First-Time-in-Human (FTIH) Study to Evaluate the Safety,... | NCT05163522 | Trialant
NCT05163522
Sponsor
ViiV Healthcare
Status
Completed
Last Update Posted
Jul 30, 2025Actual
Enrollment
73Actual
Phase
Phase 1
Conditions
HIV Infections
Interventions
VH4004280
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
NCT05163522
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
217058
Secondary IDs
Not provided
Brief Title
First-Time-in-Human (FTIH) Study to Evaluate the Safety, Tolerability and Pharmacokinetics (PK) of VH4004280 in Healthy Participants
Official Title
A Randomized, Double-Blind (Sponsor Unblinded), Placebo-Controlled Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Orally Administered VH4004280 in Healthy Participants
Acronym
Not provided
Organization
ViiV HealthcareINDUSTRY
Status Module
Record Verification Date
Jul 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
Dec 13, 2021Actual
Primary Completion Date
Jun 21, 2023Actual
Completion Date
Jun 21, 2023Actual
First Submitted Date
Dec 6, 2021
First Submission Date that Met QC Criteria
Dec 6, 2021
First Posted Date
Dec 20, 2021Actual
Results Waived
Not provided
Results First Submitted Date
Aug 1, 2024
Results First Submitted that Met QC Criteria
Jul 9, 2025
Results First Posted Date
Jul 30, 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
Jul 9, 2025
Last Update Posted Date
Jul 30, 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 VH4004280 in healthy adults. The study will be conducted in 3 parts: Part 1 will investigate single ascending doses (SAD), Part 2 will investigate multiple ascending doses and drug-drug interaction (MAD/MAD DDI) Part 3 will investigate single dose relative bioavailability (RBA) of a new formulation of VH4004280.
Detailed Description
Not provided
Conditions Module
Conditions
HIV Infections
Keywords
First-time-in-human
GSK4004280
VH4004280
HIV-1 capsid inhibitor
Single ascending doses
Multiple ascending doses
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-bottle (PiB)
Placebo Comparator
Healthy participants were given a single oral dose of placebo on Day 1 and were followed up to approximately Day 49.
Drug: Placebo
Part 1 (SAD): VH4004280 10 mg PiB
Experimental
Healthy participants were given a single oral dose of 10 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
Drug: VH4004280
Part 1 (SAD): VH4004280 50 mg PiB
Experimental
Healthy participants were given a single oral dose of 50 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
Drug: VH4004280
Part 1 (SAD): VH4004280 150 mg PiB
Experimental
Healthy participants were given a single oral dose of 150 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
Drug: VH4004280
Part 1 (SAD): VH4004280 450 mg PiB
Experimental
Healthy participants were given a single oral dose of 450 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
Interventions
Name
Type
Description
Arm Group Labels
Other Names
VH4004280
Drug
VH4004280 will be administered.
Part 1 (SAD): VH4004280 10 mg PiB
Part 1 (SAD): VH4004280 150 mg PiB
Part 1 (SAD): VH4004280 450 mg PiB
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Part 1: Number of Participants With Any Adverse Events (AEs) and 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 49
Part 2: Number of Participants With Any AEs and by Severity
The 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 63
Part 3: Number of Participants With Any AEs and by Severity
The 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.
Secondary Outcomes
Not provided
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion criteria:
Participant must be 18 to 55 years of age inclusive.
Participants who are overtly healthy.
Male or female participants of non-childbearing potential.
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.
Symptomatic herpes zoster.
Evidence of active or latent tuberculosis (TB).
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.
Live vaccine(s) within 1 month prior to screening or plans to receive such vaccines during the study.
Exposure to more than 4 new investigational products within 12 months prior to the first dosing day.
Current enrollment or 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.
Positive HIV antibody test.
User 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.
Thakkar N, Griesel R, Pierce A, Bainbridge V, Shepherd B, Angelis K, Tomlinson A, Gandhi Y, Brimhall D, Anderson D, Andrews S, Acuipil C, McCoig C, Baker M, Benn P. Clinical Pharmacokinetics and Safety of a New HIV-1 Capsid Inhibitor, VH4004280, After Oral Administration in Adults Without HIV. Infect Dis Ther. 2025 Jun;14(6):1313-1326. doi: 10.1007/s40121-025-01154-x. Epub 2025 Apr 26.
IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
Access Criteria
Access is provided after a research proposal is submitted and has received approval from the 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 can be granted, when justified, for up to another 12 months.
Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB)
Healthy participants were given a single oral dose of placebo on Day 1 and were followed up to approximately Day 49.
FG001
Part 1 (SAD): VH4004280 10 mg PiB
Healthy participants were given a single oral dose of 10 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
FG002
Part 1 (SAD): VH4004280 50 mg PiB
Healthy participants were given a single oral dose of 50 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
FG003
Part 1 (SAD): VH4004280 150 mg PiB
Healthy participants were given a single oral dose of 150 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
FG004
Part 1 (SAD): VH4004280 450 mg PiB
Healthy participants were given a single oral dose of 450 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
FG005
Part 1 (SAD): VH4004280 900 mg PiB
Healthy participants were given a single oral dose of 900 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
FG006
Part 2 Multiple Ascending Dose (MAD): Placebo PiB
Healthy participants were given a dose of placebo once daily (QD) for a 14-day period and were followed up to approximately Day 63.
FG007
Part 2 (MAD): VH4004280 100 mg PiB
Healthy participants were given a dose of 100 mg VH4004280 PiB QD for a 14-day period and were followed up to approximately Day 63.
FG008
Part 2 (MAD): VH4004280 250 mg + Midazolam (MDZ) PiB
Healthy participants were given a dose of 250 mg VH4004280 PiB QD for a 14-day period, and a single dose of Midazolam on days 1, 2, and 15, and were followed up to approximately Day 63.
FG009
Part 2 (MAD): VH4004280 350 mg PiB
Healthy participants were given a dose of 350 mg VH4004280 PiB QD for a 14-day period and were followed up to approximately Day 63.
FG010
Part 3 (Single Dose): VH4004280 450 mg Tablet
Healthy participants were given a single oral dose of VH4004280 450 mg tablet at Day 1 and were followed up to approximately Day 49.
Periods
Title
Milestones
Reasons Not Completed
Overall Study
Type
Comment
Milestone Data
STARTED
FG00010 subjects
FG0016 subjects
FG0027 subjects
FG0036 subjects
FG0046 subjects
FG0056 subjects
FG0066 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
FG0021 subjects
FG0030 subjects
FG004
Type
Comment
Reasons
Withdrawal by Subject
FG0000 subjects
FG0010 subjects
FG0021 subjects
FG003
Baseline Characteristics Module
Baseline Analysis Population Description
Not provided
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB)
Healthy participants were given a single oral dose of placebo on Day 1 and were followed up to approximately Day 49.
