First-Time-in-Human (FTIH) Study to Evaluate the Safety,... | NCT05393271 | Trialant
NCT05393271
Sponsor
ViiV Healthcare
Status
Completed
Last Update Posted
Apr 1, 2025Actual
Enrollment
73Actual
Phase
Phase 1
Conditions
HIV Infections
Interventions
VH4011499
Placebo
Midazolam
Countries
United States
Protocol Section
Identification Module
NCT ID
Results Section
Participant Flow Module
Pre-assignment Details
Annotation Section
No data available
No data is available for this block.
Document Section
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Derived Section
Miscellaneous Info Module
Version Holder
NCT05393271
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
218490
Secondary IDs
Not provided
Brief Title
First-Time-in-Human (FTIH) Study to Evaluate the Safety, Tolerability and Pharmacokinetics (PK) of VH4011499 in Healthy Participants
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
Acronym
Not provided
Organization
ViiV HealthcareINDUSTRY
Status Module
Record Verification Date
Mar 2025
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Oct 3, 2022Actual
Primary Completion Date
Apr 24, 2023Actual
Completion Date
Apr 24, 2023Actual
First Submitted Date
May 23, 2022
First Submission Date that Met QC Criteria
May 23, 2022
First Posted Date
May 26, 2022Actual
Results Waived
Not provided
Results First Submitted Date
Aug 1, 2024
Results First Submitted that Met QC Criteria
Mar 31, 2025
Results First Posted Date
Apr 1, 2025Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Mar 31, 2025
Last Update Posted Date
Apr 1, 2025Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
ViiV HealthcareINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
No
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
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.
Detailed Description
Not provided
Conditions Module
Conditions
HIV Infections
Keywords
GSK4011499
VH4011499
First-time-in-human
HIV-1 capsid inhibitor
Single ascending doses
Multiple ascending doses
Drug-drug Interaction
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 1
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
73Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
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.
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.
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.
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.
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.
Drug: VH4011499
Interventions
Name
Type
Description
Arm Group Labels
Other Names
VH4011499
Drug
VH4011499 will be administered.
Part 1 (SAD): VH4011499 125 mg PiB
Part 1 (SAD): VH4011499 1875 mg PiB
Part 1 (SAD): VH4011499 200 mg PiB
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
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.
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.
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.
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.
Up to Day 28
Part 2: Number of Participants With AEs by Severity
Secondary Outcomes
Not provided
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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).
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.
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.
Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.
Access Criteria
Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension may be granted, when justified, for up to 6 months.
Part 1 Single Ascending Dose (SAD): Placebo Powder-in-a-bottle (PiB)
Healthy participants were given a single dose of placebo on Day 1 and were followed up until Day 28.
FG001
Part 1 (SAD): VH4011499 25 mg PiB
Healthy participants were given a single dose of 25 mg VH4011499 on Day 1 and were followed up until Day 28.
FG002
Part 1 (SAD): VH4011499 125 mg PiB
Healthy participants were given a single dose of 125 mg VH4011499 on Day 1 and were followed up until Day 28.
FG003
Part 1 (SAD): VH4011499 200 mg PiB
Healthy participants were given a single dose of 200 mg VH4011499 on Day 1 and were followed up until Day 28.
FG004
Part 1 (SAD): VH4011499 625 mg PiB
Healthy participants were given a single dose of 625 mg VH4011499 on Day 1 and were followed up until Day 28.
FG005
Part 1 (SAD): VH4011499 1875 mg PiB
Healthy participants were given a single dose of 1875 mg VH4011499 on Day 1 and were followed up until Day 28.
FG006
Part 2 Multiple Ascending Dose (MAD): Placebo PiB
Healthy participants were given a dose of placebo once daily for a 14-day period and were followed up until Day 42.
FG007
Part 2 (MAD): VH4011499 200 mg PiB
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.
FG008
Part 2 (MAD): VH4011499 300 mg + Midazolam (MDZ) PiB
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.
FG009
Part 2 (MAD): VH4011499 400 mg PiB
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.
FG010
Part 3 (Single Dose): VH4011499 200 mg Tablet
Healthy participants were given a dose of VH4011499 200 mg tablet on Day 1 and were followed up until Day 28.
Periods
Title
Milestones
Reasons Not Completed
Overall Study
Type
Comment
Milestone Data
STARTED
FG00010 subjects
FG0016 subjects
FG0026 subjects
FG0036 subjects
FG0046 subjects
FG0056 subjects
FG0067 subjects
FG0076 subjects
FG0088 subjects
FG0096 subjects
FG0106 subjects
COMPLETED
FG00010 subjects
FG0016 subjects
FG0026 subjects
FG0036 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Type
Comment
Reasons
Physician Decision
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
Baseline Characteristics Module
Baseline Analysis Population Description
Baseline characteristics presented based on Exposed population.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Part 1 Single Ascending Dose (SAD): Placebo Powder-in-a-bottle (PiB)
Healthy participants were given a single dose of placebo on Day 1 and were followed up until Day 28.
BG001
Part 1 (SAD): VH4011499 25 mg PiB
Denominators
Units
Counts
Participants
BG000
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Outcome Measures Module
Outcome Measures
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
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.
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.
Posted
Count of Participants
Participants
Up to Day 28
ID
Title
Description
OG000
Part 1 Single Ascending Dose (SAD): Placebo Powder-in-a-bottle (PiB)
Healthy participants were given a single dose of placebo on Day 1 and were followed up until Day 28.
OG001
Adverse Events Module
Frequency Threshold
5
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).
Description
The analysis was performed on the Safety Set which included all participants who received at least 1 full or partial dose of study treatment.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Part 1 Single Ascending Dose (SAD): Placebo Powder-in-a-bottle (PiB)
Healthy participants were given a single dose of placebo on Day 1 and were followed up until Day 28.
