HIV Infections
Conditions
Keywords
First-time-in-human, GSK4004280, VH4004280, HIV-1 capsid inhibitor, Single ascending doses, Multiple ascending doses
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.
Interventions
DRUGVH4004280
VH4004280 will be administered.
DRUGPlacebo
Placebo will be administered.
DRUGMidazolam
Midazolam will be administered
Sponsors
ViiV Healthcare
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
This is a double-blind (sponsor unblinded) study.
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Number of Participants With Any Adverse Events (AEs) and by Severity | Up to Day 49 | An AE was defined as any untoward medical occurrence in a participant, temporally associated with the use of a study intervention whether or not considered related to the study intervention. The Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric AE was used for all AE severity grading, where Grade 1=Mild symptoms causing no or minimal interference with usual social & functional activities with intervention not indicated, 2=Moderate symptoms causing greater than minimal interference with usual social & functional activities with intervention indicated, 3=Severe symptoms causing inability to perform usual social & functional activities with intervention or hospitalization indicated, 4=Potentially life-threatening symptoms causing inability to perform basic self-care functions with intervention indicated to prevent permanent impairment, persistent disability or death, 5=Death. |
| Part 2: Number of Participants With Any AEs and by Severity | Up to Day 63 | 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. |
| Part 3: Number of Participants With Any AEs and by Severity | Up to Day 49 | 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. |
| Part 2: Number of Participants Discontinuing Treatment Due to AEs | Up to Day 63 | Number of participants who discontinued treatment due to AEs are presented. |
| Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Up to Day 49 | 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. |
| Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | Up to Day 49 | Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of ALP, ALT and AST. |
| Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Up to Day 63 | 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. |
| Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | Up to Day 63 | Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of ALP, ALT and AST. |
| Part 3: Absolute Values of Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Up to Day 49 | Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of bilirubin. |
| Part 3: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | Up to Day 49 | Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of ALP, ALT and AST. |
| Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | From Baseline (Day 1) and up to Day 49 | Change from baseline was calculated by subtracting the baseline value from the post-dose visit value. Standard Deviation (SD)=0.0000 is defined as following: if all participants analyzed for a specific parameter at a specific time point have the same value, then SD is equal with 0.0000. |
| Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | From Baseline (Day 1) and up to Day 49 | Change from baseline was calculated by subtracting the baseline value from the post-dose visit value. |
| Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | From Baseline (Day 1) and up to Day 63 | Change from baseline was calculated by subtracting the baseline value from the post-dose visit value. Standard Deviation (SD)=0.0000 is defined as following: if all participants analyzed for a specific parameter at a specific time point have the same value, then SD is equal with 0.0000. |
| Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | From Baseline (Day 1) and up to Day 63 | Change from baseline was calculated by subtracting the baseline value from the post-dose visit value. |
| Part 3: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | From Baseline (Day 1) and up to Day 49 | Change from baseline was calculated by subtracting the baseline value from the post-dose visit value. |
| Part 3: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | From Baseline (Day 1) and up to Day 49 | Change from baseline was calculated by subtracting the baseline value from the post-dose visit value. |
| Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Up to Day 49 | Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of the liver panel parameters: ALT, ALP, AST, total bilirubin and direct bilirubin. The number of participants with any grade increase (from grade 1 \[mild\] to grade 4 \[potentially life-threatening\]) have been presented. |
| Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Up to Day 63 | Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of the liver panel parameters: ALT, ALP, AST, total bilirubin and direct bilirubin. The number of participants with any grade increase (from grade 1 \[mild\] to grade 4 \[potentially life-threatening\]) have been presented. |
| Part 3: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Up to Day 49 | Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of the liver panel parameters: ALT, ALP, AST, total bilirubin and direct bilirubin. The number of participants with any grade increase (from grade 1 \[mild\] to grade 4 \[potentially life-threatening\]) have been presented. |
| Part 1: Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC[0-infinity]) Following Single Dose Administration of VH4004280 | At Day 1 | Blood samples were collected as assessed by protocol, at specific time points for pharmacokinetic (PK) analysis to determine AUC(0-inf). For AUC, a linear trapezoidal method was employed for all incremental trapezoids arising from increasing concentrations and the logarithmic trapezoidal method was used for those arising from decreasing concentrations. Geometric Coefficient of Variation was expressed in percentages. |
| Part 2: AUC Over a Dosing Interval From Time of Dosing to the Time of the Subsequent Dose (AUC[0-t]) Following Repeat Dose Administration of VH4004280 | 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 | Blood samples were collected as assessed by protocol, at specific time points for PK analysis to determine AUC(0-t). For AUC, a linear trapezoidal method was employed for all incremental trapezoids arising from increasing concentrations and the logarithmic trapezoidal method was used for those arising from decreasing concentrations. |
| Part 1: Maximum Observed Plasma Concentration (Cmax) Following Single Dose Administration of VH4004280 | At Day 1 | Blood samples were collected as assessed by protocol, at specific time points for PK analysis to determine Cmax. |
| Part 1: Time to Maximum Observed Plasma Concentration (Tmax) Following Single Dose Administration of VH4004280 | At Day 1 | Blood samples were collected as assessed by protocol, at specific time points for PK analysis to determine Tmax. |
| Part 1: Apparent Terminal Half-life (T1/2) Following Single Dose Administration of VH4004280 | Day 1 to Day 49 | Blood samples were collected as assessed by protocol, at specific time points for PK analysis to determine T1/2. |
| Part 2: Cmax Following Repeat Dose Administration of VH4004280 | 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 | Blood samples were collected as assessed by protocol, at specific time points for PK analysis to determine Cmax. |
| Part 2: T1/2 Following Repeat Dose Administration of VH4004280 | 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 | Blood samples were collected as assessed by protocol, at specific time points for PK analysis to determine T1/2. |
| Part 2: Tmax Following Repeat Dose Administration of VH4004280 | 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 | Blood samples were collected as assessed by protocol, at specific time points for PK analysis to determine Tmax. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 10 |
| 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. | 6 |
| 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. | 7 |
| 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. | 6 |
| 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. | 6 |
| 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. | 6 |
| 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. | 6 |
| 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. | 6 |
| 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. | 8 |
| 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. | 6 |
| 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. | 6 |
| Total | 73 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1 (SAD): VH4004280 10 mg PiB | Part 1 (SAD): VH4004280 50 mg PiB | Part 1 (SAD): VH4004280 150 mg PiB | Part 1 (SAD): VH4004280 450 mg PiB | Part 1 (SAD): VH4004280 900 mg PiB | Part 2 Multiple Ascending Dose (MAD): Placebo 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 | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 34.0 YEARS STANDARD_DEVIATION 7.21 | 33.8 YEARS STANDARD_DEVIATION 8.13 | 30.0 YEARS STANDARD_DEVIATION 9.36 | 31.5 YEARS STANDARD_DEVIATION 6.28 | 27.7 YEARS STANDARD_DEVIATION 6.44 | 31.5 YEARS STANDARD_DEVIATION 6.02 | 36.2 YEARS STANDARD_DEVIATION 7.68 | 33.5 YEARS STANDARD_DEVIATION 9.09 | 34.0 YEARS STANDARD_DEVIATION 10.74 | 42.3 YEARS STANDARD_DEVIATION 11.08 | 43.5 YEARS STANDARD_DEVIATION 7.06 | 34.27 YEARS STANDARD_DEVIATION 8.898 |
| Race/Ethnicity, Customized Asian | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 2 Participants | 7 Participants |
| Race/Ethnicity, Customized Black or African American | 3 Participants | 2 Participants | 1 Participants | 3 Participants | 5 Participants | 2 Participants | 2 Participants | 4 Participants | 6 Participants | 3 Participants | 3 Participants | 34 Participants |
| Race/Ethnicity, Customized Multiple | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 4 Participants | 2 Participants | 5 Participants | 3 Participants | 1 Participants | 4 Participants | 4 Participants | 0 Participants | 1 Participants | 3 Participants | 1 Participants | 28 Participants |
| Sex/Gender, Customized Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Sex/Gender, Customized Male | 10 Participants | 6 Participants | 7 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 8 Participants | 6 Participants | 5 Participants | 72 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 6 | 0 / 7 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 8 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 4 / 10 | 2 / 6 | 3 / 7 | 0 / 6 | 0 / 6 | 1 / 6 | 3 / 6 | 4 / 6 | 7 / 8 | 4 / 6 | 3 / 6 |
| serious Total, serious adverse events | 0 / 10 | 0 / 6 | 0 / 7 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 8 | 0 / 6 | 0 / 6 |
Outcome results
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.
Time frame: Up to Day 49
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 3 | 18.6 International units per liter (IU/L) | Standard Deviation 7.15 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 42 | 53.7 International units per liter (IU/L) | Standard Deviation 9.75 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 2 | 18.3 International units per liter (IU/L) | Standard Deviation 7.78 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Baseline (Day 1) | 18.4 International units per liter (IU/L) | Standard Deviation 5.6 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 49 | 54.3 International units per liter (IU/L) | Standard Deviation 7.53 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 4 | 49.3 International units per liter (IU/L) | Standard Deviation 6.6 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Baseline (Day 1) | 51.8 International units per liter (IU/L) | Standard Deviation 9.39 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 49 | 15.2 International units per liter (IU/L) | Standard Deviation 2.04 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 21 | 17.9 International units per liter (IU/L) | Standard Deviation 6.82 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 7 | 16.5 International units per liter (IU/L) | Standard Deviation 3.84 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 6 | 48.8 International units per liter (IU/L) | Standard Deviation 6.44 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 3 | 48.2 International units per liter (IU/L) | Standard Deviation 4.57 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 2 | 17.3 International units per liter (IU/L) | Standard Deviation 7.97 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 4 | 19.2 International units per liter (IU/L) | Standard Deviation 6.6 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 35 | 52.9 International units per liter (IU/L) | Standard Deviation 8.69 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 42 | 14.8 International units per liter (IU/L) | Standard Deviation 1.72 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 7 | 51.7 International units per liter (IU/L) | Standard Deviation 7.3 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 2 | 48.6 International units per liter (IU/L) | Standard Deviation 7.52 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 35 | 17.4 International units per liter (IU/L) | Standard Deviation 4.7 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 28 | 16.8 International units per liter (IU/L) | Standard Deviation 3.39 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 14 | 40.0 International units per liter (IU/L) | Standard Deviation 71.85 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 6 | 15.6 International units per liter (IU/L) | Standard Deviation 3.13 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 14 | 54.8 International units per liter (IU/L) | Standard Deviation 11.85 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 5 | 14.8 International units per liter (IU/L) | Standard Deviation 2.9 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 4 | 15.8 International units per liter (IU/L) | Standard Deviation 3.82 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 3 | 16.4 International units per liter (IU/L) | Standard Deviation 4.33 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 21 | 53.0 International units per liter (IU/L) | Standard Deviation 11.18 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Baseline (Day 1) | 17.3 International units per liter (IU/L) | Standard Deviation 5.03 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 49 | 15.0 International units per liter (IU/L) | Standard Deviation 4.34 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 42 | 14.2 International units per liter (IU/L) | Standard Deviation 3.6 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 35 | 19.8 International units per liter (IU/L) | Standard Deviation 10.78 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 28 | 20.1 International units per liter (IU/L) | Standard Deviation 10.02 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 28 | 53.9 International units per liter (IU/L) | Standard Deviation 12.35 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 5 | 48.1 International units per liter (IU/L) | Standard Deviation 8.16 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 21 | 23.4 International units per liter (IU/L) | Standard Deviation 15.94 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 14 | 26.1 International units per liter (IU/L) | Standard Deviation 21.07 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 7 | 19.9 International units per liter (IU/L) | Standard Deviation 9.97 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 6 | 18.9 International units per liter (IU/L) | Standard Deviation 7.96 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 5 | 18.1 International units per liter (IU/L) | Standard Deviation 6.3 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 21 | 58.7 International units per liter (IU/L) | Standard Deviation 9.5 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 5 | 59.2 International units per liter (IU/L) | Standard Deviation 10.32 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 6 | 62.5 International units per liter (IU/L) | Standard Deviation 10.99 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 7 | 64.3 International units per liter (IU/L) | Standard Deviation 13.6 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 28 | 57.5 International units per liter (IU/L) | Standard Deviation 7.97 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Baseline (Day 1) | 22.8 International units per liter (IU/L) | Standard Deviation 11.72 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 2 | 22.0 International units per liter (IU/L) | Standard Deviation 16.6 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 3 | 22.2 International units per liter (IU/L) | Standard Deviation 17.23 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 5 | 21.7 International units per liter (IU/L) | Standard Deviation 16.74 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 6 | 22.5 International units per liter (IU/L) | Standard Deviation 16.15 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 7 | 23.5 International units per liter (IU/L) | Standard Deviation 15.59 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 14 | 27.3 International units per liter (IU/L) | Standard Deviation 17.9 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 21 | 23.5 International units per liter (IU/L) | Standard Deviation 13.98 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 28 | 33.7 International units per liter (IU/L) | Standard Deviation 22.25 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 35 | 28.5 International units per liter (IU/L) | Standard Deviation 15.42 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Baseline (Day 1) | 17.3 International units per liter (IU/L) | Standard Deviation 5.82 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 4 | 16.7 International units per liter (IU/L) | Standard Deviation 7.76 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 5 | 14.8 International units per liter (IU/L) | Standard Deviation 6.34 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 6 | 16.0 International units per liter (IU/L) | Standard Deviation 6.42 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 28 | 23.0 International units per liter (IU/L) | Standard Deviation 6.54 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 35 | 20.5 International units per liter (IU/L) | Standard Deviation 6.19 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 14 | 62.2 International units per liter (IU/L) | Standard Deviation 6.97 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 35 | 66.3 International units per liter (IU/L) | Standard Deviation 12.8 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 4 | 23.2 International units per liter (IU/L) | Standard Deviation 17.47 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 2 | 16.3 International units per liter (IU/L) | Standard Deviation 8.31 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 3 | 16.0 International units per liter (IU/L) | Standard Deviation 7.56 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 7 | 16.8 International units per liter (IU/L) | Standard Deviation 5.38 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 14 | 18.0 International units per liter (IU/L) | Standard Deviation 6.13 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 21 | 18.7 International units per liter (IU/L) | Standard Deviation 5.28 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Baseline (Day 1) | 64.7 International units per liter (IU/L) | Standard Deviation 10.88 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 2 | 59.0 International units per liter (IU/L) | Standard Deviation 10.86 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 3 | 58.8 International units per liter (IU/L) | Standard Deviation 11.2 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 4 | 60.5 International units per liter (IU/L) | Standard Deviation 12.08 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 2 | 60.4 International units per liter (IU/L) | Standard Deviation 23.56 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 35 | 18.3 International units per liter (IU/L) | Standard Deviation 7.5 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Baseline (Day 1) | 15.1 International units per liter (IU/L) | Standard Deviation 4.85 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 21 | 18.3 International units per liter (IU/L) | Standard Deviation 8.09 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 7 | 61.7 International units per liter (IU/L) | Standard Deviation 17.18 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 28 | 17.0 International units per liter (IU/L) | Standard Deviation 6.04 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 21 | 62.2 International units per liter (IU/L) | Standard Deviation 29.88 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 3 | 15.8 International units per liter (IU/L) | Standard Deviation 7.65 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 5 | 14.8 International units per liter (IU/L) | Standard Deviation 3.92 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 4 | 15.3 International units per liter (IU/L) | Standard Deviation 3.83 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 4 | 60.5 International units per liter (IU/L) | Standard Deviation 19.36 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Baseline (Day 1) | 67.1 International units per liter (IU/L) | Standard Deviation 27.91 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 14 | 14.2 International units per liter (IU/L) | Standard Deviation 5.22 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 14 | 18.0 International units per liter (IU/L) | Standard Deviation 8.86 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 2 | 15.6 International units per liter (IU/L) | Standard Deviation 5.47 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 3 | 56.2 International units per liter (IU/L) | Standard Deviation 21.44 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 7 | 15.8 International units per liter (IU/L) | Standard Deviation 4.36 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 28 | 66.2 International units per liter (IU/L) | Standard Deviation 43.85 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 6 | 15.7 International units per liter (IU/L) | Standard Deviation 5.43 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 21 | 20.2 International units per liter (IU/L) | Standard Deviation 10.61 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 6 | 18.0 International units per liter (IU/L) | Standard Deviation 12.98 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 3 | 14.8 International units per liter (IU/L) | Standard Deviation 4.07 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 2 | 14.3 International units per liter (IU/L) | Standard Deviation 3.4 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 6 | 56.3 International units per liter (IU/L) | Standard Deviation 21.1 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 5 | 54.7 International units per liter (IU/L) | Standard Deviation 20.65 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 28 | 17.6 International units per liter (IU/L) | Standard Deviation 8.5 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 7 | 18.2 International units per liter (IU/L) | Standard Deviation 12.83 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Baseline (Day 1) | 15.1 International units per liter (IU/L) | Standard Deviation 4.14 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 4 | 16.7 International units per liter (IU/L) | Standard Deviation 8.94 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 35 | 62.3 International units per liter (IU/L) | Standard Deviation 28.22 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 14 | 59.6 International units per liter (IU/L) | Standard Deviation 19.49 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 35 | 17.8 International units per liter (IU/L) | Standard Deviation 8.35 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 5 | 17.0 International units per liter (IU/L) | Standard Deviation 10.84 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 35 | 63.8 International units per liter (IU/L) | Standard Deviation 23.56 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 6 | 24.2 International units per liter (IU/L) | Standard Deviation 13.27 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 49 | 23.3 International units per liter (IU/L) | Standard Deviation 6.15 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 7 | 24.7 International units per liter (IU/L) | Standard Deviation 14.9 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 28 | 65.5 International units per liter (IU/L) | Standard Deviation 22.95 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 14 | 29.8 International units per liter (IU/L) | Standard Deviation 21.29 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 21 | 24.5 International units per liter (IU/L) | Standard Deviation 10.54 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 28 | 24.2 International units per liter (IU/L) | Standard Deviation 9.5 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 35 | 23.5 International units per liter (IU/L) | Standard Deviation 5.75 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 21 | 66.0 International units per liter (IU/L) | Standard Deviation 22.33 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 42 | 25.5 International units per liter (IU/L) | Standard Deviation 6.02 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 49 | 27.8 International units per liter (IU/L) | Standard Deviation 9.85 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 2 | 16.5 International units per liter (IU/L) | Standard Deviation 3.78 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Baseline (Day 1) | 69.0 International units per liter (IU/L) | Standard Deviation 25.04 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 4 | 18.4 International units per liter (IU/L) | Standard Deviation 5.46 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 14 | 65.0 International units per liter (IU/L) | Standard Deviation 21.48 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 5 | 18.5 International units per liter (IU/L) | Standard Deviation 5.05 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 7 | 18.2 International units per liter (IU/L) | Standard Deviation 5.49 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 7 | 64.3 International units per liter (IU/L) | Standard Deviation 20.25 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 28 | 20.3 International units per liter (IU/L) | Standard Deviation 4.08 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 35 | 21.7 International units per liter (IU/L) | Standard Deviation 4.5 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 42 | 22.8 International units per liter (IU/L) | Standard Deviation 2.99 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 2 | 63.5 International units per liter (IU/L) | Standard Deviation 21.68 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 3 | 20.7 International units per liter (IU/L) | Standard Deviation 9.09 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 6 | 63.0 International units per liter (IU/L) | Standard Deviation 19.15 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 4 | 22.4 International units per liter (IU/L) | Standard Deviation 12.52 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Baseline (Day 1) | 17.5 International units per liter (IU/L) | Standard Deviation 3.62 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 3 | 16.7 International units per liter (IU/L) | Standard Deviation 3.44 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 6 | 17.7 International units per liter (IU/L) | Standard Deviation 5.57 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 4 | 58.6 International units per liter (IU/L) | Standard Deviation 18.84 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 14 | 20.7 International units per liter (IU/L) | Standard Deviation 7.81 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 3 | 63.0 International units per liter (IU/L) | Standard Deviation 21.25 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 49 | 67.2 International units per liter (IU/L) | Standard Deviation 27.21 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 21 | 19.5 International units per liter (IU/L) | Standard Deviation 3.78 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Baseline (Day 1) | 20.7 International units per liter (IU/L) | Standard Deviation 8.07 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 42 | 63.3 International units per liter (IU/L) | Standard Deviation 25.31 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 