BG001
Part 1 (SAD): VH4004280 10 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 Any Adverse Events (AEs) and 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 1 full dose of study treatment. The participants were analyzed according to the treatment they actually received.
Posted
Count of Participants
Participants
Up to Day 49
Adverse Events Module
Frequency Threshold
5
Time Frame
All cause mortality, serious adverse events (SAEs) and non-SAEs were collected up to a 49-day period following VH4004280 or placebo (i.e.: Day 49 for Parts 1 and 3, and Day 63 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-bottle (PiB)
Healthy participants were given a single oral dose of placebo on Day 1 and were followed up to approximately Day 49.
Healthy participants were given a single oral dose of 900 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
Drug: VH4004280
Part 2 Multiple Ascending Dose (MAD): Placebo PiB
Placebo Comparator
Healthy participants were given a dose of placebo once daily (QD) for a 14-day period and were followed up to approximately Day 63.
Drug: Placebo
Part 2 (MAD): VH4004280 100 mg PiB
Experimental
Healthy participants were given a dose of 100 mg VH4004280 PiB QD for a 14-day period and were followed up to approximately Day 63.
Drug: VH4004280
Part 2 (MAD): VH4004280 250 mg + Midazolam (MDZ) PiB
Experimental
Healthy participants were given a dose of 250 mg VH4004280 PiB QD for a 14-day period, and a single dose of Midazolam on days 1, 2, and 15, and were followed up to approximately Day 63.
Drug: VH4004280
Drug: Midazolam
Part 2 (MAD): VH4004280 350 mg PiB
Experimental
Healthy participants were given a dose of 350 mg VH4004280 PiB QD for a 14-day period and were followed up to approximately Day 63.
Drug: VH4004280
Part 3 (Single dose): VH4004280 450 mg tablet
Experimental
Healthy participants were given a single oral dose of VH4004280 450 mg tablet at Day 1 and were followed up to approximately Day 49.
Drug: VH4004280
Part 1 (SAD): VH4004280 50 mg PiB
Part 1 (SAD): VH4004280 900 mg PiB
Part 2 (MAD): VH4004280 100 mg PiB
Part 2 (MAD): VH4004280 250 mg + Midazolam (MDZ) PiB
Part 2 (MAD): VH4004280 350 mg PiB
Part 3 (Single dose): VH4004280 450 mg tablet
GSK4004280
Placebo
Drug
Placebo will be administered.
Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB)
Part 2 Multiple Ascending Dose (MAD): Placebo PiB
Midazolam
Drug
Midazolam will be administered
Part 2 (MAD): VH4004280 250 mg + Midazolam (MDZ) PiB
Up to Day 49
Part 2: Number of Participants Discontinuing Treatment Due to AEs
Number of participants who discontinued treatment due to AEs are presented.
Up to Day 63
Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin
Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of bilirubin. 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.
Up to Day 49
Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST)
Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of ALP, ALT and AST.
Up to Day 49
Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin
Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of bilirubin. Standard Deviation (SD)=0.00000 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 0.00000.
Up to Day 63
Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST
Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of ALP, ALT and AST.
Up to Day 63
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 49
Part 3: Absolute Values of Liver Panel Parameters: ALP, ALT and AST
Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of ALP, ALT and AST.
Up to Day 49
Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total 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 49
Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT 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 49
Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total 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 63
Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT 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 63
Part 3: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total 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 49
Part 3: Change From Baseline in Liver Panel Parameters: ALP, ALT 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 49
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 49
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 63
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 49
Part 1: Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC[0-infinity]) Following Single Dose Administration of VH4004280
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 (AUC[0-t]) Following Repeat Dose Administration of VH4004280
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): VH4004280 100 mg PiB and Part 2 (MAD): VH4004280 350 mg PiB groups, and at Days 2 and 15 for Part 2 (MAD): VH4004280 250 mg + Midazolam (MDZ) PiB group
Part 1: Maximum Observed Plasma Concentration (Cmax) Following Single Dose Administration of VH4004280
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 VH4004280
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 VH4004280
Blood samples were collected as assessed by protocol, at specific time points for PK analysis to determine T1/2.
Day 1 to Day 49
Part 2: Cmax Following Repeat Dose Administration of VH4004280
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): VH4004280 100 mg PiB and Part 2 (MAD): VH4004280 350 mg PiB groups, and at Days 2 and 15 for Part 2 (MAD): VH4004280 250 mg + Midazolam (MDZ) PiB group
Part 2: T1/2 Following Repeat Dose Administration of VH4004280
Blood samples were collected as assessed by protocol, at specific time points for PK analysis to determine T1/2.
Day 14 to Day 63 for Part 2 (MAD): VH4004280 100 mg PiB and Part 2 (MAD): VH4004280 350 mg PiB groups, and Day 15 to Day 63 for Part 2 (MAD): VH4004280 250 mg + Midazolam (MDZ) PiB group
Part 2: Tmax Following Repeat Dose Administration of VH4004280
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): VH4004280 100 mg PiB and Part 2 (MAD): VH4004280 350 mg PiB groups, and at Days 2 and 15 for Part 2 (MAD): VH4004280 250 mg + Midazolam (MDZ) PiB group
6 subjects
FG0056 subjects
FG0066 subjects
FG0076 subjects
FG0088 subjects
FG0096 subjects
FG0106 subjects
0 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
0 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
Healthy participants were given a single oral dose of 10 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
BG002
Part 1 (SAD): VH4004280 50 mg PiB
Healthy participants were given a single oral dose of 50 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
BG003
Part 1 (SAD): VH4004280 150 mg PiB
Healthy participants were given a single oral dose of 150 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
BG004
Part 1 (SAD): VH4004280 450 mg PiB
Healthy participants were given a single oral dose of 450 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
BG005
Part 1 (SAD): VH4004280 900 mg PiB
Healthy participants were given a single oral dose of 900 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
BG006
Part 2 Multiple Ascending Dose (MAD): Placebo PiB
Healthy participants were given a dose of placebo once daily (QD) for a 14-day period and were followed up to approximately Day 63.
BG007
Part 2 (MAD): VH4004280 100 mg PiB
Healthy participants were given a dose of 100 mg VH4004280 PiB QD for a 14-day period and were followed up to approximately Day 63.
