Phase 1 Study of GSK3228836 Pharmacokinetics in Participants With Hepatic Impairment

Study Overview
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Brief Summary
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This is a Phase 1, open-label, parallel-group study to evaluate the pharmacokinetics of GSK3228836 in participants with Child-Pugh B (CP-B) cirrhosis (moderate hepatic impairment), Child-Pugh A (CP-A) cirrhosis (mild hepatic impairment) and participants with normal hepatic function as healthy control.

Official Title
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A Phase 1, Open-label, Single-Dose Study to Evaluate the Pharmacokinetics of GSK3228836 in Adults With Hepatic Impairment and Healthy Matched Control Participants (B-Assured)

Conditions
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Hepatitis B

Intervention / Treatment
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* Drug: GSK3228836


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body weight >50 Kilogram (kg) and body mass index (BMI) within the range 19 to 40 Kilogram per square meters (kg/m2) (inclusive) Capable of giving signed informed consent. Child-Pugh B cirrhosis (moderate hepatic impairment; Part 1) or Child-Pugh A cirrhosis (mild hepatic impairment; Part 2) or a healthy control participant based on a medical evaluation including medical history, physical examination (PE), laboratory tests. Exclusion Criteria: Diagnosed or suspected hepatocellular carcinoma. History of malignancy within the past 5 years except for cancers that are cured by surgical resection (e.g., skin cancer). History of vasculitis or presence of symptoms and signs of potential vasculitis or history/presence of other diseases that may be associated with vasculitis condition. Unstable cardiac function or high blood pressure that is not controlled (based on the investigator's discretion). Any other medical condition which, in the judgment of the investigator and Medical Monitor, could jeopardize the integrity of the data derived from that participant or the safety of the participant. Participants who have taken or are currently taking any therapies not allowed by the protocol. A positive test for human immunodeficiency virus (HIV) antibody. History of sensitivity to GSK3228836 or components thereof or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Participants with Moderate (CP-B) hepatic impairment<br> | Drug: GSK3228836<br>* GSK3228836 will be administered<br>|
| Experimental: Participants with Mild (CP-A) hepatic impairment<br> | Drug: GSK3228836<br>* GSK3228836 will be administered<br>|
| Experimental: Healthy participants<br> | Drug: GSK3228836<br>* GSK3228836 will be administered<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the concentration-time curve (AUC) from time zero (pre-dose) extrapolated to infinite time [AUC(0-infinity)] |  | Up to Day 50 post-dose | 
| Maximum observed concentration (Cmax) |  | Up to Day 50 post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC from time zero (pre-dose) to 24 hours [AUC(0-24)] |  | Up to 24 hours post-dose | 
| AUC from time zero (pre-dose) to 168 hours [AUC(0-168)] |  | Up to 168 hours post-dose | 
| Plasma concentration of GSK3228836 on Day 8 |  | Day 8 post-dose | 
| Apparent terminal phase half-life (t1/2) |  | Up to Day 50 post-dose | 
| Apparent clearance (CL/F) |  | Up to Day 50 post-dose | 
| Time of occurrence of Cmax (Tmax) |  | Up to Day 50 post-dose | 
| Apparent terminal phase volume of distribution (Vz/F) |  | Up to Day 50 post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GSK3228836, Hepatitis B, Child-Pugh B (CP-B) cirrhosis, Child-Pugh A (CP-A) cirrhosis, Pharmacokinetics, B-Assured