HIV InfectionsPhase 1NCT05393271

First-Time-in-Human (FTIH) Study to Evaluate the Safety, Tolerability and Pharmacokinetics (PK) of VH4011499 in Healthy Participants

A Phase 1 study testing VH4011499 and Midazolam in people with HIV Infections, run by ViiV Healthcare at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for: HIV Infections
What is being tested?: VH4011499 and Midazolam
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 73 participants
Where: 2 sitesUnited States
Study dates: 3 Oct 2022to 24 Apr 2023
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 55 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

Participants who are overtly healthy.
Participants must have two consecutive Severe Acute Respiratory Syndrome Coronavirus 2 (SARs-CoV-2) Polymerase chain reaction (PCR) negative results prior to dosing.
Participants must have body weight > 50 kilograms (kg) and body mass index (BMI) within the range 19-32 kilograms per meter square (kg/m^2).
Male or female participants (either of non-childbearing potential or of child-bearing potential and using acceptable contraception).
Capable of giving signed informed consent.

Who cannot join

History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, neurological or psychiatric disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study drug or interfering with the interpretation of data.
Abnormal blood pressure.
Lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years.
Breast cancer within the past 10 years.
Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
QT interval corrected for heart rate according to Fridericia's formula (QTcF) greater than (>)450 milliseconds (msec).

Show all 16Show fewer

Past or intended use of over-the-counter or prescription medication including herbal medications 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, unless in the opinion of the Investigator and Sponsor, the medication will not interfere with the study medications, procedures, or compromise participant safety.
Live vaccine(s) within 1 month prior to screening or plans to receive such vaccines during the study.
Exposure to more than 4 investigational products within 12 months prior to dosing.
Current enrollment or recent past participation in another investigational study.
ALT >1.5 times upper limit of normal (ULN), total bilirubin >1.5 times ULN, and/or estimated serum creatinine clearance less than 60 milliliters per minute.
History of or current infection with hepatitis B or hepatitis C.
Positive Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) test, having signs and symptoms, or having contact with known Coronavirus Disease-2019 (COVID-19) positive person/s within 14 days.
Positive HIV antibody test.
Use of tobacco or nicotine-containing products, regular alcohol consumption and/or regular use of known drugs of abuse.
Sensitivity to the study drug, or components thereof midazolam, excipients contained therein, benzodiazepines, or drug or other allergy that, contraindicates participation in the study.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

GSK Investigational Site
Austin, Texas, 78744
GSK Investigational Site
Las Vegas, Nevada, 89113

Other trials in United States

About this study

Official title: A Randomized, Double-Blind (Sponsor Unblinded), Placebo-Controlled Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Orally Administered VH4011499 in Healthy Participants

This FTIH study aims to evaluate the safety, tolerability and PK of the novel investigational Human immunodeficiency virus (HIV)-1 capsid inhibitor VH4011499 in healthy adults. The study will be conducted in 3 parts: Part 1 will investigate single ascending doses (SAD) and Part 2 will investigate multiple ascending doses (MAD). Part 3 will investigate single dose of a new formulation of VH4011499. The transition from SAD to MAD will be based on the assessment of the Safety and Dose Escalation Committee.

Conditions: HIV Infections
Being tested: VH4011499, Placebo, Midazolam
Keywords: GSK4011499, VH4011499, First-time-in-human, HIV-1 capsid inhibitor, Single ascending doses, Multiple ascending doses, Drug-drug Interaction
Medical subject headings: HIV Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

VH4011499Drug
Also called GSK4011499
VH4011499 will be administered.
PlaceboDrug
Placebo will be administered.
MidazolamDrug
Midazolam will be administered