BG008
Part 2 (MAD): VH4004280 250 mg + Midazolam (MDZ) PiB
Healthy participants were given a dose of 250 mg VH4004280 PiB QD for a 14-day period, and a single dose of Midazolam on days 1, 2, and 15, and were followed up to approximately Day 63.
BG009
Part 2 (MAD): VH4004280 350 mg PiB
Healthy participants were given a dose of 350 mg VH4004280 PiB QD for a 14-day period and were followed up to approximately Day 63.
BG010
Part 3 (Single Dose): VH4004280 450 mg Tablet
Healthy participants were given a single oral dose of VH4004280 450 mg tablet at Day 1 and were followed up to approximately Day 49.
BG011
Total
Total of all reporting groups
10
BG0016
BG0027
BG0036
BG0046
BG0056
BG0066
BG0076
BG0088
BG0096
BG0106
BG01173
Standard Deviation
YEARS
Title
Denominators
Categories
Title
Measurements
BG00034.0± 7.21
BG00133.8± 8.13
BG00230.0± 9.36
BG00331.5± 6.28
BG00427.7± 6.44
BG00531.5± 6.02
BG00636.2± 7.68
BG00733.5± 9.09
BG00834.0± 10.74
BG00942.3± 11.08
BG01043.5± 7.06
BG01134.27± 8.898
Sex/Gender, Customized
Count of Participants
Participants
Title
Denominators
Categories
Male
Title
Measurements
BG00010
BG0016
BG0027
BG0036
BG0046
BG0056
BG0066
BG0076
BG0088
BG0096
BG0105
BG01172
Female
Title
Measurements
BG0000
BG0010
BG0020
BG003
Race/Ethnicity, Customized
Count of Participants
Participants
Title
Denominators
Categories
Asian
Title
Measurements
BG0001
BG0010
BG0021
BG0030
BG0040
BG0050
BG0060
BG0072
BG0081
BG0090
BG0102
BG0117
Black or African American
Title
Measurements
BG0003
BG0012
BG0021
BG003
Native Hawaiian or other Pacific Islander
Title
Measurements
BG0001
BG0011
BG0020
BG003
White
Title
Measurements
BG0004
BG0012
BG0025
BG003
Multiple
Title
Measurements
BG0001
BG0011
BG0020
BG003
ID
Title
Description
OG000
Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB)
Healthy participants were given a single oral dose of placebo on Day 1 and were followed up to approximately Day 49.
OG001
Part 1 (SAD): VH4004280 10 mg PiB
Healthy participants were given a single oral dose of 10 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
OG002
Part 1 (SAD): VH4004280 50 mg PiB
Healthy participants were given a single oral dose of 50 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
OG003
Part 1 (SAD): VH4004280 150 mg PiB
Healthy participants were given a single oral dose of 150 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
OG004
Part 1 (SAD): VH4004280 450 mg PiB
Healthy participants were given a single oral dose of 450 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
OG005
Part 1 (SAD): VH4004280 900 mg PiB
Healthy participants were given a single oral dose of 900 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
Units
Counts
Participants
OG00010
OG0016
OG0027
OG0036
OG0046
OG0056
Title
Denominators
Categories
Any AEs
Title
Measurements
OG0004
OG0012
OG0023
OG0030
OG0040
OG0051
Grade 1 AEs
Title
Measurements
OG0003
OG0012
OG0023
OG003
Grade 2 AEs
Title
Measurements
OG0000
OG0010
OG0020
OG003
Grade 3 AEs
Title
Measurements
OG0001
OG0010
OG0020
OG003
Grade 4 AEs
Title
Measurements
OG0000
OG0010
OG0020
OG003
Grade 5 AEs
Title
Measurements
OG0000
OG0010
OG0020
OG003
Primary
Part 2: Number of Participants With Any AEs and by Severity
The 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 actually received.
Posted
Count of Participants
Participants
Up to Day 63
ID
Title
Description
OG000
Part 2 Multiple Ascending Dose (MAD): Placebo PiB
Healthy participants were given a dose of placebo once daily (QD) for a 14-day period and were followed up to approximately Day 63.
OG001
Part 2 (MAD): VH4004280 100 mg PiB
Healthy participants were given a dose of 100 mg VH4004280 PiB QD for a 14-day period and were followed up to approximately Day 63.
OG002
Part 2 (MAD): VH4004280 250 mg + Midazolam (MDZ) PiB
Healthy participants were given a dose of 250 mg VH4004280 PiB QD for a 14-day period, and a single dose of Midazolam on days 1, 2, and 15, and were followed up to approximately Day 63.
OG003
Part 2 (MAD): VH4004280 350 mg PiB
Healthy participants were given a dose of 350 mg VH4004280 PiB QD for a 14-day period and were followed up to approximately Day 63.
Units
Counts
Participants
OG0006
OG0016
OG0028
OG003
Title
Denominators
Categories
Any AEs
Title
Measurements
OG0003
OG0014
OG0027
OG003
Primary
Part 3: Number of Participants With Any AEs and by Severity
The 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 actually received.
Posted
Count of Participants
Participants
Up to Day 49
ID
Title
Description
OG000
Part 3 (Single Dose): VH4004280 450 mg Tablet
Healthy participants were given a single oral dose of VH4004280 450 mg tablet at Day 1 and were followed up to approximately Day 49.
Units
Counts
Participants
OG0006
Title
Denominators
Categories
Any AEs
Title
Measurements
OG0003
Grade 1 AEs
Title
Measurements
OG0002
Grade 2 AEs
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 actually received.
Posted
Count of Participants
Participants
Up to Day 63
ID
Title
Description
OG000
Part 2 Multiple Ascending Dose (MAD): Placebo PiB
Healthy participants were given a dose of placebo once daily (QD) for a 14-day period and were followed up to approximately Day 63.
OG001
Part 2 (MAD): VH4004280 100 mg PiB
Healthy participants were given a dose of 100 mg VH4004280 PiB QD for a 14-day period and were followed up to approximately Day 63.
OG002
Part 2 (MAD): VH4004280 250 mg + Midazolam (MDZ) PiB
Healthy participants were given a dose of 250 mg VH4004280 PiB QD for a 14-day period, and a single dose of Midazolam on days 1, 2, and 15, and were followed up to approximately Day 63.
OG003
Part 2 (MAD): VH4004280 350 mg PiB
Healthy participants were given a dose of 350 mg VH4004280 PiB QD for a 14-day period and were followed up to approximately Day 63.