2 | 21.3 International units per liter (IU/L) | Standard Deviation 9.61 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 5 | 24.5 International units per liter (IU/L) | Standard Deviation 13.77 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 5 | 63.3 International units per liter (IU/L) | Standard Deviation 21.16 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 2 | 58.2 International units per liter (IU/L) | Standard Deviation 10.61 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 35 | 21.3 International units per liter (IU/L) | Standard Deviation 15.71 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 2 | 15.7 International units per liter (IU/L) | Standard Deviation 3.61 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 14 | 22.0 International units per liter (IU/L) | Standard Deviation 11.51 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 49 | 18.2 International units per liter (IU/L) | Standard Deviation 2.93 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 4 | 14.3 International units per liter (IU/L) | Standard Deviation 3.2 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 14 | 20.0 International units per liter (IU/L) | Standard Deviation 7.97 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 28 | 16.8 International units per liter (IU/L) | Standard Deviation 6.37 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 5 | 60.5 International units per liter (IU/L) | Standard Deviation 9.57 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 28 | 16.3 International units per liter (IU/L) | Standard Deviation 1.75 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 3 | 55.8 International units per liter (IU/L) | Standard Deviation 10.76 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Baseline (Day 1) | 15.0 International units per liter (IU/L) | Standard Deviation 3.03 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 35 | 64.7 International units per liter (IU/L) | Standard Deviation 9.14 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 2 | 15.0 International units per liter (IU/L) | Standard Deviation 2.97 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 35 | 18.5 International units per liter (IU/L) | Standard Deviation 4.32 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 6 | 62.3 International units per liter (IU/L) | Standard Deviation 10.01 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 14 | 66.4 International units per liter (IU/L) | Standard Deviation 12.72 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 49 | 66.7 International units per liter (IU/L) | Standard Deviation 11.5 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 21 | 17.3 International units per liter (IU/L) | Standard Deviation 2.94 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 21 | 61.5 International units per liter (IU/L) | Standard Deviation 12.05 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 4 | 13.3 International units per liter (IU/L) | Standard Deviation 2.42 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 4 | 63.2 International units per liter (IU/L) | Standard Deviation 10.57 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 42 | 66.2 International units per liter (IU/L) | Standard Deviation 9.54 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Baseline (Day 1) | 64.0 International units per liter (IU/L) | Standard Deviation 11.1 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 49 | 18.7 International units per liter (IU/L) | Standard Deviation 10.23 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 21 | 19.2 International units per liter (IU/L) | Standard Deviation 7.41 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 5 | 13.7 International units per liter (IU/L) | Standard Deviation 1.63 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 28 | 63.5 International units per liter (IU/L) | Standard Deviation 10.82 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 3 | 14.7 International units per liter (IU/L) | Standard Deviation 2.8 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 3 | 15.8 International units per liter (IU/L) | Standard Deviation 3.6 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 7 | 15.3 International units per liter (IU/L) | Standard Deviation 3.2 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 7 | 15.3 International units per liter (IU/L) | Standard Deviation 2.16 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 42 | 16.3 International units per liter (IU/L) | Standard Deviation 4.23 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 7 | 66.3 International units per liter (IU/L) | Standard Deviation 11.41 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 42 | 16.3 International units per liter (IU/L) | Standard Deviation 2.58 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 6 | 14.5 International units per liter (IU/L) | Standard Deviation 3.02 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 6 | 14.3 International units per liter (IU/L) | Standard Deviation 1.21 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 5 | 15.0 International units per liter (IU/L) | Standard Deviation 2.68 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Baseline (Day 1) | 14.8 International units per liter (IU/L) | Standard Deviation 2.93 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 4 | 16.2 International units per liter (IU/L) | Standard Deviation 4.12 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 28 | 16.8 International units per liter (IU/L) | Standard Deviation 1.94 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 3 | 52.5 International units per liter (IU/L) | Standard Deviation 10.29 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 35 | 16.8 International units per liter (IU/L) | Standard Deviation 3.7 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Baseline (Day 1) | 16.0 International units per liter (IU/L) | Standard Deviation 4.34 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 35 | 18.0 International units per liter (IU/L) | Standard Deviation 2.65 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 6 | 54.5 International units per liter (IU/L) | Standard Deviation 7.4 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 5 | 16.0 International units per liter (IU/L) | Standard Deviation 4.77 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 28 | 65.5 International units per liter (IU/L) | Standard Deviation 11.33 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 3 | 16.0 International units per liter (IU/L) | Standard Deviation 4.52 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 28 | 20.8 International units per liter (IU/L) | Standard Deviation 10.63 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 2 | 15.3 International units per liter (IU/L) | Standard Deviation 3.08 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Baseline (Day 1) | 16.5 International units per liter (IU/L) | Standard Deviation 3.51 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 21 | 59.2 International units per liter (IU/L) | Standard Deviation 8.7 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 2 | 54.5 International units per liter (IU/L) | Standard Deviation 9.73 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 21 | 22.2 International units per liter (IU/L) | Standard Deviation 15.66 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 35 | 62.8 International units per liter (IU/L) | Standard Deviation 8.07 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 3 | 15.2 International units per liter (IU/L) | Standard Deviation 2.14 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 49 | 18.0 International units per liter (IU/L) | Standard Deviation 5.22 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 6 | 16.7 International units per liter (IU/L) | Standard Deviation 2.34 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 5 | 57.7 International units per liter (IU/L) | Standard Deviation 9.16 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 6 | 18.8 International units per liter (IU/L) | Standard Deviation 7.96 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 14 | 22.7 International units per liter (IU/L) | Standard Deviation 13.87 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 14 | 17.5 International units per liter (IU/L) | Standard Deviation 3.62 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 7 | 20.8 International units per liter (IU/L) | Standard Deviation 10.28 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 42 | 63.2 International units per liter (IU/L) | Standard Deviation 9.79 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 2 | 15.8 International units per liter (IU/L) | Standard Deviation 2.71 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 14 | 61.3 International units per liter (IU/L) | Standard Deviation 8.62 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 49 | 17.2 International units per liter (IU/L) | Standard Deviation 5.23 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 49 | 59.7 International units per liter (IU/L) | Standard Deviation 6.41 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 4 | 15.5 International units per liter (IU/L) | Standard Deviation 2.81 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 42 | 16.8 International units per liter (IU/L) | Standard Deviation 3.19 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 5 | 15.8 International units per liter (IU/L) | Standard Deviation 2.14 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 7 | 56.8 International units per liter (IU/L) | Standard Deviation 7.44 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Baseline (Day 1) | 61.8 International units per liter (IU/L) | Standard Deviation 15.41 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 7 | 18.0 International units per liter (IU/L) | Standard Deviation 3.1 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 21 | 18.2 International units per liter (IU/L) | Standard Deviation 5.38 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 4 | 52.8 International units per liter (IU/L) | Standard Deviation 11.86 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 42 | 17.5 International units per liter (IU/L) | Standard Deviation 4.76 |
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.
Time frame: Up to Day 49
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 3 | 14.2956 Micromoles per liter (μmol/L) | Standard Deviation 6.7953 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 14 | 2.3598 Micromoles per liter (μmol/L) | Standard Deviation 0.77234 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 42 | 14.8485 Micromoles per liter (μmol/L) | Standard Deviation 12.01166 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 21 | 12.4317 Micromoles per liter (μmol/L) | Standard Deviation 5.82742 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 7 | 13.8510 Micromoles per liter (μmol/L) | Standard Deviation 7.2118 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 5 | 2.7360 Micromoles per liter (μmol/L) | Standard Deviation 1.18198 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 2 | 14.8770 Micromoles per liter (μmol/L) | Standard Deviation 7.69405 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Baseline (Day 1) | 2.5650 Micromoles per liter (μmol/L) | Standard Deviation 1.20915 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 7 | 2.8899 Micromoles per liter (μmol/L) | Standard Deviation 1.24216 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Baseline (Day 1) | 13.1670 Micromoles per liter (μmol/L) | Standard Deviation 6.84237 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 14 | 10.4139 Micromoles per liter (μmol/L) | Standard Deviation 2.46942 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 6 | 2.5650 Micromoles per liter (μmol/L) | Standard Deviation 0.684 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 42 | 2.9355 Micromoles per liter (μmol/L) | Standard Deviation 2.10105 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 28 | 2.8215 Micromoles per liter (μmol/L) | Standard Deviation 1.674 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 35 | 2.3598 Micromoles per liter (μmol/L) | Standard Deviation 1.25348 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 21 | 2.5308 Micromoles per liter (μmol/L) | Standard Deviation 1.19238 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 5 | 13.5603 Micromoles per liter (μmol/L) | Standard Deviation 6.89113 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 4 | 13.6287 Micromoles per liter (μmol/L) | Standard Deviation 8.26482 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 28 | 13.1670 Micromoles per liter (μmol/L) | Standard Deviation 9.01537 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 3 | 2.7018 Micromoles per liter (μmol/L) | Standard Deviation 1.15078 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 49 | 2.9355 Micromoles per liter (μmol/L) | Standard Deviation 1.48452 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 6 | 12.9618 Micromoles per liter (μmol/L) | Standard Deviation 4.88926 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 49 | 14.0505 Micromoles per liter (μmol/L) | Standard Deviation 7.95429 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 35 | 12.0042 Micromoles per liter (μmol/L) | Standard Deviation 7.3796 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 2 | 2.7170 Micromoles per liter (μmol/L) | Standard Deviation 1.2462 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 4 | 2.4966 Micromoles per liter (μmol/L) | Standard Deviation 1.36847 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 6 | 12.1125 Micromoles per liter (μmol/L) | Standard Deviation 3.9299 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 4 | 9.4620 Micromoles per liter (μmol/L) | Standard Deviation 3.81091 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 3 | 11.7705 Micromoles per liter (μmol/L) | Standard Deviation 3.38635 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Baseline (Day 1) | 12.5400 Micromoles per liter (μmol/L) | Standard Deviation 3.84908 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 2 | 2.5080 Micromoles per liter (μmol/L) | Standard Deviation 0.59891 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 2 | 11.9130 Micromoles per liter (μmol/L) | Standard Deviation 3.49052 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 28 | 9.1200 Micromoles per liter (μmol/L) | Standard Deviation 4.86394 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 3 | 2.4795 Micromoles per liter (μmol/L) | Standard Deviation 0.51584 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 21 | 9.6045 Micromoles per liter (μmol/L) | Standard Deviation 5.04078 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 4 | 2.0235 Micromoles per liter (μmol/L) | Standard Deviation 0.79043 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 5 | 2.6505 Micromoles per liter (μmol/L) | Standard Deviation 0.63753 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 14 | 6.7545 Micromoles per liter (μmol/L) | Standard Deviation 3.25125 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 6 | 2.6505 Micromoles per liter (μmol/L) | Standard Deviation 0.69038 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 35 | 8.5785 Micromoles per liter (μmol/L) | Standard Deviation 3.90002 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 7 | 10.6020 Micromoles per liter (μmol/L) | Standard Deviation 3.2535 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 7 | 2.4795 Micromoles per liter (μmol/L) | Standard Deviation 0.63753 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 14 | 1.7100 Micromoles per liter (μmol/L) | Standard Deviation 0 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Baseline (Day 1) | 1.9950 Micromoles per liter (μmol/L) | Standard Deviation 0.6981 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 21 | 2.1375 Micromoles per liter (μmol/L) | Standard Deviation 0.95974 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 5 | 11.6565 Micromoles per liter (μmol/L) | Standard Deviation 3.15571 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 28 | 2.0805 Micromoles per liter (μmol/L) | Standard Deviation 0.97585 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 35 | 2.1090 Micromoles per liter (μmol/L) | Standard Deviation 0.6981 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 6 | 9.6330 Micromoles per liter (μmol/L) | Standard Deviation 3.97319 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 4 | 2.7360 Micromoles per liter (μmol/L) | Standard Deviation 0.87193 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 2 | 13.4357 Micromoles per liter (μmol/L) | Standard Deviation 4.91245 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 14 | 1.5732 Micromoles per liter (μmol/L) | Standard Deviation 0.37072 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 3 | 12.1410 Micromoles per liter (μmol/L) | Standard Deviation 4.37573 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 21 | 10.2885 Micromoles per liter (μmol/L) | Standard Deviation 3.37424 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 3 | 2.7075 Micromoles per liter (μmol/L) | Standard Deviation 0.98776 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 2 | 2.9559 Micromoles per liter (μmol/L) | Standard Deviation 1.17113 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 4 | 14.2215 Micromoles per liter (μmol/L) | Standard Deviation 6.54322 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 21 | 2.3085 Micromoles per liter (μmol/L) | Standard Deviation 0.94747 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Baseline (Day 1) | 2.9314 Micromoles per liter (μmol/L) | Standard Deviation 0.83439 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 5 | 11.8275 Micromoles per liter (μmol/L) | Standard Deviation 4.79461 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 28 | 10.1916 Micromoles per liter (μmol/L) | Standard Deviation 4.40238 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 6 | 2.3085 Micromoles per liter (μmol/L) | Standard Deviation 0.77045 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Baseline (Day 1) | 14.9014 Micromoles per liter (μmol/L) | Standard Deviation 3.65613 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 7 | 9.9465 Micromoles per liter (μmol/L) | Standard Deviation 2.5373 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 35 | 2.2800 Micromoles per liter (μmol/L) | Standard Deviation 0.91556 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 35 | 10.0605 Micromoles per liter (μmol/L) | Standard Deviation 3.87143 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 28 | 2.3256 Micromoles per liter (μmol/L) | Standard Deviation 0.81651 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 7 | 2.2800 Micromoles per liter (μmol/L) | Standard Deviation 0.70643 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 5 | 2.5080 Micromoles per liter (μmol/L) | Standard Deviation 0.73085 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 14 | 7.2846 Micromoles per liter (μmol/L) | Standard Deviation 2.33087 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 49 | 8.8350 Micromoles per liter (μmol/L) | Standard Deviation 3.94512 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Baseline (Day 1) | 2.2800 Micromoles per liter (μmol/L) | Standard Deviation 1.39621 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 2 | 2.0520 Micromoles per liter (μmol/L) | Standard Deviation 1.03734 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 3 | 1.8525 Micromoles per liter (μmol/L) | Standard Deviation 1.07834 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 4 | 1.9836 Micromoles per liter (μmol/L) | Standard Deviation 0.73151 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 5 | 1.9665 Micromoles per liter (μmol/L) | Standard Deviation 0.81472 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 6 | 1.7955 Micromoles per liter (μmol/L) | Standard Deviation 0.89673 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 7 | 1.9095 Micromoles per liter (μmol/L) | Standard Deviation 0.75253 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 14 | 1.6245 Micromoles per liter (μmol/L) | Standard Deviation 0.86351 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 21 | 1.4250 Micromoles per liter (μmol/L) | Standard Deviation 0.49166 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 28 | 1.6530 Micromoles per liter (μmol/L) | Standard Deviation 0.5149 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 35 | 1.7385 Micromoles per liter (μmol/L) | Standard Deviation 0.83364 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 42 | 1.6530 Micromoles per liter (μmol/L) | Standard Deviation 0.6981 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 49 | 1.5675 Micromoles per liter (μmol/L) | Standard Deviation 0.58657 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Baseline (Day 1) | 12.2550 Micromoles per liter (μmol/L) | Standard Deviation 8.47558 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 2 | 10.7730 Micromoles per liter (μmol/L) | Standard Deviation 6.63074 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 3 | 10.4595 Micromoles per liter (μmol/L) | Standard Deviation 7.28983 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 4 | 10.6704 Micromoles per liter (μmol/L) | Standard Deviation 7.32172 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 5 | 10.6875 Micromoles per liter (μmol/L) | Standard Deviation 5.85984 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 6 | 9.3480 Micromoles per liter (μmol/L) | Standard Deviation 6.12902 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 7 | 10.7160 Micromoles per liter (μmol/L) | Standard Deviation 5.72854 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 14 | 7.9515 Micromoles per liter (μmol/L) | Standard Deviation 4.3405 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 21 | 7.5525 Micromoles per liter (μmol/L) | Standard Deviation 3.3898 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 28 | 7.9800 Micromoles per liter (μmol/L) | Standard Deviation 2.9572 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 35 | 8.4360 Micromoles per liter (μmol/L) | Standard Deviation 4.45476 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 42 | 8.2080 Micromoles per liter (μmol/L) | Standard Deviation 4.2907 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 14 | 2.2230 Micromoles per liter (μmol/L) | Standard Deviation 0.29618 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 28 | 3.2490 Micromoles per liter (μmol/L) | Standard Deviation 1.34646 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 14 | 11.1150 Micromoles per liter (μmol/L) | Standard Deviation 0.91289 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 21 | 12.4830 Micromoles per liter (μmol/L) | Standard Deviation 4.36636 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 4 | 2.2515 Micromoles per liter (μmol/L) | Standard Deviation 1.11566 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 6 | 13.9365 Micromoles per liter (μmol/L) | Standard Deviation 7.53701 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 3 | 2.3655 Micromoles per liter (μmol/L) | Standard Deviation 0.87472 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 42 | 15.5895 Micromoles per liter (μmol/L) | Standard Deviation 10.02324 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 21 | 2.4795 Micromoles per liter (μmol/L) | Standard Deviation 0.83598 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 2 | 2.7360 Micromoles per liter (μmol/L) | Standard Deviation 0.93661 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 7 | 2.3370 Micromoles per liter (μmol/L) | Standard Deviation 1.26894 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 35 | 11.3715 Micromoles per liter (μmol/L) | Standard Deviation 7.28046 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 28 | 16.7580 Micromoles per liter (μmol/L) | Standard Deviation 9.7455 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 6 | 2.3655 Micromoles per liter (μmol/L) | Standard Deviation 0.98182 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Baseline (Day 1) | 2.2800 Micromoles per liter (μmol/L) | Standard Deviation 0.88304 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Baseline (Day 1) | 11.6850 Micromoles per liter (μmol/L) | Standard Deviation 5.00498 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 5 | 15.7320 Micromoles per liter (μmol/L) | Standard Deviation 7.0447 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 7 | 16.6725 Micromoles per liter (μmol/L) | Standard Deviation 8.2064 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 2 | 17.9835 Micromoles per liter (μmol/L) | Standard Deviation 7.41865 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 4 | 15.8460 Micromoles per liter (μmol/L) | Standard Deviation 5.98125 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 49 | 2.6505 Micromoles per liter (μmol/L) | Standard Deviation 1.15852 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 35 | 2.2800 Micromoles per liter (μmol/L) | Standard Deviation 1.00682 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 42 | 2.7360 Micromoles per liter (μmol/L) | Standard Deviation 1.38499 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 49 | 14.8200 Micromoles per liter (μmol/L) | Standard Deviation 6.47967 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 3 | 15.5040 Micromoles per liter (μmol/L) | Standard Deviation 7.42594 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 5 | 2.8215 Micromoles per liter (μmol/L) | Standard Deviation 0.75512 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 3 | 15.5895 Micromoles per liter (μmol/L) | Standard Deviation 6.56018 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 28 | 2.3370 Micromoles per liter (μmol/L) | Standard Deviation 0.88304 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 4 | 13.5090 Micromoles per liter (μmol/L) | Standard Deviation 6.44718 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 21 | 2.0520 Micromoles per liter (μmol/L) | Standard Deviation 0.98529 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 5 | 14.7345 Micromoles per liter (μmol/L) | Standard Deviation 5.17813 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 14 | 2.6790 Micromoles per liter (μmol/L) | Standard Deviation 1.60291 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 7 | 2.5935 Micromoles per liter (μmol/L) | Standard Deviation 0.9577 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 35 | 8.7552 Micromoles per liter (μmol/L) | Standard Deviation 2.95786 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 6 | 14.3640 Micromoles per liter (μmol/L) | Standard Deviation 5.24388 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 6 | 2.8785 Micromoles per liter (μmol/L) | Standard Deviation 1.1719 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 21 | 8.9205 Micromoles per liter (μmol/L) | Standard Deviation 3.9492 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 7 | 12.5400 Micromoles per liter (μmol/L) | Standard Deviation 4.43239 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 5 | 2.8215 Micromoles per liter (μmol/L) | Standard Deviation 0.98381 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 4 | 2.6790 Micromoles per liter (μmol/L) | Standard Deviation 1.0241 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Baseline (Day 1) | 10.8300 Micromoles per liter (μmol/L) | Standard Deviation 5.26132 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 14 | 11.7990 Micromoles per liter (μmol/L) | Standard Deviation 7.42857 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 3 | 3.0495 Micromoles per liter (μmol/L) | Standard Deviation 1.23033 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 2 | 3.0780 Micromoles per liter (μmol/L) | Standard Deviation 1.27507 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Baseline (Day 1) | 2.8500 Micromoles per liter (μmol/L) | Standard Deviation 0.88304 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 42 | 12.9675 Micromoles per liter (μmol/L) | Standard Deviation 6.50917 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 28 | 11.4000 Micromoles per liter (μmol/L) | Standard Deviation 3.21674 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 49 | 2.6505 Micromoles per liter (μmol/L) | Standard Deviation 1.49759 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 49 | 12.7680 Micromoles per liter (μmol/L) | Standard Deviation 8.27588 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 2 | 16.2735 Micromoles per liter (μmol/L) | Standard Deviation 7.49161 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 42 | 2.7645 Micromoles per liter (μmol/L) | Standard Deviation 1.44053 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 35 | 1.9494 Micromoles per liter (μmol/L) | Standard Deviation 0.7609 |
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.
