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This is a single-dose, open-label, two part, parallel group study. This study is being conducted to determine the pharmacokinetics, safety and tolerability of GSK2336805 in subjects with varying degrees of hepatic impairment. Part 1 of the study will enroll subjects with mild and moderate hepatic impairment and healthy control subjects matched to the subjects in the moderate hepatic impairment category. The decision to commence Part 2 will be based on a review of the preliminary safety and pharmacokinetic data from subjects with moderate hepatic impairment. Part 2 will enroll subjects with severe hepatic impairment. Additionally, based on emergent data from Part 1, matched controls to the severe hepatic group may be enrolled (optional). Due to the potential difficulty in identifying eligible subjects with severe hepatic impairment, the study may be stopped prior to full enrollment in Part 2, provided that a minimum of 4 evaluable subjects with severe hepatic impairment have been enrolled. The study will consist of a Screening visit, a single dose Treatment Period and a Follow-up visit. Subjects will be screened for eligibility criteria within 30 days of enrolment. Subjects will be admitted to the clinical unit on Day -1; each subject will receive a single dose of GSK2336805 on Day 1 and will remain in the clinical unit for 5 days (check-out on Day 4). The follow-up visit will be conducted within 7-10 days after Day 1 dosing.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part 1 Cohort 1 - Mild hepatic impairment | Experimental | Subjects with mild hepatic impairment will be enrolled in Cohort 1 and will receive a single dose of 60 mg GSK2336805 |
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| Part 1 Cohort 2 - Moderate hepatic impairment | Experimental | Subjects with moderate hepatic impairment will be enrolled in Cohort 2 and will receive a single dose of 60 mg GSK2336805 |
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| Part 1 Cohort 3 - Matched healthy volunteers to Cohort 2 | Experimental | Control subjects will be matched for gender, age (+/- 10 years), body mass index (BMI) (+/- 20%), and smoking status to the subjects in the moderate hepatic impairment arm. These healthy volunteers will receive a single dose of 60 mg GSK2336805 |
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| Part 2 Cohort 4 - Severe hepatic impairment | Experimental | Subjects with severe hepatic impairment will be enrolled in Cohort 2 and will receive a single dose of 60 mg GSK2336805. The decision to move forward into Part 2 (severe hepatic impairment) will be based on a review of the preliminary safety and pharmacokinetic data from subjects with moderate hepatic impairment |
|
| Part 2 Cohort 5 - Matched healthy volunteers to Cohort 4 | Experimental |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GSK2336805 | Drug | Two 30 mg GSK2336805 tablets for a 60 mg single dose will be administered in this study |
|
| Measure | Description | Time Frame |
|---|---|---|
| Composite of plasma pharmacokinetic (PK) parameters of GSK2336805 | The following pharmacokinetic parameters will be determined: area under the plasma concentration time curve (AUC)- from time zero to infinity [AUC(0-inf)], from time zero to the last quantifiable time points [AUC(0-t)], and from time zero to 24 hours [AUC(0-24)]; maximum observed plasma concentration (Cmax); time to Cmax (tmax); concentration at 24hour post-dose (C24); absorption lag time (tlag); apparent oral clearance (CL/F), apparent volume of distribution after oral administration (Vz/F), and half-life (t½). These will be compared in subjects with hepatic impairment to healthy volunteers | Day 1: 0.25 hours (h) predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 (Day 2), 36, 48(Day 3), 60 and 72(Day 4) h post-dose |
| Measure | Description | Time Frame |
|---|---|---|
| Safety and tolerability of GSK2336805 as assessed by adverse events (AEs), concurrent medications, clinical laboratory, electrocardiograms (ECGs) and vital sign parameters | Safety and tolerability assessment will include assessment of AEs, concurrent medications, clinical laboratory, ECGs and vital sign | Up to 10 days |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Lakewood | Colorado | 80228 | United States | ||
| GSK Investigational Site |
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| Label | URL |
|---|---|
| Results for study 117380 can be found on the GSK Clinical Study Register. | View source |
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Based on emerging data from Part 1, the sponsor may decide to enroll matched controls to the severe hepatic group (i.e. in case of a change in dose or the demographics of the severe hepatic group are not well matched with the moderate control data). The subjects in this optional control cohort will be matched for gender, age (+/- 10 years), BMI (+/- 20%), and smoking status to the subjects in the severe hepatic impairment category |
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| Unbound concentration and unbound fraction of GSK2336805 in plasma |
Impact of hepatic impairment on pharmacokinetics of GSK2336805 will be assessed by evaluation of unbound concentration and unbound fraction of GSK2336805 in plasma. |
| Day 1: 2, 12 and 24 h post dose |
| Composite of plasma PK parameters of GSK2336805 in subjects with hepatic impairment compared with PK parameters of non-cirrhotic subjects with chronic Hepatitis C (CHC) | The PK parameters: AUC(0-t), AUC(0-inf), Cmax, C24, t½, CL/F, and Vz/F in subjects with hepatic impairment will be compared with PK parameters of non-cirrhotic subjects with CHC in previous studies (HAI114885 and HAI115519) | Day 1: 0.25 hours (h) predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 (Day 2), 36, 48 (Day 3), 60 and 72 (Day 4) h post-dose |
| Orlando |
| Florida |
| 32809 |
| United States |
| GSK Investigational Site | Minneapolis | Minnesota | 55404 | United States |
| GSK Investigational Site | Knoxville | Tennessee | 37920 | United States |
| ID | Term |
|---|---|
| D006526 | Hepatitis C |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D006525 | Hepatitis, Viral, Human |
| D014777 | Virus Diseases |
| D018178 | Flaviviridae Infections |
| D012327 | RNA Virus Infections |
| D006505 | Hepatitis |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
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| ID | Term |
|---|---|
| C000595241 | GSK2336805 |
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