This is a randomized and placebo-controlled study.
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
Double
Masking Description
This is a double-blind (sponsor unblinded) study.
Who Masked
ParticipantInvestigator
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.
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.
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.
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.
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.
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.
Drug: VH4011499
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
GSK4011499
Placebo
Drug
Placebo will be administered.
Part 1 Single Ascending Dose (SAD): Placebo Powder-in-a-bottle (PiB)
Part 2 Multiple Ascending Dose (MAD): Placebo PiB
Midazolam
Drug
Midazolam will be administered
Part 2 (MAD): VH4011499 300 mg + Midazolam (MDZ) PiB
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.
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.
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.
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.
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.
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.
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
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.
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
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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
Austin
Texas
78744
United States
6 subjects
FG0056 subjects
FG0066 subjects
FG0076 subjects
FG0088 subjects
FG0096 subjects
FG0106 subjects
0 subjects
FG0050 subjects
FG0061 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
0 subjects
FG0040 subjects
FG0050 subjects
FG0061 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
Healthy participants were given a single dose of 25 mg VH4011499 on Day 1 and were followed up until Day 28.
BG002
Part 1 (SAD): VH4011499 125 mg PiB
Healthy participants were given a single dose of 125 mg VH4011499 on Day 1 and were followed up until Day 28.
BG003
Part 1 (SAD): VH4011499 200 mg PiB
Healthy participants were given a single dose of 200 mg VH4011499 on Day 1 and were followed up until Day 28.
BG004
Part 1 (SAD): VH4011499 625 mg PiB
Healthy participants were given a single dose of 625 mg VH4011499 on Day 1 and were followed up until Day 28.
BG005
Part 1 (SAD): VH4011499 1875 mg PiB
Healthy participants were given a single dose of 1875 mg VH4011499 on Day 1 and were followed up until Day 28.
BG006
Part 2 Multiple Ascending Dose (MAD): Placebo PiB
Healthy participants were given a dose of placebo once daily for a 14-day period and were followed up until Day 42.
BG007
Part 2 (MAD): VH4011499 200 mg PiB
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.
BG008
Part 2 (MAD): VH4011499 300 mg + Midazolam (MDZ) PiB
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.
BG009
Part 2 (MAD): VH4011499 400 mg PiB
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.
BG010
Part 3 (Single Dose): VH4011499 200 mg Tablet
Healthy participants were given a dose of VH4011499 200 mg tablet on Day 1 and were followed up until Day 28.
BG011
Total
Total of all reporting groups
10
BG0016
BG0026
BG0036
BG0046
BG0056
BG0067
BG0076
BG0088
BG0096
BG0106
BG01173
Standard Deviation
Years
Title
Denominators
Categories
Title
Measurements
BG00037.8± 11.17
BG00135.3± 6.12
BG00236.5± 7.48
BG00345.8± 8.08
BG00440.0± 12.05
BG00539.8± 7.78
BG00637.6± 11.18
BG00735.5± 13.10
BG00838.9± 11.81
BG00932.3± 3.83
BG01037.2± 9.91
BG01137.9± 9.72
Sex/Gender, Customized
Count of Participants
Participants
Title
Denominators
Categories
Male
Title
Measurements
BG0009
BG0016
BG0026
BG0035
BG0045
BG0056
BG0067
BG0075
BG0087
BG0096
BG0106
BG01168
Female
Title
Measurements
BG0001
BG0010
BG0020
BG003
Race/Ethnicity, Customized
Count of Participants
Participants
Title
Denominators
Categories
Asian
Title
Measurements
BG0002
BG0010
BG0020
BG0032
BG0040
BG0052
BG0061
BG0070
BG0080
BG0090
BG0100
BG0117
Black or African American
Title
Measurements
BG0003
BG0013
BG0023
BG003
Native Hawaiian or other Pacific Islander
Title
Measurements
BG0000
BG0010
BG0020
BG003
White
Title
Measurements
BG0005
BG0012
BG0022
BG003
Multiple
Title
Measurements
BG0000
BG0011
BG0021
BG003
Part 1 (SAD): VH4011499 25 mg PiB
Healthy participants were given a single dose of 25 mg VH4011499 on Day 1 and were followed up until Day 28.
OG002
Part 1 (SAD): VH4011499 125 mg PiB
Healthy participants were given a single dose of 125 mg VH4011499 on Day 1 and were followed up until Day 28.
OG003
Part 1 (SAD): VH4011499 200 mg PiB
Healthy participants were given a single dose of 200 mg VH4011499 on Day 1 and were followed up until Day 28.
OG004
Part 1 (SAD): VH4011499 625 mg PiB
Healthy participants were given a single dose of 625 mg VH4011499 on Day 1 and were followed up until Day 28.
OG005
Part 1 (SAD): VH4011499 1875 mg PiB
Healthy participants were given a single dose of 1875 mg VH4011499 on Day 1 and were followed up until Day 28.
Units
Counts
Participants
OG00010
OG0016
OG0026
OG0036
OG0046
OG0056
Title
Denominators
Categories
Title
Measurements
OG0003
OG0012
OG0021
OG0033
OG0041
OG0051
Primary
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.
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.
Posted
Count of Participants
Participants
Up to Day 42
ID
Title
Description
OG000
Part 2 Multiple Ascending Dose (MAD): Placebo PiB
Healthy participants were given a dose of placebo once daily for a 14-day period and were followed up until Day 42.
OG001
Part 2 (MAD): VH4011499 200 mg PiB
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.
OG002
Part 2 (MAD): VH4011499 300 mg + Midazolam (MDZ) PiB
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.
OG003
Part 2 (MAD): VH4011499 400 mg PiB
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.
Units
Counts
Participants
OG0007
OG0016
OG0028
OG003
Title
Denominators
Categories
Title
Measurements
OG0002
OG0013
OG0023
OG003
Primary
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.