Time frame: Day 1 to Day 49
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Apparent Terminal Half-life (T1/2) Following Single Dose Administration of VH4004280 | 145.82 hours | Geometric Coefficient of Variation 40.6 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Apparent Terminal Half-life (T1/2) Following Single Dose Administration of VH4004280 | 149.91 hours | Geometric Coefficient of Variation 40.4 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Apparent Terminal Half-life (T1/2) Following Single Dose Administration of VH4004280 | 149.94 hours | Geometric Coefficient of Variation 43.47 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Apparent Terminal Half-life (T1/2) Following Single Dose Administration of VH4004280 | 177.58 hours | Geometric Coefficient of Variation 18.23 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Apparent Terminal Half-life (T1/2) Following Single Dose Administration of VH4004280 | 172.66 hours | Geometric Coefficient of Variation 29.45 |
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.
Time frame: At Day 1
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC[0-infinity]) Following Single Dose Administration of VH4004280 | 1396.25 Hour nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 28.02 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC[0-infinity]) Following Single Dose Administration of VH4004280 | 16829.76 Hour nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 17.59 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC[0-infinity]) Following Single Dose Administration of VH4004280 | 51168.22 Hour nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 51.76 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC[0-infinity]) Following Single Dose Administration of VH4004280 | 174441.72 Hour nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 33.21 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC[0-infinity]) Following Single Dose Administration of VH4004280 | 215339.87 Hour nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 42.9 |
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.
Time frame: From Baseline (Day 1) and up to Day 49
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 14 | 7.7 IU/L | Standard Deviation 16.96 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Baseline (Day 1) | 18.4 IU/L | Standard Deviation 5.6 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 7 | 1.5 IU/L | Standard Deviation 11.65 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 2 | -0.1 IU/L | Standard Deviation 4.81 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 3 | 0.2 IU/L | Standard Deviation 6.34 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 5 | -0.3 IU/L | Standard Deviation 7.97 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 4 | 0.8 IU/L | Standard Deviation 7.13 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 49 | -0.7 IU/L | Standard Deviation 1.75 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 14 | 22.7 IU/L | Standard Deviation 70.63 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 6 | 0.5 IU/L | Standard Deviation 9.57 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 42 | -1.0 IU/L | Standard Deviation 2.53 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 35 | 1.4 IU/L | Standard Deviation 9.88 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 2 | -4.2 IU/L | Standard Deviation 5.74 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 7 | -0.8 IU/L | Standard Deviation 5.87 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 42 | -1.7 IU/L | Standard Deviation 3.78 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 6 | -1.7 IU/L | Standard Deviation 5.12 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 28 | -0.5 IU/L | Standard Deviation 4.88 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 5 | -2.5 IU/L | Standard Deviation 4.48 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 4 | -1.5 IU/L | Standard Deviation 3.95 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 35 | 0.1 IU/L | Standard Deviation 2.96 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Baseline (Day 1) | 51.8 IU/L | Standard Deviation 9.39 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 5 | -3.7 IU/L | Standard Deviation 3.47 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 3 | -0.9 IU/L | Standard Deviation 3.25 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 6 | -3.0 IU/L | Standard Deviation 4.92 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 2 | -0.1 IU/L | Standard Deviation 3.69 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 7 | -0.1 IU/L | Standard Deviation 6.95 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 3 | -3.6 IU/L | Standard Deviation 5.97 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 14 | 3.0 IU/L | Standard Deviation 5.96 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Baseline (Day 1) | 17.3 IU/L | Standard Deviation 5.03 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 49 | -0.8 IU/L | Standard Deviation 2.64 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 21 | 1.2 IU/L | Standard Deviation 3.49 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 28 | 2.1 IU/L | Standard Deviation 7.29 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 28 | 1.7 IU/L | Standard Deviation 10.22 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 35 | 1.1 IU/L | Standard Deviation 4.07 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 21 | 0.6 IU/L | Standard Deviation 7.37 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 21 | 5.0 IU/L | Standard Deviation 14.54 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 42 | -1.8 IU/L | Standard Deviation 5.78 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 49 | -1.2 IU/L | Standard Deviation 4.45 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 4 | -2.5 IU/L | Standard Deviation 6.19 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 2 | -5.7 IU/L | Standard Deviation 2.88 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 6 | -1.3 IU/L | Standard Deviation 2.34 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 5 | -2.5 IU/L | Standard Deviation 2.43 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 21 | -6.0 IU/L | Standard Deviation 2.28 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 28 | 5.7 IU/L | Standard Deviation 6.56 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 35 | 3.2 IU/L | Standard Deviation 5.31 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 28 | 10.8 IU/L | Standard Deviation 20.21 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 3 | -1.3 IU/L | Standard Deviation 2.94 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 21 | 0.7 IU/L | Standard Deviation 4.76 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 5 | -5.5 IU/L | Standard Deviation 4.42 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 28 | -7.2 IU/L | Standard Deviation 7.33 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 6 | -2.2 IU/L | Standard Deviation 3.66 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 21 | 1.3 IU/L | Standard Deviation 1.75 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 2 | -1.0 IU/L | Standard Deviation 3.1 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Baseline (Day 1) | 22.8 IU/L | Standard Deviation 11.72 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 4 | -4.2 IU/L | Standard Deviation 4.92 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 7 | 0.7 IU/L | Standard Deviation 5.61 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Baseline (Day 1) | 64.7 IU/L | Standard Deviation 10.88 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 2 | -0.8 IU/L | Standard Deviation 5.64 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 6 | -0.3 IU/L | Standard Deviation 5.85 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 7 | -0.3 IU/L | Standard Deviation 5.79 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 3 | -0.7 IU/L | Standard Deviation 6.44 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 5 | -1.2 IU/L | Standard Deviation 6.18 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 4 | 0.3 IU/L | Standard Deviation 6.38 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 14 | 0.7 IU/L | Standard Deviation 3.5 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Baseline (Day 1) | 17.3 IU/L | Standard Deviation 5.82 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 14 | 4.5 IU/L | Standard Deviation 11.26 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 14 | -2.5 IU/L | Standard Deviation 5.61 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 7 | -0.5 IU/L | Standard Deviation 2.95 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 35 | 5.7 IU/L | Standard Deviation 9.54 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 3 | -5.8 IU/L | Standard Deviation 3.97 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 35 | 1.7 IU/L | Standard Deviation 5.54 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 4 | -0.7 IU/L | Standard Deviation 3.01 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 5 | 2.7 IU/L | Standard Deviation 9.37 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Baseline (Day 1) | 15.1 IU/L | Standard Deviation 4.14 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 14 | 0.6 IU/L | Standard Deviation 3.05 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 21 | 4.5 IU/L | Standard Deviation 6.35 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 2 | -6.7 IU/L | Standard Deviation 5.53 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 5 | 1.0 IU/L | Standard Deviation 3.22 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 14 | 5.2 IU/L | Standard Deviation 6.72 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 14 | -6.8 IU/L | Standard Deviation 15.22 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 2 | 0.4 IU/L | Standard Deviation 4.28 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 28 | 3.4 IU/L | Standard Deviation 3.97 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Baseline (Day 1) | 67.1 IU/L | Standard Deviation 27.91 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 21 | -3.5 IU/L | Standard Deviation 6.8 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 3 | -9.5 IU/L | Standard Deviation 9.54 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 28 | 4.8 IU/L | Standard Deviation 5.63 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 4 | -5.2 IU/L | Standard Deviation 12.46 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 6 | 3.7 IU/L | Standard Deviation 11.29 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 3 | 1.0 IU/L | Standard Deviation 3.69 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 6 | 1.8 IU/L | Standard Deviation 4.92 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 35 | 3.5 IU/L | Standard Deviation 4.76 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 35 | -3.3 IU/L | Standard Deviation 6.83 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 5 | -11.0 IU/L | Standard Deviation 10.33 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 35 | 4.5 IU/L | Standard Deviation 5.58 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 3 | 1.5 IU/L | Standard Deviation 6.09 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 2 | -0.9 IU/L | Standard Deviation 4.34 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 28 | -0.2 IU/L | Standard Deviation 12.72 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 7 | 2.0 IU/L | Standard Deviation 3.22 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 6 | -9.3 IU/L | Standard Deviation 11.66 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 7 | -4.0 IU/L | Standard Deviation 14.86 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 7 | 3.8 IU/L | Standard Deviation 10.87 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 4 | 2.3 IU/L | Standard Deviation 7.37 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 21 | 5.8 IU/L | Standard Deviation 8.42 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Baseline (Day 1) | 15.1 IU/L | Standard Deviation 4.85 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 4 | 1.5 IU/L | Standard Deviation 2.81 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 4 | -5.4 IU/L | Standard Deviation 7.3 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Baseline (Day 1) | 69.0 IU/L | Standard Deviation 25.04 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 2 | -5.5 IU/L | Standard Deviation 5.09 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 3 | -6.0 IU/L | Standard Deviation 6.2 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 5 | 3.8 IU/L | Standard Deviation 6.43 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 28 | 3.5 IU/L | Standard Deviation 4.09 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 35 | 2.8 IU/L | Standard Deviation 5.49 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 4 | 1.0 IU/L | Standard Deviation 2.83 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 21 | 2.0 IU/L | Standard Deviation 3.63 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 28 | 2.8 IU/L | Standard Deviation 3.31 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 5 | -5.7 IU/L | Standard Deviation 8.04 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 6 | -6.0 IU/L | Standard Deviation 6.63 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 7 | -4.7 IU/L | Standard Deviation 5.5 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 14 | -4.0 IU/L | Standard Deviation 5.18 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 21 | -3.0 IU/L | Standard Deviation 9.55 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 28 | -3.5 IU/L | Standard Deviation 5.89 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 35 | -5.2 IU/L | Standard Deviation 7.11 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 42 | -5.7 IU/L | Standard Deviation 3.67 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 49 | -1.8 IU/L | Standard Deviation 5.85 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Baseline (Day 1) | 20.7 IU/L | Standard Deviation 8.07 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 2 | 0.7 IU/L | Standard Deviation 1.75 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 3 | 0.0 IU/L | Standard Deviation 1.26 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 4 | 2.6 IU/L | Standard Deviation 3.85 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 6 | 3.5 IU/L | Standard Deviation 6.72 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 7 | 4.0 IU/L | Standard Deviation 7.97 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 14 | 9.2 IU/L | Standard Deviation 14.58 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 21 | 3.8 IU/L | Standard Deviation 4.54 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 42 | 4.8 IU/L | Standard Deviation 7.7 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 49 | 7.2 IU/L | Standard Deviation 8.5 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Baseline (Day 1) | 17.5 IU/L | Standard Deviation 3.62 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 2 | -1.0 IU/L | Standard Deviation 0.89 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 3 | -0.8 IU/L | Standard Deviation 2.23 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 5 | 1.0 IU/L | Standard Deviation 2.83 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 6 | 0.2 IU/L | Standard Deviation 4.17 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 7 | 0.7 IU/L | Standard Deviation 2.73 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 14 | 3.2 IU/L | Standard Deviation 5.12 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 35 | 4.2 IU/L | Standard Deviation 5.34 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 42 | 5.3 IU/L | Standard Deviation 4.72 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 49 | 5.8 IU/L | Standard Deviation 4.07 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 3 | -8.2 IU/L | Standard Deviation 4.36 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 28 | 1.3 IU/L | Standard Deviation 3.27 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 14 | 2.0 IU/L | Standard Deviation 7.04 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 21 | 2.3 IU/L | Standard Deviation 3.01 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 49 | 3.2 IU/L | Standard Deviation 4.71 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 5 | -1.3 IU/L | Standard Deviation 2.07 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 28 | -0.5 IU/L | Standard Deviation 4.51 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 7 | 2.3 IU/L | Standard Deviation 4.23 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 4 | -1.7 IU/L | Standard Deviation 2.07 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 35 | 3.5 IU/L | Standard Deviation 6.57 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 42 | 1.3 IU/L | Standard Deviation 1.37 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 6 | -0.7 IU/L | Standard Deviation 2.5 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Baseline (Day 1) | 15.0 IU/L | Standard Deviation 3.03 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 35 | 6.5 IU/L | Standard Deviation 15.36 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 35 | 0.7 IU/L | Standard Deviation 7.2 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 28 | 2.0 IU/L | Standard Deviation 4.34 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 21 | -2.5 IU/L | Standard Deviation 4.59 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 7 | 0.3 IU/L | Standard Deviation 1.63 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 6 | -1.7 IU/L | Standard Deviation 2.8 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 2 | -5.8 IU/L | Standard Deviation 3.97 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 5 | 0.2 IU/L | Standard Deviation 2.93 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 42 | 1.5 IU/L | Standard Deviation 3.62 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 2 | 0.0 IU/L | Standard Deviation 3.29 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Baseline (Day 1) | 64.0 IU/L | Standard Deviation 11.1 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 4 | -0.5 IU/L | Standard Deviation 3.73 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 14 | 6.2 IU/L | Standard Deviation 11.63 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 3 | 1.0 IU/L | Standard Deviation 3.79 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 5 | -3.5 IU/L | Standard Deviation 3.62 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 2 | 0.8 IU/L | Standard Deviation 3.66 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 14 | 4.6 IU/L | Standard Deviation 6.11 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 6 | -0.3 IU/L | Standard Deviation 3.98 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 42 | 2.2 IU/L | Standard Deviation 6.74 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 4 | -0.8 IU/L | Standard Deviation 2.86 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Baseline (Day 1) | 14.8 IU/L | Standard Deviation 2.93 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 21 | 4.3 IU/L | Standard Deviation 5.16 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 3 | -0.3 IU/L | Standard Deviation 2.5 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 7 | 0.5 IU/L | Standard Deviation 4.51 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 49 | 3.8 IU/L | Standard Deviation 9.75 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 49 | 2.7 IU/L | Standard Deviation 9.35 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 35 | 2.4 IU/L | Standard Deviation 2.41 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 14 | 6.7 IU/L | Standard Deviation 10.03 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 35 | -0.6 IU/L | Standard Deviation 9.07 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 28 | 3.7 IU/L | Standard Deviation 17.44 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 2 | -7.3 IU/L | Standard Deviation 7.23 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 21 | 6.2 IU/L | Standard Deviation 11.63 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 21 | -2.7 IU/L | Standard Deviation 10.01 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 42 | 1.5 IU/L | Standard Deviation 2.74 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 14 | -0.5 IU/L | Standard Deviation 8.29 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 49 | 1.5 IU/L | Standard Deviation 5.82 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 49 | 1.2 IU/L | Standard Deviation 4.22 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 7 | -5.0 IU/L | Standard Deviation 9.49 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Baseline (Day 1) | 16.5 IU/L | Standard Deviation 3.51 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 6 | -7.3 IU/L | Standard Deviation 10.56 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 5 | -4.2 IU/L | Standard Deviation 9.2 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 35 | 1.0 IU/L | Standard Deviation 1.58 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 2 | -0.7 IU/L | Standard Deviation 1.51 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 4 | -9.0 IU/L | Standard Deviation 5.06 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Baseline (Day 1) | 61.8 IU/L | Standard Deviation 15.41 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 3 | -1.3 IU/L | Standard Deviation 2.42 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 28 | 0.3 IU/L | Standard Deviation 4.68 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 21 | 1.7 IU/L | Standard Deviation 7.2 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 5 | -0.7 IU/L | Standard Deviation 2.34 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 4 | -1.0 IU/L | Standard Deviation 3.22 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 42 | 1.3 IU/L | Standard Deviation 6.44 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 6 | 0.2 IU/L | Standard Deviation 3.54 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 28 | 4.8 IU/L | Standard Deviation 6.88 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 42 | 0.3 IU/L | Standard Deviation 3.61 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 7 | 1.5 IU/L | Standard Deviation 4.23 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 5 | 0.0 IU/L | Standard Deviation 2.83 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 3 | -9.3 IU/L | Standard Deviation 6.47 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 3 | 0.0 IU/L | Standard Deviation 1.79 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 4 | 0.2 IU/L | Standard Deviation 2.14 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 2 | -0.7 IU/L | Standard Deviation 1.86 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 6 | 2.8 IU/L | Standard Deviation 4.96 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Baseline (Day 1) | 16.0 IU/L | Standard Deviation 4.34 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 49 | -2.2 IU/L | Standard Deviation 10.46 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 14 | 1.0 IU/L | Standard Deviation 1.79 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 7 | 4.8 IU/L | Standard Deviation 7.03 |
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.