Study groups in NCT05393271
Study group	Role	What they receive
Part 1 Single Ascending Dose (SAD): Placebo Powder-in-a-bottle (PiB)	Placebo comparator	Healthy participants were given a single dose of placebo on Day 1 and were followed up until Day 28. Receives: Drug: Placebo
Part 1 (SAD): VH4011499 25 mg PiB	Placebo comparator	Healthy participants were given a single dose of 25 mg VH4011499 on Day 1 and were followed up until Day 28. Receives: Drug: VH4011499
Part 1 (SAD): VH4011499 125 mg PiB	Experimental	Healthy participants were given a single dose of 125 mg VH4011499 on Day 1 and were followed up until Day 28. Receives: Drug: VH4011499
Part 1 (SAD): VH4011499 200 mg PiB	Experimental	Healthy participants were given a single dose of 200 mg VH4011499 on Day 1 and were followed up until Day 28. Receives: Drug: VH4011499
Part 1 (SAD): VH4011499 625 mg PiB	Experimental	Healthy participants were given a single dose of 625 mg VH4011499 on Day 1 and were followed up until Day 28. Receives: Drug: VH4011499
Part 1 (SAD): VH4011499 1875 mg PiB	Experimental	Healthy participants were given a single dose of 1875 mg VH4011499 on Day 1 and were followed up until Day 28. Receives: Drug: VH4011499
Part 2 Multiple Ascending Dose (MAD): Placebo PiB	Placebo comparator	Healthy participants were given a dose of placebo once daily for a 14-day period and were followed up until Day 42. Receives: Drug: Placebo
Part 2 (MAD): VH4011499 200 mg PiB	Experimental	Healthy participants were given a dose of VH4011499 200 mg PiB once daily for a 14-day period and were followed up until Day 42. Receives: Drug: VH4011499
Part 2 (MAD): VH4011499 300 mg + Midazolam (MDZ) PiB	Experimental	Healthy participants were given a dose of VH4011499 300 mg once daily and a single dose of Midazolam on Days 1, 2, and 15, and were followed up until Day 42. Receives: Drug: VH4011499; Drug: Midazolam
Part 2 (MAD): VH4011499 400 mg PiB	Experimental	Healthy participants were given a dose of VH4011499 400 mg PiB once daily for a 14-day period and were followed up until Day 42. Receives: Drug: VH4011499
Part 3 (Single dose): VH4011499 200 mg tablet	Experimental	Healthy participants were given a dose of VH4011499 200 mg tablet on Day 1 and were followed up until Day 28. Receives: Drug: VH4011499

What is being measured

The primary outcome is the main question the study is designed to answer.