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.
Posted
Count of Participants
Participants
Up to Day 28
ID
Title
Description
OG000
Part 3 (Single Dose): VH4011499 200 mg Tablet
Healthy participants were given a dose of VH4011499 200 mg tablet on Day 1 and were followed up until Day 28.
Units
Counts
Participants
OG0006
Title
Denominators
Categories
Title
Measurements
OG0001
Primary
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.
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.
Posted
Count of Participants
Participants
Up to Day 28
ID
Title
Description
OG000
Part 1 Single Ascending Dose (SAD): Placebo Powder-in-a-bottle (PiB)
Healthy participants were given a single dose of placebo on Day 1 and were followed up until Day 28.
OG001
Part 1 (SAD): VH4011499 25 mg PiB
Healthy participants were given a single dose of 25 mg VH4011499 on Day 1 and were followed up until Day 28.
OG002
Part 1 (SAD): VH4011499 125 mg PiB
Healthy participants were given a single dose of 125 mg VH4011499 on Day 1 and were followed up until Day 28.
OG003
Part 1 (SAD): VH4011499 200 mg PiB
Healthy participants were given a single dose of 200 mg VH4011499 on Day 1 and were followed up until Day 28.
OG004
Part 1 (SAD): VH4011499 625 mg PiB
Healthy participants were given a single dose of 625 mg VH4011499 on Day 1 and were followed up until Day 28.
OG005
Part 1 (SAD): VH4011499 1875 mg PiB
Healthy participants were given a single dose of 1875 mg VH4011499 on Day 1 and were followed up until Day 28.
Units
Counts
Participants
OG00010
OG0016
OG0026
OG003
Title
Denominators
Categories
Grade 1
Title
Measurements
OG0001
OG0011
OG0021
OG003
Primary
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.
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.
Posted
Count of Participants
Participants
Up to Day 42
ID
Title
Description
OG000
Part 2 Multiple Ascending Dose (MAD): Placebo PiB
Healthy participants were given a dose of placebo once daily for a 14-day period and were followed up until Day 42.
OG001
Part 2 (MAD): VH4011499 200 mg PiB
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.
OG002
Part 2 (MAD): VH4011499 300 mg + Midazolam (MDZ) PiB
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.
OG003
Part 2 (MAD): VH4011499 400 mg PiB
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.
Units
Counts
Participants
OG0007
OG0016
OG0028
OG003
Title
Denominators
Categories
Grade 1
Title
Measurements
OG0002
OG0013
OG0023
OG003
Primary
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.
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.
Posted
Count of Participants
Participants
Up to Day 28
ID
Title
Description
OG000
Part 3 (Single Dose): VH4011499 200 mg Tablet
Healthy participants were given a dose of VH4011499 200 mg tablet on Day 1 and were followed up until Day 28.
Units
Counts
Participants
OG0006
Title
Denominators
Categories
Grade 1
Title
Measurements
OG0001
Grade 2
Title
Measurements
OG0000
Grade 3
Primary
Part 2: Number of Participants Discontinuing Treatment Due to AEs
Number of participants who discontinued treatment due to AEs are presented.
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.
Posted
Count of Participants
Participants
Up to Day 42
ID
Title
Description
OG000
Part 2 Multiple Ascending Dose (MAD): Placebo PiB
Healthy participants were given a dose of placebo once daily for a 14-day period and were followed up until Day 42.
OG001
Part 2 (MAD): VH4011499 200 mg PiB
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.
OG002
Part 2 (MAD): VH4011499 300 mg + Midazolam (MDZ) PiB
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.
OG003
Part 2 (MAD): VH4011499 400 mg PiB
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.
Units
Counts
Participants
OG0007
OG0016
OG0028
OG003
Title
Denominators
Categories
Title
Measurements
OG0000
OG0010
OG0020
OG003
Primary
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.
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.
Posted
Mean
Standard Deviation
Micromoles per Liter (μmol/L)
Up to Day 28
ID
Title
Description
OG000
Part 1 Single Ascending Dose (SAD): Placebo Powder-in-a-bottle (PiB)
Healthy participants were given a single dose of placebo on Day 1 and were followed up until Day 28.
OG001
Part 1 (SAD): VH4011499 25 mg PiB
Healthy participants were given a single dose of 25 mg VH4011499 on Day 1 and were followed up until Day 28.
OG002
Part 1 (SAD): VH4011499 125 mg PiB
Healthy participants were given a single dose of 125 mg VH4011499 on Day 1 and were followed up until Day 28.
OG003
Part 1 (SAD): VH4011499 200 mg PiB
Healthy participants were given a single dose of 200 mg VH4011499 on Day 1 and were followed up until Day 28.
OG004
Part 1 (SAD): VH4011499 625 mg PiB
Healthy participants were given a single dose of 625 mg VH4011499 on Day 1 and were followed up until Day 28.
OG005
Part 1 (SAD): VH4011499 1875 mg PiB
Healthy participants were given a single dose of 1875 mg VH4011499 on Day 1 and were followed up until Day 28.
Units
Counts
Participants
OG00010
OG0016
OG0026
OG003
Title
Denominators
Categories
Direct Bilirubin, Baseline (Day 1)
ParticipantsOG00010
ParticipantsOG0016
ParticipantsOG0026
ParticipantsOG003
Primary
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.
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.
Posted
Mean
Standard Deviation
International Units per Liter (IU/L)
Up to Day 28
ID
Title
Description
OG000
Part 1 Single Ascending Dose (SAD): Placebo Powder-in-a-bottle (PiB)
Healthy participants were given a single dose of placebo on Day 1 and were followed up until Day 28.