Time frame: From Baseline (Day 1) and up to Day 49
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 6 | -0.2052 μmol/L | Standard Deviation 6.38797 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Baseline (Day 1) | 2.5650 μmol/L | Standard Deviation 1.20915 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 2 | 1.5770 μmol/L | Standard Deviation 4.50462 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 3 | 1.1286 μmol/L | Standard Deviation 4.54801 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 5 | 0.3933 μmol/L | Standard Deviation 5.87628 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 4 | 0.4617 μmol/L | Standard Deviation 5.19048 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 49 | -0.7695 μmol/L | Standard Deviation 4.6927 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 42 | 0.0285 μmol/L | Standard Deviation 5.67701 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 4 | -0.0684 μmol/L | Standard Deviation 1.09107 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 5 | 0.1710 μmol/L | Standard Deviation 1.19564 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 35 | -1.1628 μmol/L | Standard Deviation 4.21939 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 6 | 0.0000 μmol/L | Standard Deviation 1.01004 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 2 | 0.0570 μmol/L | Standard Deviation 0.80206 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 7 | 0.3249 μmol/L | Standard Deviation 1.18869 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 28 | 0.0000 μmol/L | Standard Deviation 4.73683 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 14 | -0.2052 μmol/L | Standard Deviation 1.04109 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 21 | -0.7353 μmol/L | Standard Deviation 3.99004 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 28 | 0.2565 μmol/L | Standard Deviation 1.3757 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 35 | -0.2052 μmol/L | Standard Deviation 1.10174 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 14 | -2.7531 μmol/L | Standard Deviation 6.09471 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 42 | 0.0855 μmol/L | Standard Deviation 1.41321 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 7 | 0.6840 μmol/L | Standard Deviation 5.49629 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 49 | 0.0855 μmol/L | Standard Deviation 1.19333 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 21 | -0.0342 μmol/L | Standard Deviation 1.03168 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Baseline (Day 1) | 13.1670 μmol/L | Standard Deviation 6.84237 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 3 | 0.1368 μmol/L | Standard Deviation 0.87861 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 3 | 0.4845 μmol/L | Standard Deviation 0.47656 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 6 | 0.6555 μmol/L | Standard Deviation 0.45134 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 5 | -0.8835 μmol/L | Standard Deviation 0.97585 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 28 | 0.0855 μmol/L | Standard Deviation 0.63753 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 3 | -0.7695 μmol/L | Standard Deviation 1.10159 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 2 | 0.5130 μmol/L | Standard Deviation 0.47141 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 28 | -3.4200 μmol/L | Standard Deviation 1.69626 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Baseline (Day 1) | 12.5400 μmol/L | Standard Deviation 3.84908 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 21 | 0.1425 μmol/L | Standard Deviation 0.80509 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 14 | -0.2850 μmol/L | Standard Deviation 0.6981 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 4 | -3.0780 μmol/L | Standard Deviation 1.471 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Baseline (Day 1) | 1.9950 μmol/L | Standard Deviation 0.6981 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 7 | 0.4845 μmol/L | Standard Deviation 0.60619 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 14 | -5.7855 μmol/L | Standard Deviation 1.36978 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 21 | -2.9355 μmol/L | Standard Deviation 2.88664 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 4 | 0.0285 μmol/L | Standard Deviation 0.39614 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 7 | -1.9380 μmol/L | Standard Deviation 1.87841 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 6 | -0.4275 μmol/L | Standard Deviation 0.98973 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 2 | -0.6270 μmol/L | Standard Deviation 1.14285 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 35 | -3.9615 μmol/L | Standard Deviation 1.41183 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 35 | 0.1140 μmol/L | Standard Deviation 0.27924 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 5 | 0.6555 μmol/L | Standard Deviation 0.36542 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 3 | -2.9640 μmol/L | Standard Deviation 1.07426 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 21 | -0.5415 μmol/L | Standard Deviation 0.86125 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 35 | -0.5700 μmol/L | Standard Deviation 0.84928 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Baseline (Day 1) | 2.9314 μmol/L | Standard Deviation 0.83439 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 6 | -0.5415 μmol/L | Standard Deviation 0.45134 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 28 | -3.8304 μmol/L | Standard Deviation 2.83984 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 7 | -5.1585 μmol/L | Standard Deviation 3.43777 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 7 | -0.5700 μmol/L | Standard Deviation 0.70643 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 6 | -5.4720 μmol/L | Standard Deviation 3.7433 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 21 | -4.8165 μmol/L | Standard Deviation 3.47667 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 14 | -1.1628 μmol/L | Standard Deviation 1.04995 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 5 | -3.2775 μmol/L | Standard Deviation 4.3198 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 5 | -0.3420 μmol/L | Standard Deviation 0.83072 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 3 | -0.1425 μmol/L | Standard Deviation 0.62518 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 28 | -0.4104 μmol/L | Standard Deviation 0.44591 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 4 | -0.8835 μmol/L | Standard Deviation 3.77816 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 2 | 0.0244 μmol/L | Standard Deviation 0.96948 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 14 | -6.7374 μmol/L | Standard Deviation 3.07705 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Baseline (Day 1) | 14.9014 μmol/L | Standard Deviation 3.65613 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 4 | -0.1140 μmol/L | Standard Deviation 0.6981 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 2 | -1.4657 μmol/L | Standard Deviation 2.08465 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 35 | -5.0445 μmol/L | Standard Deviation 4.68272 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 5 | -1.5675 μmol/L | Standard Deviation 2.7835 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Baseline (Day 1) | 2.2800 μmol/L | Standard Deviation 1.39621 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 2 | -0.2280 μmol/L | Standard Deviation 0.46726 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 3 | -0.4275 μmol/L | Standard Deviation 0.51584 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 4 | -0.4104 μmol/L | Standard Deviation 0.84295 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 5 | -0.3135 μmol/L | Standard Deviation 0.62518 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 6 | -0.4845 μmol/L | Standard Deviation 0.54524 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 7 | -0.3705 μmol/L | Standard Deviation 0.67033 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 28 | -0.6270 μmol/L | Standard Deviation 0.98331 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 35 | -0.5415 μmol/L | Standard Deviation 1.02267 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 42 | -0.6270 μmol/L | Standard Deviation 0.84928 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 49 | -0.7125 μmol/L | Standard Deviation 0.96379 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Baseline (Day 1) | 12.2550 μmol/L | Standard Deviation 8.47558 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 2 | -1.4820 μmol/L | Standard Deviation 1.96662 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 3 | -1.7955 μmol/L | Standard Deviation 1.66407 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 4 | -1.6416 μmol/L | Standard Deviation 2.98785 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 6 | -2.9070 μmol/L | Standard Deviation 2.84087 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 7 | -1.5390 μmol/L | Standard Deviation 2.91002 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 14 | -4.3035 μmol/L | Standard Deviation 5.00001 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 21 | -4.7025 μmol/L | Standard Deviation 5.15927 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 28 | -4.2750 μmol/L | Standard Deviation 5.88995 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 35 | -3.8190 μmol/L | Standard Deviation 5.34403 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 49 | -3.4200 μmol/L | Standard Deviation 4.88354 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 14 | -0.6555 μmol/L | Standard Deviation 0.68755 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 21 | -0.8550 μmol/L | Standard Deviation 0.93034 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 42 | -4.0470 μmol/L | Standard Deviation 4.70877 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Baseline (Day 1) | 11.6850 μmol/L | Standard Deviation 5.00498 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 49 | 0.3705 μmol/L | Standard Deviation 0.84756 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 14 | 0.1710 μmol/L | Standard Deviation 0.72549 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 6 | 2.2515 μmol/L | Standard Deviation 4.45049 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 42 | 0.4560 μmol/L | Standard Deviation 0.97134 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 7 | 4.9875 μmol/L | Standard Deviation 4.06738 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 35 | 0.0000 μmol/L | Standard Deviation 0.76474 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 28 | 0.9690 μmol/L | Standard Deviation 0.60859 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 14 | 1.1970 μmol/L | Standard Deviation 2.11861 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 21 | 0.1995 μmol/L | Standard Deviation 0.55586 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 2 | 0.4560 μmol/L | Standard Deviation 0.6981 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 21 | 0.7980 μmol/L | Standard Deviation 2.90532 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 7 | 0.0570 μmol/L | Standard Deviation 0.66375 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 6 | 0.0855 μmol/L | Standard Deviation 0.87695 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 28 | 5.0730 μmol/L | Standard Deviation 5.72446 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 5 | 0.5415 μmol/L | Standard Deviation 0.42464 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 4 | -0.0285 μmol/L | Standard Deviation 0.65264 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 42 | 3.9045 μmol/L | Standard Deviation 5.91316 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 35 | -0.3135 μmol/L | Standard Deviation 3.912 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 3 | 0.0855 μmol/L | Standard Deviation 0.57989 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Baseline (Day 1) | 2.2800 μmol/L | Standard Deviation 0.88304 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 49 | 3.1350 μmol/L | Standard Deviation 2.76717 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 4 | 4.1610 μmol/L | Standard Deviation 2.59033 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 3 | 3.8190 μmol/L | Standard Deviation 4.03164 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 2 | 6.2985 μmol/L | Standard Deviation 3.89252 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 5 | 4.0470 μmol/L | Standard Deviation 3.19851 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Baseline (Day 1) | 2.8500 μmol/L | Standard Deviation 0.88304 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 5 | -0.0285 μmol/L | Standard Deviation 0.58657 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 28 | 0.5700 μmol/L | Standard Deviation 6.01635 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 3 | 4.7595 μmol/L | Standard Deviation 4.71342 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 6 | 3.5340 μmol/L | Standard Deviation 2.75234 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 42 | -0.0855 μmol/L | Standard Deviation 0.77045 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 4 | -0.1710 μmol/L | Standard Deviation 0.85841 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 35 | -0.7866 μmol/L | Standard Deviation 0.67971 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 14 | -0.1710 μmol/L | Standard Deviation 1.72023 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 42 | 2.1375 μmol/L | Standard Deviation 2.03985 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 7 | 1.7100 μmol/L | Standard Deviation 3.37351 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Baseline (Day 1) | 10.8300 μmol/L | Standard Deviation 5.26132 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 28 | -0.5130 μmol/L | Standard Deviation 1.2331 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 4 | 2.5650 μmol/L | Standard Deviation 3.61332 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 2 | 0.2280 μmol/L | Standard Deviation 1.001 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 35 | -2.1888 μmol/L | Standard Deviation 4.84024 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 14 | 0.9690 μmol/L | Standard Deviation 7.12039 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 21 | -0.7980 μmol/L | Standard Deviation 0.76218 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 3 | 0.1995 μmol/L | Standard Deviation 0.96379 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 7 | -0.2565 μmol/L | Standard Deviation 0.6988 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 49 | -0.1995 μmol/L | Standard Deviation 0.9577 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 2 | 5.4435 μmol/L | Standard Deviation 4.21426 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 21 | -1.9095 μmol/L | Standard Deviation 4.5544 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 5 | 3.9045 μmol/L | Standard Deviation 2.63233 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 6 | 0.0285 μmol/L | Standard Deviation 0.95158 |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 49 | 1.9380 μmol/L | Standard Deviation 8.15487 |
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.
Time frame: At Day 1
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Maximum Observed Plasma Concentration (Cmax) Following Single Dose Administration of VH4004280 | 13.49 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 23.59 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Maximum Observed Plasma Concentration (Cmax) Following Single Dose Administration of VH4004280 | 149.77 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 27.34 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Maximum Observed Plasma Concentration (Cmax) Following Single Dose Administration of VH4004280 | 438.80 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 53.6 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Maximum Observed Plasma Concentration (Cmax) Following Single Dose Administration of VH4004280 | 1342.72 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 30.74 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Maximum Observed Plasma Concentration (Cmax) Following Single Dose Administration of VH4004280 | 1630.95 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 27.05 |
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.
Time frame: Up to Day 49
Population: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Number of Participants With Any Adverse Events (AEs) and by Severity | Grade 4 AEs | 0 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Number of Participants With Any Adverse Events (AEs) and by Severity | Grade 2 AEs | 0 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Number of Participants With Any Adverse Events (AEs) and by Severity | Grade 5 AEs | 0 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Number of Participants With Any Adverse Events (AEs) and by Severity | Grade 1 AEs | 3 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Number of Participants With Any Adverse Events (AEs) and by Severity | Grade 3 AEs | 1 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Number of Participants With Any Adverse Events (AEs) and by Severity | Any AEs | 4 Participants |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Number of Participants With Any Adverse Events (AEs) and by Severity | Grade 1 AEs | 2 Participants |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Number of Participants With Any Adverse Events (AEs) and by Severity | Grade 5 AEs | 0 Participants |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Number of Participants With Any Adverse Events (AEs) and by Severity | Grade 2 AEs | 0 Participants |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Number of Participants With Any Adverse Events (AEs) and by Severity | Grade 3 AEs | 0 Participants |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Number of Participants With Any Adverse Events (AEs) and by Severity | Grade 4 AEs | 0 Participants |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Number of Participants With Any Adverse Events (AEs) and by Severity | Any AEs | 2 Participants |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Number of Participants With Any Adverse Events (AEs) and by Severity | Any AEs | 3 Participants |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Number of Participants With Any Adverse Events (AEs) and by Severity | Grade 3 AEs | 0 Participants |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Number of Participants With Any Adverse Events (AEs) and by Severity | Grade 4 AEs | 0 Participants |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Number of Participants With Any Adverse Events (AEs) and by Severity | Grade 1 AEs | 3 Participants |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Number of Participants With Any Adverse Events (AEs) and by Severity | Grade 2 AEs | 0 Participants |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Number of Participants With Any Adverse Events (AEs) and by Severity | Grade 5 AEs | 0 Participants |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Number of Participants With Any Adverse Events (AEs) and by Severity | Any AEs | 0 Participants |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Number of Participants With Any Adverse Events (AEs) and by Severity | Grade 5 AEs | 0 Participants |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Number of Participants With Any Adverse Events (AEs) and by Severity | Grade 1 AEs | 0 Participants |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Number of Participants With Any Adverse Events (AEs) and by Severity | Grade 2 AEs | 0 Participants |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Number of Participants With Any Adverse Events (AEs) and by Severity | Grade 3 AEs | 0 Participants |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Number of Participants With Any Adverse Events (AEs) and by Severity | Grade 4 AEs | 0 Participants |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Number of Participants With Any Adverse Events (AEs) and by Severity | Grade 2 AEs | 0 Participants |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Number of Participants With Any Adverse Events (AEs) and by Severity | Grade 1 AEs | 0 Participants |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Number of Participants With Any Adverse Events (AEs) and by Severity | Any AEs | 0 Participants |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Number of Participants With Any Adverse Events (AEs) and by Severity | Grade 5 AEs | 0 Participants |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Number of Participants With Any Adverse Events (AEs) and by Severity | Grade 4 AEs | 0 Participants |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Number of Participants With Any Adverse Events (AEs) and by Severity | Grade 3 AEs | 0 Participants |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Number of Participants With Any Adverse Events (AEs) and by Severity | Grade 5 AEs | 0 Participants |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Number of Participants With Any Adverse Events (AEs) and by Severity | Any AEs | 1 Participants |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Number of Participants With Any Adverse Events (AEs) and by Severity | Grade 1 AEs | 1 Participants |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Number of Participants With Any Adverse Events (AEs) and by Severity | Grade 2 AEs | 0 Participants |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Number of Participants With Any Adverse Events (AEs) and by Severity | Grade 3 AEs | 0 Participants |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Number of Participants With Any Adverse Events (AEs) and by Severity | Grade 4 AEs | 0 Participants |
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.
