Phase 1 Study of GSK3228836 Pharmacokinetics in Participants With Hepatic Impairment

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)

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.

Study Overview

• Status: Completed
• Conditions: Hepatitis B
• Intervention / Treatment: Drug: GSK3228836

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Orlando, Florida, United States, 32809
      • GSK Investigational Site
  • Texas
    • San Antonio, Texas, United States, 78215
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): September 7, 2021
• Primary Completion (Actual): May 12, 2022
• Study Completion (Actual): May 12, 2022

Study Registration Dates

• First Submitted: June 22, 2021
• First Submitted That Met QC Criteria: July 12, 2021
• First Posted (Actual): July 22, 2021

Study Record Updates

• Last Update Posted (Actual): September 27, 2022
• Last Update Submitted That Met QC Criteria: September 26, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Hepatitis B; GSK3228836; Child-Pugh B (CP-B) cirrhosis; Child-Pugh A (CP-A) cirrhosis; B-Assured
• Additional Relevant MeSH Terms: Digestive System Diseases; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Hepatitis B; Hepatitis
• Other Study ID Numbers: 205871

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• IPD Sharing Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
• IPD Sharing Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No