OG001
Part 1 (SAD): VH4011499 25 mg PiB
Healthy participants were given a single dose of 25 mg VH4011499 on Day 1 and were followed up until Day 28.
OG002
Part 1 (SAD): VH4011499 125 mg PiB
Healthy participants were given a single dose of 125 mg VH4011499 on Day 1 and were followed up until Day 28.
OG003
Part 1 (SAD): VH4011499 200 mg PiB
Healthy participants were given a single dose of 200 mg VH4011499 on Day 1 and were followed up until Day 28.
OG004
Part 1 (SAD): VH4011499 625 mg PiB
Healthy participants were given a single dose of 625 mg VH4011499 on Day 1 and were followed up until Day 28.
OG005
Part 1 (SAD): VH4011499 1875 mg PiB
Healthy participants were given a single dose of 1875 mg VH4011499 on Day 1 and were followed up until Day 28.
Units
Counts
Participants
OG00010
OG0016
OG0026
OG003
Title
Denominators
Categories
ALP, Baseline (Day 1)
ParticipantsOG00010
ParticipantsOG0016
ParticipantsOG0026
ParticipantsOG003
Primary
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.
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. Only those participants with data available at the specified timepoints were analyzed.
Posted
Mean
Standard Deviation
μmol/L
Up to Day 42
ID
Title
Description
OG000
Part 2 Multiple Ascending Dose (MAD): Placebo PiB
Healthy participants were given a dose of placebo once daily for a 14-day period and were followed up until Day 42.
OG001
Part 2 (MAD): VH4011499 200 mg PiB
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.
OG002
Part 2 (MAD): VH4011499 300 mg + Midazolam (MDZ) PiB
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.
OG003
Part 2 (MAD): VH4011499 400 mg PiB
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.
Units
Counts
Participants
OG0007
OG0016
OG0028
OG003
Title
Denominators
Categories
Direct Bilirubin, Baseline (Day 1)
ParticipantsOG0007
ParticipantsOG0016
ParticipantsOG0028
ParticipantsOG003
Primary
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
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. Only those participants with data available at the specified timepoints were analyzed.
Posted
Mean
Standard Deviation
IU/L
Up to Day 42
ID
Title
Description
OG000
Part 2 Multiple Ascending Dose (MAD): Placebo PiB
Healthy participants were given a dose of placebo once daily for a 14-day period and were followed up until Day 42.
OG001
Part 2 (MAD): VH4011499 200 mg PiB
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.
OG002
Part 2 (MAD): VH4011499 300 mg + Midazolam (MDZ) PiB
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.
OG003
Part 2 (MAD): VH4011499 400 mg PiB
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.
Units
Counts
Participants
OG0007
OG0016
OG0028
OG003
Title
Denominators
Categories
ALP, Baseline (Day 1)
ParticipantsOG0007
ParticipantsOG0016
ParticipantsOG0028
ParticipantsOG003
Primary
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.
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.
Posted
Mean
Standard Deviation
IU/L
Up to Day 28
ID
Title
Description
OG000
Part 3 (Single Dose): VH4011499 200 mg Tablet
Healthy participants were given a dose of VH4011499 200 mg tablet on Day 1 and were followed up until Day 28.
Units
Counts
Participants
OG0006
Title
Denominators
Categories
Direct Bilirubin, Baseline (Day 1)
ParticipantsOG0006
Title
Measurements
OG0001.4250± 0.69810
Direct Bilirubin, Day 2
ParticipantsOG000
Primary
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
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.
Posted
Mean
Standard Deviation
μmol/L
Up to Day 28
ID
Title
Description
OG000
Part 3 (Single Dose): VH4011499 200 mg Tablet
Healthy participants were given a dose of VH4011499 200 mg tablet on Day 1 and were followed up until Day 28.
Units
Counts
Participants
OG0006
Title
Denominators
Categories
ALP, Baseline (Day 1)
ParticipantsOG0006
Title
Measurements
OG00052.0± 8.12
ALP, Day 2
ParticipantsOG000
Primary
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.
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.
Posted
Mean
Standard Deviation
IU/L
From Baseline (Day 1) and up to Day 28
ID
Title
Description
OG000
Part 1 Single Ascending Dose (SAD): Placebo Powder-in-a-bottle (PiB)
Healthy participants were given a single dose of placebo on Day 1 and were followed up until Day 28.
OG001
Part 1 (SAD): VH4011499 25 mg PiB
Healthy participants were given a single dose of 25 mg VH4011499 on Day 1 and were followed up until Day 28.
OG002
Part 1 (SAD): VH4011499 125 mg PiB
Healthy participants were given a single dose of 125 mg VH4011499 on Day 1 and were followed up until Day 28.
OG003
Part 1 (SAD): VH4011499 200 mg PiB
Healthy participants were given a single dose of 200 mg VH4011499 on Day 1 and were followed up until Day 28.
OG004
Part 1 (SAD): VH4011499 625 mg PiB
Healthy participants were given a single dose of 625 mg VH4011499 on Day 1 and were followed up until Day 28.
OG005
Part 1 (SAD): VH4011499 1875 mg PiB
Healthy participants were given a single dose of 1875 mg VH4011499 on Day 1 and were followed up until Day 28.
Units
Counts
Participants
OG00010
OG0016
OG0026
OG003
Title
Denominators
Categories
Direct Bilirubin, Baseline (Day 1)
ParticipantsOG00010
ParticipantsOG0016
ParticipantsOG0026
ParticipantsOG003
Primary
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.
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.
Posted
Mean
Standard Deviation
μmol/L
From Baseline (Day 1) and up to Day 28
ID
Title
Description
OG000
Part 1 Single Ascending Dose (SAD): Placebo Powder-in-a-bottle (PiB)
Healthy participants were given a single dose of placebo on Day 1 and were followed up until Day 28.