Time frame: Up to Day 49
Population: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Direct Bilirubin, Increase to Grade 1 | 0 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALT, Increase to Grade 3 | 0 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Direct Bilirubin, Increase to Grade 4 | 0 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALT, Increase to Grade 2 | 0 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALT, Increase to Grade 1 | 1 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALP, Increase to Grade 2 | 0 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Total Bilirubin, Increase to Grade 4 | 0 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Total Bilirubin, Increase to Grade 3 | 0 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALP, Increase to Grade 3 | 0 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Direct Bilirubin, Increase to Grade 2 | 0 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALP, Increase to Grade 1 | 0 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Total Bilirubin, Increase to Grade 2 | 0 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Total Bilirubin, Increase to Grade 1 | 0 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | AST, Increase to Grade 2 | 0 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | AST, Increase to Grade 4 | 0 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | AST, Increase to Grade 3 | 1 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Direct Bilirubin, Increase to Grade 3 | 0 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | AST, Increase to Grade 1 | 0 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALP, Increase to Grade 4 | 0 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALT, Increase to Grade 4 | 0 Participants |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Direct Bilirubin, Increase to Grade 1 | 0 Participants |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALT, Increase to Grade 3 | 0 Participants |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | AST, Increase to Grade 3 | 0 Participants |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALT, Increase to Grade 2 | 0 Participants |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Total Bilirubin, Increase to Grade 1 | 0 Participants |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Direct Bilirubin, Increase to Grade 4 | 0 Participants |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Total Bilirubin, Increase to Grade 4 | 0 Participants |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Direct Bilirubin, Increase to Grade 3 | 0 Participants |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALT, Increase to Grade 1 | 1 Participants |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALT, Increase to Grade 4 | 0 Participants |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | AST, Increase to Grade 2 | 0 Participants |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALP, Increase to Grade 2 | 0 Participants |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Direct Bilirubin, Increase to Grade 2 | 0 Participants |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALP, Increase to Grade 1 | 0 Participants |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Total Bilirubin, Increase to Grade 3 | 0 Participants |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | AST, Increase to Grade 4 | 0 Participants |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALP, Increase to Grade 4 | 0 Participants |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALP, Increase to Grade 3 | 0 Participants |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | AST, Increase to Grade 1 | 0 Participants |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Total Bilirubin, Increase to Grade 2 | 0 Participants |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALT, Increase to Grade 4 | 0 Participants |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALP, Increase to Grade 1 | 0 Participants |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALP, Increase to Grade 2 | 0 Participants |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALP, Increase to Grade 3 | 0 Participants |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | AST, Increase to Grade 1 | 0 Participants |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | AST, Increase to Grade 2 | 0 Participants |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | AST, Increase to Grade 3 | 0 Participants |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Total Bilirubin, Increase to Grade 4 | 0 Participants |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Direct Bilirubin, Increase to Grade 3 | 0 Participants |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Direct Bilirubin, Increase to Grade 4 | 0 Participants |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALT, Increase to Grade 1 | 0 Participants |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALT, Increase to Grade 2 | 0 Participants |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALT, Increase to Grade 3 | 0 Participants |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALP, Increase to Grade 4 | 0 Participants |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | AST, Increase to Grade 4 | 0 Participants |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Total Bilirubin, Increase to Grade 1 | 0 Participants |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Total Bilirubin, Increase to Grade 2 | 0 Participants |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Total Bilirubin, Increase to Grade 3 | 0 Participants |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Direct Bilirubin, Increase to Grade 1 | 0 Participants |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Direct Bilirubin, Increase to Grade 2 | 0 Participants |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Direct Bilirubin, Increase to Grade 2 | 0 Participants |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALT, Increase to Grade 1 | 1 Participants |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | AST, Increase to Grade 2 | 0 Participants |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Direct Bilirubin, Increase to Grade 1 | 0 Participants |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | AST, Increase to Grade 4 | 0 Participants |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Direct Bilirubin, Increase to Grade 3 | 0 Participants |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALP, Increase to Grade 3 | 0 Participants |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | AST, Increase to Grade 1 | 0 Participants |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Direct Bilirubin, Increase to Grade 4 | 0 Participants |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALT, Increase to Grade 4 | 0 Participants |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Total Bilirubin, Increase to Grade 1 | 0 Participants |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALP, Increase to Grade 1 | 0 Participants |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Total Bilirubin, Increase to Grade 4 | 0 Participants |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALT, Increase to Grade 3 | 0 Participants |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALP, Increase to Grade 2 | 0 Participants |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALP, Increase to Grade 4 | 0 Participants |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALT, Increase to Grade 2 | 0 Participants |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Total Bilirubin, Increase to Grade 3 | 0 Participants |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | AST, Increase to Grade 3 | 0 Participants |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Total Bilirubin, Increase to Grade 2 | 0 Participants |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Total Bilirubin, Increase to Grade 2 | 0 Participants |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Direct Bilirubin, Increase to Grade 3 | 0 Participants |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALT, Increase to Grade 3 | 0 Participants |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Total Bilirubin, Increase to Grade 4 | 0 Participants |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALP, Increase to Grade 3 | 0 Participants |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | AST, Increase to Grade 3 | 0 Participants |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALP, Increase to Grade 4 | 0 Participants |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | AST, Increase to Grade 2 | 0 Participants |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALT, Increase to Grade 4 | 0 Participants |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | AST, Increase to Grade 4 | 0 Participants |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | AST, Increase to Grade 1 | 0 Participants |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Total Bilirubin, Increase to Grade 1 | 1 Participants |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALT, Increase to Grade 2 | 0 Participants |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALP, Increase to Grade 2 | 0 Participants |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Direct Bilirubin, Increase to Grade 2 | 0 Participants |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Total Bilirubin, Increase to Grade 3 | 0 Participants |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALP, Increase to Grade 1 | 0 Participants |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Direct Bilirubin, Increase to Grade 4 | 0 Participants |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALT, Increase to Grade 1 | 0 Participants |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Direct Bilirubin, Increase to Grade 1 | 0 Participants |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALT, Increase to Grade 3 | 0 Participants |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALT, Increase to Grade 2 | 0 Participants |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALP, Increase to Grade 4 | 0 Participants |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALT, Increase to Grade 1 | 0 Participants |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Total Bilirubin, Increase to Grade 3 | 0 Participants |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALT, Increase to Grade 4 | 0 Participants |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALP, Increase to Grade 1 | 0 Participants |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Direct Bilirubin, Increase to Grade 1 | 0 Participants |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALP, Increase to Grade 3 | 0 Participants |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Direct Bilirubin, Increase to Grade 2 | 0 Participants |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Direct Bilirubin, Increase to Grade 4 | 0 Participants |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Direct Bilirubin, Increase to Grade 3 | 0 Participants |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Total Bilirubin, Increase to Grade 1 | 0 Participants |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | AST, Increase to Grade 1 | 0 Participants |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | AST, Increase to Grade 4 | 0 Participants |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | AST, Increase to Grade 3 | 0 Participants |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | AST, Increase to Grade 2 | 0 Participants |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Total Bilirubin, Increase to Grade 4 | 0 Participants |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Total Bilirubin, Increase to Grade 2 | 0 Participants |
| Part 1 (SAD): VH4004280 900 mg PiB | Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALP, Increase to Grade 2 | 0 Participants |
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.
Time frame: At Day 1
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 1: Time to Maximum Observed Plasma Concentration (Tmax) Following Single Dose Administration of VH4004280 | 9.63 hours | Geometric Coefficient of Variation 9.13 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 1: Time to Maximum Observed Plasma Concentration (Tmax) Following Single Dose Administration of VH4004280 | 9.90 hours | Geometric Coefficient of Variation 16.62 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 1: Time to Maximum Observed Plasma Concentration (Tmax) Following Single Dose Administration of VH4004280 | 11.15 hours | Geometric Coefficient of Variation 40.09 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 1: Time to Maximum Observed Plasma Concentration (Tmax) Following Single Dose Administration of VH4004280 | 10.31 hours | Geometric Coefficient of Variation 7.45 |
| Part 1 (SAD): VH4004280 450 mg PiB | Part 1: Time to Maximum Observed Plasma Concentration (Tmax) Following Single Dose Administration of VH4004280 | 8.53 hours | Geometric Coefficient of Variation 20.71 |
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.
Time frame: Up to Day 63
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Day 28 | 61.4 IU/L | Standard Deviation 15.98 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Day 14 | 69.5 IU/L | Standard Deviation 24.52 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Day 35 | 20.0 IU/L | Standard Deviation 5.51 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Day 35 | 25.0 IU/L | Standard Deviation 12.76 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Day 14 | 24.8 IU/L | Standard Deviation 17.5 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Day 15 | 20.0 IU/L | Standard Deviation 7.07 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Day 35 | 64.2 IU/L | Standard Deviation 17.88 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Day 42 | 26.7 IU/L | Standard Deviation 20.29 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Day 49 | 18.2 IU/L | Standard Deviation 4.97 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Day 42 | 21.5 IU/L | Standard Deviation 10.29 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Day 6 | 64.0 IU/L | Standard Deviation 4.24 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Day 49 | 19.4 IU/L | Standard Deviation 12.76 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Day 11 | 17.0 IU/L | Standard Deviation 2.83 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Day 15 | 66.0 IU/L | Standard Deviation 5.66 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Baseline (Day 1) | 66.2 IU/L | Standard Deviation 16.75 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Day 56 | 19.0 IU/L | Standard Deviation 9.49 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Day 15 | 16.0 IU/L | Standard Deviation 2.83 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Day 2 | 16.0 IU/L | Standard Deviation 9.42 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Day 5 | 64.3 IU/L | Standard Deviation 23.14 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Day 63 | 15.2 IU/L | Standard Deviation 5.85 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Day 8 | 15.0 IU/L | Standard Deviation 2.83 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Day 21 | 62.0 IU/L | Standard Deviation 19.41 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Day 3 | 68.0 IU/L | Standard Deviation 5.66 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Baseline (Day 1) | 16.2 IU/L | Standard Deviation 2.99 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Day 56 | 69.0 IU/L | Standard Deviation 19.71 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Day 3 | 19.0 IU/L | Standard Deviation 8.49 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Day 11 | 72.0 IU/L | Standard Deviation 2.83 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Day 2 | 14.8 IU/L | Standard Deviation 2.06 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Day 5 | 19.0 IU/L | Standard Deviation 8.76 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Day 2 | 69.0 IU/L | Standard Deviation 27.47 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Day 3 | 15.5 IU/L | Standard Deviation 3.54 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Day 63 | 66.5 IU/L | Standard Deviation 17.44 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Day 5 | 18.8 IU/L | Standard Deviation 3.69 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Day 21 | 17.0 IU/L | Standard Deviation 3.83 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Day 63 | 15.2 IU/L | Standard Deviation 1.72 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Day 6 | 15.0 IU/L | Standard Deviation 1.41 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Day 22 | 70.5 IU/L | Standard Deviation 4.95 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Day 7 | 19.8 IU/L | Standard Deviation 6.4 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Day 6 | 15.0 IU/L | Standard Deviation 5.66 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Day 56 | 18.0 IU/L | Standard Deviation 3.63 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Day 7 | 22.3 IU/L | Standard Deviation 12.5 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Day 22 | 17.5 IU/L | Standard Deviation 2.12 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Day 49 | 64.2 IU/L | Standard Deviation 16.81 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Day 8 | 15.0 IU/L | Standard Deviation 7.07 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Day 8 | 68.5 IU/L | Standard Deviation 9.19 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Day 11 | 21.0 IU/L | Standard Deviation 11.31 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Day 28 | 23.6 IU/L | Standard Deviation 12.2 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Day 12 | 16.5 IU/L | Standard Deviation 2.12 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Day 12 | 19.0 IU/L | Standard Deviation 8.49 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Day 12 | 71.0 IU/L | Standard Deviation 4.24 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Day 14 | 33.3 IU/L | Standard Deviation 31.36 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Day 21 | 24.5 IU/L | Standard Deviation 11.39 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Baseline (Day 1) | 18.7 IU/L | Standard Deviation 11.98 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Day 42 | 67.7 IU/L | Standard Deviation 19.31 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Day 22 | 21.5 IU/L | Standard Deviation 3.54 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Day 7 | 64.8 IU/L | Standard Deviation 25.16 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Day 28 | 31.2 IU/L | Standard Deviation 28.37 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Day 7 | 24.5 IU/L | Standard Deviation 10.88 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Day 11 | 19.5 IU/L | Standard Deviation 3.11 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Day 14 | 22.8 IU/L | Standard Deviation 6.55 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Day 56 | 20.8 IU/L | Standard Deviation 4.09 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Day 28 | 49.2 IU/L | Standard Deviation 11.69 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Day 21 | 23.3 IU/L | Standard Deviation 5.79 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Day 28 | 21.5 IU/L | Standard Deviation 5.13 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Day 49 | 19.5 IU/L | Standard Deviation 5.28 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Day 35 | 24.7 IU/L | Standard Deviation 10.03 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Baseline (Day 1) | 19.0 IU/L | Standard Deviation 6.93 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Day 42 | 22.3 IU/L | Standard Deviation 2.66 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Day 56 | 51.6 IU/L | Standard Deviation 11.15 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Day 2 | 19.2 IU/L | Standard Deviation 5.12 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Day 5 | 19.5 IU/L | Standard Deviation 5.32 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Day 49 | 51.0 IU/L | Standard Deviation 12.36 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Day 11 | 47.5 IU/L | Standard Deviation 4.2 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Day 7 | 24.7 IU/L | Standard Deviation 9.14 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Day 14 | 29.5 IU/L | Standard Deviation 14.01 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Day 11 | 20.8 IU/L | Standard Deviation 3.86 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Day 42 | 51.3 IU/L | Standard Deviation 11.76 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Day 21 | 32.8 IU/L | Standard Deviation 15.35 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Day 28 | 27.5 IU/L | Standard Deviation 13.1 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Day 35 | 53.0 IU/L | Standard Deviation 15.26 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Day 35 | 36.8 IU/L | Standard Deviation 31.13 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Day 14 | 47.7 IU/L | Standard Deviation 7.53 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Day 42 | 27.8 IU/L | Standard Deviation 10.65 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Day 63 | 53.8 IU/L | Standard Deviation 11.75 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Day 49 | 24.2 IU/L | Standard Deviation 12.19 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Day 5 | 49.8 IU/L | Standard Deviation 6.79 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Day 56 | 21.2 IU/L | Standard Deviation 11.45 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Day 7 | 48.8 IU/L | Standard Deviation 7.39 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Day 63 | 19.3 IU/L | Standard Deviation 7.69 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Baseline (Day 1) | 19.2 IU/L | Standard Deviation 4.12 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Day 21 | 50.5 IU/L | Standard Deviation 5.21 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Day 2 | 52.0 IU/L | Standard Deviation 8.97 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Day 2 | 17.2 IU/L | Standard Deviation 2.64 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Day 5 | 18.5 IU/L | Standard Deviation 4.14 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Baseline (Day 1) | 53.7 IU/L | Standard Deviation 10.01 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Day 63 | 19.8 IU/L | Standard Deviation 6.34 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Day 15 | 21.5 IU/L | Standard Deviation 10.04 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Day 6 | 55.6 IU/L | Standard Deviation 19.78 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Day 8 | 55.8 IU/L | Standard Deviation 18.98 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Day 12 | 58.3 IU/L | Standard Deviation 21.97 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Day 15 | 58.0 IU/L | Standard Deviation 19.09 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Day 22 | 62.6 IU/L | Standard Deviation 19.53 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Day 28 | 59.8 IU/L | Standard Deviation 19.2 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Baseline (Day 1) | 16.3 IU/L | Standard Deviation 5.04 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Day 3 | 18.3 IU/L | Standard Deviation 4.43 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Day 6 | 18.3 IU/L | Standard Deviation 5.26 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Day 8 | 16.8 IU/L | Standard Deviation 5.39 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Day 12 | 19.1 IU/L | Standard Deviation 8.81 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Day 22 | 24.1 IU/L | Standard Deviation 8.46 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Day 28 | 26.6 IU/L | Standard Deviation 8.02 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Day 35 | 23.8 IU/L | Standard Deviation 6.45 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Day 42 | 20.3 IU/L | Standard Deviation 8.36 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Day 49 | 18.5 IU/L | Standard Deviation 7.41 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Day 56 | 18.0 IU/L | Standard Deviation 6.14 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Day 63 | 18.4 IU/L | Standard Deviation 7.71 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Baseline (Day 1) | 14.9 IU/L | Standard Deviation 3.14 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Day 3 | 16.3 IU/L | Standard Deviation 2.25 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Day 6 | 15.3 IU/L | Standard Deviation 3.01 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Day 8 | 15.5 IU/L | Standard Deviation 2.14 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Day 12 | 16.3 IU/L | Standard Deviation 3.33 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Day 15 | 16.0 IU/L | Standard Deviation 3.59 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Day 22 | 17.9 IU/L | Standard Deviation 2.47 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Day 28 | 21.9 IU/L | Standard Deviation 18.76 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Day 35 | 19.5 IU/L | Standard Deviation 6.63 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Day 42 | 15.9 IU/L | Standard Deviation 2.95 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Day 49 | 16.1 IU/L | Standard Deviation 5.41 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Day 56 | 16.9 IU/L | Standard Deviation 6.17 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Day 63 | 16.1 IU/L | Standard Deviation 3.72 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Baseline (Day 1) | 57.5 IU/L | Standard Deviation 21.37 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Day 3 | 58.4 IU/L | Standard Deviation 20.88 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Day 35 | 59.9 IU/L | Standard Deviation 17.1 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Day 42 | 62.1 IU/L | Standard Deviation 19.58 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Day 49 | 58.8 IU/L | Standard Deviation 18.48 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Day 56 | 62.8 IU/L | Standard Deviation 20.42 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Day 63 | 58.8 IU/L | Standard Deviation 18.97 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Day 7 | 16.0 IU/L | Standard Deviation 2.83 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Day 21 | 57.5 IU/L | Standard Deviation 11.64 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Day 63 | 17.0 IU/L | Standard Deviation 3.41 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Day 5 | 15.7 IU/L | Standard Deviation 2.94 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Day 14 | 58.0 IU/L | Standard Deviation 12.2 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Baseline (Day 1) | 56.7 IU/L | Standard Deviation 11.41 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Day 2 | 17.5 IU/L | Standard Deviation 3.99 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Baseline (Day 1) | 17.8 IU/L | Standard Deviation 3.54 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Day 2 | 56.2 IU/L | Standard Deviation 10.23 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Day 63 | 15.2 IU/L | Standard Deviation 2.64 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Day 28 | 59.5 IU/L | Standard Deviation 10.73 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Day 56 | 14.7 IU/L | Standard Deviation 5.5 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Day 49 | 17.0 IU/L | Standard Deviation 6.1 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Day 5 | 57.2 IU/L | Standard Deviation 9.6 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Day 42 | 21.2 IU/L | Standard Deviation 8.86 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Day 35 | 22.8 IU/L | Standard Deviation 9.33 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Day 28 | 33.7 IU/L | Standard Deviation 34.31 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Day 63 | 57.3 IU/L | Standard Deviation 11.08 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Day 35 | 53.0 IU/L | Standard Deviation 11.56 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Day 21 | 23.2 IU/L | Standard Deviation 9.28 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Day 11 | 14.8 IU/L | Standard Deviation 5.34 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Day 11 | 54.3 IU/L | Standard Deviation 11.47 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Day 42 | 57.7 IU/L | Standard Deviation 12.09 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Day 7 | 16.5 IU/L | Standard Deviation 6.47 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Day 5 | 16.7 IU/L | Standard Deviation 6.28 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Day 14 | 16.7 IU/L | Standard Deviation 6.77 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Day 49 | 54.0 IU/L | Standard Deviation 12.71 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Day 2 | 19.8 IU/L | Standard Deviation 7.65 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Baseline (Day 1) | 19.5 IU/L | Standard Deviation 7.69 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Day 42 | 18.0 IU/L | Standard Deviation 3.35 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Day 35 | 18.8 IU/L | Standard Deviation 5.19 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Day 28 | 49.5 IU/L | Standard Deviation 80.64 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Day 7 | 56.5 IU/L | Standard Deviation 7.12 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Day 49 | 16.5 IU/L | Standard Deviation 1.97 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Day 21 | 18.8 IU/L | Standard Deviation 4.26 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Day 14 | 15.7 IU/L | Standard Deviation 2.73 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Day 56 | 56.5 IU/L | Standard Deviation 7.2 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Day 56 | 16.5 IU/L | Standard Deviation 2.17 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Day 11 | 13.8 IU/L | Standard Deviation 1.94 |
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.