Units
Counts
Participants
OG0006
OG0016
OG0028
OG003
Title
Denominators
Categories
Title
Measurements
OG0000
OG0010
OG0020
OG003
Primary
Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin
Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of bilirubin. 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 1 (SAD) who received 1 full dose of study treatment. The participants were analyzed according to the treatment they actually received. Only those participants with data available at specified time points were analyzed for the specific category titles.
Posted
Mean
Standard Deviation
Micromoles per liter (μmol/L)
Up to Day 49
ID
Title
Description
OG000
Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB)
Healthy participants were given a single oral dose of placebo on Day 1 and were followed up to approximately Day 49.
OG001
Part 1 (SAD): VH4004280 10 mg PiB
Healthy participants were given a single oral dose of 10 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
OG002
Part 1 (SAD): VH4004280 50 mg PiB
Healthy participants were given a single oral dose of 50 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
OG003
Part 1 (SAD): VH4004280 150 mg PiB
Healthy participants were given a single oral dose of 150 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
OG004
Part 1 (SAD): VH4004280 450 mg PiB
Healthy participants were given a single oral dose of 450 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
OG005
Part 1 (SAD): VH4004280 900 mg PiB
Healthy participants were given a single oral dose of 900 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
Units
Counts
Participants
OG00010
OG0016
OG0027
OG003
Title
Denominators
Categories
Direct Bilirubin, Baseline (Day 1)
ParticipantsOG00010
ParticipantsOG0016
ParticipantsOG0027
ParticipantsOG003
Primary
Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST)
Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of ALP, ALT and AST.
The analysis was performed on the Safety Set which included all enrolled participants in Part 1 (SAD) who received 1 full dose of study treatment. The participants were analyzed according to the treatment they actually received. Only those participants with data available at specified time points were analyzed for the specific category titles.
Posted
Mean
Standard Deviation
International units per liter (IU/L)
Up to Day 49
ID
Title
Description
OG000
Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB)
Healthy participants were given a single oral dose of placebo on Day 1 and were followed up to approximately Day 49.
OG001
Part 1 (SAD): VH4004280 10 mg PiB
Healthy participants were given a single oral dose of 10 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
OG002
Part 1 (SAD): VH4004280 50 mg PiB
Healthy participants were given a single oral dose of 50 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
OG003
Part 1 (SAD): VH4004280 150 mg PiB
Healthy participants were given a single oral dose of 150 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
OG004
Part 1 (SAD): VH4004280 450 mg PiB
Healthy participants were given a single oral dose of 450 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
OG005
Part 1 (SAD): VH4004280 900 mg PiB
Healthy participants were given a single oral dose of 900 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
Units
Counts
Participants
OG00010
OG0016
OG0027
OG003
Title
Denominators
Categories
ALP, Baseline (Day 1)
ParticipantsOG00010
ParticipantsOG0016
ParticipantsOG0027
ParticipantsOG003
Primary
Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin
Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of bilirubin. Standard Deviation (SD)=0.00000 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 0.00000.
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 actually received. Only those participants with data available at specified time points were analyzed for the specific category titles.
Posted
Mean
Standard Deviation
μmol/L
Up to Day 63
ID
Title
Description
OG000
Part 2 Multiple Ascending Dose (MAD): Placebo PiB
Healthy participants were given a dose of placebo once daily (QD) for a 14-day period and were followed up to approximately Day 63.
OG001
Part 2 (MAD): VH4004280 100 mg PiB
Healthy participants were given a dose of 100 mg VH4004280 PiB QD for a 14-day period and were followed up to approximately Day 63.
OG002
Part 2 (MAD): VH4004280 250 mg + Midazolam (MDZ) PiB
Healthy participants were given a dose of 250 mg VH4004280 PiB QD for a 14-day period, and a single dose of Midazolam on days 1, 2, and 15, and were followed up to approximately Day 63.
OG003
Part 2 (MAD): VH4004280 350 mg PiB
Healthy participants were given a dose of 350 mg VH4004280 PiB QD for a 14-day period and were followed up to approximately Day 63.
Units
Counts
Participants
OG0006
OG0016
OG0028
OG003
Title
Denominators
Categories
Direct Bilirubin, Baseline (Day 1)
ParticipantsOG0006
ParticipantsOG0016
ParticipantsOG0028
ParticipantsOG003
Primary
Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST
Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of ALP, ALT 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 actually received. Only those participants with data available at specified time points were analyzed for the specific category titles.
Posted
Mean
Standard Deviation
IU/L
Up to Day 63
ID
Title
Description
OG000
Part 2 Multiple Ascending Dose (MAD): Placebo PiB
Healthy participants were given a dose of placebo once daily (QD) for a 14-day period and were followed up to approximately Day 63.
OG001
Part 2 (MAD): VH4004280 100 mg PiB
Healthy participants were given a dose of 100 mg VH4004280 PiB QD for a 14-day period and were followed up to approximately Day 63.
OG002
Part 2 (MAD): VH4004280 250 mg + Midazolam (MDZ) PiB
Healthy participants were given a dose of 250 mg VH4004280 PiB QD for a 14-day period, and a single dose of Midazolam on days 1, 2, and 15, and were followed up to approximately Day 63.
OG003
Part 2 (MAD): VH4004280 350 mg PiB
Healthy participants were given a dose of 350 mg VH4004280 PiB QD for a 14-day period and were followed up to approximately Day 63.
Units
Counts
Participants
OG0006
OG0016
OG0028
OG003
Title
Denominators
Categories
ALP, Baseline (Day 1)
ParticipantsOG0006
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 actually received.
Posted
Mean
Standard Deviation
μmol/L
Up to Day 49
ID
Title
Description
OG000
Part 3 (Single Dose): VH4004280 450 mg Tablet
Healthy participants were given a single oral dose of VH4004280 450 mg tablet at Day 1 and were followed up to approximately Day 49.
Units
Counts
Participants
OG0006
Title
Denominators
Categories
Direct Bilirubin, Baseline (Day 1)
ParticipantsOG0006
Title
Measurements
OG0001.9950± 0.69810
Direct Bilirubin, Day 2
ParticipantsOG000
Primary
Part 3: Absolute Values of Liver Panel Parameters: ALP, ALT and AST
Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of ALP, ALT 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 actually received.
Posted
Mean
Standard Deviation
IU/L
Up to Day 49
ID
Title
Description
OG000
Part 3 (Single Dose): VH4004280 450 mg Tablet
Healthy participants were given a single oral dose of VH4004280 450 mg tablet at Day 1 and were followed up to approximately Day 49.