OG001
Part 1 (SAD): VH4011499 25 mg PiB
Healthy participants were given a single dose of 25 mg VH4011499 on Day 1 and were followed up until Day 28.
OG002
Part 1 (SAD): VH4011499 125 mg PiB
Healthy participants were given a single dose of 125 mg VH4011499 on Day 1 and were followed up until Day 28.
OG003
Part 1 (SAD): VH4011499 200 mg PiB
Healthy participants were given a single dose of 200 mg VH4011499 on Day 1 and were followed up until Day 28.
OG004
Part 1 (SAD): VH4011499 625 mg PiB
Healthy participants were given a single dose of 625 mg VH4011499 on Day 1 and were followed up until Day 28.
OG005
Part 1 (SAD): VH4011499 1875 mg PiB
Healthy participants were given a single dose of 1875 mg VH4011499 on Day 1 and were followed up until Day 28.
Units
Counts
Participants
OG00010
OG0016
OG0026
OG003
Title
Denominators
Categories
ALP, Baseline (Day 1)
ParticipantsOG00010
ParticipantsOG0016
ParticipantsOG0026
ParticipantsOG003
Primary
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.
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. Only those participants with data available at the specified timepoints were analyzed.
Posted
Mean
Standard Deviation
μmol/L
From Baseline (Day 1) and up to Day 42
ID
Title
Description
OG000
Part 2 Multiple Ascending Dose (MAD): Placebo PiB
Healthy participants were given a dose of placebo once daily for a 14-day period and were followed up until Day 42.
OG001
Part 2 (MAD): VH4011499 200 mg PiB
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.
OG002
Part 2 (MAD): VH4011499 300 mg + Midazolam (MDZ) PiB
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.
OG003
Part 2 (MAD): VH4011499 400 mg PiB
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.
Units
Counts
Participants
OG0007
OG0016
OG0028
OG003
Title
Denominators
Categories
Direct Bilirubin, Baseline (Day 1)
ParticipantsOG0007
ParticipantsOG0016
ParticipantsOG0028
ParticipantsOG003
Primary
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.
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. Only those participants with data available at the specified timepoints were analyzed.
Posted
Mean
Standard Deviation
IU/L
From Baseline (Day 1) and up to Day 42
ID
Title
Description
OG000
Part 2 Multiple Ascending Dose (MAD): Placebo PiB
Healthy participants were given a dose of placebo once daily for a 14-day period and were followed up until Day 42.
OG001
Part 2 (MAD): VH4011499 200 mg PiB
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.
OG002
Part 2 (MAD): VH4011499 300 mg + Midazolam (MDZ) PiB
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.
OG003
Part 2 (MAD): VH4011499 400 mg PiB
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.
Units
Counts
Participants
OG0007
OG0016
OG0028
OG003
Title
Denominators
Categories
ALP, Baseline (Day 1)
ParticipantsOG0007
ParticipantsOG0016
ParticipantsOG0028
ParticipantsOG003
Primary
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.
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.
Posted
Mean
Standard Deviation
IU/L
From Baseline (Day 1) and up to Day 28
ID
Title
Description
OG000
Part 3 (Single Dose): VH4011499 200 mg Tablet
Healthy participants were given a dose of VH4011499 200 mg tablet on Day 1 and were followed up until Day 28.
Units
Counts
Participants
OG0006
Title
Denominators
Categories
Direct Bilirubin, Baseline (Day 1)
ParticipantsOG0006
Title
Measurements
OG0001.4250± 0.69810
Direct Bilirubin, Day 2
ParticipantsOG000
Primary
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.
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.
Posted
Mean
Standard Deviation
IU/L
From Baseline (Day 1) and up to Day 28
ID
Title
Description
OG000
Part 3 (Single Dose): VH4011499 200 mg Tablet
Healthy participants were given a dose of VH4011499 200 mg tablet on Day 1 and were followed up until Day 28.
Units
Counts
Participants
OG0006
Title
Denominators
Categories
ALP, Baseline (Day 1)
ParticipantsOG0006
Title
Measurements
OG00052.0± 8.12
ALP, Day 2
ParticipantsOG000
Primary
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.
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.
Posted
Count of Participants
Participants
Up to Day 28
ID
Title
Description
OG000
Part 1 Single Ascending Dose (SAD): Placebo Powder-in-a-bottle (PiB)
Healthy participants were given a single dose of placebo on Day 1 and were followed up until Day 28.
OG001
Part 1 (SAD): VH4011499 25 mg PiB
Healthy participants were given a single dose of 25 mg VH4011499 on Day 1 and were followed up until Day 28.
OG002
Part 1 (SAD): VH4011499 125 mg PiB
Healthy participants were given a single dose of 125 mg VH4011499 on Day 1 and were followed up until Day 28.
OG003
Part 1 (SAD): VH4011499 200 mg PiB
Healthy participants were given a single dose of 200 mg VH4011499 on Day 1 and were followed up until Day 28.
OG004
Part 1 (SAD): VH4011499 625 mg PiB
Healthy participants were given a single dose of 625 mg VH4011499 on Day 1 and were followed up until Day 28.
OG005
Part 1 (SAD): VH4011499 1875 mg PiB
Healthy participants were given a single dose of 1875 mg VH4011499 on Day 1 and were followed up until Day 28.
Units
Counts
Participants
OG00010
OG0016
OG0026
OG003
Title
Denominators
Categories
ALT, Increase to Grade 1
Title
Measurements
OG0000
OG0012
OG0020
OG003
Primary
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.
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.
Posted
Count of Participants
Participants
Up to Day 42
ID
Title
Description
OG000
Part 2 Multiple Ascending Dose (MAD): Placebo PiB
Healthy participants were given a dose of placebo once daily for a 14-day period and were followed up until Day 42.
OG001
Part 2 (MAD): VH4011499 200 mg PiB
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.
