This study is a three Part, Phase 1, randomized, dose-escalation, fusion, placebo-controlled, double-blind study to determine the safety, tolerability and Pharmacokinetic (PK) profile of GSK2336805 in healthy subjects and the safety, tolerability, PK, and antiviral profile of GSK2336805 in subjects chronically infected with HCV: i. Single doses in healthy subjects and the effect of food on GSK2336805 PK (Part 1). ii. Repeat doses in healthy subjects (Part 2) iii. Single doses in chronically infected HCV positive subjects (Part 3).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
DOUBLE
Enrollment
58
single dose once daily
single dose once daily
single dose once daily
single dose once daily
repeat dose once daily for 7 days
repeat dose once daily for 7 days
single dose in HCV infected patients
single dose in HCV infected patients
single dose in HCV infected patients
GSK Investigational Site
Chula Vista, California, United States
GSK Investigational Site
Lenexa, Kansas, United States
GSK Investigational Site
Willingboro, New Jersey, United States
GSK2336805 safety parameters : adverse events
Time frame: Part 1 change from baseline for 14 days; Part 2 change from baseline for 24 days; Part 3 change from baseline for 16 days
GSK2336805 safety parameters: telemetry
Time frame: Part 1 change from baseline for 14 days; Part 2 change from baseline for 24 days; Part 3 change from baseline for 16 days
GSK2336805 safety parameters: absolute values and changes over time of hematology, clinical chemistry, urinalysis
Time frame: Part 1 change from baseline for 14 days; Part 2 change from baseline for 24 days; Part 3 change from baseline for 16 days
GSK2336805 safety parameters: vital signs (blood pressure, heart rate)
Time frame: Part 1 change from baseline for 14 days; Part 2 change from baseline for 24 days; Part 3 change from baseline for 16 days
GSK2336805 safety parameters: electrocardiogram (ECG) parameters
Time frame: Part 1 change from baseline for 14 days; Part 2 change from baseline for 24 days; Part 3 change from baseline for 16 days
GSK2336805 PK parameters following single dose administration: area under the plasma concentration curve from time zero (pre-dose) extrapolated to infinite time (AUC(0-infinity)
Time frame: Part 1 up to 48 hours; Part 2 for 7 and 14 days; Part 3 for 48 hours
GSK2336805 PK parameters following single dose administration: area under the plasma concentration curve over the dosing interval AUC(0-tau))
Time frame: Part 1 up to 48 hours; Part 2 for 7 and 14 days; Part 3 for 48 hours
GSK2336805 PK parameters following single dose administration: maximum observed concentration (Cmax)
Time frame: Part 1 up to 48 hours; Part 2 for 7 and 14 days; Part 3 for 48 hours
GSK2336805 PK parameters following single dose administration: time to maximum observed concentration (tmax)
Time frame: Part 1 up to 48 hours; Part 2 for 7 and 14 days; Part 3 for 48 hours
GSK2336805 PK parameters following single dose administration: observed concentration at 24h post-dose (C24)
Time frame: Part 1 up to 48 hours; Part 2 for 7 and 14 days; Part 3 for 48 hours
GSK2336805 PK parameters following single dose administration: terminal half-life (t1/2)
Time frame: Part 1 up to 48 hours; Part 2 for 7 and 14 days; Part 3 for 48 hours
GSK2336805 PK parameters following single dose administration: lag time (tlag)
Time frame: Part 1 up to 48 hours; Part 2 for 7 and 14 days; Part 3 for 48 hours
GSK2336805 PK parameters following single dose administration: apparent clearance (CL/F)
Time frame: Part 1 up to 48 hours; Part 2 for 7 and 14 days; Part 3 for 48 hours
GSK2336805 PK parameters following repeat dose administration:AUC(0-tau)
Time frame: Day 7 and Day 14
GSK2336805 PK parameters following repeat dose administration: Pre-dose (trough) concentration at the end of the dosing interval Ctau
Time frame: Day 7 and Day 14
GSK2336805 PK parameters following repeat dose administration: Cmax
Time frame: Day 7 and Day 14
GSK2336805 PK parameters following repeat dose administration: tmax
Time frame: Day 7 and Day 14
GSK2336805 PK parameters following repeat dose administration: t1/2,
Time frame: Day 7 and day 14
GSK2336805 PK parameters following repeat dose administration: CL/F
Time frame: Day 7 and Day 14
GSK2336805 PK parameters following single dose in HCV infected subjects: AUC(0-infinity) or AUC(0 - tau)
Time frame: for 48 hours
GSK2336805 PK parameters following single dose in HCV infected subjects: Cmax
Time frame: for 48 hours
GSK2336805 PK parameters following single dose in HCV infected subjects: C24
Time frame: for 48 hours
GSK2336805 PK parameters following single dose in HCV infected subjects: tmax
Time frame: for 48 hours
GSK2336805 PK parameters following single dose in HCV infected subjects: tlag
Time frame: for 48 hours
GSK2336805 PK parameters following single dose in HCV infected subjects: CL/F
Time frame: for 48 hours
HCV Ribonucleic acid (RNA) viral load reduction from baseline during the 24hr and post-dosing following a single dose of GSK2336805 in HCV subjects
Time frame: at baseline, 24 hours, and for 16 days
HCV RNA change from baseline to nadir (maximum change) in HCV subjects
Time frame: baseline, and for 16 days
Time course of HCV viral load at baseline, after dosing with GSK2336805, and for greater than or equal to 2 weeks after GSK2336805 dosing (Part 3)
Time frame: baseline and up to 16 days
GSK2336805 PK parameters: AUC(0-infinity) or AUC (0 - tau) following single dose administration of a given dose of GSK2336805 with and without moderate fat/calorie meal (Part 1)
Time frame: 48 hours
GSK2336805 PK parameters: Cmax following single dose administration of a given dose of GSK2336805 with and without moderate fat/calorie meal (Part 1)
Time frame: 48 hours
GSK2336805 PK parameters: tmax following single dose administration of a given dose of GSK2336805 with and without moderate fat/calorie meal (Part 1)
Time frame: 48 hours
GSK2336805 PK parameters: tlag following single dose administration of a given dose of GSK2336805 with and without moderate fat/calorie meal (Part 1)
Time frame: 48 hours
GSK2336805 AUC(0-tau) on Day 7 compared to AUC(0-24) on Day 1 to estimate accumulation ratio (R) and GSK2336805 AUC(0-tau) on Day 7 compared to AUC(0-infinity) on Day 1
Time frame: Day 1 and Day 7
Pre-dose concentrations (Ctau) on Day 2 through 7 to assess the achievement of steady state of GSK2336805 following repeat administration (Part 2)
Time frame: Day 2 through Day 7
GSK2336805 PK parameters: AUC(0-infinity), AUC(0-t), Cmax, and C24 following single dose administration
Time frame: 48 hours
GSK2336805 PK parameters: AUC(0-τ), Cτ, and Cmax following repeat administration
Time frame: for 7 days
Correlation between concentration and various safety parameters, if appropriate
Time frame: 16 days
Sequence analysis of the viral quasispecies as appropriate (Part 3).
Time frame: 16 days
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GSK2336805 AUC(0-tau) on Day 14 compared to AUC(0-24) on Day 1 to estimate accumulation ratio (R) and GSK2336805 AUC(0-tau) on Day 14 compared to AUC(0-inf) on Day 1
Time frame: 14 days
Pre-dose concentrations (Ctau) on Day 2 through 14 to assess the achievement of steady state of GSK2336805 following repeat administration (Part 2 Cohort E)
Time frame: Day 2 and Day 14