Time frame: Up to Day 63
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Baseline (Day 1) | 11.9700 μmol/L | Standard Deviation 3.42 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 35 | 9.2910 μmol/L | Standard Deviation 1.47365 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 28 | 8.3106 μmol/L | Standard Deviation 2.4171 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 2 | 10.6020 μmol/L | Standard Deviation 2.39807 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 21 | 7.6095 μmol/L | Standard Deviation 1.74666 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 12 | 11.4570 μmol/L | Standard Deviation 0.72549 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 3 | 16.3305 μmol/L | Standard Deviation 6.40851 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 11 | 9.4050 μmol/L | Standard Deviation 3.62746 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 5 | 10.6020 μmol/L | Standard Deviation 2.08498 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 8 | 16.5870 μmol/L | Standard Deviation 8.94773 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 6 | 15.1335 μmol/L | Standard Deviation 4.7157 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 12 | 1.9665 μmol/L | Standard Deviation 0.60458 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 7 | 9.0203 μmol/L | Standard Deviation 1.14604 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 14 | 1.5818 μmol/L | Standard Deviation 0.29204 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 7 | 1.8383 μmol/L | Standard Deviation 0.37917 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 56 | 1.9095 μmol/L | Standard Deviation 0.47656 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 15 | 2.7360 μmol/L | Standard Deviation 0.24183 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 28 | 1.5732 μmol/L | Standard Deviation 0.44262 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 21 | 1.7100 μmol/L | Standard Deviation 0.46307 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 22 | 19.9215 μmol/L | Standard Deviation 5.92485 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 22 | 3.5055 μmol/L | Standard Deviation 0.12092 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 6 | 2.2230 μmol/L | Standard Deviation 0 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 35 | 1.7955 μmol/L | Standard Deviation 0.28098 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 15 | 15.5610 μmol/L | Standard Deviation 4.11112 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 5 | 2.0948 μmol/L | Standard Deviation 0.35253 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 3 | 2.2230 μmol/L | Standard Deviation 0.24183 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 42 | 2.0520 μmol/L | Standard Deviation 0.58241 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 8 | 2.3940 μmol/L | Standard Deviation 0.72549 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 2 | 2.1803 μmol/L | Standard Deviation 0.4709 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Baseline (Day 1) | 2.2800 μmol/L | Standard Deviation 0.88304 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 49 | 2.1204 μmol/L | Standard Deviation 0.66887 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 14 | 7.3958 μmol/L | Standard Deviation 1.36354 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 63 | 8.9205 μmol/L | Standard Deviation 2.27993 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 56 | 10.1175 μmol/L | Standard Deviation 5.17248 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 63 | 1.7670 μmol/L | Standard Deviation 0.38491 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 11 | 2.2230 μmol/L | Standard Deviation 0.72549 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 49 | 11.5254 μmol/L | Standard Deviation 4.75214 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 42 | 10.6305 μmol/L | Standard Deviation 4.12024 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Baseline (Day 1) | 2.8500 μmol/L | Standard Deviation 1.39621 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 7 | 2.9070 μmol/L | Standard Deviation 1.75056 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 11 | 2.6505 μmol/L | Standard Deviation 1.04948 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 14 | 2.6220 μmol/L | Standard Deviation 1.07426 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 21 | 2.7360 μmol/L | Standard Deviation 1.17978 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 35 | 1.8810 μmol/L | Standard Deviation 0.63982 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 42 | 2.0805 μmol/L | Standard Deviation 0.77549 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 49 | 2.2230 μmol/L | Standard Deviation 0.80206 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 63 | 1.9095 μmol/L | Standard Deviation 0.69601 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 2 | 17.9550 μmol/L | Standard Deviation 8.54521 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 5 | 18.8670 μmol/L | Standard Deviation 10.05775 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 11 | 15.2190 μmol/L | Standard Deviation 5.69715 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 28 | 10.3170 μmol/L | Standard Deviation 3.52221 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 35 | 10.7730 μmol/L | Standard Deviation 3.04361 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 42 | 10.7445 μmol/L | Standard Deviation 3.45304 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 49 | 12.1410 μmol/L | Standard Deviation 3.91885 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 56 | 11.0466 μmol/L | Standard Deviation 4.41233 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 63 | 10.3455 μmol/L | Standard Deviation 3.58815 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 2 | 3.1065 μmol/L | Standard Deviation 1.34826 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 5 | 3.1635 μmol/L | Standard Deviation 1.82498 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 28 | 2.0235 μmol/L | Standard Deviation 0.64362 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 56 | 2.2914 μmol/L | Standard Deviation 1.08555 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Baseline (Day 1) | 15.1050 μmol/L | Standard Deviation 6.87553 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 7 | 16.5015 μmol/L | Standard Deviation 9.02436 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 14 | 14.2500 μmol/L | Standard Deviation 4.70504 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 21 | 15.8175 μmol/L | Standard Deviation 5.3211 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Baseline (Day 1) | 2.1375 μmol/L | Standard Deviation 0.79158 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 22 | 3.2276 μmol/L | Standard Deviation 0.93409 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 15 | 2.8856 μmol/L | Standard Deviation 0.78329 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 15 | 14.9839 μmol/L | Standard Deviation 4.61559 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 28 | 2.0948 μmol/L | Standard Deviation 0.61145 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 63 | 8.9775 μmol/L | Standard Deviation 3.69817 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 12 | 15.6893 μmol/L | Standard Deviation 3.63062 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 49 | 11.1791 μmol/L | Standard Deviation 2.73896 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 56 | 1.8810 μmol/L | Standard Deviation 0.51706 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 42 | 2.0306 μmol/L | Standard Deviation 0.57401 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 12 | 2.5436 μmol/L | Standard Deviation 0.76712 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 8 | 14.4281 μmol/L | Standard Deviation 3.99249 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 6 | 13.2525 μmol/L | Standard Deviation 4.38546 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 3 | 12.2051 μmol/L | Standard Deviation 3.59151 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 42 | 10.2173 μmol/L | Standard Deviation 3.00208 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 8 | 2.4795 μmol/L | Standard Deviation 0.83272 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 3 | 2.1589 μmol/L | Standard Deviation 0.78595 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 22 | 18.0833 μmol/L | Standard Deviation 4.97435 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 35 | 2.1375 μmol/L | Standard Deviation 0.59937 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 56 | 8.3149 μmol/L | Standard Deviation 1.86413 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 28 | 9.7256 μmol/L | Standard Deviation 2.84298 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 63 | 1.8596 μmol/L | Standard Deviation 0.8399 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Baseline (Day 1) | 9.6188 μmol/L | Standard Deviation 3.53265 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 49 | 2.2016 μmol/L | Standard Deviation 0.59544 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 35 | 10.3028 μmol/L | Standard Deviation 2.29739 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 6 | 2.3940 μmol/L | Standard Deviation 0.99289 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 35 | 9.1200 μmol/L | Standard Deviation 1.86591 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 49 | 9.7755 μmol/L | Standard Deviation 3.40872 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 56 | 1.7955 μmol/L | Standard Deviation 0.49265 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 56 | 8.8065 μmol/L | Standard Deviation 2.4177 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 63 | 10.1745 μmol/L | Standard Deviation 2.83829 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 42 | 1.5960 μmol/L | Standard Deviation 0.35322 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 14 | 13.9650 μmol/L | Standard Deviation 2.37109 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 2 | 2.1375 μmol/L | Standard Deviation 0.40103 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 35 | 1.7955 μmol/L | Standard Deviation 0.41536 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 7 | 2.5650 μmol/L | Standard Deviation 0.47141 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 5 | 2.1945 μmol/L | Standard Deviation 0.54524 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 28 | 1.8810 μmol/L | Standard Deviation 0.49561 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 21 | 2.5935 μmol/L | Standard Deviation 0.34905 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 49 | 1.9095 μmol/L | Standard Deviation 0.59646 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 14 | 1.9950 μmol/L | Standard Deviation 0.33625 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Baseline (Day 1) | 1.7100 μmol/L | Standard Deviation 0 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 42 | 8.8920 μmol/L | Standard Deviation 3.09505 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 5 | 13.0815 μmol/L | Standard Deviation 4.18409 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 21 | 14.9625 μmol/L | Standard Deviation 2.61076 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 11 | 13.0530 μmol/L | Standard Deviation 2.43917 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 2 | 11.6565 μmol/L | Standard Deviation 2.67858 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Baseline (Day 1) | 8.2650 μmol/L | Standard Deviation 1.28724 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 7 | 14.8770 μmol/L | Standard Deviation 3.05894 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Total Bilirubin, Day 28 | 9.7755 μmol/L | Standard Deviation 2.53499 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 11 | 2.4795 μmol/L | Standard Deviation 0.58989 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin | Direct Bilirubin, Day 63 | 1.9665 μmol/L | Standard Deviation 0.51584 |
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.
Time frame: 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
Population: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | 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 | Day 1 | 6268.14 h*ng/mL | Geometric Coefficient of Variation 17.35 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | 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 | Day 14 | 449239.54 h*ng/mL | Geometric Coefficient of Variation 53.5 |
| Part 1 (SAD): VH4004280 10 mg PiB | 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 | Day 2 | 15157.94 h*ng/mL | Geometric Coefficient of Variation 26 |
| Part 1 (SAD): VH4004280 10 mg PiB | 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 | Day 15 | 1527149.1 h*ng/mL | Geometric Coefficient of Variation 26 |
| Part 1 (SAD): VH4004280 50 mg PiB | 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 | Day 1 | 14869.75 h*ng/mL | Geometric Coefficient of Variation 23.49 |
| Part 1 (SAD): VH4004280 50 mg PiB | 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 | Day 14 | 1882862.73 h*ng/mL | Geometric Coefficient of Variation 37.66 |
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.
Time frame: From Baseline (Day 1) and up to Day 63
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 6 | -6.0 IU/L | Standard Deviation 4.24 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 11 | -7.5 IU/L | Standard Deviation 3.54 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 14 | 4.5 IU/L | Standard Deviation 14.57 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 5 | 1.5 IU/L | Standard Deviation 8.96 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 3 | -0.5 IU/L | Standard Deviation 4.95 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 3 | -2.0 IU/L | Standard Deviation 1.41 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 2 | -1.5 IU/L | Standard Deviation 5.8 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 35 | -2.0 IU/L | Standard Deviation 5.83 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 21 | 1.0 IU/L | Standard Deviation 1.15 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Baseline (Day 1) | 18.7 IU/L | Standard Deviation 11.98 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 63 | 0.3 IU/L | Standard Deviation 5.05 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 42 | 1.5 IU/L | Standard Deviation 6.47 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 15 | -2.5 IU/L | Standard Deviation 6.36 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 56 | 2.8 IU/L | Standard Deviation 9.2 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 49 | 0.8 IU/L | Standard Deviation 7.89 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 15 | -0.5 IU/L | Standard Deviation 0.71 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 21 | -3.0 IU/L | Standard Deviation 3.16 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 56 | 1.8 IU/L | Standard Deviation 2.64 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 14 | 8.8 IU/L | Standard Deviation 14.36 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 22 | 2.0 IU/L | Standard Deviation 5.66 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 12 | 0.0 IU/L | Standard Deviation 0 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 28 | -2.0 IU/L | Standard Deviation 4.85 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 11 | 2.0 IU/L | Standard Deviation 1.41 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 8 | -1.5 IU/L | Standard Deviation 0.71 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 63 | -3.5 IU/L | Standard Deviation 6.53 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 5 | -0.8 IU/L | Standard Deviation 4.5 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 7 | 3.8 IU/L | Standard Deviation 4.11 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 56 | 0.3 IU/L | Standard Deviation 3.33 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Baseline (Day 1) | 16.2 IU/L | Standard Deviation 2.99 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 63 | -1.0 IU/L | Standard Deviation 1.41 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 49 | 0.2 IU/L | Standard Deviation 1.1 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 42 | 8.0 IU/L | Standard Deviation 8.65 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 2 | -1.3 IU/L | Standard Deviation 2.06 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 49 | 2.4 IU/L | Standard Deviation 2.41 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 35 | 6.3 IU/L | Standard Deviation 5.5 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 3 | -1.0 IU/L | Standard Deviation 1.41 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 28 | 12.0 IU/L | Standard Deviation 15.98 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 5 | 2.8 IU/L | Standard Deviation 3.86 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 6 | -4.5 IU/L | Standard Deviation 3.54 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 22 | 0.5 IU/L | Standard Deviation 6.36 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 6 | -1.5 IU/L | Standard Deviation 0.71 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 21 | 7.0 IU/L | Standard Deviation 4.69 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 15 | -1.0 IU/L | Standard Deviation 2.83 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 35 | 3.8 IU/L | Standard Deviation 4.67 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 28 | 7.8 IU/L | Standard Deviation 9.31 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 14 | 15.8 IU/L | Standard Deviation 17.21 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 12 | -2.0 IU/L | Standard Deviation 1.41 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 42 | 5.3 IU/L | Standard Deviation 7.71 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Baseline (Day 1) | 66.2 IU/L | Standard Deviation 16.75 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 12 | 2.5 IU/L | Standard Deviation 4.95 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 11 | 9.0 IU/L | Standard Deviation 5.66 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 8 | -6.0 IU/L | Standard Deviation 2.83 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 2 | 4.0 IU/L | Standard Deviation 8.45 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 7 | -0.3 IU/L | Standard Deviation 5.56 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 22 | 1.0 IU/L | Standard Deviation 0 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 7 | 4.8 IU/L | Standard Deviation 8.38 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 8 | 0.0 IU/L | Standard Deviation 8.49 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 2 | -1.7 IU/L | Standard Deviation 3.33 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 5 | -3.8 IU/L | Standard Deviation 5.98 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 14 | -6.0 IU/L | Standard Deviation 6.16 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 21 | -3.2 IU/L | Standard Deviation 9.02 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 63 | 0.3 IU/L | Standard Deviation 3.88 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Baseline (Day 1) | 19.2 IU/L | Standard Deviation 4.12 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 2 | -2.0 IU/L | Standard Deviation 2.68 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 5 | -0.7 IU/L | Standard Deviation 3.5 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 35 | 5.5 IU/L | Standard Deviation 7.29 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Baseline (Day 1) | 53.7 IU/L | Standard Deviation 10.01 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 7 | -4.8 IU/L | Standard Deviation 7.47 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 11 | -2.0 IU/L | Standard Deviation 5.48 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 28 | -4.5 IU/L | Standard Deviation 6.69 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 35 | -0.7 IU/L | Standard Deviation 8.62 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 42 | -2.3 IU/L | Standard Deviation 5.43 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 49 | -2.7 IU/L | Standard Deviation 7.03 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 56 | -3.6 IU/L | Standard Deviation 3.21 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 63 | 0.2 IU/L | Standard Deviation 5.95 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Baseline (Day 1) | 19.0 IU/L | Standard Deviation 6.93 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 2 | 0.2 IU/L | Standard Deviation 2.64 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 5 | 0.5 IU/L | Standard Deviation 3.83 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 7 | 5.7 IU/L | Standard Deviation 7.81 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 11 | 4.0 IU/L | Standard Deviation 11.28 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 14 | 10.5 IU/L | Standard Deviation 13.85 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 21 | 13.8 IU/L | Standard Deviation 15.28 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 28 | 8.5 IU/L | Standard Deviation 9.65 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 35 | 17.8 IU/L | Standard Deviation 26.69 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 42 | 8.8 IU/L | Standard Deviation 7.19 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 49 | 5.2 IU/L | Standard Deviation 7.6 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 56 | 0.8 IU/L | Standard Deviation 8.44 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 7 | 5.3 IU/L | Standard Deviation 9.73 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 11 | 2.0 IU/L | Standard Deviation 6.06 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 14 | 3.7 IU/L | Standard Deviation 6.35 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 21 | 4.2 IU/L | Standard Deviation 5.81 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 28 | 2.3 IU/L | Standard Deviation 6.22 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 42 | 3.2 IU/L | Standard Deviation 5.27 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 49 | 0.3 IU/L | Standard Deviation 4.03 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 56 | 0.4 IU/L | Standard Deviation 3.85 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 63 | 0.7 IU/L | Standard Deviation 4.03 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 49 | 1.3 IU/L | Standard Deviation 3.2 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 63 | 2.1 IU/L | Standard Deviation 6.31 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 22 | 7.9 IU/L | Standard Deviation 10.29 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 3 | 1.4 IU/L | Standard Deviation 3.02 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 42 | 1.0 IU/L | Standard Deviation 2.27 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 8 | 0.6 IU/L | Standard Deviation 2.88 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 56 | 1.8 IU/L | Standard Deviation 6.71 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 3 | 0.9 IU/L | Standard Deviation 3.31 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 28 | 10.4 IU/L | Standard Deviation 9.38 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 22 | 5.1 IU/L | Standard Deviation 3.94 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 12 | 1.4 IU/L | Standard Deviation 4.44 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 8 | -1.8 IU/L | Standard Deviation 3.77 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 