistry, urinalysis) values at Screening, Day -1, Day 3 and Follow-up (7-14 days post-last dose)
Time frame: 5 days in each of the 4 dosing session
Safety and tolerability of GSK2647544 as assessed by change from Baseline in ECG readings
Safety and tolerability parameter will include the electrocardiogram (ECG) readings at Screening, Day -1, Day 1, Day 2, Day 3 and Follow-up (7-14 days post-last dose)
Time frame: 5 days in each of the 4 dosing session
Safety and tolerability of GSK2647544 as assessed by change from Baseline in Telemetry ECG parameters
Safety and tolerability parameter will include the Telemetry ECG readings from 30 minutes pre-dosing till 48 hours post-dosing
Time frame: 3 Days in each of the 4 dosing session
Safety and tolerability of GSK2647544 as assessed by change from Baseline in vital signs
Vital signs measurement include systolic and diastolic blood pressure and pulse rate at Screening, Day -1, Day 1, Day 2, Day 3, Day 4 and Follow-up (7-14 days post-last dose)
Time frame: 5 days in each of the 4 dosing session
Safety and tolerability of GSK2647544 as assessed by using the Columbia Suicide Severity Rating Scale (C-SSRS)
C-SSRS will be measured at Screening, Day -1, Day 1 (conducted prior to discharge) and Follow-up (7-14 days post-last dose)
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Time frame: 5 days in each of the 4 dosing session
Peak plasma concentration (Cmax) of GSK2647544
To assess PK profile of GSK2647544, Cmax of GSK2647544 will be measured
Time frame: 4 Days in each of the 4 dosing session
Time of peak plasma concentration (tmax) of GSK2647544
To assess PK profile of GSK2647544 tmax of GSK2647544 will be measured
Time frame: 4 Days in each of the 4 dosing session
Area under the time concentration curve (AUC) of GSK2647544
To assess PK profile of GSK2647544 AUC of GSK2647544 will be measured
Time frame: 4 Days in each of the 4 dosing session
Terminal half-life (t½ ) of GSK2647544
To assess PK profile of GSK2647544 t½ of GSK2647544 will be measured
Time frame: 4 Days in each of the 4 dosing session
Apparent oral clearance (CL/F) of GSK2647544
To assess PK profile of GSK2647544 CL/F of GSK2647544 will be measured
Time frame: 4 Days in each of the 4 dosing session
Predose plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) activity and postdose Lp-PLA2 activity
It will be measured at Day 1, Day 2, Day 3, Day 4 and Day 5
Time frame: 5 Days in each of the 4 dosing session