Units
Counts
Participants
OG0006
Title
Denominators
Categories
ALP, Baseline (Day 1)
ParticipantsOG0006
Title
Measurements
OG00055.7± 11.78
ALP, Day 2
ParticipantsOG000
Primary
Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total 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 1 (SAD) who received 1 full dose of study treatment. The participants were analyzed according to the treatment they actually received. Only those participants with data available at specified time points were analyzed for the specific category titles.
Posted
Mean
Standard Deviation
μmol/L
From Baseline (Day 1) and up to Day 49
ID
Title
Description
OG000
Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB)
Healthy participants were given a single oral dose of placebo on Day 1 and were followed up to approximately Day 49.
OG001
Part 1 (SAD): VH4004280 10 mg PiB
Healthy participants were given a single oral dose of 10 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
OG002
Part 1 (SAD): VH4004280 50 mg PiB
Healthy participants were given a single oral dose of 50 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
OG003
Part 1 (SAD): VH4004280 150 mg PiB
Healthy participants were given a single oral dose of 150 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
OG004
Part 1 (SAD): VH4004280 450 mg PiB
Healthy participants were given a single oral dose of 450 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
OG005
Part 1 (SAD): VH4004280 900 mg PiB
Healthy participants were given a single oral dose of 900 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
Units
Counts
Participants
OG00010
OG0016
OG0027
OG003
Title
Denominators
Categories
Direct Bilirubin, Baseline (Day 1)
ParticipantsOG00010
ParticipantsOG0016
ParticipantsOG0027
ParticipantsOG003
Primary
Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT 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 1 full dose of study treatment. The participants were analyzed according to the treatment they actually received. Only those participants with data available at specified time points were analyzed for the specific category titles.
Posted
Mean
Standard Deviation
IU/L
From Baseline (Day 1) and up to Day 49
ID
Title
Description
OG000
Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB)
Healthy participants were given a single oral dose of placebo on Day 1 and were followed up to approximately Day 49.
OG001
Part 1 (SAD): VH4004280 10 mg PiB
Healthy participants were given a single oral dose of 10 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
OG002
Part 1 (SAD): VH4004280 50 mg PiB
Healthy participants were given a single oral dose of 50 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
OG003
Part 1 (SAD): VH4004280 150 mg PiB
Healthy participants were given a single oral dose of 150 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
OG004
Part 1 (SAD): VH4004280 450 mg PiB
Healthy participants were given a single oral dose of 450 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
OG005
Part 1 (SAD): VH4004280 900 mg PiB
Healthy participants were given a single oral dose of 900 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
Units
Counts
Participants
OG00010
OG0016
OG0027
OG003
Title
Denominators
Categories
ALP, Baseline (Day 1)
ParticipantsOG00010
ParticipantsOG0016
ParticipantsOG0027
ParticipantsOG003
Primary
Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total 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 actually received. Only those participants with data available at specified time points were analyzed for the specific category titles.
Posted
Mean
Standard Deviation
μmol/L
From Baseline (Day 1) and up to Day 63
ID
Title
Description
OG000
Part 2 Multiple Ascending Dose (MAD): Placebo PiB
Healthy participants were given a dose of placebo once daily (QD) for a 14-day period and were followed up to approximately Day 63.
OG001
Part 2 (MAD): VH4004280 100 mg PiB
Healthy participants were given a dose of 100 mg VH4004280 PiB QD for a 14-day period and were followed up to approximately Day 63.
OG002
Part 2 (MAD): VH4004280 250 mg + Midazolam (MDZ) PiB
Healthy participants were given a dose of 250 mg VH4004280 PiB QD for a 14-day period, and a single dose of Midazolam on days 1, 2, and 15, and were followed up to approximately Day 63.
OG003
Part 2 (MAD): VH4004280 350 mg PiB
Healthy participants were given a dose of 350 mg VH4004280 PiB QD for a 14-day period and were followed up to approximately Day 63.
Units
Counts
Participants
OG0006
OG0016
OG0028
OG003
Title
Denominators
Categories
Direct Bilirubin, Baseline (Day 1)
ParticipantsOG0006
ParticipantsOG0016
ParticipantsOG0028
ParticipantsOG003
Primary
Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT 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 2 (MAD) who received at least 1 full or partial dose of study treatment. The participants were analyzed according to the treatment they actually received. Only those participants with data available at specified time points were analyzed for the specific category titles.
Posted
Mean
Standard Deviation
IU/L
From Baseline (Day 1) and up to Day 63
ID
Title
Description
OG000
Part 2 Multiple Ascending Dose (MAD): Placebo PiB
Healthy participants were given a dose of placebo once daily (QD) for a 14-day period and were followed up to approximately Day 63.
OG001
Part 2 (MAD): VH4004280 100 mg PiB
Healthy participants were given a dose of 100 mg VH4004280 PiB QD for a 14-day period and were followed up to approximately Day 63.
OG002
Part 2 (MAD): VH4004280 250 mg + Midazolam (MDZ) PiB
Healthy participants were given a dose of 250 mg VH4004280 PiB QD for a 14-day period, and a single dose of Midazolam on days 1, 2, and 15, and were followed up to approximately Day 63.
OG003
Part 2 (MAD): VH4004280 350 mg PiB
Healthy participants were given a dose of 350 mg VH4004280 PiB QD for a 14-day period and were followed up to approximately Day 63.
Units
Counts
Participants
OG0006
OG0016
OG0028
OG003
Title
Denominators
Categories
ALP, Baseline (Day 1)
ParticipantsOG0006
ParticipantsOG0016
ParticipantsOG0028
ParticipantsOG003
Primary
Part 3: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total 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 actually received.
Posted
Mean
Standard Deviation
μmol/L
From Baseline (Day 1) and up to Day 49
ID
Title
Description
OG000
Part 3 (Single Dose): VH4004280 450 mg Tablet
Healthy participants were given a single oral dose of VH4004280 450 mg tablet at Day 1 and were followed up to approximately Day 49.
Units
Counts
Participants
OG0006
Title
Denominators
Categories
Direct Bilirubin, Baseline (Day 1)
ParticipantsOG0006
Title
Measurements
OG0001.9950± 0.69810
Direct Bilirubin, Day 2
ParticipantsOG000
Primary
Part 3: Change From Baseline in Liver Panel Parameters: ALP, ALT 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 actually received.
Posted
Mean
Standard Deviation
IU/L
From Baseline (Day 1) and up to Day 49
ID
Title
Description
OG000
Part 3 (Single Dose): VH4004280 450 mg Tablet
Healthy participants were given a single oral dose of VH4004280 450 mg tablet at Day 1 and were followed up to approximately Day 49.