63 | 1.3 IU/L | Standard Deviation 4.3 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 12 | 2.9 IU/L | Standard Deviation 9.48 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 15 | 0.5 IU/L | Standard Deviation 4.99 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 35 | 4.6 IU/L | Standard Deviation 5.68 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 15 | 1.1 IU/L | Standard Deviation 4.79 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 49 | 1.3 IU/L | Standard Deviation 6.76 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 35 | 7.5 IU/L | Standard Deviation 7.29 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 42 | 4.6 IU/L | Standard Deviation 9.64 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 28 | 7.0 IU/L | Standard Deviation 17.57 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 56 | 5.3 IU/L | Standard Deviation 6.9 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 8 | 0.5 IU/L | Standard Deviation 6.02 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Baseline (Day 1) | 57.5 IU/L | Standard Deviation 21.37 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 56 | 2.0 IU/L | Standard Deviation 7.46 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 63 | 1.3 IU/L | Standard Deviation 4.37 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 42 | 4.0 IU/L | Standard Deviation 6.74 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 35 | 2.4 IU/L | Standard Deviation 7.41 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 15 | 5.3 IU/L | Standard Deviation 10.74 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Baseline (Day 1) | 16.3 IU/L | Standard Deviation 5.04 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Baseline (Day 1) | 14.9 IU/L | Standard Deviation 3.14 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 6 | 0.4 IU/L | Standard Deviation 3.89 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 12 | 0.8 IU/L | Standard Deviation 3.24 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 49 | 2.3 IU/L | Standard Deviation 6.34 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 28 | 2.3 IU/L | Standard Deviation 5.7 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 3 | 2.0 IU/L | Standard Deviation 2.33 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 6 | -1.9 IU/L | Standard Deviation 3.4 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 22 | 3.0 IU/L | Standard Deviation 3.02 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 6 | 2.0 IU/L | Standard Deviation 5.45 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 21 | 3.7 IU/L | Standard Deviation 9.48 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 7 | -0.2 IU/L | Standard Deviation 5.27 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 7 | -3.0 IU/L | Standard Deviation 3.79 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Baseline (Day 1) | 56.7 IU/L | Standard Deviation 11.41 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 56 | -1.3 IU/L | Standard Deviation 1.63 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 11 | -4.7 IU/L | Standard Deviation 4.72 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 35 | 1.0 IU/L | Standard Deviation 6.42 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 14 | -2.8 IU/L | Standard Deviation 5.53 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 28 | 31.7 IU/L | Standard Deviation 81.01 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 2 | -0.5 IU/L | Standard Deviation 2.81 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 5 | -2.2 IU/L | Standard Deviation 2.04 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 28 | 14.2 IU/L | Standard Deviation 37.02 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 2 | -0.3 IU/L | Standard Deviation 1.51 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 42 | 0.2 IU/L | Standard Deviation 3.87 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 35 | 3.3 IU/L | Standard Deviation 12.23 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Baseline (Day 1) | 17.8 IU/L | Standard Deviation 3.54 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 5 | 0.5 IU/L | Standard Deviation 4.85 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 42 | 1.7 IU/L | Standard Deviation 8.07 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 63 | -0.8 IU/L | Standard Deviation 3.54 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 49 | -2.5 IU/L | Standard Deviation 5.96 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 63 | -4.3 IU/L | Standard Deviation 5.92 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 49 | -1.3 IU/L | Standard Deviation 4.13 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 7 | -1.8 IU/L | Standard Deviation 3.06 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 56 | -4.8 IU/L | Standard Deviation 2.48 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 11 | -4.0 IU/L | Standard Deviation 2.53 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 21 | 0.8 IU/L | Standard Deviation 4.62 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 14 | -2.2 IU/L | Standard Deviation 2.93 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 42 | 1.0 IU/L | Standard Deviation 4.73 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 49 | -2.7 IU/L | Standard Deviation 4.55 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 14 | 1.3 IU/L | Standard Deviation 4.37 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 56 | -0.2 IU/L | Standard Deviation 4.96 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 35 | -3.7 IU/L | Standard Deviation 3.61 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 63 | 0.7 IU/L | Standard Deviation 2.88 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 21 | 1.0 IU/L | Standard Deviation 3.1 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Baseline (Day 1) | 19.5 IU/L | Standard Deviation 7.69 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 28 | 2.8 IU/L | Standard Deviation 3.76 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 2 | 0.3 IU/L | Standard Deviation 2.07 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 11 | -2.3 IU/L | Standard Deviation 5.05 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 5 | -2.8 IU/L | Standard Deviation 2.64 |
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.
Time frame: From Baseline (Day 1) and up to Day 63
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 42 | -0.2280 μmol/L | Standard Deviation 0.54791 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 12 | -3.0780 μmol/L | Standard Deviation 6.77125 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 5 | -0.0855 μmol/L | Standard Deviation 2.68748 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 49 | -0.2736 μmol/L | Standard Deviation 0.35459 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 2 | -0.0855 μmol/L | Standard Deviation 2.38789 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 42 | -1.3395 μmol/L | Standard Deviation 1.08913 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Baseline (Day 1) | 2.2800 μmol/L | Standard Deviation 0.88304 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 7 | -1.6673 μmol/L | Standard Deviation 1.34192 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 49 | -0.7866 μmol/L | Standard Deviation 1.704 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 2 | 0.0428 μmol/L | Standard Deviation 0.84208 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 5 | -0.0428 μmol/L | Standard Deviation 1.1375 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 35 | -2.6790 μmol/L | Standard Deviation 2.91336 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 6 | -0.3420 μmol/L | Standard Deviation 1.20915 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 7 | -0.2993 μmol/L | Standard Deviation 1.01044 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 8 | -0.1710 μmol/L | Standard Deviation 0.48366 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 63 | -3.0495 μmol/L | Standard Deviation 1.72504 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 11 | 0.5130 μmol/L | Standard Deviation 0.72549 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 28 | -4.0014 μmol/L | Standard Deviation 3.67869 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 12 | -0.5985 μmol/L | Standard Deviation 1.81373 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 8 | 2.0520 μmol/L | Standard Deviation 2.90197 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 14 | -0.5558 μmol/L | Standard Deviation 0.68932 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 22 | 5.3865 μmol/L | Standard Deviation 0.12092 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 15 | 0.1710 μmol/L | Standard Deviation 0.96732 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 21 | -0.4275 μmol/L | Standard Deviation 0.86632 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 22 | 0.9405 μmol/L | Standard Deviation 1.08824 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 11 | -0.8550 μmol/L | Standard Deviation 3.62746 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 28 | -0.8208 μmol/L | Standard Deviation 1.13041 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 21 | -3.0780 μmol/L | Standard Deviation 1.45769 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 35 | -0.4845 μmol/L | Standard Deviation 0.79043 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 15 | 1.0260 μmol/L | Standard Deviation 1.93464 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 6 | 0.5985 μmol/L | Standard Deviation 1.33007 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 3 | -0.3420 μmol/L | Standard Deviation 0.96732 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 56 | -0.3705 μmol/L | Standard Deviation 0.83364 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 14 | -3.2918 μmol/L | Standard Deviation 0.9405 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 3 | 1.7955 μmol/L | Standard Deviation 0.36275 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 63 | -0.5130 μmol/L | Standard Deviation 0.6489 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Baseline (Day 1) | 11.9700 μmol/L | Standard Deviation 3.42 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 56 | -1.8525 μmol/L | Standard Deviation 2.73047 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 49 | -0.6270 μmol/L | Standard Deviation 0.84928 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 56 | -6.0534 μmol/L | Standard Deviation 4.17394 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 5 | 0.3135 μmol/L | Standard Deviation 0.97585 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 42 | -0.7695 μmol/L | Standard Deviation 0.80024 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 56 | -0.7866 μmol/L | Standard Deviation 0.82542 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 14 | -0.2280 μmol/L | Standard Deviation 0.95923 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 7 | 1.3965 μmol/L | Standard Deviation 4.31166 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 35 | -0.9690 μmol/L | Standard Deviation 0.91556 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 63 | -0.9405 μmol/L | Standard Deviation 1.25542 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 14 | -0.8550 μmol/L | Standard Deviation 5.47307 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 2 | 2.8500 μmol/L | Standard Deviation 3.18017 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 7 | 0.0570 μmol/L | Standard Deviation 0.82837 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Baseline (Day 1) | 15.1050 μmol/L | Standard Deviation 6.87553 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 28 | -4.7880 μmol/L | Standard Deviation 6.47907 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 28 | -0.8265 μmol/L | Standard Deviation 0.87472 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 63 | -4.7595 μmol/L | Standard Deviation 5.8615 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 42 | -4.3605 μmol/L | Standard Deviation 5.7051 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 5 | 3.7620 μmol/L | Standard Deviation 4.99952 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 49 | -2.9640 μmol/L | Standard Deviation 4.81803 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 11 | 3.6765 μmol/L | Standard Deviation 2.12893 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Baseline (Day 1) | 2.8500 μmol/L | Standard Deviation 1.39621 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 11 | 0.5130 μmol/L | Standard Deviation 0.60859 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 21 | -0.1140 μmol/L | Standard Deviation 1.001 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 21 | 0.7125 μmol/L | Standard Deviation 4.72334 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 2 | 0.2565 μmol/L | Standard Deviation 0.67323 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 35 | -4.3320 μmol/L | Standard Deviation 5.66489 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 3 | 2.5864 μmol/L | Standard Deviation 2.03655 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 3 | 0.0214 μmol/L | Standard Deviation 0.51249 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 6 | 3.6338 μmol/L | Standard Deviation 2.33168 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 8 | 4.8094 μmol/L | Standard Deviation 3.07316 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 12 | 6.0705 μmol/L | Standard Deviation 2.0418 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 42 | 0.5985 μmol/L | Standard Deviation 4.89669 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Baseline (Day 1) | 2.1375 μmol/L | Standard Deviation 0.79158 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 6 | 0.2565 μmol/L | Standard Deviation 0.78095 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 8 | 0.3420 μmol/L | Standard Deviation 0.69611 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 12 | 0.4061 μmol/L | Standard Deviation 0.78062 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 15 | 0.7481 μmol/L | Standard Deviation 0.46551 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 22 | 1.0901 μmol/L | Standard Deviation 0.85225 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 28 | -0.0428 μmol/L | Standard Deviation 0.67632 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 35 | 0.0000 μmol/L | Standard Deviation 0.80725 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 42 | -0.1069 μmol/L | Standard Deviation 1.08896 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 49 | 0.0641 μmol/L | Standard Deviation 0.45645 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 56 | -0.2565 μmol/L | Standard Deviation 0.62663 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 63 | -0.2779 μmol/L | Standard Deviation 0.80174 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Baseline (Day 1) | 9.6188 μmol/L | Standard Deviation 3.53265 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 15 | 5.3651 μmol/L | Standard Deviation 2.82455 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 22 | 8.4645 μmol/L | Standard Deviation 4.99216 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 28 | 0.1069 μmol/L | Standard Deviation 3.4382 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 35 | 0.6840 μmol/L | Standard Deviation 1.99837 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 49 | 1.5604 μmol/L | Standard Deviation 2.81789 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 56 | -1.3039 μmol/L | Standard Deviation 2.45421 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 63 | -0.6413 μmol/L | Standard Deviation 2.44536 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 11 | 4.7880 μmol/L | Standard Deviation 1.89494 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 28 | 0.1710 μmol/L | Standard Deviation 0.49561 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 21 | 0.8835 μmol/L | Standard Deviation 0.34905 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 21 | 6.6975 μmol/L | Standard Deviation 1.87139 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 14 | 0.2850 μmol/L | Standard Deviation 0.33625 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 63 | 1.9095 μmol/L | Standard Deviation 2.35811 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 11 | 0.7695 μmol/L | Standard Deviation 0.58989 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 7 | 0.8550 μmol/L | Standard Deviation 0.47141 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 56 | 0.5415 μmol/L | Standard Deviation 1.86199 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 28 | 1.5105 μmol/L | Standard Deviation 3.13339 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 5 | 0.4845 μmol/L | Standard Deviation 0.54524 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 2 | 0.4275 μmol/L | Standard Deviation 0.40103 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 7 | 6.6120 μmol/L | Standard Deviation 2.54018 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 35 | 0.8550 μmol/L | Standard Deviation 1.00294 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Baseline (Day 1) | 1.7100 μmol/L | Standard Deviation 0 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 42 | 0.6270 μmol/L | Standard Deviation 2.71598 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 5 | 4.8165 μmol/L | Standard Deviation 3.79823 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 49 | 1.5105 μmol/L | Standard Deviation 2.40233 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 14 | 5.7000 μmol/L | Standard Deviation 1.55099 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Baseline (Day 1) | 8.2650 μmol/L | Standard Deviation 1.28724 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 63 | 0.2565 μmol/L | Standard Deviation 0.51584 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 2 | 3.3915 μmol/L | Standard Deviation 2.22541 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 56 | 0.0855 μmol/L | Standard Deviation 0.49265 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 49 | 0.1995 μmol/L | Standard Deviation 0.59646 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 42 | -0.1140 μmol/L | Standard Deviation 0.35322 |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 35 | 0.0855 μmol/L | Standard Deviation 0.41536 |
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.
Time frame: 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
Population: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Cmax Following Repeat Dose Administration of VH4004280 | Day 1 | 422.68 ng/mL | Geometric Coefficient of Variation 15.53 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Cmax Following Repeat Dose Administration of VH4004280 | Day 14 | 1725.63 ng/mL | Geometric Coefficient of Variation 36.64 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Cmax Following Repeat Dose Administration of VH4004280 | Day 2 | 972.51 ng/mL | Geometric Coefficient of Variation 26.49 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Cmax Following Repeat Dose Administration of VH4004280 | Day 15 | 4487.14 ng/mL | Geometric Coefficient of Variation 42.27 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Cmax Following Repeat Dose Administration of VH4004280 | Day 1 | 957.92 ng/mL | Geometric Coefficient of Variation 21.7 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Cmax Following Repeat Dose Administration of VH4004280 | Day 14 | 7573.63 ng/mL | Geometric Coefficient of Variation 66.1 |
Primary
Part 2: Number of Participants Discontinuing Treatment Due to AEs
Number of participants who discontinued treatment due to AEs are presented.
Time frame: Up to Day 63
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Number of Participants Discontinuing Treatment Due to AEs | 0 Participants |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Number of Participants Discontinuing Treatment Due to AEs | 0 Participants |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Number of Participants Discontinuing Treatment Due to AEs | 0 Participants |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Number of Participants Discontinuing Treatment Due to AEs | 0 Participants |
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.
Time frame: Up to Day 63
Population: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Number of Participants With Any AEs and by Severity | Any AEs | 3 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Number of Participants With Any AEs and by Severity | Grade 1 AEs | 3 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Number of Participants With Any AEs and by Severity | Grade 2 AEs | 0 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Number of Participants With Any AEs and by Severity | Grade 3 AEs | 0 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Number of Participants With Any AEs and by Severity | Grade 4 AEs | 0 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Number of Participants With Any AEs and by Severity | Grade 5 AEs | 0 Participants |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Number of Participants With Any AEs and by Severity | Grade 5 AEs | 0 Participants |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Number of Participants With Any AEs and by Severity | Grade 3 AEs | 0 Participants |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Number of Participants With Any AEs and by Severity | Any AEs | 4 Participants |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Number of Participants With Any AEs and by Severity | Grade 2 AEs | 0 Participants |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Number of Participants With Any AEs and by Severity | Grade 1 AEs | 4 Participants |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Number of Participants With Any AEs and by Severity | Grade 4 AEs | 0 Participants |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Number of Participants With Any AEs and by Severity | Grade 1 AEs | 4 Participants |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Number of Participants With Any AEs and by Severity | Grade 2 AEs | 3 Participants |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Number of Participants With Any AEs and by Severity | Grade 3 AEs | 0 Participants |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Number of Participants With Any AEs and by Severity | Grade 5 AEs | 0 Participants |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Number of Participants With Any AEs and by Severity | Grade 4 AEs | 0 Participants |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Number of Participants With Any AEs and by Severity | Any AEs | 7 Participants |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Number of Participants With Any AEs and by Severity | Grade 4 AEs | 1 Participants |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Number of Participants With Any AEs and by Severity | Grade 5 AEs | 0 Participants |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Number of Participants With Any AEs and by Severity | Grade 1 AEs | 2 Participants |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Number of Participants With Any AEs and by Severity | Grade 3 AEs | 1 Participants |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Number of Participants With Any AEs and by Severity | Any AEs | 4 Participants |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Number of Participants With Any AEs and by Severity | Grade 2 AEs | 0 Participants |
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.