OG002
Part 2 (MAD): VH4011499 300 mg + Midazolam (MDZ) PiB
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.
OG003
Part 2 (MAD): VH4011499 400 mg PiB
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.
Units
Counts
Participants
OG0007
OG0016
OG0028
OG003
Title
Denominators
Categories
ALT, Increase to Grade 1
Title
Measurements
OG0000
OG0011
OG0020
OG003
Primary
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.
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.
Posted
Count of Participants
Participants
Up to Day 28
ID
Title
Description
OG000
Part 3 (Single Dose): VH4011499 200 mg Tablet
Healthy participants were given a dose of VH4011499 200 mg tablet on Day 1 and were followed up until Day 28.
Units
Counts
Participants
OG0006
Title
Denominators
Categories
ALT, Increase to Grade 1
Title
Measurements
OG0000
ALT, Increase to Grade 2
Title
Measurements
OG0000
ALT, Increase to Grade 3
Primary
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.
The analysis was performed on the VH4011499 PK Set which included all participants in the Part 1 (SAD) Safety Set who received at least 1 full dose of study treatment with at least one non-missing PK assessment. The participants were analyzed according to the treatment they received.
Posted
Geometric Mean
Geometric Coefficient of Variation
Hour nanogram per milliliter (h*ng/mL)
At Day 1
ID
Title
Description
OG000
Part 1 (SAD): VH4011499 25 mg PiB
Healthy participants were given a single dose of 25 mg VH4011499 on Day 1 and were followed up until Day 28.
OG001
Part 1 (SAD): VH4011499 125 mg PiB
Healthy participants were given a single dose of 125 mg VH4011499 on Day 1 and were followed up until Day 28.
OG002
Part 1 (SAD): VH4011499 200 mg PiB
Healthy participants were given a single dose of 200 mg VH4011499 on Day 1 and were followed up until Day 28.
OG003
Part 1 (SAD): VH4011499 625 mg PiB
Healthy participants were given a single dose of 625 mg VH4011499 on Day 1 and were followed up until Day 28.
OG004
Part 1 (SAD): VH4011499 1875 mg PiB
Healthy participants were given a single dose of 1875 mg VH4011499 on Day 1 and were followed up until Day 28.
Units
Counts
Participants
OG0006
OG0016
OG0026
OG003
Title
Denominators
Categories
Title
Measurements
OG0002759.51± 53.69
OG0018458.88± 20.39
OG00211627.63± 36.01
OG003
Primary
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.
The analysis was performed on the VH4011499 PK Set which included all participants in the Part 2 (MAD) Safety Set who received at least 1 full dose of study treatment with at least one non-missing PK assessment. The participants were analyzed according to the treatment they received.
Posted
Geometric Mean
Geometric Coefficient of Variation
h*ng/mL
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
ID
Title
Description
OG000
Part 2 (MAD): VH4011499 200 mg PiB
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.
OG001
Part 2 (MAD): VH4011499 300 mg + Midazolam (MDZ) PiB
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.
OG002
Part 2 (MAD): VH4011499 400 mg PiB
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.
Units
Counts
Participants
OG0006
OG0018
OG0026
Title
Denominators
Categories
Day 1/2
Title
Measurements
OG0004211.67± 15.36
OG0015385.19± 21.74
OG0024879.14± 36.00
Day 14/15
Primary
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.
The analysis was performed on the VH4011499 PK Set which included all participants in the Part 1 (SAD) Safety Set who received at least 1 full dose of study treatment with at least one non-missing PK assessment. The participants were analyzed according to the treatment they received.
Posted
Geometric Mean
Geometric Coefficient of Variation
nanogram per milliliter (ng/mL)
At Day 1
ID
Title
Description
OG000
Part 1 (SAD): VH4011499 25 mg PiB
Healthy participants were given a single dose of 25 mg VH4011499 on Day 1 and were followed up until Day 28.
OG001
Part 1 (SAD): VH4011499 125 mg PiB
Healthy participants were given a single dose of 125 mg VH4011499 on Day 1 and were followed up until Day 28.
OG002
Part 1 (SAD): VH4011499 200 mg PiB
Healthy participants were given a single dose of 200 mg VH4011499 on Day 1 and were followed up until Day 28.
OG003
Part 1 (SAD): VH4011499 625 mg PiB
Healthy participants were given a single dose of 625 mg VH4011499 on Day 1 and were followed up until Day 28.
OG004
Part 1 (SAD): VH4011499 1875 mg PiB
Healthy participants were given a single dose of 1875 mg VH4011499 on Day 1 and were followed up until Day 28.
Units
Counts
Participants
OG0006
OG0016
OG0026
OG003
Title
Denominators
Categories
Title
Measurements
OG00026.85± 26.18
OG001106.90± 17.24
OG002168.88± 36.25
OG003
Primary
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.
The analysis was performed on the VH4011499 PK Set which included all participants in the Part 1 (SAD) Safety Set who received at least 1 full dose of study treatment with at least one non-missing PK assessment. The participants were analyzed according to the treatment they received.
Posted
Geometric Mean
Geometric Coefficient of Variation
hours
At Day 1
ID
Title
Description
OG000
Part 1 (SAD): VH4011499 25 mg PiB
Healthy participants were given a single dose of 25 mg VH4011499 on Day 1 and were followed up until Day 28.
OG001
Part 1 (SAD): VH4011499 125 mg PiB
Healthy participants were given a single dose of 125 mg VH4011499 on Day 1 and were followed up until Day 28.
OG002
Part 1 (SAD): VH4011499 200 mg PiB
Healthy participants were given a single dose of 200 mg VH4011499 on Day 1 and were followed up until Day 28.
OG003
Part 1 (SAD): VH4011499 625 mg PiB
Healthy participants were given a single dose of 625 mg VH4011499 on Day 1 and were followed up until Day 28.
