COMPLETED

A Study to Investigate Safety, Tolerability, and Pharmacokinetics (PK) of VH4524184 and the Potential for Changes in Cytochrome P450 3A (CYP3A) Activity

Conditions

HIV Infections First-time-in-human GSK4524184 Healthy volunteers Multiple Ascending Dose Single Ascending Dose VH4524184

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This study is designed to investigate the safety, tolerability and PK of VH4524184 (GSK4524184) and the potential of VH4524184 to inhibit or induce CYP3A activity in healthy participants.

Official Title

A Phase 1 Double-Blind (Sponsor-unblinded), Placebo-Controlled Randomized, Single and Multiple Ascending Dose First-Time-in-Human Study to Investigate the Safety, Tolerability, and Pharmacokinetics of VH4524184 and the Potential for Changes in Cytochrome P450 3A (CYP3A) Activity

Quick Facts

Study Start:2022-12-02

Study Completion:2023-07-27

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:COMPLETED

Study ID

NCT05631704

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 50 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:Yes

Standard Ages:ADULT

Inclusion Criteria	Exclusion Criteria
* Participant must be 18 to 50 years of age. * Participants who are overtly healthy. * Body weight \>=50.0 kilograms (kg) (110 pounds \[lbs\]) for men and \>=45.0 kg (99 lbs) for women and body mass index within the range 18.5 to 32.0 kilograms per meter square (kg/m\^2) (inclusive). * Male or female. Male Participants: No contraceptive restrictions for male participants. Female Participants: A female participant (female sex assigned at birth) is eligible to participate if she is not pregnant, or breastfeeding and is not physically able to have a baby.	* History or presence of clinical condition that could significantly alter how medicines are absorbed, broken down or eliminated from the body; be risky to the participant, or make it difficult to interpret the data from the study. * Pre-existing clinically relevant gastro-intestinal disorders. * Abnormal blood pressure. * Certain blood or other cancers within the past 5 years. * Breast cancer within the past 10 years * Current or chronic history of liver disease or liver or bile tract abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). * QT interval corrected for heart rate according to Fridericia's formula (QTcF) \>450 milliseconds (msec). * Medical history of cardiac arrhythmias or cardiac disease or a family and personal history of long QT syndrome. * History of seizure * Any known or suspected pre-existing psychiatric condition, including depression, anxiety and insomnia/sleep disturbances. * Any positive (abnormal) response to the Columbia Suicide Severity Rating Scale (CSSRS). * Past or intended use of over-the-counter or prescription medication within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to dosing and for the duration of the study. * Receipt of any live vaccine(s) or vaccines against Coronavirus disease 2019 (Covid-19) within 28 days prior to screening or plans to receive such vaccines during the study. * Exposure to more than 4 new investigational products (including long-acting investigational products) within 12 months prior to the first dosing day. * Current enrollment or past participation in another investigational study in which an investigational intervention (e.g., drug, human blood product, monoclonal antibody, vaccine, invasive device) was administered within the last 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer) before signing of consent (OR screening) any other clinical study. * Participation in the study would result in loss of blood or blood products in excess of 500 milliliters (mL) over a 56-day period. * Current enrollment or past participation in this clinical study. * Estimated Glomerular Filtration Rate (eGFR) \<90 milliliters per minute (mL/min) (calculated using Chronic Kidney Disease Epidemiology Collaboration equation) or serum creatinine \>1.1 times Upper limit of normal (ULN). * Hemoglobin \<12.5 grams per deciliter (g/dL) for men and \<11 g/dL for women * ALT or AST \>1.5 times ULN * Total bilirubin \>1.5 times ULN (isolated bilirubin \>1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35 percent \[%\]). * Any significant arrhythmia or Electrocardiogram (ECG) finding * Exclusion criteria for Screening ECG (a single repeat is allowed for eligibility determination): Heart rate:\<45 or \>100 beats per minute (bpm) (Males), \<50 or \>100 bpm (Females); PR interval: \<120 or \>220 msec; QRS duration: \<70 or \>120 msec and QTcF interval: \>450 msec. * Presence of hepatitis B surface antigen (HBsAg) at screening. * Positive Hepatitis C antibody test result at screening * Positive pre-study drug/alcohol screen. * Positive human immunodeficiency virus (HIV) antibody test. * Regular alcohol consumption within 6 months prior to the study * Regular use of known drugs of abuse * Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening and at admission. * Sensitivity to the study drug, or components thereof, midazolam (For Part 2, midazolam probe cohort), excipients contained therein, benzodiazepines, or other drug or other allergy that, in the opinion of the investigator or Sponsor Medical Monitor, contraindicates participation in the study.