Units
Counts
Participants
OG0006
Title
Denominators
Categories
ALP, Baseline (Day 1)
ParticipantsOG0006
Title
Measurements
OG00055.7± 11.78
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 1 full dose of study treatment. The participants were analyzed according to the treatment they actually received.
Posted
Count of Participants
Participants
Up to Day 49
ID
Title
Description
OG000
Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB)
Healthy participants were given a single oral dose of placebo on Day 1 and were followed up to approximately Day 49.
OG001
Part 1 (SAD): VH4004280 10 mg PiB
Healthy participants were given a single oral dose of 10 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
OG002
Part 1 (SAD): VH4004280 50 mg PiB
Healthy participants were given a single oral dose of 50 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
OG003
Part 1 (SAD): VH4004280 150 mg PiB
Healthy participants were given a single oral dose of 150 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
OG004
Part 1 (SAD): VH4004280 450 mg PiB
Healthy participants were given a single oral dose of 450 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
OG005
Part 1 (SAD): VH4004280 900 mg PiB
Healthy participants were given a single oral dose of 900 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
Units
Counts
Participants
OG00010
OG0016
OG0027
OG003
Title
Denominators
Categories
ALT, Increase to Grade 1
Title
Measurements
OG0001
OG0011
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 actually received.
Posted
Count of Participants
Participants
Up to Day 63
ID
Title
Description
OG000
Part 2 Multiple Ascending Dose (MAD): Placebo PiB
Healthy participants were given a dose of placebo once daily (QD) for a 14-day period and were followed up to approximately Day 63.
OG001
Part 2 (MAD): VH4004280 100 mg PiB
Healthy participants were given a dose of 100 mg VH4004280 PiB QD for a 14-day period and were followed up to approximately Day 63.
OG002
Part 2 (MAD): VH4004280 250 mg + Midazolam (MDZ) PiB
Healthy participants were given a dose of 250 mg VH4004280 PiB QD for a 14-day period, and a single dose of Midazolam on days 1, 2, and 15, and were followed up to approximately Day 63.
OG003
Part 2 (MAD): VH4004280 350 mg PiB
Healthy participants were given a dose of 350 mg VH4004280 PiB QD for a 14-day period and were followed up to approximately Day 63.
Units
Counts
Participants
OG0006
OG0016
OG0028
OG003
Title
Denominators
Categories
ALT, Increase to Grade 1
Title
Measurements
OG0001
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 actually received.
Posted
Count of Participants
Participants
Up to Day 49
ID
Title
Description
OG000
Part 3 (Single Dose): VH4004280 450 mg Tablet
Healthy participants were given a single oral dose of VH4004280 450 mg tablet at Day 1 and were followed up to approximately Day 49.
Units
Counts
Participants
OG0006
Title
Denominators
Categories
ALT, Increase to Grade 1
Title
Measurements
OG0000
ALT, Increase to Grade 2
Title
Measurements
OG0001
ALT, Increase to Grade 3
Primary
Part 1: Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC[0-infinity]) Following Single Dose Administration of VH4004280
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 VH4004280 PK Set which included all participants in the Part 1 (SAD) Safety Set who received 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): VH4004280 10 mg PiB
Healthy participants were given a single oral dose of 10 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
OG001
Part 1 (SAD): VH4004280 50 mg PiB
Healthy participants were given a single oral dose of 50 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
OG002
Part 1 (SAD): VH4004280 150 mg PiB
Healthy participants were given a single oral dose of 150 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
OG003
Part 1 (SAD): VH4004280 450 mg PiB
Healthy participants were given a single oral dose of 450 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
OG004
Part 1 (SAD): VH4004280 900 mg PiB
Healthy participants were given a single oral dose of 900 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
Units
Counts
Participants
OG0006
OG0017
OG0026
OG003
Title
Denominators
Categories
Title
Measurements
OG0001396.25± 28.02
OG00116829.76± 17.59
OG00251168.22± 51.76
OG003
Primary
Part 2: AUC Over a Dosing Interval From Time of Dosing to the Time of the Subsequent Dose (AUC[0-t]) Following Repeat Dose Administration of VH4004280
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 VH4004280 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): VH4004280 100 mg PiB and Part 2 (MAD): VH4004280 350 mg PiB groups, and at Days 2 and 15 for Part 2 (MAD): VH4004280 250 mg + Midazolam (MDZ) PiB group
ID
Title
Description
OG000
Part 2 (MAD): VH4004280 100 mg PiB
Healthy participants were given a dose of 100 mg VH4004280 PiB QD for a 14-day period and were followed up to approximately Day 63.
OG001
Part 2 (MAD): VH4004280 250 mg + Midazolam (MDZ) PiB
Healthy participants were given a dose of 250 mg VH4004280 PiB QD for a 14-day period, and a single dose of Midazolam on days 1, 2, and 15, and were followed up to approximately Day 63.
OG002
Part 2 (MAD): VH4004280 350 mg PiB
Healthy participants were given a dose of 350 mg VH4004280 PiB QD for a 14-day period and were followed up to approximately Day 63.
Units
Counts
Participants
OG0006
OG0018
OG0026
Title
Denominators
Categories
Day 1
ParticipantsOG0006
ParticipantsOG0010
ParticipantsOG0026
Title
Measurements
Primary
Part 1: Maximum Observed Plasma Concentration (Cmax) Following Single Dose Administration of VH4004280
Blood samples were collected as assessed by protocol, at specific time points for PK analysis to determine Cmax.
The analysis was performed on the VH4004280 PK Set which included all participants in the Part 1 (SAD) Safety Set who received 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): VH4004280 10 mg PiB
Healthy participants were given a single oral dose of 10 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
OG001
Part 1 (SAD): VH4004280 50 mg PiB
Healthy participants were given a single oral dose of 50 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
OG002
Part 1 (SAD): VH4004280 150 mg PiB
Healthy participants were given a single oral dose of 150 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
OG003
Part 1 (SAD): VH4004280 450 mg PiB
Healthy participants were given a single oral dose of 450 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
OG004
Part 1 (SAD): VH4004280 900 mg PiB
Healthy participants were given a single oral dose of 900 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
Units
Counts
Participants
OG0006
OG0017
OG0026
OG003
Title
Denominators
Categories
Title
Measurements
OG00013.49± 23.59
OG001149.77± 27.34
OG002438.80± 53.60
OG003
Primary
Part 1: Time to Maximum Observed Plasma Concentration (Tmax) Following Single Dose Administration of VH4004280
Blood samples were collected as assessed by protocol, at specific time points for PK analysis to determine Tmax.
