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

Phase 1RecruitingNCT07636928

ViiV Healthcare9 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

Purpose

BASIC_SCIENCE

Masking

NONE

Enrollment

Conditions

HIV Infections

Interventions

VH4524184DRUG

One dose of VH4524184 is administered to participants at time zero on Day 1 (Period 1).

[14C]VH4524184 microdoseDRUG

A radiolabelled microdose of \[14C\]VH4524184 is administered 2.5 hours after VH4524184 dose administration on Day 1 (Period1).

[14C]VH4524184DRUG

One dose of radiolabelled \[14C\]VH4524184 is administered to participants at Day 15 (Period 2).

Eligibility

Sex: ALLMin age: 18 YearsMax age: 55 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (1)

GSK Investigational Site

Groningen, Netherlands

RECRUITING

Outcomes

Primary Outcomes

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)

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).

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)

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).

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)

Central Contacts

US GSK Clinical Trials Call Center

CONTACT

877-379-3718 GSKClinicalSupportHD@gsk.com

EU GSK Clinical Trials Call Center

CONTACT

+44 (0) 20 89904466 GSKClinicalSupportHD@gsk.com

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Time frame: 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).

Time frame: 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).

Time frame: 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).

Time frame: Day 1 up to Day 14

Fraction of TRA excreted in urine (fe urine) (Period 2)

Time frame: 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).

Time frame: Day 1 up to Day 14

Fraction of TRA excreted in feces (fe feces) (Period 2)

Time frame: Day 15 up to Day 43

Fraction of TRA excreted in vomitus (fe vomit) (Period 1)

Time frame: At Day 1

Fraction of TRA excreted in vomitus (fe vomit) (Period 2)

Time frame: 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).

Time frame: 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).

Time frame: Day 15 up to Day 43

Maximum concentration (Cmax) of VH4524184 in plasma (Period 1)

Time frame: Day 1 to Day 14

Maximum concentration (Cmax) of VH4524184 in plasma (Period 2)

Time frame: Day 15 to Day 43

Maximum concentration (Cmax) of [14C]VH4524184 in plasma (Period 1)

Time frame: Day 1 to Day 14

Maximum concentration (Cmax) of TRA in plasma (Period 1)

Time frame: Day 1 to Day 14

Maximum concentration (Cmax) of TRA in plasma (Period 2)

Time frame: Day 15 to Day 43

Cmax of TRA in whole blood (Period 1)

Time frame: Day 1 to Day 14

Cmax of TRA in whole blood (Period 2)

Time frame: Day 15 to Day 43

Time to maximum concentration (tmax) of VH4524184 in plasma (Period 1)

Time frame: Day 1 to Day 14

Time to maximum concentration (tmax) of VH4524184 in plasma (Period 2)

Time frame: Day 15 to Day 43

Time to maximum concentration (tmax) of [14C]VH4524184 in plasma (Period 1)

Time frame: Day 1 to Day 14

Time to maximum concentration (tmax) of TRA in plasma (Period 1)

Time frame: Day 1 to Day 14

Time to maximum concentration (tmax) of TRA in plasma (Period 2)

Time frame: Day 15 to Day 43

Time to maximum concentration (tmax) of TRA in whole blood (Period 1)

Time frame: Day 1 to Day 14

Time to maximum concentration (tmax) of TRA in whole blood (Period 2)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: Day 15 to Day 43

Amount of VH4524184 excreted in urine (Ae urine) (Period 2)

Time frame: Day 15 to Day 43

Fraction of VH4524184 excreted in urine (fe urine) (Period 2)

Time frame: Day 15 to Day 43

Renal clearance of VH4524184 (CL R) (Period 2)

Time frame: Day 15 to Day 43

Secondary Outcomes

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)

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.

Time frame: Day 1 to Day 14 (Period 1) and Day 15 to Day 28 (Period 2)