Part 1: Number of Participants With Adverse Events (AEs)
An AE was defined as any untoward medical occurrence in a participant, temporally associated with the use of a study intervention whether or not considered related to the study intervention.
Measured: Up to Day 28
Part 2: Number of Participants With AEs
An AE was defined as any untoward medical occurrence in a participant, temporally associated with the use of a study intervention whether or not considered related to the study intervention.
Measured: Up to Day 42
Part 3: Number of Participants With AEs
An AE was defined as any untoward medical occurrence in a participant, temporally associated with the use of a study intervention whether or not considered related to the study intervention.
Measured: Up to Day 28
Part 1: Number of Participants With AEs by Severity
An AE was defined as any untoward medical occurrence in a participant, temporally associated with the use of a study intervention whether or not considered related to the study intervention. The Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric AE was used for all AE severity grading, where Grade 1=Mild symptoms causing no or minimal interference with usual social \& functional activities with intervention not indicated, 2=Moderate symptoms causing greater than minimal interference with usual social \& functional activities with intervention indicated, 3=Severe symptoms causing inability to perform usual social \& functional activities with intervention or hospitalization indicated, 4=Potentially life-threatening symptoms causing inability to perform basic self-care functions with intervention indicated to prevent permanent impairment, persistent disability or death, 5=Death.
Measured: Up to Day 28
Part 2: Number of Participants With AEs by Severity
An AE was defined as any untoward medical occurrence in a participant, temporally associated with the use of a study intervention whether or not considered related to the study intervention. The Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric AE was used for all AE severity grading, where Grade 1=Mild symptoms causing no or minimal interference with usual social \& functional activities with intervention not indicated, 2=Moderate symptoms causing greater than minimal interference with usual social \& functional activities with intervention indicated, 3=Severe symptoms causing inability to perform usual social \& functional activities with intervention or hospitalization indicated, 4=Potentially life-threatening symptoms causing inability to perform basic self-care functions with intervention indicated to prevent permanent impairment, persistent disability or death, 5=Death.
Measured: Up to Day 42
Part 3: Number of Participants With AEs by Severity
An AE was defined as any untoward medical occurrence in a participant, temporally associated with the use of a study intervention whether or not considered related to the study intervention. The Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric AE was used for all AE severity grading, where Grade 1=Mild symptoms causing no or minimal interference with usual social \& functional activities with intervention not indicated, 2=Moderate symptoms causing greater than minimal interference with usual social \& functional activities with intervention indicated, 3=Severe symptoms causing inability to perform usual social \& functional activities with intervention or hospitalization indicated, 4=Potentially life-threatening symptoms causing inability to perform basic self-care functions with intervention indicated to prevent permanent impairment, persistent disability or death, 5=Death.
Measured: Up to Day 28
Part 2: Number of Participants Discontinuing Treatment Due to AEs
Number of participants who discontinued treatment due to AEs are presented.
Measured: Up to Day 42
Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin, Total Bilirubin
Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of bilirubin.
Measured: Up to Day 28
Part 1: Absolute Values of Liver Panel Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP) and Aspartate Aminotransferase (AST)
Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of ALT, ALP and AST.
Measured: Up to Day 28
Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin, Total Bilirubin
Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of bilirubin.
Measured: Up to Day 42
Part 2: Absolute Values of Liver Panel Parameters: ALT, ALP and AST
Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of ALT, ALP and AST
Measured: Up to Day 42
Part 3: Absolute Values of Liver Panel Parameters: Direct Bilirubin, Total Bilirubin
Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of bilirubin.
Measured: Up to Day 28
Part 3: Absolute Values of Liver Panel Parameters: ALT, ALP and AST
Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of ALT, ALP and AST
Measured: Up to Day 28
Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin
Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of bilirubin. Change from baseline was calculated by subtracting the baseline value from the post-dose visit value.
Measured: From Baseline (Day 1) and up to Day 28
Part 1: Change From Baseline in Liver Panel Parameters: ALT, ALP and AST
Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of ALT, ALP and AST. Change from baseline was calculated by subtracting the baseline value from the post-dose visit value.
Measured: From Baseline (Day 1) and up to Day 28
Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin
Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of bilirubin. Change from baseline was calculated by subtracting the baseline value from the post-dose visit value. Standard Deviation (SD)=0.0000 is defined as following: if all participants analyzed for a specific parameter at a specific time point have the same value, then SD is equal with 0.0000.
Measured: From Baseline (Day 1) and up to Day 42
Part 2: Change From Baseline in Liver Panel Parameters: ALT, ALP and AST
Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of ALT, ALP and AST. Change from baseline was calculated by subtracting the baseline value from the post-dose visit value. SD=0.00 is defined as following: if all participants analyzed for a specific parameter at a specific time point have the same value, then SD is equal with 0.00.
Measured: From Baseline (Day 1) and up to Day 42
Part 3: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin
Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of bilirubin. Change from baseline was calculated by subtracting the baseline value from the post-dose visit value.
Measured: From Baseline (Day 1) and up to Day 28
Part 3: Change From Baseline in Liver Panel Parameters: ALT, ALP and AST
Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of ALT, ALP and AST. Change from baseline was calculated by subtracting the baseline value from the post-dose visit value.
Measured: From Baseline (Day 1) and up to Day 28
Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters
Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of the liver panel parameters: ALT, ALP, AST, total bilirubin and direct bilirubin. The number of participants with any grade increase (from grade 1 [mild] to grade 4 [potentially life-threatening]) have been presented.
Measured: Up to Day 28
Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters
Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of the liver panel parameters: ALT, ALP, AST, total bilirubin and direct bilirubin. The number of participants with any grade increase (from grade 1 [mild] to grade 4 [potentially life-threatening]) have been presented.
Measured: Up to Day 42
Part 3: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters
Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of the liver panel parameters: ALT, ALP, AST, total bilirubin and direct bilirubin. The number of participants with any grade increase (from grade 1 [mild] to grade 4 [potentially life-threatening]) have been presented.
Measured: Up to Day 28
Part 1: Area Under the Plasma Concentration Time Curve (AUC) From Time Zero to Infinity (0-inf) Following Single Dose Administration of VH4011499
Blood samples were collected as assessed by protocol, at specific time points for pharmacokinetic (PK) analysis to determine AUC(0-inf). For AUC, a linear trapezoidal method was employed for all incremental trapezoids arising from increasing concentrations and the logarithmic trapezoidal method was used for those arising from decreasing concentrations. Geometric Coefficient of Variation was expressed in percentages.
Measured: At Day 1
Part 2: AUC Over a Dosing Interval From Time of Dosing to the Time of the Subsequent Dose (0-t) Following Repeat Dose Administration of VH4011499
Blood samples were collected as assessed by protocol, at specific time points for PK analysis to determine AUC(0-t). For AUC, a linear trapezoidal method was employed for all incremental trapezoids arising from increasing concentrations and the logarithmic trapezoidal method was used for those arising from decreasing concentrations.
Measured: At Days 1 and 14 for Part 2 (MAD): VH4011499 200 mg PiB and Part 2 (MAD): VH4011499 400 mg PiB groups, and at Days 2 and 15 for Part 2 (MAD): VH4011499 300 mg + Midazolam PiB group
Part 1: Maximum Observed Plasma Concentration (Cmax) Following Single Dose Administration of VH4011499.
Blood samples were collected as assessed by protocol, at specific time points for PK analysis to determine Cmax.
Measured: At Day 1
Part 1: Time to Maximum Observed Plasma Concentration (Tmax) Following Single Dose Administration of VH4011499
Blood samples were collected as assessed by protocol, at specific time points for PK analysis to determine Tmax.
Measured: At Day 1
Part 1: Apparent Terminal Half-life (T1/2) Following Single Dose Administration of VH4011499
Blood samples were collected as assessed by protocol, at specific time points for PK analysis to determine T1/2.
Measured: At Day 1
Part 2: Cmax Following Repeat Dose Administration of VH4011499
Blood samples were collected as assessed by protocol, at specific time points for PK analysis to determine Cmax.
Measured: At Days 1 and 14 for Part 2 (MAD): VH4011499 200 mg PiB and Part 2 (MAD): VH4011499 400 mg PiB groups, and at Days 2 and 15 for Part 2 (MAD): VH4011499 300 mg + Midazolam PiB group
Part 2: Tmax Following Repeat Dose Administration of VH4011499
Blood samples were collected as assessed by protocol, at specific time points for PK analysis to determine Tmax.
Measured: At Days 1 and 14 for Part 2 (MAD): VH4011499 200 mg PiB and Part 2 (MAD): VH4011499 400 mg PiB groups, and at Days 2 and 15 for Part 2 (MAD): VH4011499 300 mg + Midazolam PiB group
Part 2: T1/2 Following Repeat Dose Administration of VH4011499
Blood samples were collected as assessed by protocol, at specific time points for PK analysis to determine T1/2.
Measured: At Day 14 for Part 2 (MAD): VH4011499 200 mg PiB and Part 2 (MAD): VH4011499 400 mg PiB groups, and at Day 15 for Part 2 (MAD): VH4011499 300 mg + Midazolam PiB group