The analysis was performed on the VH4004280 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): VH4004280 10 mg PiB
Healthy participants were given a single oral dose of 10 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
OG001
Part 1 (SAD): VH4004280 50 mg PiB
Healthy participants were given a single oral dose of 50 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
OG002
Part 1 (SAD): VH4004280 150 mg PiB
Healthy participants were given a single oral dose of 150 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
OG003
Part 1 (SAD): VH4004280 450 mg PiB
Healthy participants were given a single oral dose of 450 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
OG004
Part 1 (SAD): VH4004280 900 mg PiB
Healthy participants were given a single oral dose of 900 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
Units
Counts
Participants
OG0006
OG0017
OG0026
OG003
Title
Denominators
Categories
Title
Measurements
OG0009.63± 9.13
OG0019.90± 16.62
OG00211.15± 40.09
OG003
Primary
Part 1: Apparent Terminal Half-life (T1/2) Following Single Dose Administration of VH4004280
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 VH4004280 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
Day 1 to Day 49
ID
Title
Description
OG000
Part 1 (SAD): VH4004280 10 mg PiB
Healthy participants were given a single oral dose of 10 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
OG001
Part 1 (SAD): VH4004280 50 mg PiB
Healthy participants were given a single oral dose of 50 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
OG002
Part 1 (SAD): VH4004280 150 mg PiB
Healthy participants were given a single oral dose of 150 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
OG003
Part 1 (SAD): VH4004280 450 mg PiB
Healthy participants were given a single oral dose of 450 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
OG004
Part 1 (SAD): VH4004280 900 mg PiB
Healthy participants were given a single oral dose of 900 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
Units
Counts
Participants
OG0006
OG0017
OG0026
OG003
Title
Denominators
Categories
Title
Measurements
OG000145.82± 40.60
OG001149.91± 40.40
OG002149.94± 43.47
OG003
Primary
Part 2: Cmax Following Repeat Dose Administration of VH4004280
Blood samples were collected as assessed by protocol, at specific time points for PK analysis to determine Cmax.
The analysis was performed on the VH4004280 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): VH4004280 100 mg PiB and Part 2 (MAD): VH4004280 350 mg PiB groups, and at Days 2 and 15 for Part 2 (MAD): VH4004280 250 mg + Midazolam (MDZ) PiB group
ID
Title
Description
OG000
Part 2 (MAD): VH4004280 100 mg PiB
Healthy participants were given a dose of 100 mg VH4004280 PiB QD for a 14-day period and were followed up to approximately Day 63.
OG001
Part 2 (MAD): VH4004280 250 mg + Midazolam (MDZ) PiB
Healthy participants were given a dose of 250 mg VH4004280 PiB QD for a 14-day period, and a single dose of Midazolam on days 1, 2, and 15, and were followed up to approximately Day 63.
OG002
Part 2 (MAD): VH4004280 350 mg PiB
Healthy participants were given a dose of 350 mg VH4004280 PiB QD for a 14-day period and were followed up to approximately Day 63.
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 VH4004280
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 VH4004280 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
Day 14 to Day 63 for Part 2 (MAD): VH4004280 100 mg PiB and Part 2 (MAD): VH4004280 350 mg PiB groups, and Day 15 to Day 63 for Part 2 (MAD): VH4004280 250 mg + Midazolam (MDZ) PiB group
ID
Title
Description
OG000
Part 2 (MAD): VH4004280 100 mg PiB
Healthy participants were given a dose of 100 mg VH4004280 PiB QD for a 14-day period and were followed up to approximately Day 63.
OG001
Part 2 (MAD): VH4004280 250 mg + Midazolam (MDZ) PiB
Healthy participants were given a dose of 250 mg VH4004280 PiB QD for a 14-day period, and a single dose of Midazolam on days 1, 2, and 15, and were followed up to approximately Day 63.
OG002
Part 2 (MAD): VH4004280 350 mg PiB
Healthy participants were given a dose of 350 mg VH4004280 PiB QD for a 14-day period and were followed up to approximately Day 63.
Units
Counts
Participants
OG0006
OG0018
OG0026
Title
Denominators
Categories
Day 14 to Day 63
ParticipantsOG0006
ParticipantsOG0010
ParticipantsOG0026
Title
Measurements
Primary
Part 2: Tmax Following Repeat Dose Administration of VH4004280
Blood samples were collected as assessed by protocol, at specific time points for PK analysis to determine Tmax.
The analysis was performed on the VH4004280 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): VH4004280 100 mg PiB and Part 2 (MAD): VH4004280 350 mg PiB groups, and at Days 2 and 15 for Part 2 (MAD): VH4004280 250 mg + Midazolam (MDZ) PiB group
ID
Title
Description
OG000
Part 2 (MAD): VH4004280 100 mg PiB
Healthy participants were given a dose of 100 mg VH4004280 PiB QD for a 14-day period and were followed up to approximately Day 63.
OG001
Part 2 (MAD): VH4004280 250 mg + Midazolam (MDZ) PiB
Healthy participants were given a dose of 250 mg VH4004280 PiB QD for a 14-day period, and a single dose of Midazolam on days 1, 2, and 15, and were followed up to approximately Day 63.
OG002
Part 2 (MAD): VH4004280 350 mg PiB
Healthy participants were given a dose of 350 mg VH4004280 PiB QD for a 14-day period and were followed up to approximately Day 63.
Units
Counts
Participants
OG0006
OG0018
OG0026
Title
Denominators
Categories
Day 1
ParticipantsOG0006
ParticipantsOG0010
ParticipantsOG0026
Title
Measurements
0
10
0
10
4
10
EG001
Part 1 (SAD): VH4004280 10 mg PiB
Healthy participants were given a single oral dose of 10 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
0
6
0
6
2
6
EG002
Part 1 (SAD): VH4004280 50 mg PiB
Healthy participants were given a single oral dose of 50 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
0
7
0
7
3
7
EG003
Part 1 (SAD): VH4004280 150 mg PiB
Healthy participants were given a single oral dose of 150 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
0
6
0
6
0
6
EG004
Part 1 (SAD): VH4004280 450 mg PiB
Healthy participants were given a single oral dose of 450 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
0
6
0
6
0
6
EG005
Part 1 (SAD): VH4004280 900 mg PiB
Healthy participants were given a single oral dose of 900 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
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 (QD) for a 14-day period and were followed up to approximately Day 63.
