Mass Balance and Absolute Oral Bioavailability of [14C]VH4524184

A Phase 1, Open-Label, Single Dose Study to Assess the Absolute Bioavailability, Mass Balance, Pharmacokinetics, Metabolism, and Excretion of [14C]VH4524184 in Healthy Participants

The purpose of the study is to assess the bioavailability, mass balance, pharmacokinetics, metabolism and excretion of radiolabeled (14C) VH4524184.

Study Overview

• Status: Not yet recruiting
• Conditions: HIV Infections
• Intervention / Treatment: Drug: VH4524184; Drug: [14C]VH4524184 microdose; Drug: [14C]VH4524184

• Study Type: Interventional
• Enrollment (Estimated): 9
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: US GSK Clinical Trials Call Center; Phone Number: 877-379-3718; Email: GSKClinicalSupportHD@gsk.com
• Study Contact Backup: Name: EU GSK Clinical Trials Call Center; Phone Number: +44 (0) 20 89904466; Email: GSKClinicalSupportHD@gsk.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Willing and able to sign the Informed Consent Form (ICF).
2. Sex at birth: male or female; female participants must be of non-childbearing potential, or postmenopausal.
3. Age: 18 to 55 years, inclusive, at screening.
4. BMI: 18.0 to 32.0 kg/m^2, inclusive, at screening.
5. Female participants of non-childbearing potential must have unequivocal documentation that they are not of childbearing potential Postmenopausal female participants must have a serum follicle-stimulating hormone (FSH) concentration >33.4 milli-international units per milliliter (mIU/mL) at screening to confirm menopause.
6. Male participants, if not surgically sterilized and who have a female partner of childbearing potential, must agree to use a condom during any sexual intercourse until the completion of the follow-up visit.
7. Male participants must agree not to donate sperm from admission on Day -1 until the completion of the follow-up visit.
8. All prescribed medication must have been stopped at least 30 days and >5 half-lives prior to admission to the clinical site on Day -1.
9. All over-the-counter medication, vitamin preparations and other food supplements, or herbal medications must have been stopped at least 14 days prior to admission to the clinical site on Day -1. An exception is made for paracetamol that is allowed up to admission to the clinical site on Day -1.
10. Ability and willingness to abstain from alcohol from 48 hours prior to screening and admission to the clinical site on Day -1 until the last PK sample.
11. Ability and willingness to abstain from methylxanthine-containing beverages or food (coffee, black tea, green tea, white tea, cola, chocolate, energy drinks), and grapefruit (juice) from 48 hours prior to admission to the clinical site.
12. Good physical and mental health based on medical history, physical examination, clinical laboratory, electrocardiogram (ECG), and vital signs, as judged by the Investigator.

Exclusion Criteria:

1. Employee of ICON, the Sponsor, GSK or associated vendors.
2. History of relevant drug and/or food allergies.
3. History of drug hypersensitivity, delayed-type hypersensitivity, or severe hypersensitivity reactions, as well as history of sensitivity to the study drug.
4. Using tobacco/nicotine products within 60 days prior to the first study drug administration.
5. History of alcohol abuse or drug addiction within 5 years prior to screening.
6. Positive drug and/or alcohol screen at screening or admission to the clinical site.
7. Average intake of more than 24 units of alcohol per week.
8. Positive screen for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibodies, or human immunodeficiency virus (HIV) 1 and 2 antibodies at screening.
9. Participation in a drug study with a small molecule drug within 30 days or 5 half-lives if known (whichever is longer) prior to the first study drug administration in the current study. Participation in a clinical study with a biological within 90 days or 5 half-lives if known (whichever is longer) prior to the first study drug administration in the current study. Participation in 4 or more other drug studies in the 12 months prior to the first study drug administration in the current study.
10. Donation or loss of more than 450 mL of blood within 60 days prior to the first study drug administration. Donation or loss of more than 1.5 L of blood (for male participants)/more than 1.0 L of blood (for female participants) in the 10 months prior to the first study drug administration in the current study.
11. Significant and/or acute illness within 14 days prior to the first study drug administration that may impact safety assessments, in the opinion of the Investigator.
12. Any significant current/ongoing known or suspected pre-existing psychiatric condition, including depression, anxiety, and/or insomnia/sleep disturbances and/or suicidal ideation, in the opinion of the Investigator.
13. Unsuitable veins for infusion or blood sampling.
14. Participation in a study with a 14C dose of ≥0.1 megabecquerel (MBq) in the period of 1 year prior to screening.
15. Irregular defecation pattern.
16. Pre-existing clinically relevant, in the opinion of the Investigator in discussion with the Sponsor medical monitor, gastro-intestinal pathology or diagnosis, eg, irritable bowel syndrome, inflammatory bowel disease, and/or significant baseline signs and symptoms.
17. History or presence of clinical condition or disorder that could be capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study drugs, interfering with the interpretation of data or would make the participant unsuitable for the study; unable to comply with dosing requirements; or unable to comply with study visits, in the opinion of the Investigator. The Investigator may contact the Sponsor medical monitor to discuss the inclusion of participants who have a history of specific conditions that are not expected to interfere with their participation in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: VH4524184 Group; Participants will receive a dose of VH4524184 under fasting conditions, followed by a microdose of radiolabelled [14C]VH4524184 administered 2.5 hours after first dose administration at time zero on Day 1 (Period1). After a 14 days wash-out period participants will receive a radiolabelled dose of [14C]VH4524184 on Day 15 under fasting conditions.	Drug: VH4524184; One dose of VH4524184 is administered to participants at time zero on Day 1 (Period 1).; Drug: [14C]VH4524184 microdose; A radiolabelled microdose of [14C]VH4524184 is administered 2.5 hours after VH4524184 dose administration on Day 1 (Period1).; Drug: [14C]VH4524184; One dose of radiolabelled [14C]VH4524184 is administered to participants at Day 15 (Period 2).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute bioavailability (F oral) of VH4524184 (Period 1)		Day 1 up to Day 14
Amount of total radioactivity (TRA) excreted in urine (Ae urine) (Period 1)	Urine is collected until amount of radioactivity recovered in excreta (urine and feces) is at least 90% of administered radioactivity and <1% has been recovered from excreta from 2 consecutive days (ie, the total for urine and feces is <1% on 2 consecutive days).	Day 1 up to Day 14
Amount of TRA excreted in urine (Ae urine) (Period 2)	Urine is collected until amount of radioactivity recovered in excreta (urine and feces) is at least 90% of administered radioactivity and <1% has been recovered from excreta from 2 consecutive days (ie, the total for urine and feces is <1% on 2 consecutive days).	Day 15 up to Day 43
Amount of TRA excreted in feces (Ae feces) (Period 1)	Feces are collected until amount of radioactivity recovered in excreta (urine and feces) is at least 90% of administered radioactivity and <1% has been recovered from excreta from 2 consecutive days (ie, the total for urine and feces is <1% on 2 consecutive days).	Day 1 up to Day 14
Amount of TRA excreted in feces (Ae feces) (Period 2)	Feces are collected until amount of radioactivity recovered in excreta (urine and feces) is at least 90% of administered radioactivity and <1% has been recovered from excreta from 2 consecutive days (ie, the total for urine and feces is <1% on 2 consecutive days).	Day 15 up to Day 43
Amount of TRA excreted in vomitus (Ae vomit) (Period 1)		At Day 1
Amount of TRA excreted in vomitus (Ae vomit) (Period 2)		At Day 15
Total amount of TRA excreted (Ae total) (Period 1)	The Ae of TRA measured in urine, feces and vomitus (if applicable on Day 1 only). Urine and feces are collected until amount of radioactivity recovered in excreta (urine and feces) is at least 90% of administered radioactivity and <1% has been recovered from excreta from 2 consecutive days (ie, the total for urine and feces is <1% on 2 consecutive days).	From Day 1 up to Day 14
Total amount of TRA excreted (Ae total) (Period 2)	The Ae of TRA measured in urine, feces and vomitus (if applicable on Day 15 only). Urine and feces are collected until amount of radioactivity recovered in excreta (urine and feces) is at least 90% of administered radioactivity and <1% has been recovered from excreta from 2 consecutive days (ie, the total for urine and feces is <1% on 2 consecutive days).	Day 15 up to Day 43
Fraction of TRA excreted in urine (fe urine) (Period 1)	Urine is collected until the amount of radioactivity recovered in excreta (urine and feces) is at least 90% of administered radioactivity and <1% has been recovered from excreta from 2 consecutive days (ie, the total for urine and feces is <1% on 2 consecutive days).	Day 1 up to Day 14
Fraction of TRA excreted in urine (fe urine) (Period 2)	Urine is collected until amount of radioactivity recovered in excreta (urine and feces) is at least 90% of administered radioactivity and <1% has been recovered from excreta from 2 consecutive days (ie, the total for urine and feces is <1% on 2 consecutive days).	Day 15 up to Day 43
Fraction of TRA excreted in feces (fe feces) (Period 1)	Feces is collected until amount of radioactivity recovered in excreta (urine and feces) is at least 90% of administered radioactivity and <1% has been recovered from excreta from 2 consecutive days (ie, the total for urine and feces is <1% on 2 consecutive days).	Day 1 up to Day 14
Fraction of TRA excreted in feces (fe feces) (Period 2)	Feces is collected until amount of radioactivity recovered in excreta (urine and feces) is at least 90% of administered radioactivity and <1% has been recovered from excreta from 2 consecutive days (ie, the total for urine and feces is <1% on 2 consecutive days).	Day 15 up to Day 43
Fraction of TRA excreted in vomitus (fe vomit) (Period 1)		At Day 1
Fraction of TRA excreted in vomitus (fe vomit) (Period 2)		At Day 15
Total fraction of TRA excreted (fe total) (Period 1)	The fe of TRA measured in urine, feces and vomitus (if applicable on Day 1 only). Urine and feces are collected until amount of radioactivity recovered in excreta (urine and feces) is at least 90% of administered radioactivity and <1% has been recovered from excreta from 2 consecutive days (ie, the total for urine and feces is <1% on 2 consecutive days).	Day 1 up to Day 14
Total fraction of TRA excreted (fe total) (Period 2)	The fe of TRA measured in urine, feces and vomitus (if applicable on Day 15 only). Urine and feces are collected until amount of radioactivity recovered in excreta (urine and feces) is at least 90% of administered radioactivity and <1% has been recovered from excreta from 2 consecutive days (ie, the total for urine and feces is <1% on 2 consecutive days).	Day 15 up to Day 43
Maximum concentration (Cmax) of VH4524184 in plasma (Period 1)		Day 1 to Day 14
Maximum concentration (Cmax) of VH4524184 in plasma (Period 2)		Day 15 to Day 43
Maximum concentration (Cmax) of [14C]VH4524184 in plasma (Period 1)		Day 1 to Day 14
Maximum concentration (Cmax) of TRA in plasma (Period 1)		Day 1 to Day 14
Maximum concentration (Cmax) of TRA in plasma (Period 2)		Day 15 to Day 43
Cmax of TRA in whole blood (Period 1)		Day 1 to Day 14
Cmax of TRA in whole blood (Period 2)		Day 15 to Day 43
Time to maximum concentration (tmax) of VH4524184 in plasma (Period 1)		Day 1 to Day 14
Time to maximum concentration (tmax) of VH4524184 in plasma (Period 2)		Day 15 to Day 43
Time to maximum concentration (tmax) of [14C]VH4524184 in plasma (Period 1)		Day 1 to Day 14
Time to maximum concentration (tmax) of TRA in plasma (Period 1)		Day 1 to Day 14
Time to maximum concentration (tmax) of TRA in plasma (Period 2)		Day 15 to Day 43
Time to maximum concentration (tmax) of TRA in whole blood (Period 1)		Day 1 to Day 14
Time to maximum concentration (tmax) of TRA in whole blood (Period 2)		Day 15 to Day 43
Area under the concentration-time curve from time zero to the last measured timepoint (AUC 0-t) of VH4524184 in plasma (Period 1)		Day 1 to Day 14
Area under the concentration-time curve from time zero to the last measured timepoint (AUC 0-t) of VH4524184 in plasma (Period 2)		Day 15 to Day 43
Area under the concentration-time curve from time zero to the last measured timepoint (AUC 0-t) of [14C]VH4524184 in plasma (Period 1)		Day 1 to Day 14
Area under the concentration-time curve from time zero to the last measured timepoint (AUC 0-t) of TRA in plasma (Period 1)		Day 1 to Day 14
Area under the concentration-time curve from time zero to the last measured timepoint (AUC 0-t) of TRA in plasma (Period 2)		Day 15 to Day 43
Area under the concentration-time curve from time zero to the last measured timepoint (AUC 0-t) of TRA in whole blood (Period 1)		Day 1 to Day 14
Area under the concentration-time curve from time zero to the last measured timepoint (AUC 0-t) of TRA in whole blood (Period 2)		Day 15 to Day 43
Area under the concentration-time curve from time zero to infinity (AUC 0-inf) of VH4524184 in plasma (Period 1)		Day 1 to Day 14
Area under the concentration-time curve from time zero to infinity (AUC 0-inf) of VH4524184 in plasma (Period 2)		Day 15 up to Day 43
Area under the concentration-time curve from time zero to infinity (AUC 0-inf) of [14C]VH4524184 in plasma (Period 1)		Day 1 to Day 14
Area under the concentration-time curve from time zero to infinity (AUC 0-inf) of TRA in plasma (Period 1)		Day 1 to Day 14
Area under the concentration-time curve from time zero to infinity (AUC 0-inf) of TRA in plasma (Period 2)		Day 15 to 43
Area under the concentration-time curve from time zero to infinity (AUC 0-inf) of TRA in whole blood (Period 1)		Day 1 to Day 14
Area under the concentration-time curve from time zero to infinity (AUC 0-inf) of TRA in whole blood (Period 2)		Day 15 to Day 43
Amount of VH4524184 excreted in urine (Ae urine) (Period 2)		Day 15 to Day 43
Fraction of VH4524184 excreted in urine (fe urine) (Period 2)		Day 15 to Day 43
Renal clearance of VH4524184 (CL R) (Period 2)		Day 15 to Day 43

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse events (AE), overall and by severity (Periods 1 and 2)		Day 1 to Day 50
Number of participants who discontinue treatment due to AEs (Periods 1 and 2)		Day 1 to Day 50
Change from baseline for aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, and alkaline phosphatase (Periods 1 and 2)		On Days 2, 14, 16, 28 and 42
Maximum toxicity grade increase from baseline for AST, ALT, total bilirubin, and alkaline phosphatase (Periods 1 and 2)		On Days 2, 14, 16, 28 and 42
Blood to plasma ratio of TRA (Periods 1 and 2)	Cmax, AUC(0-t) and AUC(0-inf) TRA measured in whole blood compared to Cmax, AUC(0-t) and AUC(0-inf) TRA measured in plasma in Period 1 and Period 2.	Day 1 to Day 14 (Period 1) and Day 15 to Day 28 (Period 2)

Collaborators and Investigators

• Sponsor: ViiV Healthcare

Study record dates

Study Major Dates

• Study Start (Estimated): June 15, 2026
• Primary Completion (Estimated): August 20, 2026
• Study Completion (Estimated): August 20, 2026

Study Registration Dates

• First Submitted: May 29, 2026
• First Submitted That Met QC Criteria: June 3, 2026
• First Posted (Actual): June 9, 2026

Study Record Updates

• Last Update Posted (Actual): June 9, 2026
• Last Update Submitted That Met QC Criteria: June 3, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: VH4524184; Human immunodeficiency virus (HIV)
• Additional Relevant MeSH Terms: Blood-Borne Infections; Urogenital Diseases; Genital Diseases; Immune System Diseases; Infections; RNA Virus Infections; Virus Diseases; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Slow Virus Diseases; HIV Infections; Acquired Immunodeficiency Syndrome
• Other Study ID Numbers: 223803; 2026-525590-40 (Other Identifier: EU CT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Study Sponsor will assess requests from qualified researchers for anonymized individual patient-level data and related study documents. Data sharing is subject to certain criteria, conditions, and exceptions. For further information, refer to https://www.viiv-studyregister.com/documents/About_ViiV_Patient_Level_Data_Sharing_Final_25Sep2023.pdf
• IPD Sharing Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or asset(s) with development terminated across all indications.
• IPD Sharing Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an 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 may be granted, when justified, for up to 6 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; 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
• product manufactured in and exported from the U.S.: Yes