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

Официальное название

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

Обзор

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

Вмешательства

• Препарат VH4524184
  One dose of VH4524184 is administered to participants at time zero on Day 1 (Period 1).
• Препарат [14C]VH4524184 microdose
  A radiolabelled microdose of \[14C\]VH4524184 is administered 2.5 hours after VH4524184 dose administration on Day 1 (Period1).
• Препарат [14C]VH4524184
  One dose of radiolabelled \[14C\]VH4524184 is administered to participants at Day 15 (Period 2).

Первичные конечные точки

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

Вторичные конечные точки (5)

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

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Фундаментальное исследование

Центры проведения

Нидерланды · 1 центр

• GSK Investigational Site — Groningen

Идентификаторы

NCT: NCT07636928 · 223803 · 2026-525590-40

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