OG004
Part 1 (SAD): VH4011499 1875 mg PiB
Healthy participants were given a single dose of 1875 mg VH4011499 on Day 1 and were followed up until Day 28.
Units
Counts
Participants
OG0006
OG0016
OG0026
OG003
Title
Denominators
Categories
Title
Measurements
OG00011.30± 9.51
OG00110.26± 14.77
OG0029.28± 11.56
OG003
Primary
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.
The analysis was performed on the VH4011499 PK Set which included all participants in the Part 1 (SAD) Safety Set who received at least 1 full dose of study treatment with at least one non-missing PK assessment. The participants were analyzed according to the treatment they received.
Posted
Geometric Mean
Geometric Coefficient of Variation
hours
At Day 1
ID
Title
Description
OG000
Part 1 (SAD): VH4011499 25 mg PiB
Healthy participants were given a single dose of 25 mg VH4011499 on Day 1 and were followed up until Day 28.
OG001
Part 1 (SAD): VH4011499 125 mg PiB
Healthy participants were given a single dose of 125 mg VH4011499 on Day 1 and were followed up until Day 28.
OG002
Part 1 (SAD): VH4011499 200 mg PiB
Healthy participants were given a single dose of 200 mg VH4011499 on Day 1 and were followed up until Day 28.
OG003
Part 1 (SAD): VH4011499 625 mg PiB
Healthy participants were given a single dose of 625 mg VH4011499 on Day 1 and were followed up until Day 28.
OG004
Part 1 (SAD): VH4011499 1875 mg PiB
Healthy participants were given a single dose of 1875 mg VH4011499 on Day 1 and were followed up until Day 28.
Units
Counts
Participants
OG0006
OG0016
OG0026
OG003
Title
Denominators
Categories
Title
Measurements
OG00063.97± 21.07
OG00154.44± 23.86
OG00261.61± 29.57
OG003
Primary
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.
The analysis was performed on the VH4011499 PK Set which included all participants in the Part 2 (MAD) Safety Set who received at least 1 full dose of study treatment with at least one non-missing PK assessment. The participants were analyzed according to the treatment they received.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng/mL
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
ID
Title
Description
OG000
Part 2 (MAD): VH4011499 200 mg PiB
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.
OG001
Part 2 (MAD): VH4011499 300 mg + Midazolam (MDZ) PiB
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.
OG002
Part 2 (MAD): VH4011499 400 mg PiB
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.
Units
Counts
Participants
OG0006
OG0018
OG0026
Title
Denominators
Categories
Day 1
ParticipantsOG0006
ParticipantsOG0010
ParticipantsOG0026
Title
Measurements
Primary
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.
The analysis was performed on the VH4011499 PK Set which included all participants in the Part 2 (MAD) Safety Set who received at least 1 full dose of study treatment with at least one non-missing PK assessment. The participants were analyzed according to the treatment they received.
Posted
Geometric Mean
Geometric Coefficient of Variation
hours
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
ID
Title
Description
OG000
Part 2 (MAD): VH4011499 200 mg PiB
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.
OG001
Part 2 (MAD): VH4011499 300 mg + Midazolam (MDZ) PiB
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.
OG002
Part 2 (MAD): VH4011499 400 mg PiB
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.
Units
Counts
Participants
OG0006
OG0018
OG0026
Title
Denominators
Categories
Day 1
ParticipantsOG0006
ParticipantsOG0010
ParticipantsOG0026
Title
Measurements
Primary
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.
The analysis was performed on the VH4011499 PK Set which included all participants in the Part 2 (MAD) Safety Set who received at least 1 full dose of study treatment with at least one non-missing PK assessment. The participants were analyzed according to the treatment they received.
Posted
Geometric Mean
Geometric Coefficient of Variation
hours
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
ID
Title
Description
OG000
Part 2 (MAD): VH4011499 200 mg PiB
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.
OG001
Part 2 (MAD): VH4011499 300 mg + Midazolam (MDZ) PiB
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.
OG002
Part 2 (MAD): VH4011499 400 mg PiB
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.
Units
Counts
Participants
OG0006
OG0018
OG0026
Title
Denominators
Categories
Day 14
ParticipantsOG0006
ParticipantsOG0010
ParticipantsOG0026
Title
Measurements
0
10
1
10
3
10
EG001
Part 1 (SAD): VH4011499 25 mg PiB
Healthy participants were given a single dose of 25 mg VH4011499 on Day 1 and were followed up until Day 28.
0
6
0
6
2
6
EG002
Part 1 (SAD): VH4011499 125 mg PiB
Healthy participants were given a single dose of 125 mg VH4011499 on Day 1 and were followed up until Day 28.
0
6
0
6
1
6
EG003
Part 1 (SAD): VH4011499 200 mg PiB
Healthy participants were given a single dose of 200 mg VH4011499 on Day 1 and were followed up until Day 28.
0
6
0
6
3
6
EG004
Part 1 (SAD): VH4011499 625 mg PiB
Healthy participants were given a single dose of 625 mg VH4011499 on Day 1 and were followed up until Day 28.
0
6
0
6
1
6
EG005
Part 1 (SAD): VH4011499 1875 mg PiB
Healthy participants were given a single dose of 1875 mg VH4011499 on Day 1 and were followed up until Day 28.
0
6
0
6
1
6
EG006
Part 2 Multiple Ascending Dose (MAD): Placebo PiB
Healthy participants were given a dose of placebo once daily for a 14-day period and were followed up until Day 42.
0
7
0
7
2
7
EG007
Part 2 (MAD): VH4011499 200 mg PiB
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.
0
6
0
6
3
6
EG008
Part 2 (MAD): VH4011499 300 mg + Midazolam (MDZ) PiB
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.