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

3 Oct 202224 Apr 2023

First posted26 May 2022
Study start3 Oct 2022
Primary completion24 Apr 2023
Study completion24 Apr 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for HIV InfectionsStudies of the same condition, open and under way.
More trials run by ViiV HealthcareThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Sequential
Model description: This is a randomized and placebo-controlled study.
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 73 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05393271
Sponsor's protocol ID: 218490
Status last verified: Mar 2025
First submitted: 23 May 2022
Last updated: 1 Apr 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: 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

Publications

Thakkar N, Griesel R, Pierce A, Bainbridge V, Shepherd B, Angelis K, Tomlinson A, Gandhi Y, Brimhall D, Spears B, Anderson D, Pinnick E, Acuipil C, McCoig C, Baker M, Benn P. Clinical Pharmacokinetics and Safety of Orally Administered VH4011499, a New HIV-1 Capsid Inhibitor, in Adults Without HIV. Infect Dis Ther. 2025 May;14(5):1011-1025. doi: 10.1007/s40121-025-01129-y. Epub 2025 Apr 2.
PubMed 40172795

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 1 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized, Double-Blind (Sponsor Unblinded), Placebo-Controlled Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Orally Administered VH4011499 in Healthy Participants
ClinicalTrials.gov ID: NCT05393271
Acronym / sponsor ID: 218490
Conditions: HIV Infections
Keywords: GSK4011499, VH4011499, First-time-in-human, HIV-1 capsid inhibitor, Single ascending doses, Multiple ascending doses, Drug-drug Interaction
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 73 participants (actual)
Lead sponsor: ViiV HealthcareIndustry (pharma, biotech, devices)
Study start: 3 Oct 2022 (actual)
Primary completion: 24 Apr 2023 (actual)
Study completion: 24 Apr 2023 (actual)
First posted: 26 May 2022 (actual)
Results: Posted 1 Apr 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Sequential
Masking: Double blind (participant, investigator)
Number of arms: 11
Model description: This is a randomized and placebo-controlled study.

Arm	Type	Receives
Part 1 Single Ascending Dose (SAD): Placebo Powder-in-a-bottle (PiB)	Placebo comparator	Drug: PlaceboHealthy participants were given a single dose of placebo on Day 1 and were followed up until Day 28.
Part 1 (SAD): VH4011499 25 mg PiB	Placebo comparator	Drug: VH4011499Healthy participants were given a single dose of 25 mg VH4011499 on Day 1 and were followed up until Day 28.
Part 1 (SAD): VH4011499 125 mg PiB	Experimental	Drug: VH4011499Healthy participants were given a single dose of 125 mg VH4011499 on Day 1 and were followed up until Day 28.
Part 1 (SAD): VH4011499 200 mg PiB	Experimental	Drug: VH4011499Healthy participants were given a single dose of 200 mg VH4011499 on Day 1 and were followed up until Day 28.
Part 1 (SAD): VH4011499 625 mg PiB	Experimental	Drug: VH4011499Healthy participants were given a single dose of 625 mg VH4011499 on Day 1 and were followed up until Day 28.
Part 1 (SAD): VH4011499 1875 mg PiB	Experimental	Drug: VH4011499Healthy participants were given a single dose of 1875 mg VH4011499 on Day 1 and were followed up until Day 28.
Part 2 Multiple Ascending Dose (MAD): Placebo PiB	Placebo comparator	Drug: PlaceboHealthy participants were given a dose of placebo once daily for a 14-day period and were followed up until Day 42.
Part 2 (MAD): VH4011499 200 mg PiB	Experimental	Drug: VH4011499Healthy participants were given a dose of VH4011499 200 mg PiB once daily for a 14-day period and were followed up until Day 42.
Part 2 (MAD): VH4011499 300 mg + Midazolam (MDZ) PiB	Experimental	Drug: VH4011499, Drug: MidazolamHealthy participants were given a dose of VH4011499 300 mg once daily and a single dose of Midazolam on Days 1, 2, and 15, and were followed up until Day 42.
Part 2 (MAD): VH4011499 400 mg PiB	Experimental	Drug: VH4011499Healthy participants were given a dose of VH4011499 400 mg PiB once daily for a 14-day period and were followed up until Day 42.
Part 3 (Single dose): VH4011499 200 mg tablet	Experimental	Drug: VH4011499Healthy participants were given a dose of VH4011499 200 mg tablet on Day 1 and were followed up until Day 28.

