GSK2878175 is a site IV NS5B non-nucleoside inhibitor (NNI) being developed for the treatment of chronic hepatitis C virus (HCV) infection. The purpose of this study is to investigate the effects of GSK2878175, at different doses in men and women infected with chronic hepatitis C virus. The study will investigate how much of the drug gets into the blood stream and how long the body takes to get rid of it. The study will also investigate if GSK2878175 has any important side effects. The study will also measure what effect GSK2878175 has on the hepatitis C virus infection after taking the study medication for 2 days. Approximately 44 people will take part in this study. Depending on the type of chronic hepatitis C infection a subject will be enrolled into 1 of 4 groups randomly. Each group will participate in one dosing session. One dosing session consists of GSK2878175 or a placebo (sugar pill) given once per day for 2 days. Group A, B, and C is made up of 8 participants per group. In each of these groups 6 participants will receive GSK2878175 and 2 participants will receive placebo. Group D is made up of 20 participants. 15 participants will receive GSK2878175 and 5 participants will receive placebo. The treatment groups will be dosed in sequence. Group A will be the first to take the study medication, then Group B, and so on. The plan is to dose subjects in Group A with 10 mg, Group B with 30 mg, Group C with 60 mg, and Group D with 60 mg of GSK2878175 or placebo. The next treatment group's actual dose will be decided after looking at the results from the previous group. The doses may therefore be higher or lower than planned depending on the previous group's results. The number of participants enrolled in the next group may also change depending on the results from the previous group.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
37
Round tablets (5.0mg) given once daily repeated (to 2 days), oral dose.
Round tablets (5.0mg) given once daily repeated (to 2 days), oral dose visually matching GSK2878175.
GSK Investigational Site
San Juan, Puerto Rico
Safety as assessed by the collection of adverse events (AEs).
AEs will be collected from the start of Study Treatment and until 14 days post last-dose (at follow up).
Time frame: Screening to 14 days post last-dose
Safety as assessed by hematology, clinical chemistry, urinalysis, vital signs, electrocardiogram (ECG) intervals, ECG rhythm telemetry, pulmonary function tests, respiratory rate and lung auscultation.
Absolute values and changes over time of hematology, clinical chemistry, urinalysis, vital signs (blood pressure \[BP\], FSH/Estradiol (Women), Urine β-hCG (Women) temperature, and heart rate), 12 LED ECG, and Holter monitoring, ECG intervals, ECG rhythm, and telemetry will be measured. Telemetry is the continuous monitoring of a subject's heart rate and rhythm from a remote location. Pulmonary function testing includes a group of tests that measure how well the lung is functioning.
Time frame: Pre-dose to 14 days post last-dose
Composite of PK parameters (Day 1) following repeat dose administration of GSK2878175.
PK parameters include: AUC (0-24), Tmax, Cmax,C24, t1/2, tlag, CL/F for Day 1
Time frame: Pre Dose, 0.5hr, 1.5hr, 4hr, 6hr, 12hr
Composite of PK parameters (Day 2) following repeat dose administration of GSK2878175.
PK parameters include: AUC (0-t), Ct, Cmax, tmax, t1/2, CL/F for Day 2.
Time frame: Day 2 Pre Doseand Post Day 1 Dose at 24hr, 24.5hr, 25.5hr, 28hr, 30hr, 33hr, 36hr, 48hr, 72hr, 96hr, 144hr, 192hr, 240hr and 360hr
Antiviral activity as assessed by HCV RNA viral load.
HCV RNA viral load reduction from baseline at the 24 hr, 48 hr, and 72 hr timepoints during dosing of GSK2878175 in HCV subjects
Time frame: Baseline, 24 hr, 48 hr, and 72 hr
Antiviral activity as assessed by HCV RNA maximum change.
HCV RNA change from baseline to nadir (maximum change) in CHC subjects.
Time frame: Pre-dose to 14 days post last-dose.
Antiviral activity as assessed by Time course of HCV viral load.
Time course of HCV viral load at baseline, during, and after dosing with GSK2878175.
Time frame: Baseline, Day1, Day 2, Day 3, Day 4, Day 5, Day 7, Day 9, Day 11, and Day 16 (Follow Up Visit)
Viral quasi-species population.
Sequence analysis of the viral quasispecies population as appropriate before and after a repeat dose.
Time frame: Pre Dose and 12hr on Day 1 and at 24hr, 30hr, 36hr, 48hr, 72hr, 96hr, 144hr, 192hr, 240hr and 360hr Post 1st Dose
IL28B rs12979860 status on GSK2878175 pharmacokinetics.
Determination of IL28B status (C/C versus carriage of the T allele) status on GSK2878175 pharmacokinetics or exposure-response relationship.
Time frame: Day 1 Pre Dose.
Exposure-response relationships for various safety parameters, if appropriate.
Correlation between PK parameters and various safety parameters, if appropriate.
Time frame: Pre-dose to 14 days post last-dose
Exposure-response relationship for antiviral effect.
Correlation between PK parameters and changes in HCV RNA viral load at 24, 48 and 72 hours after the first dose.
Time frame: 24, 48 and 72 hours after the first dose.
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