Time frame: Up to Day 63
Population: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | AST, Increase to Grade 3 | 0 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALT, Increase to Grade 1 | 1 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | AST, Increase to Grade 4 | 0 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Total Bilirubin, Increase to Grade 3 | 0 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Total Bilirubin, Increase to Grade 1 | 0 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALT, Increase to Grade 4 | 0 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Total Bilirubin, Increase to Grade 2 | 0 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALP, Increase to Grade 4 | 0 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Direct Bilirubin, Increase to Grade 3 | 0 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALP, Increase to Grade 1 | 0 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALT, Increase to Grade 2 | 0 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALP, Increase to Grade 2 | 0 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Direct Bilirubin, Increase to Grade 2 | 0 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALP, Increase to Grade 3 | 0 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Direct Bilirubin, Increase to Grade 4 | 0 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Direct Bilirubin, Increase to Grade 1 | 0 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | AST, Increase to Grade 1 | 1 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALT, Increase to Grade 3 | 0 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | AST, Increase to Grade 2 | 0 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Total Bilirubin, Increase to Grade 4 | 0 Participants |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Direct Bilirubin, Increase to Grade 2 | 0 Participants |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | AST, Increase to Grade 3 | 0 Participants |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Total Bilirubin, Increase to Grade 4 | 0 Participants |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Total Bilirubin, Increase to Grade 3 | 0 Participants |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALP, Increase to Grade 2 | 0 Participants |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | AST, Increase to Grade 4 | 0 Participants |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Direct Bilirubin, Increase to Grade 3 | 0 Participants |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALT, Increase to Grade 2 | 0 Participants |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALT, Increase to Grade 3 | 0 Participants |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Total Bilirubin, Increase to Grade 1 | 0 Participants |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | AST, Increase to Grade 1 | 0 Participants |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Total Bilirubin, Increase to Grade 2 | 0 Participants |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALP, Increase to Grade 3 | 0 Participants |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALT, Increase to Grade 4 | 0 Participants |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALT, Increase to Grade 1 | 1 Participants |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Direct Bilirubin, Increase to Grade 4 | 0 Participants |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Direct Bilirubin, Increase to Grade 1 | 0 Participants |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALP, Increase to Grade 4 | 0 Participants |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALP, Increase to Grade 1 | 0 Participants |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | AST, Increase to Grade 2 | 0 Participants |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALT, Increase to Grade 3 | 0 Participants |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALT, Increase to Grade 1 | 0 Participants |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALT, Increase to Grade 2 | 0 Participants |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALT, Increase to Grade 4 | 0 Participants |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALP, Increase to Grade 1 | 0 Participants |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALP, Increase to Grade 2 | 0 Participants |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALP, Increase to Grade 3 | 0 Participants |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALP, Increase to Grade 4 | 0 Participants |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | AST, Increase to Grade 1 | 1 Participants |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | AST, Increase to Grade 2 | 0 Participants |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | AST, Increase to Grade 3 | 0 Participants |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | AST, Increase to Grade 4 | 0 Participants |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Total Bilirubin, Increase to Grade 1 | 0 Participants |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Total Bilirubin, Increase to Grade 2 | 0 Participants |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Total Bilirubin, Increase to Grade 3 | 0 Participants |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Total Bilirubin, Increase to Grade 4 | 0 Participants |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Direct Bilirubin, Increase to Grade 1 | 0 Participants |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Direct Bilirubin, Increase to Grade 2 | 0 Participants |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Direct Bilirubin, Increase to Grade 3 | 0 Participants |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Direct Bilirubin, Increase to Grade 4 | 0 Participants |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | AST, Increase to Grade 2 | 0 Participants |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | AST, Increase to Grade 1 | 0 Participants |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Direct Bilirubin, Increase to Grade 3 | 0 Participants |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Total Bilirubin, Increase to Grade 4 | 0 Participants |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALP, Increase to Grade 4 | 0 Participants |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALP, Increase to Grade 3 | 0 Participants |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALT, Increase to Grade 2 | 0 Participants |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Direct Bilirubin, Increase to Grade 1 | 0 Participants |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALP, Increase to Grade 2 | 0 Participants |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALP, Increase to Grade 1 | 0 Participants |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALT, Increase to Grade 1 | 1 Participants |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Direct Bilirubin, Increase to Grade 2 | 0 Participants |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALT, Increase to Grade 4 | 0 Participants |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Total Bilirubin, Increase to Grade 1 | 0 Participants |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALT, Increase to Grade 3 | 0 Participants |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Total Bilirubin, Increase to Grade 2 | 0 Participants |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | AST, Increase to Grade 4 | 0 Participants |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | AST, Increase to Grade 3 | 1 Participants |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Direct Bilirubin, Increase to Grade 4 | 0 Participants |
| Part 1 (SAD): VH4004280 150 mg PiB | Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Total Bilirubin, Increase to Grade 3 | 0 Participants |
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.
Time frame: 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
Population: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: T1/2 Following Repeat Dose Administration of VH4004280 | Day 14 to Day 63 | 166.29 hours | Geometric Coefficient of Variation 34.95 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: T1/2 Following Repeat Dose Administration of VH4004280 | Day 15 to Day 63 | 207.76 hours | Geometric Coefficient of Variation 35.36 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: T1/2 Following Repeat Dose Administration of VH4004280 | Day 14 to Day 63 | 147.93 hours | Geometric Coefficient of Variation 56.42 |
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.
Time frame: 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
Population: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Tmax Following Repeat Dose Administration of VH4004280 | Day 1 | 9.28 hours | Geometric Coefficient of Variation 11.56 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 2: Tmax Following Repeat Dose Administration of VH4004280 | Day 14 | 9.58 hours | Geometric Coefficient of Variation 15.72 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Tmax Following Repeat Dose Administration of VH4004280 | Day 2 | 9.68 hours | Geometric Coefficient of Variation 13.38 |
| Part 1 (SAD): VH4004280 10 mg PiB | Part 2: Tmax Following Repeat Dose Administration of VH4004280 | Day 15 | 9.33 hours | Geometric Coefficient of Variation 21.14 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Tmax Following Repeat Dose Administration of VH4004280 | Day 1 | 9.57 hours | Geometric Coefficient of Variation 15.66 |
| Part 1 (SAD): VH4004280 50 mg PiB | Part 2: Tmax Following Repeat Dose Administration of VH4004280 | Day 14 | 15.49 hours | Geometric Coefficient of Variation 50.84 |
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.
Time frame: Up to Day 49
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Baseline (Day 1) | 55.7 IU/L | Standard Deviation 11.78 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Day 2 | 47.8 IU/L | Standard Deviation 10.76 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Day 3 | 50.2 IU/L | Standard Deviation 10.63 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Day 4 | 50.8 IU/L | Standard Deviation 9.68 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Day 5 | 48.8 IU/L | Standard Deviation 7.94 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Day 6 | 49.7 IU/L | Standard Deviation 10.84 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Day 7 | 50.3 IU/L | Standard Deviation 9.29 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Day 14 | 60.2 IU/L | Standard Deviation 18.27 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Day 21 | 58.0 IU/L | Standard Deviation 15.47 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Day 28 | 59.7 IU/L | Standard Deviation 18.99 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Day 35 | 59.5 IU/L | Standard Deviation 16.43 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Day 42 | 58.2 IU/L | Standard Deviation 8.81 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALP, Day 49 | 55.8 IU/L | Standard Deviation 13.39 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Baseline (Day 1) | 24.3 IU/L | Standard Deviation 17.07 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Day 2 | 19.2 IU/L | Standard Deviation 13.04 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Day 3 | 19.2 IU/L | Standard Deviation 11 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Day 4 | 19.2 IU/L | Standard Deviation 8.8 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Day 5 | 18.7 IU/L | Standard Deviation 8.36 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Day 6 | 20.3 IU/L | Standard Deviation 9.2 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Day 7 | 21.3 IU/L | Standard Deviation 10.78 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Day 14 | 44.7 IU/L | Standard Deviation 64.91 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Day 21 | 31.3 IU/L | Standard Deviation 34.51 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Day 28 | 41.8 IU/L | Standard Deviation 57.78 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Day 35 | 26.7 IU/L | Standard Deviation 22.9 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Day 42 | 34.6 IU/L | Standard Deviation 47.24 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | ALT, Day 49 | 26.3 IU/L | Standard Deviation 30.8 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Baseline (Day 1) | 17.5 IU/L | Standard Deviation 4.28 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Day 2 | 15.2 IU/L | Standard Deviation 3.49 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Day 3 | 15.2 IU/L | Standard Deviation 3.37 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Day 4 | 15.7 IU/L | Standard Deviation 2.42 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Day 5 | 15.3 IU/L | Standard Deviation 2.8 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Day 6 | 17.5 IU/L | Standard Deviation 4.68 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Day 7 | 17.2 IU/L | Standard Deviation 5.23 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Day 14 | 24.3 IU/L | Standard Deviation 19.58 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Day 21 | 20.0 IU/L | Standard Deviation 7.97 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Day 28 | 24.5 IU/L | Standard Deviation 16.72 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Day 35 | 21.2 IU/L | Standard Deviation 7.91 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Day 42 | 28.2 IU/L | Standard Deviation 27.31 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Absolute Values of Liver Panel Parameters: ALP, ALT and AST | AST, Day 49 | 19.5 IU/L | Standard Deviation 9.71 |
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.
Time frame: Up to Day 49
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Absolute Values of Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Baseline (Day 1) | 1.9950 μmol/L | Standard Deviation 0.6981 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Absolute Values of Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 2 | 2.3085 μmol/L | Standard Deviation 0.68186 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Absolute Values of Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 3 | 2.2515 μmol/L | Standard Deviation 0.59646 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Absolute Values of Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 4 | 2.1660 μmol/L | Standard Deviation 0.66375 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Absolute Values of Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 5 | 1.9380 μmol/L | Standard Deviation 0.57905 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Absolute Values of Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 6 | 2.2800 μmol/L | Standard Deviation 0.55848 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Absolute Values of Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 7 | 1.7670 μmol/L | Standard Deviation 0.6981 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Absolute Values of Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 14 | 1.7385 μmol/L | Standard Deviation 0.77549 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Absolute Values of Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 21 | 1.9380 μmol/L | Standard Deviation 1.02979 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Absolute Values of Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 28 | 1.8525 μmol/L | Standard Deviation 0.79043 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Absolute Values of Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 35 | 1.8525 μmol/L | Standard Deviation 0.72077 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Absolute Values of Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 42 | 1.9494 μmol/L | Standard Deviation 0.56196 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Absolute Values of Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 4 | 10.4025 μmol/L | Standard Deviation 2.63898 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Absolute Values of Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 5 | 10.7730 μmol/L | Standard Deviation 3.30875 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Absolute Values of Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 6 | 11.3715 μmol/L | Standard Deviation 2.69888 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Absolute Values of Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 7 | 8.8635 μmol/L | Standard Deviation 3.39669 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Absolute Values of Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 14 | 8.7780 μmol/L | Standard Deviation 5.31551 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Absolute Values of Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 21 | 9.0915 μmol/L | Standard Deviation 5.22647 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Absolute Values of Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 28 | 8.8920 μmol/L | Standard Deviation 4.03357 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Absolute Values of Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 35 | 10.0890 μmol/L | Standard Deviation 5.11859 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Absolute Values of Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 42 | 8.8920 μmol/L | Standard Deviation 2.2524 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Absolute Values of Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 49 | 8.4645 μmol/L | Standard Deviation 2.29866 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Absolute Values of Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 49 | 1.6530 μmol/L | Standard Deviation 0.39981 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Absolute Values of Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Baseline (Day 1) | 9.9750 μmol/L | Standard Deviation 4.2464 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Absolute Values of Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 2 | 12.2550 μmol/L | Standard Deviation 4.312 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Absolute Values of Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 3 | 11.0580 μmol/L | Standard Deviation 3.23487 |
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.
Time frame: From Baseline (Day 1) and up to Day 49
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Baseline (Day 1) | 55.7 IU/L | Standard Deviation 11.78 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 2 | -7.8 IU/L | Standard Deviation 3.13 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 3 | -5.5 IU/L | Standard Deviation 3.02 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 4 | -4.8 IU/L | Standard Deviation 2.86 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 5 | -6.8 IU/L | Standard Deviation 5.64 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 6 | -6.0 IU/L | Standard Deviation 2.61 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 7 | -5.3 IU/L | Standard Deviation 4.89 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 14 | 4.5 IU/L | Standard Deviation 9.81 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 21 | 2.3 IU/L | Standard Deviation 9.87 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 28 | 4.0 IU/L | Standard Deviation 12.2 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 35 | 3.8 IU/L | Standard Deviation 8.16 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 42 | -0.2 IU/L | Standard Deviation 5.93 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALP, Day 49 | 0.2 IU/L | Standard Deviation 6.05 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Baseline (Day 1) | 24.3 IU/L | Standard Deviation 17.07 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 2 | -5.2 IU/L | Standard Deviation 4.49 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 3 | -5.2 IU/L | Standard Deviation 6.4 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 4 | -5.2 IU/L | Standard Deviation 8.57 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 5 | -5.7 IU/L | Standard Deviation 8.87 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 6 | -4.0 IU/L | Standard Deviation 8.44 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 7 | -3.0 IU/L | Standard Deviation 7.32 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 14 | 20.3 IU/L | Standard Deviation 48.5 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 21 | 7.0 IU/L | Standard Deviation 17.85 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 28 | 17.5 IU/L | Standard Deviation 41.15 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 35 | 2.3 IU/L | Standard Deviation 6.53 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 42 | 10.2 IU/L | Standard Deviation 28.44 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | ALT, Day 49 | 2.0 IU/L | Standard Deviation 15.07 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Baseline (Day 1) | 17.5 IU/L | Standard Deviation 4.28 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 2 | -2.3 IU/L | Standard Deviation 2.58 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 3 | -2.3 IU/L | Standard Deviation 3.33 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 4 | -1.8 IU/L | Standard Deviation 3.13 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 5 | -2.2 IU/L | Standard Deviation 2.79 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 6 | 0.0 IU/L | Standard Deviation 3.63 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 7 | -0.3 IU/L | Standard Deviation 3.08 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 14 | 6.8 IU/L | Standard Deviation 15.46 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 21 | 2.5 IU/L | Standard Deviation 4.04 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 28 | 7.0 IU/L | Standard Deviation 12.59 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 35 | 3.7 IU/L | Standard Deviation 6.35 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 42 | 10.6 IU/L | Standard Deviation 22.61 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST | AST, Day 49 | 2.0 IU/L | Standard Deviation 6.87 |
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.
Time frame: From Baseline (Day 1) and up to Day 49
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 35 | -0.1425 μmol/L | Standard Deviation 0.22729 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 42 | -0.1026 μmol/L | Standard Deviation 0.72145 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 49 | -0.3420 μmol/L | Standard Deviation 0.50727 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Baseline (Day 1) | 9.9750 μmol/L | Standard Deviation 4.2464 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 2 | 2.2800 μmol/L | Standard Deviation 1.65673 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 3 | 1.0830 μmol/L | Standard Deviation 2.1073 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 4 | 0.4275 μmol/L | Standard Deviation 2.53346 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 5 | 0.7980 μmol/L | Standard Deviation 2.64396 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 6 | 1.3965 μmol/L | Standard Deviation 2.58072 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 7 | -1.1115 μmol/L | Standard Deviation 3.1153 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 14 | -1.1970 μmol/L | Standard Deviation 2.45193 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 21 | -0.8835 μmol/L | Standard Deviation 2.28249 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 28 | -1.0830 μmol/L | Standard Deviation 2.22344 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 35 | 0.1140 μmol/L | Standard Deviation 3.42285 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 42 | -2.0520 μmol/L | Standard Deviation 4.26987 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Total Bilirubin, Day 49 | -1.5105 μmol/L | Standard Deviation 2.99795 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Baseline (Day 1) | 1.9950 μmol/L | Standard Deviation 0.6981 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 2 | 0.3135 μmol/L | Standard Deviation 0.4382 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 3 | 0.2565 μmol/L | Standard Deviation 0.40103 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 4 | 0.1710 μmol/L | Standard Deviation 0.55146 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 5 | -0.0570 μmol/L | Standard Deviation 0.62752 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 6 | 0.2850 μmol/L | Standard Deviation 0.50341 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 7 | -0.2280 μmol/L | Standard Deviation 0.65488 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 14 | -0.2565 μmol/L | Standard Deviation 0.23571 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 21 | -0.0570 μmol/L | Standard Deviation 0.54791 |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin | Direct Bilirubin, Day 28 | -0.1425 μmol/L | Standard Deviation 0.39614 |
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.
Time frame: Up to Day 49
Population: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Number of Participants With Any AEs and by Severity | Any AEs | 3 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Number of Participants With Any AEs and by Severity | Grade 1 AEs | 2 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Number of Participants With Any AEs and by Severity | Grade 2 AEs | 0 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Number of Participants With Any AEs and by Severity | Grade 3 AEs | 1 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Number of Participants With Any AEs and by Severity | Grade 4 AEs | 0 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Number of Participants With Any AEs and by Severity | Grade 5 AEs | 0 Participants |
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.
Time frame: Up to Day 49
Population: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALT, Increase to Grade 3 | 0 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALT, Increase to Grade 4 | 0 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALP, Increase to Grade 1 | 0 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALP, Increase to Grade 2 | 0 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALP, Increase to Grade 3 | 0 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALP, Increase to Grade 4 | 0 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | AST, Increase to Grade 1 | 1 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | AST, Increase to Grade 2 | 0 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | AST, Increase to Grade 3 | 0 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | AST, Increase to Grade 4 | 0 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Total Bilirubin, Increase to Grade 1 | 0 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Total Bilirubin, Increase to Grade 2 | 0 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Total Bilirubin, Increase to Grade 3 | 0 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Total Bilirubin, Increase to Grade 4 | 0 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Direct Bilirubin, Increase to Grade 1 | 0 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Direct Bilirubin, Increase to Grade 2 | 0 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Direct Bilirubin, Increase to Grade 3 | 0 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | Direct Bilirubin, Increase to Grade 4 | 0 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALT, Increase to Grade 1 | 0 Participants |
| Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) | Part 3: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters | ALT, Increase to Grade 2 | 1 Participants |