0
6
0
6
3
6
EG007
Part 2 (MAD): VH4004280 100 mg PiB
Healthy participants were given a dose of 100 mg VH4004280 PiB QD for a 14-day period and were followed up to approximately Day 63.
0
6
0
6
4
6
EG008
Part 2 (MAD): VH4004280 250 mg + Midazolam (MDZ) PiB
Healthy participants were given a dose of 250 mg VH4004280 PiB QD for a 14-day period, and a single dose of Midazolam on days 1, 2, and 15, and were followed up to approximately Day 63.
0
8
0
8
7
8
EG009
Part 2 (MAD): VH4004280 350 mg PiB
Healthy participants were given a dose of 350 mg VH4004280 PiB QD for a 14-day period and were followed up to approximately Day 63.
0
6
0
6
4
6
EG010
Part 3 (Single Dose): VH4004280 450 mg Tablet
Healthy participants were given a single oral dose of VH4004280 450 mg tablet at Day 1 and were followed up to approximately Day 49.
0
6
0
6
3
6
EG0000 events0 affected10 at risk
EG0010 events0 affected6 at risk
EG0022 events2 affected7 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected6 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected6 at risk
Chapped lips
Gastrointestinal disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected10 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected7 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected6 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected6 at risk
Diarrhoea
Gastrointestinal disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected10 at risk
EG0010 events0 affected6 at risk
EG0022 events2 affected7 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected6 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected6 at risk
Dry mouth
Gastrointestinal disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected10 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected7 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected6 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected6 at risk
Nausea
Gastrointestinal disorders
MedDRA 25.1
Systematic Assessment
EG0001 events1 affected10 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected7 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected6 at risk
EG0070 events0 affected6 at risk
EG0081 events1 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected6 at risk
Fatigue
General disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected10 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected7 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0061 events1 affected6 at risk
EG0070 events0 affected6 at risk
EG0085 events5 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected6 at risk
Influenza like illness
General disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected10 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected7 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected6 at risk
EG0071 events1 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected6 at risk
Nasopharyngitis
Infections and infestations
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected10 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected7 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0061 events1 affected6 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected6 at risk
Periorbital haemorrhage
Injury, poisoning and procedural complications
MedDRA 25.1
Systematic Assessment
EG0001 events1 affected10 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected7 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected6 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected6 at risk
Alanine aminotransferase increased
Investigations
MedDRA 25.1
Systematic Assessment
EG0001 events1 affected10 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected7 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0061 events1 affected6 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0091 events1 affected6 at risk
EG0101 events1 affected6 at risk
Amylase increased
Investigations
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected10 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected7 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected6 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0101 events1 affected6 at risk
Aspartate aminotransferase increased
Investigations
MedDRA 25.1
Systematic Assessment
EG0001 events1 affected10 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected7 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0061 events1 affected6 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0091 events1 affected6 at risk
EG0101 events1 affected6 at risk
Bile acids increased
Investigations
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected10 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected7 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected6 at risk
EG0071 events1 affected6 at risk
EG0080 events0 affected8 at risk
EG0091 events1 affected6 at risk
EG0101 events1 affected6 at risk
Blood bilirubin increased
Investigations
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected10 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected7 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected6 at risk
EG0071 events1 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected6 at risk
Blood cholesterol increased
Investigations
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected10 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected7 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected6 at risk
EG0070 events0 affected6 at risk
EG0081 events1 affected8 at risk
EG0091 events1 affected6 at risk
EG0100 events0 affected6 at risk
Blood creatine phosphokinase increased
Investigations
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected10 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected7 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected6 at risk
EG0070 events0 affected6 at risk
EG0082 events2 affected8 at risk
EG0091 events1 affected6 at risk
EG0100 events0 affected6 at risk
Blood pressure increased
Investigations
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected10 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected7 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected6 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0101 events1 affected6 at risk
Body temperature increased
Investigations
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected10 at risk
EG0010 events0 affected6 at risk
EG0021 events1 affected7 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected6 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
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected10 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected7 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected6 at risk
EG0070 events0 affected6 at risk
EG0081 events1 affected8 at risk
EG0091 events1 affected6 at risk
EG0101 events1 affected6 at risk
Low density lipoprotein increased
Investigations
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected10 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected7 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected6 at risk
EG0070 events0 affected6 at risk
EG0082 events2 affected8 at risk
EG0091 events1 affected6 at risk
EG0100 events0 affected6 at risk
Decreased appetite
Metabolism and nutrition disorders
MedDRA 25.1
Systematic Assessment
EG0001 events1 affected10 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected7 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected6 at risk
EG0071 events1 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected6 at risk
Dyslipidaemia
Metabolism and nutrition disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected10 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected7 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected6 at risk
EG0072 events2 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected6 at risk
Flank pain
Musculoskeletal and connective tissue disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected10 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected7 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0061 events1 affected6 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected6 at risk
Myalgia
Musculoskeletal and connective tissue disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected10 at risk
EG0010 events0 affected6 at risk
EG0021 events1 affected7 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected6 at risk
EG0070 events0 affected6 at risk
EG0081 events1 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected6 at risk
Neck pain
Musculoskeletal and connective tissue disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected10 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected7 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected6 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected6 at risk
Dizziness
Nervous system disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected10 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected7 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0061 events1 affected6 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected6 at risk
Headache
Nervous system disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected10 at risk
EG0010 events0 affected6 at risk
EG0021 events1 affected7 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0051 events1 affected6 at risk
EG0061 events1 affected6 at risk
EG0071 events1 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected6 at risk
Paraesthesia
Nervous system disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected10 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected7 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0061 events1 affected6 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected6 at risk
Nasal congestion
Respiratory, thoracic and mediastinal disorders
MedDRA 25.1
Systematic Assessment
EG0000 events0 affected10 at risk
EG0010 events0 affected6 at risk
EG0021 events1 affected7 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected6 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected6 at risk
Dermatitis contact
Skin and subcutaneous tissue disorders
MedDRA 25.1
Systematic Assessment
EG0001 events1 affected10 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected7 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0061 events1 affected6 at risk
EG0070 events0 affected6 at risk
EG0081 events1 affected8 at risk
EG0090 events0 affected6 at risk
EG0101 events1 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.