Who may qualify

Ages: 18 to 55 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (5 listed)

Participants who are overtly healthy.
Participants must have two consecutive Severe Acute Respiratory Syndrome Coronavirus 2 (SARs-CoV-2) Polymerase chain reaction (PCR) negative results prior to dosing.
Participants must have body weight > 50 kilograms (kg) and body mass index (BMI) within the range 19-32 kilograms per meter square (kg/m^2).
Male or female participants (either of non-childbearing potential or of child-bearing potential and using acceptable contraception).
Capable of giving signed informed consent.

Key exclusion criteria (16 listed)

History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, neurological or psychiatric disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study drug or interfering with the interpretation of data.
Abnormal blood pressure.
Lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years.
Breast cancer within the past 10 years.
Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
VH4011499Also: GSK4011499VH4011499 will be administered.	Drug	Part 1 (SAD): VH4011499 125 mg PiB, Part 1 (SAD): VH4011499 1875 mg PiB, Part 1 (SAD): VH4011499 200 mg PiB, Part 1 (SAD): VH4011499 25 mg PiB, Part 1 (SAD): VH4011499 625 mg PiB, Part 2 (MAD): VH4011499 200 mg PiB, Part 2 (MAD): VH4011499 300 mg + Midazolam (MDZ) PiB, Part 2 (MAD): VH4011499 400 mg PiB, Part 3 (Single dose): VH4011499 200 mg tablet
PlaceboPlacebo will be administered.	Drug	Part 1 Single Ascending Dose (SAD): Placebo Powder-in-a-bottle (PiB), Part 2 Multiple Ascending Dose (MAD): Placebo PiB
MidazolamMidazolam will be administered	Drug	Part 2 (MAD): VH4011499 300 mg + Midazolam (MDZ) PiB

