This study is the first administration of GSK2881078 to humans. The intention of this study is to provide sufficient confidence in the safety of the molecule to inform progression to further repeat dose and proof of concept studies. This study will include approximately 52 subjects and consist of 2 parts. Part A will consist of two cohorts of 8 subjects to assess the safety, tolerability, and pharmacokinetic (PK) of ascending single oral doses of GSK2881078. Cohorts 1 and 2 will include healthy male subjects. Part B (Cohorts 3, 4 and 5) will include three cohorts of 12 healthy male subjects to examine the safety, tolerability, PK, and pharmacodynamic (PD) of repeated doses of GSK2881078 over 14 days. The total duration of the study including screening and follow-up, is not expected to exceed 70 days.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
99
Hot melt solution within Capsule for oral single ascending doses or repeat dose administration with planned dose level and strength of 0.1, 0.3, 1.0, 2.0, 4.0, 8.0, and 10.0 mg
Hot melt solution within Capsule for oral single ascending doses or repeat doses administration.
GSK Investigational Site
Overland Park, Kansas, United States
GSK Investigational Site
Baltimore, Maryland, United States
Vital sign assessment following single doses as a measure of safety and tolerability
Vital signs include: systolic blood pressure, diastolic blood pressure and heart rate
Time frame: Up to 61 days
Vital sign assessment following repeat doses as a measure of safety and tolerability
Vital signs include: systolic blood pressure, diastolic blood pressure and heart rate
Time frame: Up to 56 days
Cardiac telemetry following single doses as a measure of safety and tolerability
Continuous cardiac telemetry will be performed for at least 12 hours post dose in each treatment period in Part A.
Time frame: Up to 19 days
Cardiac telemetry following repeat doses as a measure of safety and tolerability
Continuous cardiac telemetry will be performed for at least 8 hours post dose in Days 1, 4, 7, 10, and 14 in Part B
Time frame: 14 days
Electrocardiogram (ECG) assessment following single doses as a measure of safety and tolerability
12-lead ECGs will be obtained during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QT duration corrected for heart rate by Fridericia's formula (QTcF intervals) at each timepoint
Time frame: Up to 61 days
ECG assessment following repeat doses as a measure of safety and tolerability
12-lead ECGs will be obtained during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QT duration corrected for heart rate by Fridericia's formula (QTcF intervals) at each timepoint
Time frame: Up to 56 days
Laboratory parameters assessment following single doses as a measure of safety and tolerability
Laboratory parameters include: hematology, clinical chemistry, and urinalysis
Time frame: Up to 61 days
Laboratory parameters following repeat doses as measure of safety and tolerability
Laboratory parameters include: hematology, clinical chemistry, and urinalysis
Time frame: Up to 56 days
Number of participants with adverse events following single doses as a measure of safety and tolerability
AEs will be collected from the start of Study Treatment and until the follow-up contact
Time frame: 33 days
Number of participants with adverse events following repeat doses as a measure of safety and tolerability
AEs will be collected from the start of Study Treatment and until the follow-up contact
Time frame: 28 days
Composite of PK parameters following single doses
PK parameters include: area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC\[0-infinite\]), area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration (AUC\[0-t\]), maximum observed concentration (Cmax), time of occurrence of Cmax (tmax), terminal phase half-life (t1/2)
Time frame: PK samples will be collected at pre-dose and 0.2, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 and 48 hours post dose in each of the four dosing session
Composite of PK parameters following repeat doses
PK parameters include: AUC (0-infinite), area under the concentration-time curve over the dosing interval (AUC \[0-tau\]), AUC (0-t), Cmax, tmax, t1/2 and accumulation ratio
Time frame: Up to 17 days
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