0
8
0
8
3
8
EG009
Part 2 (MAD): VH4011499 400 mg PiB
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.
0
6
0
6
2
6
EG010
Part 3 (Single Dose): VH4011499 200 mg Tablet
Healthy participants were given a dose of VH4011499 200 mg tablet on Day 1 and were followed up until Day 28.
0
6
0
6
1
6
EG0001 events1 affected10 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected7 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected6 at risk
EG0000 events0 affected10 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected7 at risk
EG0072 events2 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected6 at risk
Infrequent bowel movements
Gastrointestinal disorders
v25.1
Systematic Assessment
EG0000 events0 affected10 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected7 at risk
EG0071 events1 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected6 at risk
Nausea
Gastrointestinal disorders
v25.1
Systematic Assessment
EG0000 events0 affected10 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected7 at risk
EG0072 events2 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected6 at risk
Toothache
Gastrointestinal disorders
v25.1
Systematic Assessment
EG0000 events0 affected10 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected7 at risk
EG0070 events0 affected6 at risk
EG0081 events1 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected6 at risk
Vomiting
Gastrointestinal disorders
v25.1
Systematic Assessment
EG0000 events0 affected10 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected7 at risk
EG0073 events2 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected6 at risk
Feeling abnormal
General disorders
v25.1
Systematic Assessment
EG0000 events0 affected10 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected7 at risk
EG0070 events0 affected6 at risk
EG0081 events1 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected6 at risk
Influenza like illness
General disorders
v25.1
Systematic Assessment
EG0000 events0 affected10 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected7 at risk
EG0071 events1 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected6 at risk
Medical device site dermatitis
General disorders
v25.1
Systematic Assessment
EG0000 events0 affected10 at risk
EG0010 events0 affected6 at risk
EG0021 events1 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected7 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0101 events1 affected6 at risk
Gastroenteritis
Infections and infestations
v25.1
Systematic Assessment
EG0000 events0 affected10 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0041 events1 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected7 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected6 at risk
Nasopharyngitis
Infections and infestations
v25.1
Systematic Assessment
EG0000 events0 affected10 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected7 at risk
EG0071 events1 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected6 at risk
Skin abrasion
Injury, poisoning and procedural complications
v25.1
Systematic Assessment
EG0000 events0 affected10 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected7 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0091 events1 affected6 at risk
EG0100 events0 affected6 at risk
Activated partial thromboplastin time prolonged
Investigations
v25.1
Systematic Assessment
EG0000 events0 affected10 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0032 events2 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected7 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected6 at risk
Blood creatine phosphokinase increased
Investigations
v25.1
Systematic Assessment
EG0002 events2 affected10 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected7 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected6 at risk
Blood triglycerides increased
Investigations
v25.1
Systematic Assessment
EG0000 events0 affected10 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0031 events1 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected7 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected6 at risk
Haematocrit decreased
Investigations
v25.1
Systematic Assessment
EG0000 events0 affected10 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected7 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected6 at risk
Haemoglobin decreased
Investigations
v25.1
Systematic Assessment
EG0000 events0 affected10 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected7 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected6 at risk
Lipase increased
Investigations
v25.1
Systematic Assessment
EG0000 events0 affected10 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0031 events1 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected7 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected6 at risk
Total bile acids increased
Investigations
v25.1
Systematic Assessment
EG0000 events0 affected10 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0051 events1 affected6 at risk
EG0060 events0 affected7 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected6 at risk
Back pain
Musculoskeletal and connective tissue disorders
v25.1
Systematic Assessment
EG0001 events1 affected10 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0063 events1 affected7 at risk
EG0071 events1 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected6 at risk
Dizziness
Nervous system disorders
v25.1
Systematic Assessment
EG0000 events0 affected10 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected7 at risk
EG0070 events0 affected6 at risk
EG0081 events1 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected6 at risk
Headache
Nervous system disorders
v25.1
Systematic Assessment
EG0000 events0 affected10 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected7 at risk
EG0073 events2 affected6 at risk
EG0081 events1 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected6 at risk
Presyncope
Nervous system disorders
v25.1
Systematic Assessment
EG0000 events0 affected10 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected7 at risk
EG0071 events1 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected6 at risk
Somnolence
Nervous system disorders
v25.1
Systematic Assessment
EG0000 events0 affected10 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected7 at risk
EG0070 events0 affected6 at risk
EG0083 events2 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected6 at risk
Depressed mood
Psychiatric disorders
v25.1
Systematic Assessment
EG0001 events1 affected10 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected7 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected6 at risk
Epistaxis
Respiratory, thoracic and mediastinal disorders
v25.1
Systematic Assessment
EG0000 events0 affected10 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected7 at risk
EG0071 events1 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected6 at risk
Dry skin
Skin and subcutaneous tissue disorders
v25.1
Systematic Assessment
EG0000 events0 affected10 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected7 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0091 events1 affected6 at risk
EG0100 events0 affected6 at risk
Pruritus
Skin and subcutaneous tissue disorders
v25.1
Systematic Assessment
EG0000 events0 affected10 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected7 at risk
EG0071 events1 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected6 at risk
Abdominal pain
Gastrointestinal disorders
MedDRA v25.1
Systematic Assessment
EG0000 events0 affected10 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0061 events1 affected7 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected6 at risk
Tinnitus
Ear and labyrinth disorders
MedDRA v25.1
Systematic Assessment
EG0000 events0 affected10 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0061 events1 affected7 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected6 at risk
Anxiety
Psychiatric disorders
MedDRA v25.1
Systematic Assessment
EG0000 events0 affected10 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0061 events1 affected7 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected6 at risk
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single site data not precede the primary publication of the entire clinical trial.