Primary outcome

Part 1: Number of Participants With Adverse Events (AEs)
Time frame: Up to Day 28
An AE was defined as any untoward medical occurrence in a participant, temporally associated with the use of a study intervention whether or not considered related to the study intervention.
Part 2: Number of Participants With AEs
Time frame: Up to Day 42
An AE was defined as any untoward medical occurrence in a participant, temporally associated with the use of a study intervention whether or not considered related to the study intervention.
Part 3: Number of Participants With AEs
Time frame: Up to Day 28
An AE was defined as any untoward medical occurrence in a participant, temporally associated with the use of a study intervention whether or not considered related to the study intervention.
Part 1: Number of Participants With AEs by Severity
Time frame: Up to Day 28
An AE was defined as any untoward medical occurrence in a participant, temporally associated with the use of a study intervention whether or not considered related to the study intervention. The Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric AE was used for all AE severity grading, where Grade 1=Mild symptoms causing no or minimal interference with usual social \& functional activities with intervention not indicated, 2=Moderate symptoms causing greater than minimal interference with usual social \& functional activities with intervention indicated, 3=Severe symptoms causing inability to perform usual social \& functional activities with intervention or hospitalization indicated, 4=Potentially life-threatening symptoms causing inability to perform basic self-care functions with intervention indicated to prevent permanent impairment, persistent disability or death, 5=Death.
Part 2: Number of Participants With AEs by Severity
Time frame: Up to Day 42
An AE was defined as any untoward medical occurrence in a participant, temporally associated with the use of a study intervention whether or not considered related to the study intervention. The Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric AE was used for all AE severity grading, where Grade 1=Mild symptoms causing no or minimal interference with usual social \& functional activities with intervention not indicated, 2=Moderate symptoms causing greater than minimal interference with usual social \& functional activities with intervention indicated, 3=Severe symptoms causing inability to perform usual social \& functional activities with intervention or hospitalization indicated, 4=Potentially life-threatening symptoms causing inability to perform basic self-care functions with intervention indicated to prevent permanent impairment, persistent disability or death, 5=Death.
Part 3: Number of Participants With AEs by Severity
Time frame: Up to Day 28
An AE was defined as any untoward medical occurrence in a participant, temporally associated with the use of a study intervention whether or not considered related to the study intervention. The Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric AE was used for all AE severity grading, where Grade 1=Mild symptoms causing no or minimal interference with usual social \& functional activities with intervention not indicated, 2=Moderate symptoms causing greater than minimal interference with usual social \& functional activities with intervention indicated, 3=Severe symptoms causing inability to perform usual social \& functional activities with intervention or hospitalization indicated, 4=Potentially life-threatening symptoms causing inability to perform basic self-care functions with intervention indicated to prevent permanent impairment, persistent disability or death, 5=Death.
Part 2: Number of Participants Discontinuing Treatment Due to AEs
Time frame: Up to Day 42
Number of participants who discontinued treatment due to AEs are presented.
Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin, Total Bilirubin
Time frame: Up to Day 28
Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of bilirubin.
Part 1: Absolute Values of Liver Panel Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP) and Aspartate Aminotransferase (AST)
Time frame: Up to Day 28
Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of ALT, ALP and AST.
Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin, Total Bilirubin
Time frame: Up to Day 42
Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of bilirubin.
Part 2: Absolute Values of Liver Panel Parameters: ALT, ALP and AST
Time frame: Up to Day 42
Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of ALT, ALP and AST
Part 3: Absolute Values of Liver Panel Parameters: Direct Bilirubin, Total Bilirubin
Time frame: Up to Day 28
Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of bilirubin.
Part 3: Absolute Values of Liver Panel Parameters: ALT, ALP and AST
Time frame: Up to Day 28
Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of ALT, ALP and AST
Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin
Time frame: From Baseline (Day 1) and up to Day 28
Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of bilirubin. Change from baseline was calculated by subtracting the baseline value from the post-dose visit value.
Part 1: Change From Baseline in Liver Panel Parameters: ALT, ALP and AST
Time frame: From Baseline (Day 1) and up to Day 28
Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of ALT, ALP and AST. Change from baseline was calculated by subtracting the baseline value from the post-dose visit value.
Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin
Time frame: From Baseline (Day 1) and up to Day 42
Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of bilirubin. Change from baseline was calculated by subtracting the baseline value from the post-dose visit value. Standard Deviation (SD)=0.0000 is defined as following: if all participants analyzed for a specific parameter at a specific time point have the same value, then SD is equal with 0.0000.
Part 2: Change From Baseline in Liver Panel Parameters: ALT, ALP and AST
Time frame: From Baseline (Day 1) and up to Day 42
Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of ALT, ALP and AST. Change from baseline was calculated by subtracting the baseline value from the post-dose visit value. SD=0.00 is defined as following: if all participants analyzed for a specific parameter at a specific time point have the same value, then SD is equal with 0.00.
Part 3: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin
Time frame: From Baseline (Day 1) and up to Day 28
Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of bilirubin. Change from baseline was calculated by subtracting the baseline value from the post-dose visit value.
Part 3: Change From Baseline in Liver Panel Parameters: ALT, ALP and AST
Time frame: From Baseline (Day 1) and up to Day 28
Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of ALT, ALP and AST. Change from baseline was calculated by subtracting the baseline value from the post-dose visit value.
Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters
Time frame: Up to Day 28
Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of the liver panel parameters: ALT, ALP, AST, total bilirubin and direct bilirubin. The number of participants with any grade increase (from grade 1 [mild] to grade 4 [potentially life-threatening]) have been presented.
Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters
Time frame: Up to Day 42
Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of the liver panel parameters: ALT, ALP, AST, total bilirubin and direct bilirubin. The number of participants with any grade increase (from grade 1 [mild] to grade 4 [potentially life-threatening]) have been presented.
Part 3: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters
Time frame: Up to Day 28
Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of the liver panel parameters: ALT, ALP, AST, total bilirubin and direct bilirubin. The number of participants with any grade increase (from grade 1 [mild] to grade 4 [potentially life-threatening]) have been presented.
Part 1: Area Under the Plasma Concentration Time Curve (AUC) From Time Zero to Infinity (0-inf) Following Single Dose Administration of VH4011499
Time frame: At Day 1
Blood samples were collected as assessed by protocol, at specific time points for pharmacokinetic (PK) analysis to determine AUC(0-inf). For AUC, a linear trapezoidal method was employed for all incremental trapezoids arising from increasing concentrations and the logarithmic trapezoidal method was used for those arising from decreasing concentrations. Geometric Coefficient of Variation was expressed in percentages.
Part 2: AUC Over a Dosing Interval From Time of Dosing to the Time of the Subsequent Dose (0-t) Following Repeat Dose Administration of VH4011499
Time frame: At Days 1 and 14 for Part 2 (MAD): VH4011499 200 mg PiB and Part 2 (MAD): VH4011499 400 mg PiB groups, and at Days 2 and 15 for Part 2 (MAD): VH4011499 300 mg + Midazolam PiB group
Blood samples were collected as assessed by protocol, at specific time points for PK analysis to determine AUC(0-t). For AUC, a linear trapezoidal method was employed for all incremental trapezoids arising from increasing concentrations and the logarithmic trapezoidal method was used for those arising from decreasing concentrations.
Part 1: Maximum Observed Plasma Concentration (Cmax) Following Single Dose Administration of VH4011499.
Time frame: At Day 1
Blood samples were collected as assessed by protocol, at specific time points for PK analysis to determine Cmax.
Part 1: Time to Maximum Observed Plasma Concentration (Tmax) Following Single Dose Administration of VH4011499
Time frame: At Day 1
Blood samples were collected as assessed by protocol, at specific time points for PK analysis to determine Tmax.
Part 1: Apparent Terminal Half-life (T1/2) Following Single Dose Administration of VH4011499
Time frame: At Day 1
Blood samples were collected as assessed by protocol, at specific time points for PK analysis to determine T1/2.
Part 2: Cmax Following Repeat Dose Administration of VH4011499
Time frame: At Days 1 and 14 for Part 2 (MAD): VH4011499 200 mg PiB and Part 2 (MAD): VH4011499 400 mg PiB groups, and at Days 2 and 15 for Part 2 (MAD): VH4011499 300 mg + Midazolam PiB group
Blood samples were collected as assessed by protocol, at specific time points for PK analysis to determine Cmax.
Part 2: Tmax Following Repeat Dose Administration of VH4011499
Time frame: At Days 1 and 14 for Part 2 (MAD): VH4011499 200 mg PiB and Part 2 (MAD): VH4011499 400 mg PiB groups, and at Days 2 and 15 for Part 2 (MAD): VH4011499 300 mg + Midazolam PiB group
Blood samples were collected as assessed by protocol, at specific time points for PK analysis to determine Tmax.
Part 2: T1/2 Following Repeat Dose Administration of VH4011499
Time frame: At Day 14 for Part 2 (MAD): VH4011499 200 mg PiB and Part 2 (MAD): VH4011499 400 mg PiB groups, and at Day 15 for Part 2 (MAD): VH4011499 300 mg + Midazolam PiB group
Blood samples were collected as assessed by protocol, at specific time points for PK analysis to determine T1/2.

Results and safety

Results posted to the registry on 1 Apr 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Part 1 Single Ascending Dose (SAD): Placebo Powder-in-a-bottle (PiB)	10	10
Part 1 (SAD): VH4011499 25 mg PiB	6	6
Part 1 (SAD): VH4011499 125 mg PiB	6	6
Part 1 (SAD): VH4011499 200 mg PiB	6	6
Part 1 (SAD): VH4011499 625 mg PiB	6	6
Part 1 (SAD): VH4011499 1875 mg PiB	6	6
Part 2 Multiple Ascending Dose (MAD): Placebo PiB	7	6
Part 2 (MAD): VH4011499 200 mg PiB	6	6
Part 2 (MAD): VH4011499 300 mg + Midazolam (MDZ) PiB	8	8
Part 2 (MAD): VH4011499 400 mg PiB	6	6
Part 3 (Single Dose): VH4011499 200 mg Tablet	6	6

Primary outcome: Part 1: Number of Participants With Adverse Events (AEs)

Time frame: Up to Day 28. Count of participants. Unit: Participants

Measure	Part 1 Single Ascending Dose (SAD): Placebo Powder-in-a-bottle (PiB) n = 10	Part 1 (SAD): VH4011499 25 mg PiB n = 6	Part 1 (SAD): VH4011499 125 mg PiB n = 6	Part 1 (SAD): VH4011499 200 mg PiB n = 6	Part 1 (SAD): VH4011499 625 mg PiB n = 6	Part 1 (SAD): VH4011499 1875 mg PiB n = 6
Value	3	2	1	3	1	1

Population analysed: The analysis was performed on the Safety Set which included all enrolled participants in Part 1 (SAD) who received at least 1 full or partial dose of study treatment. The participants were analyzed according to the treatment they received.

Primary outcome: Part 2: Number of Participants With AEs

Time frame: Up to Day 42. Count of participants. Unit: Participants

Measure	Part 2 Multiple Ascending Dose (MAD): Placebo PiB n = 7	Part 2 (MAD): VH4011499 200 mg PiB n = 6	Part 2 (MAD): VH4011499 300 mg + Midazolam (MDZ) PiB n = 8	Part 2 (MAD): VH4011499 400 mg PiB n = 6
Value	2	3	3	2

Population analysed: The analysis was performed on the Safety Set which included all enrolled participants in Part 2 (MAD) who received at least 1 full or partial dose of study treatment. The participants were analyzed according to the treatment they received.

Primary outcome: Part 3: Number of Participants With AEs

Time frame: Up to Day 28. Count of participants. Unit: Participants

Measure	Part 3 (Single Dose): VH4011499 200 mg Tablet n = 6
Value	1

Population analysed: The analysis was performed on the Safety Set which included all enrolled participants in Part 3 (Single Dose) who received 1 single dose of study treatment. The participants were analyzed according to the treatment they received.

Primary outcome: Part 1: Number of Participants With AEs by Severity

Time frame: Up to Day 28. Count of participants. Unit: Participants

Measure	Part 1 Single Ascending Dose (SAD): Placebo Powder-in-a-bottle (PiB) n = 10	Part 1 (SAD): VH4011499 25 mg PiB n = 6	Part 1 (SAD): VH4011499 125 mg PiB n = 6	Part 1 (SAD): VH4011499 200 mg PiB n = 6	Part 1 (SAD): VH4011499 625 mg PiB n = 6	Part 1 (SAD): VH4011499 1875 mg PiB n = 6
Grade 1	1	1	1	2	1	1
Grade 2	1	0	0	0	0	0
Grade 3	1	0	0	1	0	0
Grade 4	0	1	0	0	0	0
Grade 5	0	0	0	0	0	0

Adverse events

Time frame: All-cause mortality, non-serious adverse events and serious adverse events were collected up to 28-days following final dose of VH4011499 or placebo (Day 28 for Part 1 and Part 3, and Day 42 for Part 2).. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Part 1 Single Ascending Dose (SAD): Placebo Powder-in-a-bottle (PiB)	1 of 10 (10%)	3 of 10 (30%)	0 of 10
Part 1 (SAD): VH4011499 25 mg PiB	0 of 6 (0%)	2 of 6 (33.3%)	0 of 6
Part 1 (SAD): VH4011499 125 mg PiB	0 of 6 (0%)	1 of 6 (16.7%)	0 of 6
Part 1 (SAD): VH4011499 200 mg PiB	0 of 6 (0%)	3 of 6 (50%)	0 of 6
Part 1 (SAD): VH4011499 625 mg PiB	0 of 6 (0%)	1 of 6 (16.7%)	0 of 6
Part 1 (SAD): VH4011499 1875 mg PiB	0 of 6 (0%)	1 of 6 (16.7%)	0 of 6
Part 2 Multiple Ascending Dose (MAD): Placebo PiB	0 of 7 (0%)	2 of 7 (28.6%)	0 of 7
Part 2 (MAD): VH4011499 200 mg PiB	0 of 6 (0%)	3 of 6 (50%)	0 of 6
Part 2 (MAD): VH4011499 300 mg + Midazolam (MDZ) PiB	0 of 8 (0%)	3 of 8 (37.5%)	0 of 8
Part 2 (MAD): VH4011499 400 mg PiB	0 of 6 (0%)	2 of 6 (33.3%)	0 of 6
Part 3 (Single Dose): VH4011499 200 mg Tablet	0 of 6 (0%)	1 of 6 (16.7%)	0 of 6

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 1 Apr 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 40172795Thakkar N, Griesel R, Pierce A, Bainbridge V, Shepherd B, Angelis K, Tomlinson A, Gandhi Y, Brimhall D, Spears B, Anderson D, Pinnick E, Acuipil C, McCoig C, Baker M, Benn P. Clinical Pharmacokinetics and Safety of Orally Administered VH4011499, a New HIV-1 Capsid Inhibitor, in Adults Without HIV. Infect Dis Ther. 2025 May;14(5):1011-1025. doi: 10.1007/s40121-025-01129-y. Epub 2025 Apr 2.
Individual participant dataSharing planned: Yes. 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

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

GSK Clinical Trials study director

ViiV Healthcare

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing VH4011499 and Midazolam in people with HIV Infections, run by ViiV Healthcare at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Apr 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part 1: Number of Participants With Adverse Events (AEs) (time frame: Up to Day 28). The study lists 30 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05393271, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Apr 2025.