Inclusion Criteria

Exclusion Criteria

* Participant must be 18 to 50 years of age.
* Participants who are overtly healthy.
* Body weight \>=50.0 kilograms (kg) (110 pounds \[lbs\]) for men and \>=45.0 kg (99 lbs) for women and body mass index within the range 18.5 to 32.0 kilograms per meter square (kg/m\^2) (inclusive).
* Male or female. Male Participants: No contraceptive restrictions for male participants. Female Participants: A female participant (female sex assigned at birth) is eligible to participate if she is not pregnant, or breastfeeding and is not physically able to have a baby.

* History or presence of clinical condition that could significantly alter how medicines are absorbed, broken down or eliminated from the body; be risky to the participant, or make it difficult to interpret the data from the study.
* Pre-existing clinically relevant gastro-intestinal disorders.
* Abnormal blood pressure.
* Certain blood or other cancers within the past 5 years.
* Breast cancer within the past 10 years
* Current or chronic history of liver disease or liver or bile tract abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
* QT interval corrected for heart rate according to Fridericia's formula (QTcF) \>450 milliseconds (msec).
* Medical history of cardiac arrhythmias or cardiac disease or a family and personal history of long QT syndrome.
* History of seizure
* Any known or suspected pre-existing psychiatric condition, including depression, anxiety and insomnia/sleep disturbances.
* Any positive (abnormal) response to the Columbia Suicide Severity Rating Scale (CSSRS).
* Past or intended use of over-the-counter or prescription medication within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to dosing and for the duration of the study.
* Receipt of any live vaccine(s) or vaccines against Coronavirus disease 2019 (Covid-19) within 28 days prior to screening or plans to receive such vaccines during the study.
* Exposure to more than 4 new investigational products (including long-acting investigational products) within 12 months prior to the first dosing day.
* Current enrollment or past participation in another investigational study in which an investigational intervention (e.g., drug, human blood product, monoclonal antibody, vaccine, invasive device) was administered within the last 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer) before signing of consent (OR screening) any other clinical study.
* Participation in the study would result in loss of blood or blood products in excess of 500 milliliters (mL) over a 56-day period.
* Current enrollment or past participation in this clinical study.
* Estimated Glomerular Filtration Rate (eGFR) \<90 milliliters per minute (mL/min) (calculated using Chronic Kidney Disease Epidemiology Collaboration equation) or serum creatinine \>1.1 times Upper limit of normal (ULN).
* Hemoglobin \<12.5 grams per deciliter (g/dL) for men and \<11 g/dL for women
* ALT or AST \>1.5 times ULN
* Total bilirubin \>1.5 times ULN (isolated bilirubin \>1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35 percent \[%\]).
* Any significant arrhythmia or Electrocardiogram (ECG) finding
* Exclusion criteria for Screening ECG (a single repeat is allowed for eligibility determination): Heart rate:\<45 or \>100 beats per minute (bpm) (Males), \<50 or \>100 bpm (Females); PR interval: \<120 or \>220 msec; QRS duration: \<70 or \>120 msec and QTcF interval: \>450 msec.
* Presence of hepatitis B surface antigen (HBsAg) at screening.
* Positive Hepatitis C antibody test result at screening
* Positive pre-study drug/alcohol screen.
* Positive human immunodeficiency virus (HIV) antibody test.
* Regular alcohol consumption within 6 months prior to the study
* Regular use of known drugs of abuse
* Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening and at admission.
* Sensitivity to the study drug, or components thereof, midazolam (For Part 2, midazolam probe cohort), excipients contained therein, benzodiazepines, or other drug or other allergy that, in the opinion of the investigator or Sponsor Medical Monitor, contraindicates participation in the study.

Contacts and Locations

Principal Investigator

GSK Clinical Trials

STUDY_DIRECTOR

ViiV Healthcare

Study Locations (Sites)

GSK Investigational Site

Baltimore, Maryland, 21225

United States

Collaborators and Investigators

Sponsor: ViiV Healthcare

GSK Clinical Trials, STUDY_DIRECTOR, ViiV Healthcare

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2022-12-02

Study Completion Date2023-07-27

Study Record Updates

Study Start Date2022-12-02

Study Completion Date2023-07-27

Terms related to this study

Keywords Provided by Researchers

First-time-in-human
GSK4524184
Healthy volunteers
Multiple Ascending Dose
Single Ascending Dose
VH4524184

Additional Relevant MeSH Terms

HIV Infections