GSK2838232 is a novel human immune virus (HIV) maturation inhibitor being developed for the treatment of chronic HIV infection. This study is the first administration of GSK2838232 in humans to establish the initial safety, tolerability, and pharmacokinetic profile following single doses of GSK2838232 and to evaluate the effect of food and ritonavir (RTV) on GSK2838232 in healthy subjects. There will be 2 cohorts in this study. In Cohort 1, approximately 8 healthy subjects will be enrolled (6 active and 2 placebo) at each dose visit. There will be four dosing sessions for each subject with subjects randomized to receive placebo in a random sequence. In Cohort 2, approximately 8 healthy subjects will be enrolled (6 active doses and 2 placebo doses at each dose visit). Cohort 2 will have four dosing sessions for each subject with subjects randomized to receive placebo in a random sequence.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
17
Bottled powder with 5, 10 and 20mg unit dose strength per single dose for re-constituted oral suspension given once daily
Visually matching GSK2838232
100mg tablets once daily for 12 days
GSK Investigational Site
Baltimore, Maryland, United States
Number of subjects with adverse events (AEs) as a measure of safety and tolerability in cohort 1
AEs will be collected from the start of Study Treatment and until 5 days post last-dose (at follow up).
Time frame: Up to 16 weeks
Number of subjects with AEs as a measure of safety and tolerability in cohort 2.
AEs will be collected from the start of Study Treatment and until 5 days post last-dose (at follow up).
Time frame: Up to 12 weeks
Absolute values and changes over time of hematology as a measure of safety and tolerability in cohort 1.
Time frame: Up to 16 weeks
Absolute values and changes over time of hematology as a measure of safety and tolerability in cohort 2
Time frame: Up to 12 weeks
Absolute values and changes over time of clinical chemistry as a measure of safety and tolerability in cohort 1.
Time frame: Up to 16 weeks
Absolute values and changes over time of clinical chemistry as a measure of safety and tolerability in cohort 2.
Time frame: Up to 12 weeks
Absolute values and changes over time of urinalysis as a measure of safety and tolerability in cohort 1.
Time frame: Up to 16 weeks
Absolute values and changes over time of urinalysis as a measure of safety and tolerability in cohort 2
Time frame: Up to 12 weeks
Absolute values and changes over time of vital signs as a measure of safety and tolerability in cohort 1
Vital signs include blood pressure, temperature and heart rate measurement
Time frame: Up to 16 weeks.
Absolute values and changes over time of vital signs as a measure of safety and tolerability in cohort 2.
Vital signs include blood pressure, temperature and heart rate measurement
Time frame: Up to 12 weeks
Absolute values and changes over time of ECG intervals and ECG rhythm as a measure of safety and tolerability in cohort 1.
Time frame: Up to 16 weeks.
Absolute values and changes over time of ECG intervals and ECG rhythm as a measure of safety and tolerability in cohort 2.
Time frame: Up to 12 weeks
Real time collection and review of heart rhythm using telemetry as a measure of safety and tolerability in cohort 1.
Time frame: Up to 16 weeks.
Real time collection and review of heart rhythm using telemetry as a measure of safety and tolerability in cohort 2.
Time frame: Up to 12 weeks
Composite of pharmacokinetics (PK) parameters following single dose administration of GSK2838232 in cohort 1
PK parameters include: area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC \[0-infinity\]), 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 to maximum observed concentration (Tmax), observed concentration at 24hour post-dose (C24), last observed quantifiable concentration (Ct), lag time before observation of drug concentrations in sampled matrix (tlag), terminal half-life (t1/2), and apparent oral clearance (CL/F).
Time frame: PK samples will be collected at pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, and 72 hours post dose in each dosing session and at follow up visit.
Composite of pharmacokinetics parameters following single dose administration of GSK2838232 in cohort 2.
PK parameters include: AUC (0-infinity), AUC (0-t), Cmax, Tmax, C24, Ct, tlag, t1/2 and CL/F.
Time frame: PK samples will be collected at pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, and 72 hours post dose in each dosing session and at follow up visit.
Composite of pharmacokinetics parameters following single dose administration of GSK2838232 with and without food in cohort 2.
PK parameters include: AUC (0-infinity), AUC (0-t), Cmax, Tmax, C24 and t1/2. Food will be normal fat meal.
Time frame: PK samples will be collected at pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, and 72 hours post dose in each dosing session and at follow up visit.
Composite of pharmacokinetics parameters following single dose administration of GSK2838232 with co-administration of ritonavir in cohort 2.
PK parameters include: AUC (0-infinity), AUC (0-t), Cmax, Tmax, C24 and t1/2.
Time frame: PK samples will be collected at pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, and 72 hours post dose in each dosing session and at follow up visit.
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