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Report for Clinical Trial NCT02014571

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

A Randomized, Single Blind, Dose Escalation, Placebo-Controlled Study to Assess the Safety, Pharmacokinetics, and Antiviral Activity of Repeat Doses of GSK2878175 in Subjects With Chronic Hepatitis C.

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.

NCT02014571 Hepatitis C, Chronic
MeSH:Hepatitis A Hepatitis C Hepatitis C, Chronic Hepatitis Hepatitis, Chronic
HPO:Chronic active hepatitis Chronic hepatitis Hepatitis

2 Interventions

Name: GSK2878175

Description: Round tablets (5.0mg) given once daily repeated (to 2 days), oral dose.
Type: Drug
Group Labels: 4

Cohort A Cohort B Cohort C Cohort D

Name: Placebo

Description: Round tablets (5.0mg) given once daily repeated (to 2 days), oral dose visually matching GSK2878175.
Type: Drug
Group Labels: 4

Cohort A Cohort B Cohort C Cohort D


Primary Outcomes

Description: AEs will be collected from the start of Study Treatment and until 14 days post last-dose (at follow up).

Measure: Safety as assessed by the collection of adverse events (AEs).

Time: Screening to 14 days post last-dose

Description: Absolute values and changes over time of hematology, clinical chemistry, urinalysis, vital signs (blood pressure [BP], FSH/Estradiol (Women), Urine ╬▓-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.

Measure: Safety as assessed by hematology, clinical chemistry, urinalysis, vital signs, electrocardiogram (ECG) intervals, ECG rhythm telemetry, pulmonary function tests, respiratory rate and lung auscultation.

Time: Pre-dose to 14 days post last-dose

Description: PK parameters include: AUC (0-24), Tmax, Cmax,C24, t1/2, tlag, CL/F for Day 1

Measure: Composite of PK parameters (Day 1) following repeat dose administration of GSK2878175.

Time: Pre Dose, 0.5hr, 1.5hr, 4hr, 6hr, 12hr

Description: PK parameters include: AUC (0-t), Ct, Cmax, tmax, t1/2, CL/F for Day 2.

Measure: Composite of PK parameters (Day 2) following repeat dose administration of GSK2878175.

Time: 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

Description: HCV RNA viral load reduction from baseline at the 24 hr, 48 hr, and 72 hr timepoints during dosing of GSK2878175 in HCV subjects

Measure: Antiviral activity as assessed by HCV RNA viral load.

Time: Baseline, 24 hr, 48 hr, and 72 hr

Description: HCV RNA change from baseline to nadir (maximum change) in CHC subjects.

Measure: Antiviral activity as assessed by HCV RNA maximum change.

Time: Pre-dose to 14 days post last-dose.

Description: Time course of HCV viral load at baseline, during, and after dosing with GSK2878175.

Measure: Antiviral activity as assessed by Time course of HCV viral load.

Time: Baseline, Day1, Day 2, Day 3, Day 4, Day 5, Day 7, Day 9, Day 11, and Day 16 (Follow Up Visit)

Secondary Outcomes

Description: Sequence analysis of the viral quasispecies population as appropriate before and after a repeat dose.

Measure: Viral quasi-species population.

Time: Pre Dose and 12hr on Day 1 and at 24hr, 30hr, 36hr, 48hr, 72hr, 96hr, 144hr, 192hr, 240hr and 360hr Post 1st Dose

Description: Determination of IL28B status (C/C versus carriage of the T allele) status on GSK2878175 pharmacokinetics or exposure-response relationship.

Measure: IL28B rs12979860 status on GSK2878175 pharmacokinetics.

Time: Day 1 Pre Dose.

Description: Correlation between PK parameters and various safety parameters, if appropriate.

Measure: Exposure-response relationships for various safety parameters, if appropriate.

Time: Pre-dose to 14 days post last-dose

Description: Correlation between PK parameters and changes in HCV RNA viral load at 24, 48 and 72 hours after the first dose.

Measure: Exposure-response relationship for antiviral effect.

Time: 24, 48 and 72 hours after the first dose.

Purpose: Treatment

Allocation: Randomized

Single Group Assignment


There is one SNP

SNPs


1 rs12979860

Antiviral activity as assessed by HCV RNA maximum change.. HCV RNA change from baseline to nadir (maximum change) in CHC subjects.. 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.. Viral quasi-species population.. Sequence analysis of the viral quasispecies population as appropriate before and after a repeat 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.. Exposure-response relationships for various safety parameters, if appropriate.. Correlation between PK parameters and various safety parameters, if appropriate.. 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.. Inclusion Criteria: - Has chronic genotype 1 (subtypes 1a or 1b) or genotype 2 or genotype 3 or genotype 4 (as assessed by VERSANT® HCV Genotype assay 2.0 (LiPA); VERSANT is a registered trademark of the Siemens Healthcare company.)



HPO Nodes


HPO: