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

Official title

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

Overview

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

Interventions

• 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).

Primary outcome measures

• Absolute bioavailability (F oral) of VH4524184 (Period 1) [Time frame: Day 1 up to Day 14]
• Amount of total radioactivity (TRA) excreted in urine (Ae urine) (Period 1) [Time frame: Day 1 up to Day 14]
• Amount of TRA excreted in urine (Ae urine) (Period 2) [Time frame: Day 15 up to Day 43]
• Amount of TRA excreted in feces (Ae feces) (Period 1) [Time frame: Day 1 up to Day 14]
• Amount of TRA excreted in feces (Ae feces) (Period 2) [Time frame: Day 15 up to Day 43]
• Amount of TRA excreted in vomitus (Ae vomit) (Period 1) [Time frame: At Day 1]
• Amount of TRA excreted in vomitus (Ae vomit) (Period 2) [Time frame: At Day 15]
• Total amount of TRA excreted (Ae total) (Period 1) [Time frame: From Day 1 up to Day 14]
• Total amount of TRA excreted (Ae total) (Period 2) [Time frame: Day 15 up to Day 43]
• Fraction of TRA excreted in urine (fe urine) (Period 1) [Time frame: Day 1 up to Day 14]

Secondary outcome measures (5)

• Number of participants with adverse events (AE), overall and by severity (Periods 1 and 2) [Time frame: Day 1 to Day 50]
• Number of participants who discontinue treatment due to AEs (Periods 1 and 2) [Time frame: Day 1 to Day 50]
• Change from baseline for aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, and alkaline phosphatase (Periods 1 and 2) [Time frame: 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) [Time frame: On Days 2, 14, 16, 28 and 42]
• Blood to plasma ratio of TRA (Periods 1 and 2) [Time frame: Day 1 to Day 14 (Period 1) and Day 15 to Day 28 (Period 2)]

Eligibility criteria

Inclusion criteria

• Willing and able to sign the Informed Consent Form (ICF).
• Sex at birth: male or female; female participants must be of non-childbearing potential, or postmenopausal.
• Age: 18 to 55 years, inclusive, at screening.
• BMI: 18.0 to 32.0 kg/m\^2, inclusive, at screening.
• 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.
• 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.
• Male participants must agree not to donate sperm from admission on Day -1 until the completion of the follow-up visit.
• 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.
• 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.
• 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.
• 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.
• 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

• Employee of ICON, the Sponsor, GSK or associated vendors.
• History of relevant drug and/or food allergies.
• History of drug hypersensitivity, delayed-type hypersensitivity, or severe hypersensitivity reactions, as well as history of sensitivity to the study drug.
• Using tobacco/nicotine products within 60 days prior to the first study drug administration.
• History of alcohol abuse or drug addiction within 5 years prior to screening.
• Positive drug and/or alcohol screen at screening or admission to the clinical site.
• Average intake of more than 24 units of alcohol per week.
• Positive screen for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibodies, or human immunodeficiency virus (HIV) 1 and 2 antibodies at screening.
• 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.
• 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.
• 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.
• 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.
• Unsuitable veins for infusion or blood sampling.
• Participation in a study with a 14C dose of ≥0.1 megabecquerel (MBq) in the period of 1 year prior to screening.
• Irregular defecation pattern.
• 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.
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Basic science

Study locations

Netherlands · 1 center

• GSK Investigational Site — Groningen

Identifiers

NCT: NCT07636928 · 223803 · 2026-525590-40

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